SlideShare a Scribd company logo

Decreasing or Increasing Role of Autologous Stem Cell Transplantation in Multiple Myeloma?

During the past four decades, autologous stem cell transplantation (ASCT) has been the first choice and the standard option for the treatment of newly diagnosed patients with multiple myeloma. The introduction of new agents such as thalidomide, lenalidomide, and bortezomib has led to a clear improvement in basic approach and those agents became the standard of care in the induction phase; however, they were not able to play the role of ASCT in term of progression-free survival and overall survival. Debate continues about the best induction, consolidation, and maintenance taking into account the toxicities of these new agents. The new monoclonal antibody (anti CD38) starts to take its place in the induction setting and it seems to be a promising agent in the high-risk group. Until recently, ASCT is the standard treatment for newly diagnosed patients.

1 of 6
Download to read offline
Clinical Research in Hematology  •  Vol 3  •  Issue 1  •  2020 12
INTRODUCTION
Multiple myeloma (MM) forms about 10% of hematologic
malignancies and the first indication for autologous stem cell
transplantation (ASCT) among these malignancies.[1,2]
The
introduction of high-dose chemotherapy (HDC) followed by
ASCT has become the standard of care in newly diagnosed
patients[3,4]
after huge efforts and trials conducted in both
Europe and the United States.[5,6]
Koreth et al. demonstrated
that ASCT has failed to add the maximum to the overall
survival (OS); however, the event-free survival was
improved.[7]
Debate is still ongoing about the precise timing
of ASCT, is it upfront, after complete response (CR) or upon
progression or relapse?[6]
During the last three decades, we
have witnessed a dramatic shift in MM patients’ approach
after the introduction of the new agents such as thalidomide,
lenalidomide, and bortezomib before or after HD/ASCT.
This new combination has improved CR on the molecular
level.[8]
New trials are evaluating the new monoclonal
antibodies (anti-CD38) in both induction and maintenance
setting. To which extent, the introduction of these new
agents may influence the utilization of ASCT? In this review,
we are going to answer this question and other questions
regarding the feasibility of ASCT taking into account several
variables such as age, performance status, renal function, best
induction, best maintenance, and other related issues.
UPFRONT ASCT IN NEWLY
DIAGNOSED ELIGIBLE PATIENTS
ASCT proceeded by conditioning with high-dose Melphalan
is considered the standard of care in newly diagnosed patients
with MM.[9,10]
First reports defined eligible patients as those
younger than 65 years old as a cutoff; however, several bone
marrow transplantation communities extended the cutoff age
to exceed 65 years.[11]
Trials are conducted to evaluate high-
dose Melphalan in patients older than 65 years and found
that treatment-related mortality (TRM) was zero at day +100
when comparing 140 mg/m2
and 200 mg/m2
.[12]
Other trials
compared 200 mg/m2
in younger patients versus 100mg/
m2
in a tandem mode in patients between 65 and 75 years
old with no difference in progression-free survival (PFS),
OS, or TRM.[13]
However, other factors should be taken into
consideration in older age groups such as renal functions,
REVIEW ARTICLE
Decreasing or Increasing Role of Autologous Stem
Cell Transplantation in Multiple Myeloma?
Maher Salamoon
Department of Medical Oncology, Al Bairouni University Cancer Center, Damascus University, Damascus, Syria
ABSTRACT
During the past four decades, autologous stem cell transplantation (ASCT) has been the first choice and the standard option
for the treatment of newly diagnosed patients with multiple myeloma. The introduction of new agents such as thalidomide,
lenalidomide, and bortezomib has led to a clear improvement in basic approach and those agents became the standard of
care in the induction phase; however, they were not able to play the role of ASCT in term of progression-free survival and
overall survival. Debate continues about the best induction, consolidation, and maintenance taking into account the toxicities
of these new agents. The new monoclonal antibody (anti CD38) starts to take its place in the induction setting and it seems
to be a promising agent in the high-risk group. Until recently, ASCT is the standard treatment for newly diagnosed patients.
Key words: Autologous, multiple, myeloma, stem cell, transplantation
Address for correspondence:
Maher Salamoon, Department of Medical Oncology, Al Bairouni University Cancer Center, Damascus University,
Damascus, Syria. Phone: +963933771086.
https://doi.org/10.33309/2639-8354.030103 www.asclepiusopen.com
© 2020 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license.
Salamoon: Role of ASCT in multiple myeloma
 Clinical Research in Hematology  •  Vol 3  •  Issue 1  •  2020
performance status, and other comorbidities. In some centers,
ASCTs are performed on elderly patients according to every
patient’s characteristics and outside clinical trials.
Renal function impairment is one of the most important
presenting signs in patients with MM attributed to high light
chain burden. This impairment is much more profound in
patients over 65 years; however, there is no contraindication
for ASCT in this subgroup of patients. In these cases,
toxicities attributed to HD chemotherapy are more frequent
than those with normal renal functions.[14,15]
Report from the
Polish society of MM demonstrated that dialysis-dependent
cases are more likely to develop toxicities such as infections
and mucositis; however, PFS and OS rates were comparable
to other patients presenting with normal functions.[16]
HISTORY AND PRESENT OF
INDUCTION CHEMOTHERAPY
Before and after the era of ASCT, induction chemotherapy
was the major treatment that aims to reduce the burden of
plasma cell in bone marrow, improving the local environment
and facilitate engraftment as well. The first induction
backbone was the alkylating agents, then the triplet of
vincristine, doxorubicin, and dexamethasone (VAD).[1]
This
induction was replaced by either thalidomide or bortezomib
or both which proven to better than VAD in term of complete
response (CR).[17,18]
Later trials showed that the triplet of
bortezomib, thalidomide, and dexamethasone (VTD) was
superior to VD and TD.[19,20]
Thus, VTD became the standard
induction of choice in MM patients prepared for ASCT with
3–4 cycles given. Some centers give six cycles to attain a
more profound response; however, peripheral neuropathy
may limit this trend in some patients.[20]
Soon after, VTD
was replaced by many MM societies by VRD after replacing
thalidomide with the newer version lenalidomide. VRD
demonstrated better PFS and OS when compared to VTD.[21]
The new monoclonal antibody against CD38 daratumumab
(DARA) was evaluated in the induction phase in combination
with VRD and VTD, showing some encouraging results when
compared with VRD alone.[22,23]
DARA was also combined
in a Phase II trial with bortezomib, cyclophosphamide,
and dexamethasone and also used in a Phase Ib trial with
carfilzomib and lenalidomide demonstrating a response rate
exceeding 95% in both trials.[24,25]
CHEMOPRIMING
Mobilization of hematopoietic stem cells (CD34) with a
minimum of 2 × 106
CD34 per kg of body weight is essential
for good engraftment; however, the optimal amount is 5 × 106
CD34/kg which can be done by a steady-state mobilization
after giving granulocytes colony-stimulating factor (G-CSF)
over several days or chemopriming through preparation with
chemotherapeutic agents.[26]
The two approved cytokines
for mobilization are filgrastim (10 μg/kg/day for 4–6 days
and apheresis on days 5 or 6) according to the optimal
number of CD34 in peripheral blood. The other cytokines
are lenograstim (10 μg/kg/day for 4–6 days and apheresis
between days 5 and 7); however, mobilization using G-CSF
alone is still suboptimal.[27]
The most commonly used agent
for chemopriming is high-dose cyclophosphamide (2–4 g/m2
),
followed by filgrastim or lenograstim (5 μg/kg/day 1–5 days
after completion of chemotherapy. This procedure can offer
a good CD34 amount; however, the time to transplantation
is prolonged and toxicities are reported as well.[28]
In some
patients who fail to mobilize the optimal amount of CD34, the
chemokine receptor-4 (CXCR-4) antagonist (plerixafor) can
increase the mobilization effect of G-CSF.[27]
Trials compared
to the addition of cytarabine to G-CSF versus G-CSF alone
in Phase III randomized trials reported better results in the
cytarabine arm; however, toxicity profile was high.[29]
We
should stress that using lenalidomide in the induction may
impair mobilization process through upgrading CXCR-4
receptors; however, this process can be antagonist by
plerixafor which found to be effective in this case.[30]
CONDITIONING
Intravenous Melphalan at a dose of 200 mg/m2
is the
best high-dose conditioning regimen so far. Attempts to
replace it with oral Melphalan or intravenous busulfan
have failed.[31]
The combination of intravenous busulfan
130 mg/m2
over 4 days and Melphalan 70 mg/m2
for
over 2 days demonstrated better PFS with no significant
improvement in response rate.[32]
In a randomized trial
conducted by Bensinger et al., a comparison between
Melphalan 200 mg/m2
and 280 mg/m2
demonstrated better
ORR with no impact on PFS and OS.[33]
THE ROLE OF CONSOLIDATION
AND MAINTENANCE AFTER ASCT
The Italian myeloma study group reported better CR and PFS
rates using VTD compared with the TD arm in both induction
and consolidation after ASCT[34]
and this result was better
in patients demonstrating good response after ASCT which
reflected in complete pathologic and molecular response.[8]
Sonneveld et al. reported better PFS with two cycles of VRD
proceeding lenalidomide compared with lenalidomide as
consolidation;[35]
however, VRD failed to prolong PFS in
patients with a high-risk profile of cytogenetic abnormalities
[t(4:14) and/or del17p and/or t(14:16)].[35]
These results
indicate that VRD as consolidation before maintenance with
lenalidomide is of benefit in those young patients with low-
risk cytogenetic profile. Results do not support the regular
indication of consolidation after ASCT and more randomized
trials are needed to support the former idea.
Salamoon: Role of ASCT in multiple myeloma
Clinical Research in Hematology  •  Vol 3  •  Issue 1  •  2020 14
Consolidation and maintenance are thought to deepen the
first response obtained after ASCT and to prevent relapse and
prolong survival; however, ASCT is not a curative procedure
that is why concentration was made on maintenance therapy
with the new agents such as thalidomide and lenalidomide.[36]
Thalidomide was the first agent to use in the maintenance
setting after being tested in several randomized trials. This
agent showed a good response; however, the OS rate was
not encouraging. Since thalidomide can lead to a profound
peripheral neuropathy, the duration of use was limited to
6–12 months, as reported Spencer et al.[37]
Lenalidomide was
also tested in maintenance and demonstrated better response
than placebo and led to prolongation of PFS in all subgroups
of patients, especially in those attained more deep response
after ASCT. OS improved in the lenalidomide arm except in
women older than 60 years, presenting with a bad cytogenetic
profile.[38]
The treatment-limiting duration of lenalidomide
is determined by the progression of secondary tumor which
was reported and toxicities. Thus, thalidomide is given at a
dose of 100 mg/day and lenalidomide at a low dose for a
period of time in the light of side effects.[38]
A designed plan
is illustrated in Figure 1 showing the current practice and
the future direction in treatment of newly diagnosed cases
of MM.
NON-TRANSPLANT STRATEGY
Before the era of the new agents, two large trials compared
HDC followed by ASCT with HDC alone demonstrated
prolonged of both PFS and OS.[5,6]
Most trials were conducted
before 2010 and did not include the new agents until recently
where four phase III trials compared HDC followed by
ASCT with a combination of the new agents, as illustrated
in Table 1.
Speed look on the former four trials demonstrates that
induction followed by ASCT was better in term of PFS and
OS than non-transplant strategy. The most important trial
thereafter was the IFM 2009 where 700 newly diagnosed
patients to receive three RVD cycles then divided into
two arms: The first arm received one course of high-dose
Melphalan followed by ASCT then another two RVD cycles,
where patients in the second arm received another five cycles
of RVD. Higher complete remission rates were observed in
the ASCT arm (59% vs. 48%; P = 0.03) and minimal residual
disease negativity (79% vs. 65%; P  0.001); however,
no difference in term of OS was observed at 4 years.[6]
All
conducted trials comparing ASCT versus non-ASCT arm
demonstrated better response and PFS rates; however, OS was
not significant unless in two trials, therefore, ASCT continues
to be the standard of care in newly diagnosed patients. Early
ASCT was evaluated in three trials with the improvement of
interval to relapse; however, no difference was reported in
term of OS.[39]
In real practice, to answer the question whether
early or delayed ASCT, randomized trials are needed with
stratification of patients according to their clinical, biologic,
and cytogenetic profile, then we can know which patient will
get a better benefit from early or delayed one.
Table 1: The main four Phase III randomized trials comparing HD-chemotherapy followed by ASCT with
treatment with new agents
Author Study design PFS OS
Attal et al. RVD × 5 cycles versus HD-M + ASCT (×1) +
RVD × 2 cycles
50 versus 36 mon.
P0.001
4 y: 81% versus 80%
P:NS
Cavo et al. VMP × 4 cycles versus HD-M + ASCT (×1 versus ×2) 3 y: 66% versus 58%
P0.037
NA
Gay et al. CRD × 6 cycles versus HD-M + ASCT (×2) 43 versus 29 mon. 4 y: 86% versus 73%
P0.004
Palumbo et al. MPR × 6 cycles versus HD-M + ASCT (×2) 43 versus 22 mon.
P0.001
4 y: 82% versus 65%
P=0.02
