Miguel A Sanz is a professor of oncology, hematology, and bone marrow transplant in Valencia, Spain. He discusses donor selection considerations when an HLA-matched sibling donor is available for hematopoietic cell transplantation. Younger donor age is preferred, as is matching donor and recipient CMV status. Male donors and nulliparous female donors may be associated with less graft-versus-host disease. Minor ABO mismatches are acceptable, while peripheral blood is now preferred over bone marrow as the stem cell source due to faster engraftment, except in diseases with very low relapse risk.
call girls in Kamla Market (DELHI) 🔝 >༒9953330565🔝 genuine Escort Service 🔝✔️✔️
Miguel A Sanz, MD: Younger Donor Age Preferable for Older Hematopoietic Transplant Recipients
1. MIGUEL A SANZ, MD
Valencia, Spain
• Professor and Head of Department, of
Oncology, Hematology and Bone Marrow
Transplant Unit, University Hospital La Fe in
Valencia, Spain
• Professor Sanz is chairman of the Spanish PETHEMA
Group and leads the working parties of acute
promyelocytic leukemia, acute myeloid leukemia and
infections in neutropenic patients. He is currently a
reviewer for numerous high-profile medical journals
including all top hematology journals, and has
authored more than 470 peer-reviewed papers,
numerous book chapters, and in excess of 1000
abstracts at national and international meetings.
Professor Sanz has also lectured widely in Europe,
North, central and South America, as well as in Middle
East and Asia, serving as lecturer at the American
Society of Hematology in 2004, 2005 and 2010.
2. Donor selection for hematopoietic cell
transplantation when a matched
sibling donor is available
The 6th International Hematologic Malignancies
Conference: Bridging the Gap 2015 (BTG2015)
Beijing, China (January 31, 2014)
Miguel A. Sanz
Departamento de Medicina de la Universidad de Valencia
Servicio de Hematología y Hemoterapia
Hospital Universitario La Fe
Valencia, Spain
3. • Requirements for donating bone marrow or blood for
HCT.
• Variables to be considered in donor selection:
- Age of the donor
- Sex and parity
- CMV status
- ABO compatibility
• Bone marrow versus peripheral blood as source for
allogeneic HSCT from HLA-identical sibling donor
Donor selection for HSCT
Outline
3
4. Donor selection for HCT
Requirements for donating BM/PB for HCT
4
• The donor must be in good health that permits the safe
collection of the cells from either bone marrow or
peripheral blood:
– Adequate cardiac, pulmonary, hepatic, and renal
function.
– If being considered for bone marrow harvest, the
donor must be able to tolerate anesthesia (either
general or regional).
– For sibling donors with a history of a malignant
condition, a five-year disease-free period without
recurrence is usually considered adequate for
subsequent collection.
5. Donor selection for HCT
Requirements for donating BM/PB for HCT
5
• Donors must be negative for both anti-HIV antibodies
and HIV RNA.
• Serologic tests for hepatitis B and C are also required at
most transplant centers.
• Donors with active viral hepatitis are usually excluded,
although exceptions are occasionally made with sibling
donors, depending upon the clinical urgency.
• In certain circumstances, antiviral therapy may be
considered if time permits for an adequate course1
.
1. Strasser SI, McDonald GB. Hepatitis viruses and hematopoietic cell transplantation: A guide to patient
and donor management.Blood. 1999;93(4):1127
6. Donor selection for HCT when ≥2 HLA-
matched siblings are available
6
Sibling donors and recipients
are usually of similar age
7. Having a younger-adult donor was a predictor of less GVHD,
better OS and DFS.
Matched sibling donors
The effect of donor age
7
Kollman C et al. Blood 2001;98:2043-2051
8. 8
Would it be better to choose a young,
matched unrelated donor instead of
an older-aged sibling?
9. Who is the better donor for older hematopoietic
transplant recipients: an older-aged sibling or a
young, matched unrelated volunteer?
by Amin M. Alousi, Jennifer Le-Rademacher, Rima M. Saliba, Frederick R.
Appelbaum, Andrew Artz, Jonathan Benjamin, Steven M. Devine, Fangyu Kan, Mary J.
Laughlin, Hillard M. Lazarus, Jane Liesveld, Miguel-Angel Perales, Richard T. Maziarz,
Mitchell Sabloff, Edmund K. Waller, Mary Eapen, and Richard E. Champlin
Blood
Volume 121(13):2567-2573
March 28, 2013
These data favor an
MSD over a MUD for
transplant recipients
older than age 50 years.
11Blood 2013; 121(13):2567-2573
11. Matched sibling donors
The effect of donor sex and parity
13
Kollman C et al. Blood 2001;98:2043-2051
The sex of neither donor nor recipient affected survival.
12. Matched sibling donors
The effect of donor sex and parity
14
Kollman C et al. Blood 2001;98:2043-2051
The cumulative incidence of chronic GVHD was higher with
multiparous female donors.
14. CMV serostatus still has an important prognostic
impact in de novo acute leukemia patients after
allogeneic stem cell transplantation: a report from the
Acute Leukemia Working Party of EBMT
by Martin Schmidt-Hieber, Myriam Labopin, Dietrich Beelen, Liisa Volin, Gerhard
Ehninger, Jürgen Finke, Gerard Socié, Rainer Schwerdtfeger, Nicolaus Kröger, Arnold
Ganser, Dietger Niederwieser, Emmanuelle Polge, Igor W. Blau, and Mohamad Mohty
Blood
Volume 122(19):3359-3364
November 7, 2013
16
15. Matched sibling donors
The effect of donor/recipient CMV serostatus
17
Kollman C et al. Blood 2001;98:2043-2051
17. Matched sibling donors
The effect of ABO and Rh compatibility
20
• Donor-recipient Rh mismatch is not a risk factor in allo-
HCT and does not affect transplant outcomes.
