A landmark study from Medical Research Council/Eastern Cooperative Oncology Group showed improved survival (∼53%) for patients allocated to sibling HCT versus either consolidation/maintenance chemotherapy or autologous HCT. Matched unrelated donors (MUD) are an option for patients without a SIB available and we retrospectively analyzed disease outcomes after SIB and MUD in adult ALL patients.

Between 2001and 2012, 204 adult ALL patients with a median age of 36 years (range, 18-64) were transplanted with a SIB (n=112) or 8/8 MUD (n=92). Disease status at HCT was first or second complete remission and beyond (CR1, n=113, 55.5% and CR2+, n=91, 44.5%). Conditioning was myeloablative in 177 (86.8%) and reduced intensity (RIC) in 27 patients (13.2%). All but 2 patients received graft versus host disease (GVHD) immunosuppression with tacrolimus and methotrexate. Patient and disease characteristics including age, sex, histological subtypes and high risk disease features (WBC and cytogenetic classification at diagnosis), disease status at HCT and conditioning intensity were similar between SIB and MUD recipients. As expected, MUD patients had bone marrow (BM) as the stem cell source more commonly than SIB (69.6% vs. 7.1, p<0.001). The median follow-up of 96 survivors was 36 months. The univariate point estimates at the stated timepoints and multivariate outcomes are summarized in the Table1 and 2.
Table1

The summary outcomes

SIB (%)MUD (%)P
Neutrophil recovery at day 42 96.4 97.8 0.6 
Platelet recovery at day 100 92 81.5 0.03 
Grade II-IV aGVHD 30.2 48.3 0.009 
3 year TRM in CR1 24.6 28.7 0.6 
3 year TRM in CR2+ 21.0 23.1 0.8 
3 year relapse incidence in CR1 24.4 20.6 0.6 
3 year relapse incidence in CR2+ 49.9 39.6 0.3 
3 year OS in CR1 55.9 55.6 0.8 
3 year OS in CR2+ 33.1 37.9 0.8 
SIB (%)MUD (%)P
Neutrophil recovery at day 42 96.4 97.8 0.6 
Platelet recovery at day 100 92 81.5 0.03 
Grade II-IV aGVHD 30.2 48.3 0.009 
3 year TRM in CR1 24.6 28.7 0.6 
3 year TRM in CR2+ 21.0 23.1 0.8 
3 year relapse incidence in CR1 24.4 20.6 0.6 
3 year relapse incidence in CR2+ 49.9 39.6 0.3 
3 year OS in CR1 55.9 55.6 0.8 
3 year OS in CR2+ 33.1 37.9 0.8 
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Table 2

Multivariate results for OS*

HR95%CIP
CR1 Ref   
CR2 1.7 1.1-2.5 0.01 
Age <35 Ref   
Age>=35 1.7 1.1-2.6 0.01 
HR95%CIP
CR1 Ref   
CR2 1.7 1.1-2.5 0.01 
Age <35 Ref   
Age>=35 1.7 1.1-2.6 0.01 
*

Adjusted for cytogenetics and WBC at diagnosis, donor type and conditioning intensity.

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Figure 1
Figure 1. Overall survival by disease status and donor type
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Overall survival by disease status and donor type

Figure 1
Figure 1. Overall survival by disease status and donor type
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Overall survival by disease status and donor type

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In summary, hematopoietic transplantation using a MUD was associated with slower platelet recovery which could be due to more common use of BM as the stem cell source. Acute GVHD incidence was also higher with MUD transplants but OS was comparable between donor types, even when patients were transplanted in CR1. Thus, in the absence of a SIB donor, a matched unrelated donor is an acceptable donor source for HCT with comparable overall survival.

Disclosures:

Qazilbash:Celgene: Membership on an entity’s Board of Directors or advisory committees Other; Millenium: Membership on an entity’s Board of Directors or advisory committees, Membership on an entity’s Board of Directors or advisory committees Other.

Topics:
cell transplantation, complete remission, donors, leukemia, relationship - sibling, graft-versus-host disease, follow-up, graft-versus-host disease, acute, maintenance chemotherapy, methotrexate

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2013 by The American Society of Hematology
2013
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