HD-M: High-dose Melphalan, RVD: Lenalidomide, bortezomib, and dexamethasone, CRD: Cyclophosphamide, lenalidomide, and
dexamethasone, MPR: Melphalan, prednisolone and lenalidomide, VMP: Bortezomib, Melphalan, and prednisolone, PFS: Progression-free
survival, OS: Overall survival, ASCT: Autologous stem cell transplantation
Figure 1: The present practice and future direction in
approaching newly diagnosed patients with multiple myeloma
Salamoon: Role of ASCT in multiple myeloma
15 Clinical Research in Hematology  •  Vol 3  •  Issue 1  •  2020
Another issue to be raised is the difference between single
versus tandem ASCT. The IFM trial demonstrated that
tandem transplant showed longer PFS (36 vs. 25 months
P = 0.03) and better OS (58 vs. 48 P = 0.01). In a subgroup
analysis, patients with better results were those who have not
had a near-complete response after the first ASCT.[40]
The former results were supported by an Italian study
conducted by Cavo et al. demonstrated better response and
PFS rates; however, OS was similar in both arms (median,
71 vs. 65 months; P = 0.9).[41]
Cavo et al. also published data
from pooled three trials reporting better PFS and OS in the
tandem arm compared with the single ASCT.[42]
DISCUSSION AND CONCLUSION
The introduction of new agents did not replace the role of
ASCT, which remains so far the standard of care in newly
diagnosed patients with MM. during the past 4 decades,
ASCT has been compared with the HDC; however, the new
agents replaced the high-dose in comparison and it is early
to talk about complete replacement of ASCT by the new
agents. The first step was comparing RD with VRD which
showed superior results in term of PFS and OS. VRD seems
to be comparable to ASCT in term of PFS and OS as well.
[21]
The emerging role of the new agents was clarified in
four Phase III trials illustrated in Table 1. Trials should be
conducted in a randomized fashion to evaluate the real role of
the new agents with and without ASCT. The new monoclonal
antibody daratumumab should be included in the induction
phase in combination with VRD because of its encouraging
results. Most societies concentrate on adding a new agent to
the known triplet VRD then compare it with ASCT; however,
studies should be oriented toward improving the induction
to serve those ASCT ineligible patients. The development
of induction is also an important trend toward improving
results in a high-risk group. As we know, ASCT is a process
that takes time (induction, chemopriming, and stem cell
mobilization and conditioning) and this time takes about 3
months in the median which is not calculated when PFS and
OS are studied which is a great bias. If we omit the time to
perform the procedure, then VRD could exceedASCT in term
of OS since results are comparable. Finally, it is early to talk
about a decreasing role of ASCT in MM; however, the new
agents along with the monoclonal antibodies may delay the
procedure in some patients the thing that must be determined
after conducting a big randomized trial for this purpose.
REFERENCES
1.	 Harousseau JL, Moreau P. Autologous hematopoietic stem-
cell transplantation for multiple myeloma. N Engl J Med
2009;360:2645-54.
2.	 Becker N. Epidemiology of multiple myeloma. Recent Results
Cancer Res 2011;183:25-35.
3.	 McElwain TJ, Powles RL. High-dose intravenous melphalan
for plasma-cell leukaemia and myeloma. Lancet 1983;2:822-4.
4.	 Mohty M, Harousseau JL. Treatment of autologous stem cell
transplant-eligible multiple myeloma patients: Ten questions
and answers. Haematologica 2014;99:408-16.
5.	 Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE,
Hawkins  K, et al. High-dose chemotherapy with hematopoietic
stem-cell rescue for multiple myeloma. N Engl J Med
2003;348:1875-83.
6.	 Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D,
Escoffre M, et al. Lenalidomide, bortezomib, and
dexamethasone with transplantation in myeloma. N Engl J
Med 2017;376:1311-20.
7.	 Koreth J, Cutler CS, Djulbegovic B, Behl R, Schlossman RL,
Munshi NC, et al. High-dose therapy with single autologous
transplantation versus chemotherapy for newly diagnosed
multiple myeloma: A systematic review and meta-analysis of
randomized controlled trials. Biol Blood Marrow Transplant
2007;13:183-96.
8.	 Ladetto M, Pagliano G, Ferrero S, Cavallo F, Drandi D,
Santo L, et al. Major tumor shrinking and persistent molecular
remissions after consolidation with bortezomib, thalidomide,
and dexamethasone in patients with autografted myeloma. J
Clin Oncol 2010;28:2077-84.
9.	 Shah N, Callander N, Ganguly S, Gul Z, Hamadani M, Costa L,
et al. Hematopoietic stem cell transplantation for multiple
myeloma: Guidelines from the American society for blood
and marrow transplantation. Biol Blood Marrow Transplant
2015;21:1155-66.
10.	 Gay F, Engelhardt M, Terpos E, Wäsch R, Giaccone L,
Auner HW, et al. From transplant to novel cellular therapies in
multiple myeloma: European myeloma network guidelines and
future perspectives. Haematologica 2018;103:197-211.
11.	 Auner HW, Szydlo R, Hoek J, Goldschmidt H, Stoppa AM,
Morgan GJ, et al. Trends in autologous hematopoietic cell
transplantation for multiple myeloma in Europe: Increased
use and improved outcomes in elderly patients in recent years.
Bone Marrow Transplant 2015;50:209-15.
12.	 Garderet L, Beohou E, Caillot D, Stoppa AM, Touzeau C,
Chretien ML, et al. Upfront autologous stem cell
transplantation for newly diagnosed elderly multiple myeloma
patients: A prospective multicenter study. Haematologica
2016;101:1390-7.
13.	 Neukirchen J, Arat P, Teutloff C, Gerrlich C, Niedenhoff DL,
Boquoi A, et al. Favourable outcome of elderly patients with
multiple myeloma treated with tandem melphalan 100 high-
dose therapy, autologous stem cell transplantation and novel
agents-a single center experience. Blood 2016;128:3460.
14.	 Straka C, Liebisch P, Salwender H, Hennemann B,
Metzner B, Knop S, et al. Autotransplant with and without
induction chemotherapy in older multiple myeloma patients:
Long-term outcome of a randomized trial. Haematologica
2016;101:1398-406.
15.	 Badros A, Barlogie B, Siegel E, Roberts J, Langmaid C,
Zangari M, et al. Results of autologous stem cell transplant in
multiple myeloma patients with renal failure. Br J Haematol
2001;114:822-9.
16.	 Waszczuk-Gajda A, Lewandowski Z, Drozd-Sokołowska J,
Boguradzki P, Dybko J, Wróbel T, et al. Autologous peripheral
blood stem cell transplantation in dialysis-dependent multiple
Salamoon: Role of ASCT in multiple myeloma
Clinical Research in Hematology  •  Vol 3  •  Issue 1  •  2020 16
myeloma patients-DAUTOS study of the polish myeloma
study group. Eur J Haematol 2018;101:475-85.
17.	 Harousseau JL, Attal M, Avet-Loiseau H, Marit G, Caillot D,
Mohty M, et al. Bortezomib plus dexamethasone is superior to
vincristine plus doxorubicin plus dexamethasone as induction
treatment prior to autologous stem-cell transplantation in
newly diagnosed multiple myeloma: Results of the IFM 2005-
01 Phase III trial. J Clin Oncol 2010;28:4621-9.
18.	 Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ,
Navarro Coy N, et al. Cyclophosphamide, thalidomide, and
dexamethasone as induction therapy for newly diagnosed
multiple myeloma patients destined for autologous stem-cell
transplantation: MRC Myeloma IX randomized trial results.
Haematologica 2012;97:442-50.
19.	 Moreau P, Avet-Loiseau H, Facon T, Attal M, Tiab M, Hulin C,
et al. Bortezomib plus dexamethasone versus reduced-dose
bortezomib, thalidomide plus dexamethasone as induction
treatment before autologous stem cell transplantation in newly
diagnosed multiple myeloma. Blood 2011;118:5752-8.
20.	 Rosiñol L, Oriol A, Teruel AI, Hernández D, López-Jiménez J,
De la Rubia J, et al. Superiority of bortezomib, thalidomide, and
dexamethasone (VTD) as induction pretransplantation therapy
in multiple myeloma: A randomized Phase 3 PETHEMA/GEM
study. Blood 2012;120:1589-96.
21.	 Durie BG, Hoering A, Abidi MH, Rajkumar SV, Epstein J,
Kahanic SP, et al. Bortezomib with lenalidomide and
dexamethasone versus lenalidomide and dexamethasone alone
in patients with newly diagnosed myeloma without intent for
immediate autologous stem-cell transplant (SWOG S0777): A
randomised, open-label, Phase 3 trial. Lancet 2017;389:519-27.
22.	 MoreauP,AttalM,HulinC,ArnulfB,BelhadjK,Benboubker L,
et al. Bortezomib, thalidomide, and dexamethasone with
or without daratumumab before and after autologous stem-
cell transplantation for newly diagnosed multiple myeloma
(CASSIOPEIA): A randomised, open-label, phase 3 study.
Lancet 2019;394:29-38.
23.	 Voorhees PM, Costa LJ, Reeves B, Nathwani N, Rodriguez C,
Lutska Y, et al. Interim safety analysis of a Phase 2 randomized
study of daratumumab (Dara), lenalidomide (R), bortezomib
(V), and dexamethasone (d; Dara-RVd) vs. RVd in patients
(Pts) with newly diagnosed multiple myeloma (MM) eligible
for high-dose therapy (HDT) and autologous stem cell
transplantation (ASCT). Blood 2017;130:1879.
24.	 Yimer H, Melear J, Faber E, Bensinger W, Burke JM,
Narang  M, et al. Lyra:APhase 2 study of daratumumab (Dara)
plus cyclophosphamide, bortezomib, and dexamethasone
(Cybord) in newly diagnosed and relapsed patients (Pts) with
multiple myeloma (MM). Blood 2018;132:152.
25.	 Jakubowiak AJ, Chari A, Lonial S, Weiss BM, Comenzo RL,
Wu K, et al. Daratumumab (DARA) in combination with
carfilzomib, lenalidomide, and dexamethasone (KRd) in
patients (pts) with newly diagnosed multiple myeloma
(MMY1001): An open-label, Phase 1b study. J Clin Oncol
2017;35:8000.
26.	 Mohty M, Ho AD. In and out of the niche: Perspectives
in mobilization of hematopoietic stem cells. Exp Hematol
2011;39:723-9.
27.	 Mohty M, Duarte RF, Croockewit S, Hübel K, Kvalheim G,
Russell N. The role of plerixafor in optimizing peripheral blood
stem cell mobilization for autologous stem cell transplantation.
Leukemia 2011;25:1-6.
28.	 Bensinger W, DiPersio JF, McCarty JM. Improving stem
cell mobilization strategies: Future directions. Bone Marrow
Transplant 2009;43:181-95.
29.	 Czerw T, Sadus-Wojciechowska M, Michalak K, Najda J,
Mendrek W, Sobczyk-Kruszelnicka M, et al. Increased
efficacy of stem cell chemomobilization with intermediate-
dose cytarabine plus granulocyte colony-stimulating factor
(G-CSF) compared with G-CSF alone in patients with multiple
myeloma: Results of a randomized trial. Biol Blood Marrow
Transplant 2019;25:248-55.
30.	 Malard F, Kröger N, Gabriel IH, Hübel K, Apperley JF,
Basak GW, et al. Plerixafor for autologous peripheral blood
stem cell mobilization in patients previously treated with
fludarabine or lenalidomide. Biol Blood Marrow Transplant
2012;18:314-7.
31.	 Lahuerta JJ, Mateos MV, Martínez-López J, Grande C, De la
Rubia J, Rosiñol L, et al. Busulfan 12 mg/kg plus melphalan
140 mg/m2 versus melphalan 200 mg/m2 as conditioning
regimens for autologous transplantation in newly diagnosed
multiple myeloma patients included in the PETHEMA/
GEM2000 study. Haematologica 2010;95:1913-20.
32.	 Qazilbash MH, Thall P, Fox PS, Kebriaei P, Bashir Q, Shah N,
et al. A randomized phase III trial of Busulfan+Melphalan
vs Melphalan alone for multiple myeloma. J Clin Oncol
2015;21:S87-8.
33.	 Bensinger WI, Becker PS, Gooley TA, Chauncey TR,
Maloney DG, Gopal AK, et al. A randomized study of
melphalan 200 mg/m(2) vs 280 mg/m(2) as a preparative
regimen for patients with multiple myeloma undergoing auto-
SCT. Bone Marrow Transplant 2016;51:67-71.
34.	 Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L,
Galli M,etal.Bortezomibwiththalidomideplusdexamethasone
compared with thalidomide plus dexamethasone as induction
therapy before, and consolidation therapy after, double
autologous stem-cell transplantation in newly diagnosed
multiple myeloma: A randomised Phase 3 study. Lancet
2010;376:2075-85.
35.	 Sonneveld P, Beksaç M, Holt B, Dimopoulos M, Carella A,
Ludwig H, et al. Consolidation followed by maintenance
therapy versus maintenance alone in newly diagnosed,
transplant eligible patients with multiple myeloma (MM): A
randomized Phase 3 study of the European myeloma network
(EMN02/HO95 MM Trial). Blood 2016;128:242.
36.	 Paiva B, Gutiérrez NC, Rosiñol L, Vídriales MB,
Montalbán  MÁ, Martínez-López J, et al. High-risk
cytogenetics and persistent minimal residual disease by
multiparameter flow cytometry predict unsustained complete
response after autologous stem cell transplantation in multiple
myeloma. Blood 2012;119:687-91.
37.	 SpencerA, Prince HM, RobertsAW, Prosser IW, Bradstock KF,
Coyle L, et al. Consolidation therapy with low-dose
thalidomide and prednisolone prolongs the survival of multiple
myeloma patients undergoing a single autologous stem-cell
transplantation procedure. J Clin Oncol 2009;27:1788-93.
38.	 McCarthy PL, Holstein SA, Petrucci MT, Richardson PG,
Hulin C,TosiP,etal.Lenalidomidemaintenanceafterautologous
stem-cell transplantation in newly diagnosed multiple myeloma:
A meta-analysis. J Clin Oncol 2017;35:3279-89.
39.	 Barlogie B, Kyle RA, Anderson KC, Greipp PR, Lazarus HM,
Salamoon: Role of ASCT in multiple myeloma
17 Clinical Research in Hematology  •  Vol 3  •  Issue 1  •  2020
Hurd DD, et al. Standard chemotherapy compared with
high-dose chemoradiotherapy for multiple myeloma: Final
results of phase III US intergroup trial S9321. J Clin Oncol
2006;24:929-36.
40.	 Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C,
Fuzibet JG, et al. Single versus double autologous stem-
cell transplantation for multiple myeloma. N Engl J Med
2003;349:2495-502.
41.	 Cavo M, Tosi P, Zamagni E, Cellini C, Tacchetti P,
Patriarca F, et al. Prospective, randomized study of single
compared with double autologous stem-cell transplantation
for multiple myeloma: Bologna 96 clinical study. J Clin Oncol
2007;25:2434-41.
42.	 Cavo M, Salwender H, Rosinol L, Moreau P, Petrucci MT,
Blau IW, et al. Double vs single autologous stem cell
transplantation after bortezomib-based induction regimens for
multiple myeloma: An integrated analysis of patient-level data
from phase European III studies. Blood 2013;122:767.
How to cite this article: Salamoon M. Decreasing or
Increasing Role of Autologous Stem Cell Transplantation
in Multiple Myeloma? Clin Res Hematol 2020;3(1):12-17