• ABO compatibility between the donor and recipient is not
required:
- If major mismatches are present, additional manipulation of the
hematopoietic cell product, such as depleting the product of red
cells, is required.
- Hemolysis, delayed erythropoietic engraftment, and pure red
cell aplasia may complicate ABO-incompatible transplantation
after either marrow or PBPC transplantation. However, these
complications are not common.
- A meta-analysis with 1208 cases demonstrates no adverse
association between any ABO mismatching and survival.
18. Matched sibling donors
The effect of ABO and Rh compatibility
21
Among related stem cell recipients, ABO matching
had no significant influence on OS
Kanda J, et al.Transfusion. 2009;49(4):624.
19. Donor selection for HCT when ≥2 HLA-
matched siblings are available
22
younger donor age
preferable
matching for CMV
status preferred
males and nulliparous
females preferred
Preferred
No>minor>major
mismatches
20. 23
Peripheral Blood versus Bone Marrow
as a Source for Allogeneic
Hematopoietic Cell Transplantation
from Matched-Sibling Donor
22. BM vs. PB allogeneic hematopietic
stem cell transplantation
• PBSC is the optimal stem cell source in terms of both
overall and quality-adjusted life expectancy, except in
conditions with a very low relapse probability, in which
BM provides optimal outcomes:
- Severe aplastic anaemia
- Congenital marrow failures
- Malignancies with <5% risk of relapse at 1 y
Holtick U, et al. Cochrane Database Syst Rev. 2014 25
23. • High-quality evidence that overall survival following
allo-HSCT using the current clinical standard stem cell
source - PBSC - was similar to BMSC in adults with
hematological malignancies.
• Moderate-quality evidence that PBSCT was associated
with:
- faster engraftment of neutrophils and platelets
- higher risk of GvHD (in terms of more overall and
extensive chronic GvHD).
• Quality of life, which is severely affected by GvHD, was
not evaluated.
BM vs. PB allogeneic hematopietic
stem cell transplantation
Holtick U, et al. Cochrane Database Syst Rev. 2014 26
25. Allogeneic HCT from HLA-identical
sibling by stem cell source in Spain
28
PB 83%PB 83%
Editor's Notes
Constellation of factors
The effect of donor age was best demonstrated in a retrospective analysis from the NMDP of 6978 HCT from MUD.
Overall survival decreased with increasing donor age. This effect was highly significant.
The probabilities of acute and chronic GVHD, non-relapse mortality, and overall survival. (A)The unadjusted cumulative incidence of grade 2 to 4 acute GVHD for recipients of MSD transplants with donors age 50 years or older and MUD transplants with donors age younger than 50 years. (B) The unadjusted cumulative incidence of chronic GVHD for recipients of MSD transplants with donors age 50 years or older and MUD transplants with donors age younger than 50 years.
(C) The unadjusted cumulative incidences of NRM for recipients of MSD transplants with donors age 50 years or older and performance scores 90 or 100 (group A), MSD transplants with donors age 50 years or older and performance scores 80 or lower (group B), MUD transplants with donors age younger than 50 years and performance scores 90 or 100 (group C) and MUD transplants with donors age younger than 50 years and performance scores 80 or lower (group D). (D) Probabilities of OS adjusted for conditioning regimen, patient age, disease, and disease status for recipients of MSD transplants with donors age 50 years or older and performance scores 90 or 100 (group A), MSD transplants with donors age 50 years or older and performance scores 80 or lower (group B), MUD transplants with donors age younger than 50 years and performance scores 90 or 100 (group C) and MUD transplants with donors age younger than 50 years and performance scores of 80 or lower (group D).
Constellation of factors
The cumulative incidence of chronic GVHD was higher with multiparous female donors.Results with male donors and female donors without pregnancies were similar, whereas an increasing incidence of chronic GVHD was associated with female donors with one or more pregnancies. Results were similar in female and male recipients. Twenty-two cases that were evaluable for chronic GVHD were excluded from this analysis because parity data were unavailable.
The cumulative incidence of chronic GVHD was higher with multiparous female donors.Results with male donors and female donors without pregnancies were similar, whereas an increasing incidence of chronic GVHD was associated with female donors with one or more pregnancies. Results were similar in female and male recipients. Twenty-two cases that were evaluable for chronic GVHD were excluded from this analysis because parity data were unavailable.
Constellation of factors
Impact of donor/recipient CMV serostatus on OS. Impact in (A) ALL vs (B) AML.
Donor CMV serologic status did not affect survival of either seronegative or seropositive recipients.CMV-seropositive recipients had decreased survival, regardless of the donor&apos;s CMV serologic status. Cases were excluded from these curves if the CMV serologic status of either the recipient (n = 56) or the donor (n = 339) was unknown.
Constellation of factors
Constellation of factors
Slide 11: Among patients older than 20, there has also been an increase in the number of unrelated donor transplants which surpassed the number of related donor transplants. Peripheral blood is the most common graft source for unrelated donor transplants in adults. In 2010 and 2011, utilization of umbilical cord blood in adults reached 12% of all unrelated donor transplants. During the same most recent period, bone marrow grafts are utilized routinely in 16% and 13% of related and unrelated donor transplants, respectively.