Myeloablative Umbilical Cord Blood Transplantation for Hematologic Malignancies is Comparable to Unrelated Donor Transplantation: a Retrospective Single Center Study
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Myeloablative Umbilical Cord Blood Transplantation for Hematologic Malignancies is Comparable to Unrelated Donor Transplantation: a Retrospective Single Center Study
1. Myeloablative umbilical cord blood transplantation for
hematologic malignancies is comparable to unrelated
donor transplantation: a retrospective single center study
Filippo Milano, MD, PhD
Clinical Research Division
Fred Hutchinson Cancer Research
Center
Seattle, WA, USA
2. Background
Umbilical cord blood transplantation has become a
widely and acceptable stem cell source for
transplantation.
Several studies have shown comparable survival rates
for both adult and pediatric cord blood transplant
recipients when compared to unrelated donor
transplantation. 1,3
Growing evidence of low incidence of relapse after
cord blood transplantation. 4
1. Laughlin M. et al. N Engl J Med 2004; 4351: 2265–227.5
2. Eapen M. et al. Lancet 2007; 369: 1947–1954.
3. Brunstein C. et al Blood 2010; 116: 4693–4699.
4. Verneris M. Blood 2009; 114: 4293-4299.
3. Study design
Between January 2006 and December 2012 we retrospectively analyzed
outcomes for 566 patients undergoing first allogeneic hematopoietic stem
cell transplantation for hematologic malignancies with either cord blood
(CBT) or unrelated donor (URD).
In the CBT group (n=112) selected cord blood units were required to be
matched to the recipient at ≥ 4 of the 6 HLA loci based on intermediate
resolution typing at HLA-A and –B and allele-level for HLA-DRB1.
All patients received a double CB graft except for 16 patients (14%) who
received a single CB graft. In addition, 29 (26%) patients received an ex
vivo expanded CB unit as part of either a single or double CBT.
In the URD group (n=447), patients received either HLA 10/10 (n=332)
allele matched URD (MURD) or 1 (n=115) allele mismatched URD
(MMURD).
4. Definitions/Statistical Methods
The primary endpoint was evaluation of disease free survival,
relapse and non-relapse mortality.
Hematopoietic recovery was evaluated comparing time to
neutrophil recovery (≥ 500/µl by day 45).
Chronic GVHD was assessed using old classification criteria.
The patient’s underlying disease was categorized as low,
intermediate, high and very high-risk based upon previously
described criteria*.
Time-to-event outcomes were compared between groups using Cox
regression, and logistic regression was used for acute and chronic
GVHD. All models were adjusted for age, race, year of HCT, disease
risk and CMV serostatus.
*Armand Philippe et al. A disease risk index for patients undergoing allogeneic stem cell
transplantation. Blood 2012; 120(4):905-13.
5. Patient characteristics (1)
UCB
(n=112)
MURD
(n=332)
MMURD
(n=115)
Age in years median, (range) 28 (0.6-67) 42 (1-67) 47 (2-65)
Gender, n (%)
Female 52 (46) 141 (42) 50 (43)
Weight in kg median, (range) 70 (8-139) 75 (10-158) 79 (12-142)
Race, n (%)
Caucasian
Other
45 (45)
57 (55)
272 (87)
39 (13)
82 (75)
27 (25)
CMV serostatus, n (%)
Pos
Neg
75 (68)
35 (32)
173 (53)
153 (47)
60 (53)
52 (47)
Diagnosis, n (%)
AML
ALL
MDS
Myeloproliferative disorders
CLL/Lymphoma
Other
57 (51)
34 (30)
10 (9)
6 (5)
3 (3)
2 (2)
132 (40)
80 (24)
51 (15)
56 (17)
11 (3)
2 (<1)
50 (43)
26 (23)
15 (13)
22 (19)
2 (2)
-
8. Neutrophil engraftment
0.2.4.6.81
Probability
0 20 40 60 80 100
Days after HCT
Non-Matched
Cryopreserved
Median=19 days
PB
Median=17 daysPartially Matched
Median=11 days
Conventional CBT
Median=23 days
BM
Median=21 days
20. 0.2.4.6
Probability
0 1 2 3
Years after HCT
p=0.10
Unrelated matched 26%
Cord Blood 16%
0.000.250.500.751.00
Probability
0 1 2 3
Years after HCT
p=0.94
Cord Blood 54%
Unrelated matched 59%
Treo/Flu/TBI – UCB vs URD
Relapse
0.2.4.6
Probability
0 1 2 3
Years after HCT
p=0.07
Unrelated matched 14%
Cord Blood 29%
Non-Relapse Mortality
Disease Free-Survival
21. 0.2.4.6
Probability
0 1 2 3 4 5
Years after HCT
Cord Blood 21% Unrelated Mismatched
21%
Unrelated Matched 14%
0.2.4.6
Probability
0 1 2 3 4 5
Years after HCT
Cord Blood 11%
p=0.003
Unrelated Mismatch
34%
Unrelated Matched
24%
0.000.250.500.751.00
Probability
0 1 2 3 4 5
Years after HCT
Cord Blood 67%
Unrelated matched 60%
Unrelated Mismatched 45%
p=0.03
p=0.83
High-dose TBI – UCB vs MURD vs MMURD
Disease Free-Survival
Non-Relapse Mortality Relapse
22. 0.000.250.500.751.00
Probability
0 2 4 6
Years after CBT
Disease free survival in UCBT by disease
DFS at 4 years
ALL 78%
MDS/CML 74%
AML 62%
AML
MDS/CML
ALL
23. Conclusions
Disease free survival, relapse free survival and non-relapse mortality
after CBT were not inferior to those observed after URD
transplantation.
Speed of engraftment in CBT recipients receiving ex-vivo expanded
cells was similar to what observed after peripheral blood and bone
marrow.
“Younger” CBT patients appear to have an advantage over “younger”
URD patients in terms of lower risk of overall mortality, however this
advantage appears to disappear for “older” patients.
Relapse occurred less frequently for CBT recipients when compared
to both MMURD and MURD.
The risk of chronic GVHD was lower for patients receiving MURD with
BM but similar between the other groups.
24. Things to do….
Add other variables to the analysis:
- HCT-CI score
- Presence of minimal residual disease at time of
transplantation
- Evaluation of allele mismatching among the
MMURD
Use NIH GVHD classification for all patients
25. Future directions
Results are encouraging but can we do better?
The use of non-matched cryopreserved ex-vivo
expanded CD34+ cells might reduce the early mortality
due to the delayed hematopoietic recovery and
potentially increase GVL effect (Protocol 2603)
How we do improve access to transplant for all patients
in need?
Set-up a randomized study between CBT and URD
recipients
26. ACKNOWLEDGEMENTS
Colleen Delaney
Ted Gooley
Bau Ellie
Rachel Salit
Riffkin Ivy
Ziegler Denise
Fred Appelbaum
Ann Woolfrey
Boglarka Gyurkocza
Bob Whiterspoon
Paul O’Donnell
Joachim Deeg
Harrington Liz
Adrienne Papermaster
Connie Nakano
Lisa Getzendaner
Celia Evans