Recommended

Abnormal expression of Pygopus 2 correlates with a malignant phenotype in hum...
Abnormal expression of Pygopus 2 correlates with a malignant phenotype in hum...Abnormal expression of Pygopus 2 correlates with a malignant phenotype in hum...
Abnormal expression of Pygopus 2 correlates with a malignant phenotype in hum...Enrique Moreno Gonzalez
 
Disruption of focal adhesion kinase and p53 interaction with small molecule c...
Disruption of focal adhesion kinase and p53 interaction with small molecule c...Disruption of focal adhesion kinase and p53 interaction with small molecule c...
Disruption of focal adhesion kinase and p53 interaction with small molecule c...Enrique Moreno Gonzalez
 
Correlation of Base-Line Trough Tacrolimus Level With Early Rejection
Correlation of Base-Line Trough Tacrolimus Level With Early RejectionCorrelation of Base-Line Trough Tacrolimus Level With Early Rejection
Correlation of Base-Line Trough Tacrolimus Level With Early RejectionCrimsonpublisherssmoaj
 
Poster_Molecular analysis of BRAF and RAS family genes in thyroid carcinoma i...
Poster_Molecular analysis of BRAF and RAS family genes in thyroid carcinoma i...Poster_Molecular analysis of BRAF and RAS family genes in thyroid carcinoma i...
Poster_Molecular analysis of BRAF and RAS family genes in thyroid carcinoma i...Alexandra Papadopoulou
 
oligoblastic AML
oligoblastic AMLoligoblastic AML
oligoblastic AMLspa718
 
Differentiation of irradiation and cetuximab induced skin reactions in patien...
Differentiation of irradiation and cetuximab induced skin reactions in patien...Differentiation of irradiation and cetuximab induced skin reactions in patien...
Differentiation of irradiation and cetuximab induced skin reactions in patien...Enrique Moreno Gonzalez
 
Relapsed AML: Steve Kornblau
Relapsed AML: Steve KornblauRelapsed AML: Steve Kornblau
Relapsed AML: Steve Kornblauspa718
 
Dr_Döhner aml st. petersburg_04.03.2016
Dr_Döhner aml st. petersburg_04.03.2016Dr_Döhner aml st. petersburg_04.03.2016
Dr_Döhner aml st. petersburg_04.03.2016EAFO2014
 

More Related Content

What's hot

thalassemia
thalassemiathalassemia
thalassemiaspa718
 
Hodgkin's Lymphoma
Hodgkin's LymphomaHodgkin's Lymphoma
Hodgkin's Lymphomaspa718
 
High Risk Lymphoma
High Risk LymphomaHigh Risk Lymphoma
High Risk Lymphomaspa718
 
acute lymphocytic leukemia
acute lymphocytic leukemiaacute lymphocytic leukemia
acute lymphocytic leukemiaspa718
 
Haematology trials 2017
Haematology trials 2017Haematology trials 2017
Haematology trials 2017Fadel Omar
 
1 s2.0-s0092867412010616-main
1 s2.0-s0092867412010616-main1 s2.0-s0092867412010616-main
1 s2.0-s0092867412010616-mainDragon Yott
 
Donor Selection: Unrealted donor transplant. Prof. Richard Champlin
Donor Selection: Unrealted donor transplant. Prof. Richard ChamplinDonor Selection: Unrealted donor transplant. Prof. Richard Champlin
Donor Selection: Unrealted donor transplant. Prof. Richard Champlinspa718
 
Thalassemia Transplant Update. Dr. Suradej Hongeng
Thalassemia Transplant Update. Dr. Suradej HongengThalassemia Transplant Update. Dr. Suradej Hongeng
Thalassemia Transplant Update. Dr. Suradej Hongengspa718
 
Impaired mitochondrial beta-oxidation in patients with chronic hepatitis C: r...
Impaired mitochondrial beta-oxidation in patients with chronic hepatitis C: r...Impaired mitochondrial beta-oxidation in patients with chronic hepatitis C: r...
Impaired mitochondrial beta-oxidation in patients with chronic hepatitis C: r...Enrique Moreno Gonzalez
 
oligoblastic AML
oligoblastic AMLoligoblastic AML
oligoblastic AMLspa718
 
Ohio State's 2016 ASH Review - BEST OF ASH 2015 MULTIPLE MYELOMA AND PLASMA C...
Ohio State's 2016 ASH Review - BEST OF ASH 2015 MULTIPLE MYELOMA AND PLASMA C...Ohio State's 2016 ASH Review - BEST OF ASH 2015 MULTIPLE MYELOMA AND PLASMA C...
Ohio State's 2016 ASH Review - BEST OF ASH 2015 MULTIPLE MYELOMA AND PLASMA C...OSUCCC - James
 
Lymphoma
LymphomaLymphoma
Lymphomaspa718
 
Translation of microarray data into clinically relevant cancer diagnostic tes...
Translation of microarray data into clinically relevant cancer diagnostic tes...Translation of microarray data into clinically relevant cancer diagnostic tes...
Translation of microarray data into clinically relevant cancer diagnostic tes...Tapan Baral
 
ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grad...
ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grad...ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grad...
ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grad...Enrique Moreno Gonzalez
 
Bmt ctn protocol 1101, double cord vs Haploidentical HCT
Bmt ctn protocol 1101, double cord vs Haploidentical HCTBmt ctn protocol 1101, double cord vs Haploidentical HCT
Bmt ctn protocol 1101, double cord vs Haploidentical HCTLakshmanan Krishnamurti
 
Risk Stratification for High Risk AML
Risk Stratification for High Risk AMLRisk Stratification for High Risk AML
Risk Stratification for High Risk AMLspa718
 

What's hot (20)

thalassemia
thalassemiathalassemia
thalassemia
 
Hodgkin's Lymphoma
Hodgkin's LymphomaHodgkin's Lymphoma
Hodgkin's Lymphoma
 
High Risk Lymphoma
High Risk LymphomaHigh Risk Lymphoma
High Risk Lymphoma
 
acute lymphocytic leukemia
acute lymphocytic leukemiaacute lymphocytic leukemia
acute lymphocytic leukemia
 
Haematology trials 2017
Haematology trials 2017Haematology trials 2017
Haematology trials 2017
 
1 s2.0-s0092867412010616-main
1 s2.0-s0092867412010616-main1 s2.0-s0092867412010616-main
1 s2.0-s0092867412010616-main
 
Donor Selection: Unrealted donor transplant. Prof. Richard Champlin
Donor Selection: Unrealted donor transplant. Prof. Richard ChamplinDonor Selection: Unrealted donor transplant. Prof. Richard Champlin
Donor Selection: Unrealted donor transplant. Prof. Richard Champlin
 
Aml incidencia
Aml incidenciaAml incidencia
Aml incidencia
 
Thalassemia Transplant Update. Dr. Suradej Hongeng
Thalassemia Transplant Update. Dr. Suradej HongengThalassemia Transplant Update. Dr. Suradej Hongeng
Thalassemia Transplant Update. Dr. Suradej Hongeng
 
Dr. Goy MCL
Dr. Goy MCLDr. Goy MCL
Dr. Goy MCL
 
Alterative Donor HSCT
Alterative Donor HSCTAlterative Donor HSCT
Alterative Donor HSCT
 
Impaired mitochondrial beta-oxidation in patients with chronic hepatitis C: r...
Impaired mitochondrial beta-oxidation in patients with chronic hepatitis C: r...Impaired mitochondrial beta-oxidation in patients with chronic hepatitis C: r...
Impaired mitochondrial beta-oxidation in patients with chronic hepatitis C: r...
 
oligoblastic AML
oligoblastic AMLoligoblastic AML
oligoblastic AML
 
Ohio State's 2016 ASH Review - BEST OF ASH 2015 MULTIPLE MYELOMA AND PLASMA C...
Ohio State's 2016 ASH Review - BEST OF ASH 2015 MULTIPLE MYELOMA AND PLASMA C...Ohio State's 2016 ASH Review - BEST OF ASH 2015 MULTIPLE MYELOMA AND PLASMA C...
Ohio State's 2016 ASH Review - BEST OF ASH 2015 MULTIPLE MYELOMA AND PLASMA C...
 
