Abstract

Abstract 3135

Background:

When an HLA-matched donor is not available for allogeneic Hematopoietic Stem Cell Transplantation (HSCT), the use of an alternative HLA-mismatched stem cell source may be considered. In Europe, HLA compatibility for HSCT is calculated for 10 alleles (HLA-A, -B, -C, -DRB1, -DQB1). The aim of this study was to retrospectively compare outcomes after transplantation from 10/10 HLA-MUD, 9/10 HLA-MMUD and UCB performed at the Hospital Saint Louis (Paris, Fr).

Methods:

Patients receiving a first allogeneic transplantation from a 10/10, 9/10 UD or UCB from 2000 to 2011 were included.

High resolution HLA typing was performed by PCR SSO and SSP for HLA loci: A, B, C, DRB1 and DQB1. The following variables were studied as risk factors for transplant outcomes: disease, disease risk (standard/high risk), age at transplant, gender, donor/recipient sex-matching, ABO matching, donor/recipient CMV status, conditioning regimen, and use of anti-thymoglobulin (ATG).

Results:

355 consecutive patients with hematologic malignancies were analyzed. One hundred and ninety-six were transplanted with MUD, 84 with MMUD (mismatches for HLA-A: 16%, -B: 16%, -C: 39%, -DRB1: 8%, -DQB1: 21%) and 75 with UCB (52% with single and 48% with two UCB unit; 87% of all UCB transplants were 4–6/6 HLA-matched). Median patient age was 31 (range: 5–55). Patient characteristics differed between the 3 groups: (i) median age at transplant: 36 in MUD, 31 in MMUD, 22 in UCB (p<0.0001), (ii) high risk disease: 37%, 51%, 68% (p<0.0001), (iii) CMV negative donor/positive recipient: 31%, 36%, 60% (p<0.0001), (iv) use of ATG: 37%, 64%, 55% (p<0.0001).

Cumulative incidences of grade II-IV and grade III-IV acute GvHD disease (aGvHD) were 61% (66% for MUD, 60% for MMUD and 48% for UCB) and 17% (17%, 24% and 15%), respectively. Three-year cumulative incidence of chronic GvHD (cGvHD) was 46% (51% for MUD, 49% for MMUD and 29% for UCB). Three-year NRM was 34% (28% for MUD, 31% for MMUD and 51% for UCB). Graft failure occurred in 15% of UCB patient, 8% in MMUD group and 3% in MUD group (significant difference between UCB and MUD: OR=5.44, 95%CI 1.93–15.3, p=0.001).

Multivariate analysis is summarized in table 1. It showed that MMUD tented to have a higher incidence of aGvHD III-IV than MUD and UCB. UCB had a lower incidence of cGvHD than MMUD. No significant effect of HSCT source on NRM was demonstrated.

Conclusion:

Compared to MMUD, UCB-HSCT induces less cGvHD and non significantly increased NRM. Compared to MUD, MMUD and UCB-HSCT did not result in a clear increase of NRM. UCB and 9/10 HLA-MMUD are both suitable stem cell sources for patients who cannot benefit from 10/10 HLA-MUD transplant.

Table 1:

Multivariate analysis of outcomes

 Adjusted HR (p value) 
 aGvHD II-IV aGvHD III-IV cGvHD NRM 
10/10 MUD 
9/10 MMUD 0.90 (p=0.54) 1.75 (p=0.054) 1.30 (p=0.18) 1.18 (p=0.50) 
UCB 0.63 (p=0.074)* 0.86 (p=0.67)* 0.75 (p=0.23)* 1.82 (p=0.099)* 
CMV status D-/R-    
D-/R+    2.05 (p=0.001) 
Major ABO incompatibility: no    
yes 1.40 (p=0.019)    
ATG: no  
yes 0.40 (p<0.0001) 0.29 (p<0.0001) 0.40 (p<0.0001)  
 Adjusted HR (p value) 
 aGvHD II-IV aGvHD III-IV cGvHD NRM 
10/10 MUD 
9/10 MMUD 0.90 (p=0.54) 1.75 (p=0.054) 1.30 (p=0.18) 1.18 (p=0.50) 
UCB 0.63 (p=0.074)* 0.86 (p=0.67)* 0.75 (p=0.23)* 1.82 (p=0.099)* 
CMV status D-/R-    
D-/R+    2.05 (p=0.001) 
Major ABO incompatibility: no    
yes 1.40 (p=0.019)    
ATG: no  
yes 0.40 (p<0.0001) 0.29 (p<0.0001) 0.40 (p<0.0001)  
*

UCB vs 9/10 MMUD: HR 0.69 (p=0.22) for aGvHD II-IV, HR 0.49 (p=0.061) for aGvHD III-IV, HR 0.58 (p=0.039) for cGvHD and HR 1.53 (p=0.30) for NRM.

Disclosures:

No relevant conflicts of interest to declare.

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Author notes

*

Asterisk with author names denotes non-ASH members.