Lymphoma
LymphomaLymphoma
Lymphoma
 
CRC CHP final PDF
CRC CHP final PDFCRC CHP final PDF
CRC CHP final PDF
 
Translation of microarray data into clinically relevant cancer diagnostic tes...
Translation of microarray data into clinically relevant cancer diagnostic tes...Translation of microarray data into clinically relevant cancer diagnostic tes...
Translation of microarray data into clinically relevant cancer diagnostic tes...
 
ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grad...
ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grad...ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grad...
ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grad...
 
Bmt ctn protocol 1101, double cord vs Haploidentical HCT
Bmt ctn protocol 1101, double cord vs Haploidentical HCTBmt ctn protocol 1101, double cord vs Haploidentical HCT
Bmt ctn protocol 1101, double cord vs Haploidentical HCT
 
Risk Stratification for High Risk AML
Risk Stratification for High Risk AMLRisk Stratification for High Risk AML
Risk Stratification for High Risk AML
 

Similar to Decreasing or Increasing Role of Autologous Stem Cell Transplantation in Multiple Myeloma?

Newly Diagnosed Myeloma
Newly Diagnosed MyelomaNewly Diagnosed Myeloma
Newly Diagnosed Myelomaspa718
 
MolMed ASCO Prolonged Survival Times Patients With Acute Leukaemia Treated Wi...
MolMed ASCO Prolonged Survival Times Patients With Acute Leukaemia Treated Wi...MolMed ASCO Prolonged Survival Times Patients With Acute Leukaemia Treated Wi...
MolMed ASCO Prolonged Survival Times Patients With Acute Leukaemia Treated Wi...social_molmed
 
Real-World Treatment Patterns in Relapsed/Refractory Multiple Myeloma Patient...
Real-World Treatment Patterns in Relapsed/Refractory Multiple Myeloma Patient...Real-World Treatment Patterns in Relapsed/Refractory Multiple Myeloma Patient...
Real-World Treatment Patterns in Relapsed/Refractory Multiple Myeloma Patient...Howard Friedman
 
Extended criteria donors in liver transplantation Part II reviewing the impac...
Extended criteria donors in liver transplantation Part II reviewing the impac...Extended criteria donors in liver transplantation Part II reviewing the impac...
Extended criteria donors in liver transplantation Part II reviewing the impac...Balázs Nemes
 
multiple myeloma & daratumumab
multiple myeloma & daratumumabmultiple myeloma & daratumumab
multiple myeloma & daratumumabshubham769
 
Melphalan, Dexametasone and Thalidomide, Autoloogous Stem Cell and Maintenanc...
Melphalan, Dexametasone and Thalidomide, Autoloogous Stem Cell and Maintenanc...Melphalan, Dexametasone and Thalidomide, Autoloogous Stem Cell and Maintenanc...
Melphalan, Dexametasone and Thalidomide, Autoloogous Stem Cell and Maintenanc...semualkaira
 
An Overview: Treatment of Lung Cancer on Researcher Point of View
An Overview: Treatment of Lung Cancer on Researcher Point of ViewAn Overview: Treatment of Lung Cancer on Researcher Point of View
An Overview: Treatment of Lung Cancer on Researcher Point of ViewEswar Publications
 
Thomas John Lung Cancer Highlights 2014
Thomas John Lung Cancer Highlights 2014Thomas John Lung Cancer Highlights 2014
Thomas John Lung Cancer Highlights 2014Carlea Bauman
 
CCO Rational Options in Breast Cancer : How Molecular Understanding Informs T...
CCO Rational Options in Breast Cancer : How Molecular Understanding Informs T...CCO Rational Options in Breast Cancer : How Molecular Understanding Informs T...
CCO Rational Options in Breast Cancer : How Molecular Understanding Informs T...Adonis Guancia
 
Unmet need in multiple myeloma
Unmet need in multiple myelomaUnmet need in multiple myeloma
Unmet need in multiple myelomaPLMMedical
 
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...clinicsoncology
 
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...pateldrona
 
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...georgemarini
 
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...komalicarol
 
smoldering myeloma
smoldering myelomasmoldering myeloma
smoldering myelomaspa718
 
Chariot ms 4_ms-society_feb2018_4_slsh
Chariot ms 4_ms-society_feb2018_4_slshChariot ms 4_ms-society_feb2018_4_slsh
Chariot ms 4_ms-society_feb2018_4_slshKlaus Schmierer
 

Similar to Decreasing or Increasing Role of Autologous Stem Cell Transplantation in Multiple Myeloma? (20)

Newly Diagnosed Myeloma
Newly Diagnosed MyelomaNewly Diagnosed Myeloma
Newly Diagnosed Myeloma
 
MolMed ASCO Prolonged Survival Times Patients With Acute Leukaemia Treated Wi...
MolMed ASCO Prolonged Survival Times Patients With Acute Leukaemia Treated Wi...MolMed ASCO Prolonged Survival Times Patients With Acute Leukaemia Treated Wi...
MolMed ASCO Prolonged Survival Times Patients With Acute Leukaemia Treated Wi...
 
Real-World Treatment Patterns in Relapsed/Refractory Multiple Myeloma Patient...
Real-World Treatment Patterns in Relapsed/Refractory Multiple Myeloma Patient...Real-World Treatment Patterns in Relapsed/Refractory Multiple Myeloma Patient...
Real-World Treatment Patterns in Relapsed/Refractory Multiple Myeloma Patient...
 
Extended criteria donors in liver transplantation Part II reviewing the impac...
Extended criteria donors in liver transplantation Part II reviewing the impac...Extended criteria donors in liver transplantation Part II reviewing the impac...
Extended criteria donors in liver transplantation Part II reviewing the impac...
 
multiple myeloma & daratumumab
multiple myeloma & daratumumabmultiple myeloma & daratumumab
multiple myeloma & daratumumab
 
Melphalan, Dexametasone and Thalidomide, Autoloogous Stem Cell and Maintenanc...
Melphalan, Dexametasone and Thalidomide, Autoloogous Stem Cell and Maintenanc...Melphalan, Dexametasone and Thalidomide, Autoloogous Stem Cell and Maintenanc...
Melphalan, Dexametasone and Thalidomide, Autoloogous Stem Cell and Maintenanc...
 
An Overview: Treatment of Lung Cancer on Researcher Point of View
An Overview: Treatment of Lung Cancer on Researcher Point of ViewAn Overview: Treatment of Lung Cancer on Researcher Point of View
An Overview: Treatment of Lung Cancer on Researcher Point of View
 
Exploring Clinical Decisions in the New Era of Myeloma Management: The Impact...
Exploring Clinical Decisions in the New Era of Myeloma Management: The Impact...Exploring Clinical Decisions in the New Era of Myeloma Management: The Impact...
Exploring Clinical Decisions in the New Era of Myeloma Management: The Impact...
 
Thomas John Lung Cancer Highlights 2014
Thomas John Lung Cancer Highlights 2014Thomas John Lung Cancer Highlights 2014
Thomas John Lung Cancer Highlights 2014
 
CCO Rational Options in Breast Cancer : How Molecular Understanding Informs T...
CCO Rational Options in Breast Cancer : How Molecular Understanding Informs T...CCO Rational Options in Breast Cancer : How Molecular Understanding Informs T...
CCO Rational Options in Breast Cancer : How Molecular Understanding Informs T...
 
Unmet need in multiple myeloma
Unmet need in multiple myelomaUnmet need in multiple myeloma
Unmet need in multiple myeloma
 
GSK's Jemperli.pdf
GSK's Jemperli.pdfGSK's Jemperli.pdf
GSK's Jemperli.pdf
 
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
 
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
 
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
 
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
Clinical Outcomes of Patients with Advanced Solid Tumors of Cutaneous Capilla...
 
smoldering myeloma
smoldering myelomasmoldering myeloma
smoldering myeloma
 
Carfilzomib in multiple myeloma
Carfilzomib in multiple myelomaCarfilzomib in multiple myeloma
Carfilzomib in multiple myeloma
 
IJSR.pdf
IJSR.pdfIJSR.pdf
IJSR.pdf
 
Chariot ms 4_ms-society_feb2018_4_slsh
Chariot ms 4_ms-society_feb2018_4_slshChariot ms 4_ms-society_feb2018_4_slsh
Chariot ms 4_ms-society_feb2018_4_slsh
 

More from asclepiuspdfs

Convalescent Plasma and COVID-19: Ancient Therapy Re-emerged
Convalescent Plasma and COVID-19: Ancient Therapy Re-emergedConvalescent Plasma and COVID-19: Ancient Therapy Re-emerged
Convalescent Plasma and COVID-19: Ancient Therapy Re-emergedasclepiuspdfs
 
The Coexistence of Polycythemia Vera and Iron Deficiency Anemia
The Coexistence of Polycythemia Vera and Iron Deficiency AnemiaThe Coexistence of Polycythemia Vera and Iron Deficiency Anemia
The Coexistence of Polycythemia Vera and Iron Deficiency Anemiaasclepiuspdfs
 
Iron Deficiency Anemia: Insights into the Prevalence, Causes, Iron Metabolism...
Iron Deficiency Anemia: Insights into the Prevalence, Causes, Iron Metabolism...Iron Deficiency Anemia: Insights into the Prevalence, Causes, Iron Metabolism...
Iron Deficiency Anemia: Insights into the Prevalence, Causes, Iron Metabolism...asclepiuspdfs
 
Hemodynamics of Maintaining Transportation of All Nutrients in Blood Flowing:...
Hemodynamics of Maintaining Transportation of All Nutrients in Blood Flowing:...Hemodynamics of Maintaining Transportation of All Nutrients in Blood Flowing:...
Hemodynamics of Maintaining Transportation of All Nutrients in Blood Flowing:...asclepiuspdfs
 
Spurious Augmentation of Mean Corpuscular Hemoglobin Concentration: Facts and...
Spurious Augmentation of Mean Corpuscular Hemoglobin Concentration: Facts and...Spurious Augmentation of Mean Corpuscular Hemoglobin Concentration: Facts and...
Spurious Augmentation of Mean Corpuscular Hemoglobin Concentration: Facts and...asclepiuspdfs
 
The Negative Clinical Consequences Due to the Lack of the Elaboration of a Sc...
The Negative Clinical Consequences Due to the Lack of the Elaboration of a Sc...The Negative Clinical Consequences Due to the Lack of the Elaboration of a Sc...
The Negative Clinical Consequences Due to the Lack of the Elaboration of a Sc...asclepiuspdfs
 
A Review on the Potential Therapeutic Properties of Angiotensin 1-7 in Most S...
A Review on the Potential Therapeutic Properties of Angiotensin 1-7 in Most S...A Review on the Potential Therapeutic Properties of Angiotensin 1-7 in Most S...
A Review on the Potential Therapeutic Properties of Angiotensin 1-7 in Most S...asclepiuspdfs
 
Anemias Necessitating Transfusion Support
Anemias Necessitating Transfusion SupportAnemias Necessitating Transfusion Support
Anemias Necessitating Transfusion Supportasclepiuspdfs
 
Hyponatremia Caused by Cyclophosphamide-containing Chemotherapy for Malignant...
Hyponatremia Caused by Cyclophosphamide-containing Chemotherapy for Malignant...Hyponatremia Caused by Cyclophosphamide-containing Chemotherapy for Malignant...
Hyponatremia Caused by Cyclophosphamide-containing Chemotherapy for Malignant...asclepiuspdfs
 
Morphological Diagnosis and Immunophenotypic Characterization of Onco-hematol...
Morphological Diagnosis and Immunophenotypic Characterization of Onco-hematol...Morphological Diagnosis and Immunophenotypic Characterization of Onco-hematol...
Morphological Diagnosis and Immunophenotypic Characterization of Onco-hematol...asclepiuspdfs
 
Hematological-genetics, Reproductive Health and Family Welfare in Madhya Prad...
Hematological-genetics, Reproductive Health and Family Welfare in Madhya Prad...Hematological-genetics, Reproductive Health and Family Welfare in Madhya Prad...
Hematological-genetics, Reproductive Health and Family Welfare in Madhya Prad...asclepiuspdfs
 
Next-generation Sequencing in Acute Myeloid Leukemia
Next-generation Sequencing in Acute Myeloid LeukemiaNext-generation Sequencing in Acute Myeloid Leukemia
Next-generation Sequencing in Acute Myeloid Leukemiaasclepiuspdfs
 
Comorbidity of Iron Indices and Inflammatory Markers among Sudanese Hemodialy...
Comorbidity of Iron Indices and Inflammatory Markers among Sudanese Hemodialy...Comorbidity of Iron Indices and Inflammatory Markers among Sudanese Hemodialy...
Comorbidity of Iron Indices and Inflammatory Markers among Sudanese Hemodialy...asclepiuspdfs
 
Comparison of the Hypocalcemic Effects of Erythropoietin and U-74389G
Comparison of the Hypocalcemic Effects of Erythropoietin and U-74389GComparison of the Hypocalcemic Effects of Erythropoietin and U-74389G
Comparison of the Hypocalcemic Effects of Erythropoietin and U-74389Gasclepiuspdfs
 
Management of Immunogenic Heparin-induced Thrombocytopenia
Management of Immunogenic Heparin-induced ThrombocytopeniaManagement of Immunogenic Heparin-induced Thrombocytopenia
Management of Immunogenic Heparin-induced Thrombocytopeniaasclepiuspdfs
 
The Genetic Determinants for Long-term Response to Hydroxyurea Therapy in Ind...
The Genetic Determinants for Long-term Response to Hydroxyurea Therapy in Ind...The Genetic Determinants for Long-term Response to Hydroxyurea Therapy in Ind...
The Genetic Determinants for Long-term Response to Hydroxyurea Therapy in Ind...asclepiuspdfs
 
Acute Promyelocytic Leukemia Presenting Unusual Case with Additional Cytogene...
Acute Promyelocytic Leukemia Presenting Unusual Case with Additional Cytogene...Acute Promyelocytic Leukemia Presenting Unusual Case with Additional Cytogene...
Acute Promyelocytic Leukemia Presenting Unusual Case with Additional Cytogene...asclepiuspdfs
 
Comparison of the Hypertransferasemic Effects of Erythropoietin and U-74389G ...
Comparison of the Hypertransferasemic Effects of Erythropoietin and U-74389G ...Comparison of the Hypertransferasemic Effects of Erythropoietin and U-74389G ...
Comparison of the Hypertransferasemic Effects of Erythropoietin and U-74389G ...asclepiuspdfs
 
Adult Still’s Disease Resembling Drug-related Scratch Dermatitis
Adult Still’s Disease Resembling Drug-related Scratch DermatitisAdult Still’s Disease Resembling Drug-related Scratch Dermatitis
Adult Still’s Disease Resembling Drug-related Scratch Dermatitisasclepiuspdfs
 

More from asclepiuspdfs (20)

Convalescent Plasma and COVID-19: Ancient Therapy Re-emerged
Convalescent Plasma and COVID-19: Ancient Therapy Re-emergedConvalescent Plasma and COVID-19: Ancient Therapy Re-emerged
Convalescent Plasma and COVID-19: Ancient Therapy Re-emerged
 
The Coexistence of Polycythemia Vera and Iron Deficiency Anemia
The Coexistence of Polycythemia Vera and Iron Deficiency AnemiaThe Coexistence of Polycythemia Vera and Iron Deficiency Anemia
The Coexistence of Polycythemia Vera and Iron Deficiency Anemia
 
Iron Deficiency Anemia: Insights into the Prevalence, Causes, Iron Metabolism...
Iron Deficiency Anemia: Insights into the Prevalence, Causes, Iron Metabolism...Iron Deficiency Anemia: Insights into the Prevalence, Causes, Iron Metabolism...
Iron Deficiency Anemia: Insights into the Prevalence, Causes, Iron Metabolism...
 
Hemodynamics of Maintaining Transportation of All Nutrients in Blood Flowing:...
Hemodynamics of Maintaining Transportation of All Nutrients in Blood Flowing:...Hemodynamics of Maintaining Transportation of All Nutrients in Blood Flowing:...
Hemodynamics of Maintaining Transportation of All Nutrients in Blood Flowing:...
 
Spurious Augmentation of Mean Corpuscular Hemoglobin Concentration: Facts and...
Spurious Augmentation of Mean Corpuscular Hemoglobin Concentration: Facts and...Spurious Augmentation of Mean Corpuscular Hemoglobin Concentration: Facts and...
Spurious Augmentation of Mean Corpuscular Hemoglobin Concentration: Facts and...
 
The Negative Clinical Consequences Due to the Lack of the Elaboration of a Sc...
The Negative Clinical Consequences Due to the Lack of the Elaboration of a Sc...The Negative Clinical Consequences Due to the Lack of the Elaboration of a Sc...
The Negative Clinical Consequences Due to the Lack of the Elaboration of a Sc...
 
A Review on the Potential Therapeutic Properties of Angiotensin 1-7 in Most S...
A Review on the Potential Therapeutic Properties of Angiotensin 1-7 in Most S...A Review on the Potential Therapeutic Properties of Angiotensin 1-7 in Most S...
A Review on the Potential Therapeutic Properties of Angiotensin 1-7 in Most S...
 
Anemias Necessitating Transfusion Support
Anemias Necessitating Transfusion SupportAnemias Necessitating Transfusion Support
Anemias Necessitating Transfusion Support
 
Hyponatremia Caused by Cyclophosphamide-containing Chemotherapy for Malignant...
Hyponatremia Caused by Cyclophosphamide-containing Chemotherapy for Malignant...Hyponatremia Caused by Cyclophosphamide-containing Chemotherapy for Malignant...
Hyponatremia Caused by Cyclophosphamide-containing Chemotherapy for Malignant...
 
Morphological Diagnosis and Immunophenotypic Characterization of Onco-hematol...
Morphological Diagnosis and Immunophenotypic Characterization of Onco-hematol...Morphological Diagnosis and Immunophenotypic Characterization of Onco-hematol...
Morphological Diagnosis and Immunophenotypic Characterization of Onco-hematol...
 
Hematological-genetics, Reproductive Health and Family Welfare in Madhya Prad...
Hematological-genetics, Reproductive Health and Family Welfare in Madhya Prad...Hematological-genetics, Reproductive Health and Family Welfare in Madhya Prad...
Hematological-genetics, Reproductive Health and Family Welfare in Madhya Prad...
 
Next-generation Sequencing in Acute Myeloid Leukemia
Next-generation Sequencing in Acute Myeloid LeukemiaNext-generation Sequencing in Acute Myeloid Leukemia
Next-generation Sequencing in Acute Myeloid Leukemia
 
Comorbidity of Iron Indices and Inflammatory Markers among Sudanese Hemodialy...
Comorbidity of Iron Indices and Inflammatory Markers among Sudanese Hemodialy...Comorbidity of Iron Indices and Inflammatory Markers among Sudanese Hemodialy...
Comorbidity of Iron Indices and Inflammatory Markers among Sudanese Hemodialy...
 
Comparison of the Hypocalcemic Effects of Erythropoietin and U-74389G
Comparison of the Hypocalcemic Effects of Erythropoietin and U-74389GComparison of the Hypocalcemic Effects of Erythropoietin and U-74389G
Comparison of the Hypocalcemic Effects of Erythropoietin and U-74389G
 
Refractory Anemia
Refractory AnemiaRefractory Anemia
Refractory Anemia
 
Management of Immunogenic Heparin-induced Thrombocytopenia
Management of Immunogenic Heparin-induced ThrombocytopeniaManagement of Immunogenic Heparin-induced Thrombocytopenia
Management of Immunogenic Heparin-induced Thrombocytopenia
 
The Genetic Determinants for Long-term Response to Hydroxyurea Therapy in Ind...
The Genetic Determinants for Long-term Response to Hydroxyurea Therapy in Ind...The Genetic Determinants for Long-term Response to Hydroxyurea Therapy in Ind...
The Genetic Determinants for Long-term Response to Hydroxyurea Therapy in Ind...
 
Acute Promyelocytic Leukemia Presenting Unusual Case with Additional Cytogene...
Acute Promyelocytic Leukemia Presenting Unusual Case with Additional Cytogene...Acute Promyelocytic Leukemia Presenting Unusual Case with Additional Cytogene...
Acute Promyelocytic Leukemia Presenting Unusual Case with Additional Cytogene...
 
Comparison of the Hypertransferasemic Effects of Erythropoietin and U-74389G ...
Comparison of the Hypertransferasemic Effects of Erythropoietin and U-74389G ...Comparison of the Hypertransferasemic Effects of Erythropoietin and U-74389G ...
Comparison of the Hypertransferasemic Effects of Erythropoietin and U-74389G ...
 
Adult Still’s Disease Resembling Drug-related Scratch Dermatitis
Adult Still’s Disease Resembling Drug-related Scratch DermatitisAdult Still’s Disease Resembling Drug-related Scratch Dermatitis
Adult Still’s Disease Resembling Drug-related Scratch Dermatitis
 

Recently uploaded

Tuberculosis .pptx Department of Physiotherapy, SHUATS, Prayagraj
Tuberculosis .pptx Department of Physiotherapy, SHUATS, PrayagrajTuberculosis .pptx Department of Physiotherapy, SHUATS, Prayagraj
Tuberculosis .pptx Department of Physiotherapy, SHUATS, PrayagrajSurabhi Srivastava
 
Seminario Biología Molecular Manuela Álvarez Ramírez
Seminario Biología Molecular Manuela Álvarez RamírezSeminario Biología Molecular Manuela Álvarez Ramírez
Seminario Biología Molecular Manuela Álvarez Ramírezmanuelaalvarezr
 
Malaria Disease.pptx Department of Physiotherapy, SHUATS, Prayagraj
Malaria Disease.pptx Department of Physiotherapy, SHUATS, PrayagrajMalaria Disease.pptx Department of Physiotherapy, SHUATS, Prayagraj
Malaria Disease.pptx Department of Physiotherapy, SHUATS, PrayagrajSurabhi Srivastava
 
1030am-CLEAR-OUTCOMES-acc-2023- Bemp.pdf
1030am-CLEAR-OUTCOMES-acc-2023- Bemp.pdf1030am-CLEAR-OUTCOMES-acc-2023- Bemp.pdf
1030am-CLEAR-OUTCOMES-acc-2023- Bemp.pdfthomasbetancourtmd
 
PTERYGIUM ,clinical picture and its management.pptx
PTERYGIUM ,clinical picture and its management.pptxPTERYGIUM ,clinical picture and its management.pptx
PTERYGIUM ,clinical picture and its management.pptxvideosfildr
 
Namburi phased spot test - NPST To identify bhasma and sindhura - A Qualitat...
Namburi phased spot test - NPST  To identify bhasma and sindhura - A Qualitat...Namburi phased spot test - NPST  To identify bhasma and sindhura - A Qualitat...
Namburi phased spot test - NPST To identify bhasma and sindhura - A Qualitat...Dr. Madduru Muni Haritha
 
Introducing amazing Healthy habits and fitness
Introducing amazing Healthy habits and fitnessIntroducing amazing Healthy habits and fitness
Introducing amazing Healthy habits and fitnessFredrick Amos
 
How to be a successful physician intrapreneur
How to be a successful physician intrapreneurHow to be a successful physician intrapreneur
How to be a successful physician intrapreneurArlen Meyers, MD, MBA
 
Population of India and Family welfare programme.pptx
Population of India and Family welfare programme.pptxPopulation of India and Family welfare programme.pptx
Population of India and Family welfare programme.pptxDr. Dheeraj Kumar
 
Seminario biologia molecular-Universidad Pontificia Bolivariana.
Seminario biologia molecular-Universidad Pontificia Bolivariana.Seminario biologia molecular-Universidad Pontificia Bolivariana.
Seminario biologia molecular-Universidad Pontificia Bolivariana.JULIANA BENAVIDES GUERRERO
 
Seminario biología molecular Kevin Duque
Seminario biología molecular Kevin DuqueSeminario biología molecular Kevin Duque
Seminario biología molecular Kevin Duquekevinestebanduque
 
Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe D...
Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe D...Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe D...
Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe D...Golden Helix
 
Influenza.pptx Department of Physiotherapy, SHUATS, Prayagraj
Influenza.pptx Department of Physiotherapy, SHUATS, PrayagrajInfluenza.pptx Department of Physiotherapy, SHUATS, Prayagraj
Influenza.pptx Department of Physiotherapy, SHUATS, PrayagrajSurabhi Srivastava
 
Measles.pptx Department of Physiotherapy, SHUATS, Prayagraj
Measles.pptx Department of Physiotherapy, SHUATS, PrayagrajMeasles.pptx Department of Physiotherapy, SHUATS, Prayagraj
Measles.pptx Department of Physiotherapy, SHUATS, PrayagrajSurabhi Srivastava
 
USG,CT AND MR IMAGING OF HEPATIC MASS LESIONS.
USG,CT AND MR IMAGING OF HEPATIC MASS LESIONS.USG,CT AND MR IMAGING OF HEPATIC MASS LESIONS.
USG,CT AND MR IMAGING OF HEPATIC MASS LESIONS.vrchk912
 
Work-role of Radiation Therapists in the Consequences of Adaptive Radiotherap...
Work-role of Radiation Therapists in the Consequences of Adaptive Radiotherap...Work-role of Radiation Therapists in the Consequences of Adaptive Radiotherap...
Work-role of Radiation Therapists in the Consequences of Adaptive Radiotherap...Subrata Roy
 
Bioavailability & Bioequivalence Studies- Definitions, Methods of Measureme...
Bioavailability & Bioequivalence  Studies- Definitions, Methods  of Measureme...Bioavailability & Bioequivalence  Studies- Definitions, Methods  of Measureme...
Bioavailability & Bioequivalence Studies- Definitions, Methods of Measureme...Rajshri
 
A complete guide to the Human Digestive System
A complete guide to the Human Digestive SystemA complete guide to the Human Digestive System
A complete guide to the Human Digestive Systemantoneymichael992
 
Autism and Savant Syndrome|Study|The Good doctor .pptx
Autism and Savant Syndrome|Study|The Good doctor .pptxAutism and Savant Syndrome|Study|The Good doctor .pptx
Autism and Savant Syndrome|Study|The Good doctor .pptxScripted Symptoms
 
GLANDS IN THE SKIN,FUNCTIONS AND ABNORMALITIES ..pptx
GLANDS IN THE SKIN,FUNCTIONS AND ABNORMALITIES ..pptxGLANDS IN THE SKIN,FUNCTIONS AND ABNORMALITIES ..pptx
GLANDS IN THE SKIN,FUNCTIONS AND ABNORMALITIES ..pptxWINCY THIRUMURUGAN
 

Recently uploaded (20)

Tuberculosis .pptx Department of Physiotherapy, SHUATS, Prayagraj
Tuberculosis .pptx Department of Physiotherapy, SHUATS, PrayagrajTuberculosis .pptx Department of Physiotherapy, SHUATS, Prayagraj
Tuberculosis .pptx Department of Physiotherapy, SHUATS, Prayagraj
 
Seminario Biología Molecular Manuela Álvarez Ramírez
Seminario Biología Molecular Manuela Álvarez RamírezSeminario Biología Molecular Manuela Álvarez Ramírez
Seminario Biología Molecular Manuela Álvarez Ramírez
 
Malaria Disease.pptx Department of Physiotherapy, SHUATS, Prayagraj
Malaria Disease.pptx Department of Physiotherapy, SHUATS, PrayagrajMalaria Disease.pptx Department of Physiotherapy, SHUATS, Prayagraj
Malaria Disease.pptx Department of Physiotherapy, SHUATS, Prayagraj
 
1030am-CLEAR-OUTCOMES-acc-2023- Bemp.pdf
1030am-CLEAR-OUTCOMES-acc-2023- Bemp.pdf1030am-CLEAR-OUTCOMES-acc-2023- Bemp.pdf
1030am-CLEAR-OUTCOMES-acc-2023- Bemp.pdf
 
PTERYGIUM ,clinical picture and its management.pptx
PTERYGIUM ,clinical picture and its management.pptxPTERYGIUM ,clinical picture and its management.pptx
PTERYGIUM ,clinical picture and its management.pptx
 
Namburi phased spot test - NPST To identify bhasma and sindhura - A Qualitat...
Namburi phased spot test - NPST  To identify bhasma and sindhura - A Qualitat...Namburi phased spot test - NPST  To identify bhasma and sindhura - A Qualitat...
Namburi phased spot test - NPST To identify bhasma and sindhura - A Qualitat...
 
Introducing amazing Healthy habits and fitness
Introducing amazing Healthy habits and fitnessIntroducing amazing Healthy habits and fitness
Introducing amazing Healthy habits and fitness
 
How to be a successful physician intrapreneur
How to be a successful physician intrapreneurHow to be a successful physician intrapreneur
How to be a successful physician intrapreneur
 
Population of India and Family welfare programme.pptx
Population of India and Family welfare programme.pptxPopulation of India and Family welfare programme.pptx
Population of India and Family welfare programme.pptx
 
Seminario biologia molecular-Universidad Pontificia Bolivariana.
Seminario biologia molecular-Universidad Pontificia Bolivariana.Seminario biologia molecular-Universidad Pontificia Bolivariana.
Seminario biologia molecular-Universidad Pontificia Bolivariana.
 
Seminario biología molecular Kevin Duque
Seminario biología molecular Kevin DuqueSeminario biología molecular Kevin Duque
Seminario biología molecular Kevin Duque
 
Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe D...
Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe D...Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe D...
Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe D...
 
Influenza.pptx Department of Physiotherapy, SHUATS, Prayagraj
Influenza.pptx Department of Physiotherapy, SHUATS, PrayagrajInfluenza.pptx Department of Physiotherapy, SHUATS, Prayagraj
Influenza.pptx Department of Physiotherapy, SHUATS, Prayagraj
 
Measles.pptx Department of Physiotherapy, SHUATS, Prayagraj
Measles.pptx Department of Physiotherapy, SHUATS, PrayagrajMeasles.pptx Department of Physiotherapy, SHUATS, Prayagraj
Measles.pptx Department of Physiotherapy, SHUATS, Prayagraj
 
USG,CT AND MR IMAGING OF HEPATIC MASS LESIONS.
USG,CT AND MR IMAGING OF HEPATIC MASS LESIONS.USG,CT AND MR IMAGING OF HEPATIC MASS LESIONS.
USG,CT AND MR IMAGING OF HEPATIC MASS LESIONS.
 
Work-role of Radiation Therapists in the Consequences of Adaptive Radiotherap...
Work-role of Radiation Therapists in the Consequences of Adaptive Radiotherap...Work-role of Radiation Therapists in the Consequences of Adaptive Radiotherap...
Work-role of Radiation Therapists in the Consequences of Adaptive Radiotherap...
 
Bioavailability & Bioequivalence Studies- Definitions, Methods of Measureme...
Bioavailability & Bioequivalence  Studies- Definitions, Methods  of Measureme...Bioavailability & Bioequivalence  Studies- Definitions, Methods  of Measureme...
Bioavailability & Bioequivalence Studies- Definitions, Methods of Measureme...
 
A complete guide to the Human Digestive System
A complete guide to the Human Digestive SystemA complete guide to the Human Digestive System
A complete guide to the Human Digestive System
 
Autism and Savant Syndrome|Study|The Good doctor .pptx
Autism and Savant Syndrome|Study|The Good doctor .pptxAutism and Savant Syndrome|Study|The Good doctor .pptx
Autism and Savant Syndrome|Study|The Good doctor .pptx
 
GLANDS IN THE SKIN,FUNCTIONS AND ABNORMALITIES ..pptx
GLANDS IN THE SKIN,FUNCTIONS AND ABNORMALITIES ..pptxGLANDS IN THE SKIN,FUNCTIONS AND ABNORMALITIES ..pptx
GLANDS IN THE SKIN,FUNCTIONS AND ABNORMALITIES ..pptx
 

Decreasing or Increasing Role of Autologous Stem Cell Transplantation in Multiple Myeloma?

  • 1. Clinical Research in Hematology  •  Vol 3  •  Issue 1  •  2020 12 INTRODUCTION Multiple myeloma (MM) forms about 10% of hematologic malignancies and the first indication for autologous stem cell transplantation (ASCT) among these malignancies.[1,2] The introduction of high-dose chemotherapy (HDC) followed by ASCT has become the standard of care in newly diagnosed patients[3,4] after huge efforts and trials conducted in both Europe and the United States.[5,6] Koreth et al. demonstrated that ASCT has failed to add the maximum to the overall survival (OS); however, the event-free survival was improved.[7] Debate is still ongoing about the precise timing of ASCT, is it upfront, after complete response (CR) or upon progression or relapse?[6] During the last three decades, we have witnessed a dramatic shift in MM patients’ approach after the introduction of the new agents such as thalidomide, lenalidomide, and bortezomib before or after HD/ASCT. This new combination has improved CR on the molecular level.[8] New trials are evaluating the new monoclonal antibodies (anti-CD38) in both induction and maintenance setting. To which extent, the introduction of these new agents may influence the utilization of ASCT? In this review, we are going to answer this question and other questions regarding the feasibility of ASCT taking into account several variables such as age, performance status, renal function, best induction, best maintenance, and other related issues. UPFRONT ASCT IN NEWLY DIAGNOSED ELIGIBLE PATIENTS ASCT proceeded by conditioning with high-dose Melphalan is considered the standard of care in newly diagnosed patients with MM.[9,10] First reports defined eligible patients as those younger than 65 years old as a cutoff; however, several bone marrow transplantation communities extended the cutoff age to exceed 65 years.[11] Trials are conducted to evaluate high- dose Melphalan in patients older than 65 years and found that treatment-related mortality (TRM) was zero at day +100 when comparing 140 mg/m2 and 200 mg/m2 .[12] Other trials compared 200 mg/m2 in younger patients versus 100mg/ m2 in a tandem mode in patients between 65 and 75 years old with no difference in progression-free survival (PFS), OS, or TRM.[13] However, other factors should be taken into consideration in older age groups such as renal functions, REVIEW ARTICLE Decreasing or Increasing Role of Autologous Stem Cell Transplantation in Multiple Myeloma? Maher Salamoon Department of Medical Oncology, Al Bairouni University Cancer Center, Damascus University, Damascus, Syria ABSTRACT During the past four decades, autologous stem cell transplantation (ASCT) has been the first choice and the standard option for the treatment of newly diagnosed patients with multiple myeloma. The introduction of new agents such as thalidomide, lenalidomide, and bortezomib has led to a clear improvement in basic approach and those agents became the standard of care in the induction phase; however, they were not able to play the role of ASCT in term of progression-free survival and overall survival. Debate continues about the best induction, consolidation, and maintenance taking into account the toxicities of these new agents. The new monoclonal antibody (anti CD38) starts to take its place in the induction setting and it seems to be a promising agent in the high-risk group. Until recently, ASCT is the standard treatment for newly diagnosed patients. Key words: Autologous, multiple, myeloma, stem cell, transplantation Address for correspondence: Maher Salamoon, Department of Medical Oncology, Al Bairouni University Cancer Center, Damascus University, Damascus, Syria. Phone: +963933771086. https://doi.org/10.33309/2639-8354.030103 www.asclepiusopen.com © 2020 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license.
  • 2. Salamoon: Role of ASCT in multiple myeloma Clinical Research in Hematology  •  Vol 3  •  Issue 1  •  2020 performance status, and other comorbidities. In some centers, ASCTs are performed on elderly patients according to every patient’s characteristics and outside clinical trials. Renal function impairment is one of the most important presenting signs in patients with MM attributed to high light chain burden. This impairment is much more profound in patients over 65 years; however, there is no contraindication for ASCT in this subgroup of patients. In these cases, toxicities attributed to HD chemotherapy are more frequent than those with normal renal functions.[14,15] Report from the Polish society of MM demonstrated that dialysis-dependent cases are more likely to develop toxicities such as infections and mucositis; however, PFS and OS rates were comparable to other patients presenting with normal functions.[16] HISTORY AND PRESENT OF INDUCTION CHEMOTHERAPY Before and after the era of ASCT, induction chemotherapy was the major treatment that aims to reduce the burden of plasma cell in bone marrow, improving the local environment and facilitate engraftment as well. The first induction backbone was the alkylating agents, then the triplet of vincristine, doxorubicin, and dexamethasone (VAD).[1] This induction was replaced by either thalidomide or bortezomib or both which proven to better than VAD in term of complete response (CR).[17,18] Later trials showed that the triplet of bortezomib, thalidomide, and dexamethasone (VTD) was superior to VD and TD.[19,20] Thus, VTD became the standard induction of choice in MM patients prepared for ASCT with 3–4 cycles given. Some centers give six cycles to attain a more profound response; however, peripheral neuropathy may limit this trend in some patients.[20] Soon after, VTD was replaced by many MM societies by VRD after replacing thalidomide with the newer version lenalidomide. VRD demonstrated better PFS and OS when compared to VTD.[21] The new monoclonal antibody against CD38 daratumumab (DARA) was evaluated in the induction phase in combination with VRD and VTD, showing some encouraging results when compared with VRD alone.[22,23] DARA was also combined in a Phase II trial with bortezomib, cyclophosphamide, and dexamethasone and also used in a Phase Ib trial with carfilzomib and lenalidomide demonstrating a response rate exceeding 95% in both trials.[24,25] CHEMOPRIMING Mobilization of hematopoietic stem cells (CD34) with a minimum of 2 × 106 CD34 per kg of body weight is essential for good engraftment; however, the optimal amount is 5 × 106 CD34/kg which can be done by a steady-state mobilization after giving granulocytes colony-stimulating factor (G-CSF) over several days or chemopriming through preparation with chemotherapeutic agents.[26] The two approved cytokines for mobilization are filgrastim (10 μg/kg/day for 4–6 days and apheresis on days 5 or 6) according to the optimal number of CD34 in peripheral blood. The other cytokines are lenograstim (10 μg/kg/day for 4–6 days and apheresis between days 5 and 7); however, mobilization using G-CSF alone is still suboptimal.[27] The most commonly used agent for chemopriming is high-dose cyclophosphamide (2–4 g/m2 ), followed by filgrastim or lenograstim (5 μg/kg/day 1–5 days after completion of chemotherapy. This procedure can offer a good CD34 amount; however, the time to transplantation is prolonged and toxicities are reported as well.[28] In some patients who fail to mobilize the optimal amount of CD34, the chemokine receptor-4 (CXCR-4) antagonist (plerixafor) can increase the mobilization effect of G-CSF.[27] Trials compared to the addition of cytarabine to G-CSF versus G-CSF alone in Phase III randomized trials reported better results in the cytarabine arm; however, toxicity profile was high.[29] We should stress that using lenalidomide in the induction may impair mobilization process through upgrading CXCR-4 receptors; however, this process can be antagonist by plerixafor which found to be effective in this case.[30] CONDITIONING Intravenous Melphalan at a dose of 200 mg/m2 is the best high-dose conditioning regimen so far. Attempts to replace it with oral Melphalan or intravenous busulfan have failed.[31] The combination of intravenous busulfan 130 mg/m2 over 4 days and Melphalan 70 mg/m2 for over 2 days demonstrated better PFS with no significant improvement in response rate.[32] In a randomized trial conducted by Bensinger et al., a comparison between Melphalan 200 mg/m2 and 280 mg/m2 demonstrated better ORR with no impact on PFS and OS.[33] THE ROLE OF CONSOLIDATION AND MAINTENANCE AFTER ASCT The Italian myeloma study group reported better CR and PFS rates using VTD compared with the TD arm in both induction and consolidation after ASCT[34] and this result was better in patients demonstrating good response after ASCT which reflected in complete pathologic and molecular response.[8] Sonneveld et al. reported better PFS with two cycles of VRD proceeding lenalidomide compared with lenalidomide as consolidation;[35] however, VRD failed to prolong PFS in patients with a high-risk profile of cytogenetic abnormalities [t(4:14) and/or del17p and/or t(14:16)].[35] These results indicate that VRD as consolidation before maintenance with lenalidomide is of benefit in those young patients with low- risk cytogenetic profile. Results do not support the regular indication of consolidation after ASCT and more randomized trials are needed to support the former idea.
  • 3. Salamoon: Role of ASCT in multiple myeloma Clinical Research in Hematology  •  Vol 3  •  Issue 1  •  2020 14 Consolidation and maintenance are thought to deepen the first response obtained after ASCT and to prevent relapse and prolong survival; however, ASCT is not a curative procedure that is why concentration was made on maintenance therapy with the new agents such as thalidomide and lenalidomide.[36] Thalidomide was the first agent to use in the maintenance setting after being tested in several randomized trials. This agent showed a good response; however, the OS rate was not encouraging. Since thalidomide can lead to a profound peripheral neuropathy, the duration of use was limited to 6–12 months, as reported Spencer et al.[37] Lenalidomide was also tested in maintenance and demonstrated better response than placebo and led to prolongation of PFS in all subgroups of patients, especially in those attained more deep response after ASCT. OS improved in the lenalidomide arm except in women older than 60 years, presenting with a bad cytogenetic profile.[38] The treatment-limiting duration of lenalidomide is determined by the progression of secondary tumor which was reported and toxicities. Thus, thalidomide is given at a dose of 100 mg/day and lenalidomide at a low dose for a period of time in the light of side effects.[38] A designed plan is illustrated in Figure 1 showing the current practice and the future direction in treatment of newly diagnosed cases of MM. NON-TRANSPLANT STRATEGY Before the era of the new agents, two large trials compared HDC followed by ASCT with HDC alone demonstrated prolonged of both PFS and OS.[5,6] Most trials were conducted before 2010 and did not include the new agents until recently where four phase III trials compared HDC followed by ASCT with a combination of the new agents, as illustrated in Table 1. Speed look on the former four trials demonstrates that induction followed by ASCT was better in term of PFS and OS than non-transplant strategy. The most important trial thereafter was the IFM 2009 where 700 newly diagnosed patients to receive three RVD cycles then divided into two arms: The first arm received one course of high-dose Melphalan followed by ASCT then another two RVD cycles, where patients in the second arm received another five cycles of RVD. Higher complete remission rates were observed in the ASCT arm (59% vs. 48%; P = 0.03) and minimal residual disease negativity (79% vs. 65%; P 0.001); however, no difference in term of OS was observed at 4 years.[6] All conducted trials comparing ASCT versus non-ASCT arm demonstrated better response and PFS rates; however, OS was not significant unless in two trials, therefore, ASCT continues to be the standard of care in newly diagnosed patients. Early ASCT was evaluated in three trials with the improvement of interval to relapse; however, no difference was reported in term of OS.[39] In real practice, to answer the question whether early or delayed ASCT, randomized trials are needed with stratification of patients according to their clinical, biologic, and cytogenetic profile, then we can know which patient will get a better benefit from early or delayed one. Table 1: The main four Phase III randomized trials comparing HD-chemotherapy followed by ASCT with treatment with new agents Author Study design PFS OS Attal et al. RVD × 5 cycles versus HD-M + ASCT (×1) + RVD × 2 cycles 50 versus 36 mon. P0.001 4 y: 81% versus 80% P:NS Cavo et al. VMP × 4 cycles versus HD-M + ASCT (×1 versus ×2) 3 y: 66% versus 58% P0.037 NA Gay et al. CRD × 6 cycles versus HD-M + ASCT (×2) 43 versus 29 mon. 4 y: 86% versus 73% P0.004 Palumbo et al. MPR × 6 cycles versus HD-M + ASCT (×2) 43 versus 22 mon. P0.001 4 y: 82% versus 65% P=0.02 HD-M: High-dose Melphalan, RVD: Lenalidomide, bortezomib, and dexamethasone, CRD: Cyclophosphamide, lenalidomide, and dexamethasone, MPR: Melphalan, prednisolone and lenalidomide, VMP: Bortezomib, Melphalan, and prednisolone, PFS: Progression-free survival, OS: Overall survival, ASCT: Autologous stem cell transplantation Figure 1: The present practice and future direction in approaching newly diagnosed patients with multiple myeloma
  • 4. Salamoon: Role of ASCT in multiple myeloma 15 Clinical Research in Hematology  •  Vol 3  •  Issue 1  •  2020 Another issue to be raised is the difference between single versus tandem ASCT. The IFM trial demonstrated that tandem transplant showed longer PFS (36 vs. 25 months P = 0.03) and better OS (58 vs. 48 P = 0.01). In a subgroup analysis, patients with better results were those who have not had a near-complete response after the first ASCT.[40] The former results were supported by an Italian study conducted by Cavo et al. demonstrated better response and PFS rates; however, OS was similar in both arms (median, 71 vs. 65 months; P = 0.9).[41] Cavo et al. also published data from pooled three trials reporting better PFS and OS in the tandem arm compared with the single ASCT.[42] DISCUSSION AND CONCLUSION The introduction of new agents did not replace the role of ASCT, which remains so far the standard of care in newly diagnosed patients with MM. during the past 4 decades, ASCT has been compared with the HDC; however, the new agents replaced the high-dose in comparison and it is early to talk about complete replacement of ASCT by the new agents. The first step was comparing RD with VRD which showed superior results in term of PFS and OS. VRD seems to be comparable to ASCT in term of PFS and OS as well. [21] The emerging role of the new agents was clarified in four Phase III trials illustrated in Table 1. Trials should be conducted in a randomized fashion to evaluate the real role of the new agents with and without ASCT. The new monoclonal antibody daratumumab should be included in the induction phase in combination with VRD because of its encouraging results. Most societies concentrate on adding a new agent to the known triplet VRD then compare it with ASCT; however, studies should be oriented toward improving the induction to serve those ASCT ineligible patients. The development of induction is also an important trend toward improving results in a high-risk group. As we know, ASCT is a process that takes time (induction, chemopriming, and stem cell mobilization and conditioning) and this time takes about 3 months in the median which is not calculated when PFS and OS are studied which is a great bias. If we omit the time to perform the procedure, then VRD could exceedASCT in term of OS since results are comparable. Finally, it is early to talk about a decreasing role of ASCT in MM; however, the new agents along with the monoclonal antibodies may delay the procedure in some patients the thing that must be determined after conducting a big randomized trial for this purpose. REFERENCES 1. Harousseau JL, Moreau P. Autologous hematopoietic stem- cell transplantation for multiple myeloma. N Engl J Med 2009;360:2645-54. 2. Becker N. Epidemiology of multiple myeloma. Recent Results Cancer Res 2011;183:25-35. 3. McElwain TJ, Powles RL. High-dose intravenous melphalan for plasma-cell leukaemia and myeloma. Lancet 1983;2:822-4. 4. Mohty M, Harousseau JL. Treatment of autologous stem cell transplant-eligible multiple myeloma patients: Ten questions and answers. Haematologica 2014;99:408-16. 5. Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins  K, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003;348:1875-83. 6. Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation in myeloma. N Engl J Med 2017;376:1311-20. 7. Koreth J, Cutler CS, Djulbegovic B, Behl R, Schlossman RL, Munshi NC, et al. High-dose therapy with single autologous transplantation versus chemotherapy for newly diagnosed multiple myeloma: A systematic review and meta-analysis of randomized controlled trials. Biol Blood Marrow Transplant 2007;13:183-96. 8. Ladetto M, Pagliano G, Ferrero S, Cavallo F, Drandi D, Santo L, et al. Major tumor shrinking and persistent molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in patients with autografted myeloma. J Clin Oncol 2010;28:2077-84. 9. Shah N, Callander N, Ganguly S, Gul Z, Hamadani M, Costa L, et al. Hematopoietic stem cell transplantation for multiple myeloma: Guidelines from the American society for blood and marrow transplantation. Biol Blood Marrow Transplant 2015;21:1155-66. 10. Gay F, Engelhardt M, Terpos E, Wäsch R, Giaccone L, Auner HW, et al. From transplant to novel cellular therapies in multiple myeloma: European myeloma network guidelines and future perspectives. Haematologica 2018;103:197-211. 11. Auner HW, Szydlo R, Hoek J, Goldschmidt H, Stoppa AM, Morgan GJ, et al. Trends in autologous hematopoietic cell transplantation for multiple myeloma in Europe: Increased use and improved outcomes in elderly patients in recent years. Bone Marrow Transplant 2015;50:209-15. 12. Garderet L, Beohou E, Caillot D, Stoppa AM, Touzeau C, Chretien ML, et al. Upfront autologous stem cell transplantation for newly diagnosed elderly multiple myeloma patients: A prospective multicenter study. Haematologica 2016;101:1390-7. 13. Neukirchen J, Arat P, Teutloff C, Gerrlich C, Niedenhoff DL, Boquoi A, et al. Favourable outcome of elderly patients with multiple myeloma treated with tandem melphalan 100 high- dose therapy, autologous stem cell transplantation and novel agents-a single center experience. Blood 2016;128:3460. 14. Straka C, Liebisch P, Salwender H, Hennemann B, Metzner B, Knop S, et al. Autotransplant with and without induction chemotherapy in older multiple myeloma patients: Long-term outcome of a randomized trial. Haematologica 2016;101:1398-406. 15. Badros A, Barlogie B, Siegel E, Roberts J, Langmaid C, Zangari M, et al. Results of autologous stem cell transplant in multiple myeloma patients with renal failure. Br J Haematol 2001;114:822-9. 16. Waszczuk-Gajda A, Lewandowski Z, Drozd-Sokołowska J, Boguradzki P, Dybko J, Wróbel T, et al. Autologous peripheral blood stem cell transplantation in dialysis-dependent multiple
  • 5. Salamoon: Role of ASCT in multiple myeloma Clinical Research in Hematology  •  Vol 3  •  Issue 1  •  2020 16 myeloma patients-DAUTOS study of the polish myeloma study group. Eur J Haematol 2018;101:475-85. 17. Harousseau JL, Attal M, Avet-Loiseau H, Marit G, Caillot D, Mohty M, et al. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: Results of the IFM 2005- 01 Phase III trial. J Clin Oncol 2010;28:4621-9. 18. Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Navarro Coy N, et al. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. Haematologica 2012;97:442-50. 19. Moreau P, Avet-Loiseau H, Facon T, Attal M, Tiab M, Hulin C, et al. Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus dexamethasone as induction treatment before autologous stem cell transplantation in newly diagnosed multiple myeloma. Blood 2011;118:5752-8. 20. Rosiñol L, Oriol A, Teruel AI, Hernández D, López-Jiménez J, De la Rubia J, et al. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: A randomized Phase 3 PETHEMA/GEM study. Blood 2012;120:1589-96. 21. Durie BG, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): A randomised, open-label, Phase 3 trial. Lancet 2017;389:519-27. 22. MoreauP,AttalM,HulinC,ArnulfB,BelhadjK,Benboubker L, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem- cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): A randomised, open-label, phase 3 study. Lancet 2019;394:29-38. 23. Voorhees PM, Costa LJ, Reeves B, Nathwani N, Rodriguez C, Lutska Y, et al. Interim safety analysis of a Phase 2 randomized study of daratumumab (Dara), lenalidomide (R), bortezomib (V), and dexamethasone (d; Dara-RVd) vs. RVd in patients (Pts) with newly diagnosed multiple myeloma (MM) eligible for high-dose therapy (HDT) and autologous stem cell transplantation (ASCT). Blood 2017;130:1879. 24. Yimer H, Melear J, Faber E, Bensinger W, Burke JM, Narang  M, et al. Lyra:APhase 2 study of daratumumab (Dara) plus cyclophosphamide, bortezomib, and dexamethasone (Cybord) in newly diagnosed and relapsed patients (Pts) with multiple myeloma (MM). Blood 2018;132:152. 25. Jakubowiak AJ, Chari A, Lonial S, Weiss BM, Comenzo RL, Wu K, et al. Daratumumab (DARA) in combination with carfilzomib, lenalidomide, and dexamethasone (KRd) in patients (pts) with newly diagnosed multiple myeloma (MMY1001): An open-label, Phase 1b study. J Clin Oncol 2017;35:8000. 26. Mohty M, Ho AD. In and out of the niche: Perspectives in mobilization of hematopoietic stem cells. Exp Hematol 2011;39:723-9. 27. Mohty M, Duarte RF, Croockewit S, Hübel K, Kvalheim G, Russell N. The role of plerixafor in optimizing peripheral blood stem cell mobilization for autologous stem cell transplantation. Leukemia 2011;25:1-6. 28. Bensinger W, DiPersio JF, McCarty JM. Improving stem cell mobilization strategies: Future directions. Bone Marrow Transplant 2009;43:181-95. 29. Czerw T, Sadus-Wojciechowska M, Michalak K, Najda J, Mendrek W, Sobczyk-Kruszelnicka M, et al. Increased efficacy of stem cell chemomobilization with intermediate- dose cytarabine plus granulocyte colony-stimulating factor (G-CSF) compared with G-CSF alone in patients with multiple myeloma: Results of a randomized trial. Biol Blood Marrow Transplant 2019;25:248-55. 30. Malard F, Kröger N, Gabriel IH, Hübel K, Apperley JF, Basak GW, et al. Plerixafor for autologous peripheral blood stem cell mobilization in patients previously treated with fludarabine or lenalidomide. Biol Blood Marrow Transplant 2012;18:314-7. 31. Lahuerta JJ, Mateos MV, Martínez-López J, Grande C, De la Rubia J, Rosiñol L, et al. Busulfan 12 mg/kg plus melphalan 140 mg/m2 versus melphalan 200 mg/m2 as conditioning regimens for autologous transplantation in newly diagnosed multiple myeloma patients included in the PETHEMA/ GEM2000 study. Haematologica 2010;95:1913-20. 32. Qazilbash MH, Thall P, Fox PS, Kebriaei P, Bashir Q, Shah N, et al. A randomized phase III trial of Busulfan+Melphalan vs Melphalan alone for multiple myeloma. J Clin Oncol 2015;21:S87-8. 33. Bensinger WI, Becker PS, Gooley TA, Chauncey TR, Maloney DG, Gopal AK, et al. A randomized study of melphalan 200 mg/m(2) vs 280 mg/m(2) as a preparative regimen for patients with multiple myeloma undergoing auto- SCT. Bone Marrow Transplant 2016;51:67-71. 34. Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M,etal.Bortezomibwiththalidomideplusdexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: A randomised Phase 3 study. Lancet 2010;376:2075-85. 35. Sonneveld P, Beksaç M, Holt B, Dimopoulos M, Carella A, Ludwig H, et al. Consolidation followed by maintenance therapy versus maintenance alone in newly diagnosed, transplant eligible patients with multiple myeloma (MM): A randomized Phase 3 study of the European myeloma network (EMN02/HO95 MM Trial). Blood 2016;128:242. 36. Paiva B, Gutiérrez NC, Rosiñol L, Vídriales MB, Montalbán  MÁ, Martínez-López J, et al. High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma. Blood 2012;119:687-91. 37. SpencerA, Prince HM, RobertsAW, Prosser IW, Bradstock KF, Coyle L, et al. Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol 2009;27:1788-93. 38. McCarthy PL, Holstein SA, Petrucci MT, Richardson PG, Hulin C,TosiP,etal.Lenalidomidemaintenanceafterautologous stem-cell transplantation in newly diagnosed multiple myeloma: A meta-analysis. J Clin Oncol 2017;35:3279-89. 39. Barlogie B, Kyle RA, Anderson KC, Greipp PR, Lazarus HM,
  • 6. Salamoon: Role of ASCT in multiple myeloma 17 Clinical Research in Hematology  •  Vol 3  •  Issue 1  •  2020 Hurd DD, et al. Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: Final results of phase III US intergroup trial S9321. J Clin Oncol 2006;24:929-36. 40. Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG, et al. Single versus double autologous stem- cell transplantation for multiple myeloma. N Engl J Med 2003;349:2495-502. 41. Cavo M, Tosi P, Zamagni E, Cellini C, Tacchetti P, Patriarca F, et al. Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study. J Clin Oncol 2007;25:2434-41. 42. Cavo M, Salwender H, Rosinol L, Moreau P, Petrucci MT, Blau IW, et al. Double vs single autologous stem cell transplantation after bortezomib-based induction regimens for multiple myeloma: An integrated analysis of patient-level data from phase European III studies. Blood 2013;122:767. How to cite this article: Salamoon M. Decreasing or Increasing Role of Autologous Stem Cell Transplantation in Multiple Myeloma? Clin Res Hematol 2020;3(1):12-17