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Background:
Reduced intensity conditioning (RIC) has expanded allogeneic hematopoietic stem cell transplantation (HCT) to elderly patients and to those with additional comorbidities. There is inconclusive evidence suggesting that the risk of adverse events, such as pure red cell aplasia (PRCA), delayed engraftment, or shortened survival, is increased with ABO incompatibility. We sought to better elucidate these issues.
Methods:
After IRB approval, consecutive patients with myeloid neoplasms (MDS and AML) who underwent their first RIC allo HCT from 2005 to 2014 were identified. All clinical and transplant data were retrospectively abstracted. Conditioning regimens, GVHD prophylaxis and transfusions were according to institutional standards.
Results:
Of 148 patients (median age 61, male 62%), 97 (65%) had AML, 29 (20%) had MDS with excess blasts and 22 (15%) had MDS without excess blasts. At last follow up, 31(21%) relapses and 63 (48%) deaths were noted (median follow up 17 months).
Transfusion and engraftment data are shown in Table 1. PRCA was diagnosed in 6 (20% of the major mismatch group), all of whom had an A to O mismatch. ABO major mismatches had higher RBC and PLT transfusion needs at 100 days (p<0.0001 for RBC and 0.004 for PLT transfusion), and at 1 year (p=0.004 for RBC and 0.007 for PLT transfusion), as well as delayed RBC (p<0.001) and PLT (p<0.001) engraftment compared with the ABO compatible group. This was true even after excluding patients with PRCA. PMN engraftment was not affected by ABO compatibility.
There was no difference in overall survival (OS) among the 3 groups (p=0.51) (Figure 1). For the total cohort, median disease free survival (DFS) and OS estimates were 43 and 44 months, respectively. Relapse rate (RR) was 22%, and non-relapse mortality (NRM) was 21% at the end of 1 year. Acute and chronic GVHD were seen in 58% and 59%, respectively. After univariate and multivariate analyses, the only factors with impact on OS were the degree of HLA matching (p=0.005) (Figure 2) and the presence of chronic GVHD (p<0.0001) (Figure 3). There was no difference in DFS (p=0.97) or OS (p=0.78) between patients with AML and MDS.
Conclusions:
Our analysis of a large cohort of AML/MDS patients who underwent RIC allo HCT shows that ABO incompatibility has no impact on DFS, OS, RR, NRM, or acute and chronic GVHD. However, higher RBC and PLT transfusion needs, and PRCA are frequent complications adding to the morbidity.
Table 1: Transfusion and engraftment data according to ABO compatibility groups in 148 AML/MDS patients who underwent RIC allo-HSCT
Total patients: 148* | ABO Compatible (n=89) | Major Mismatch (n=29) | Minor Mismatch (n=25) | p. Value | |
Median RBC units | 100 days | 3 | 12 | 2 | <0.0001 |
1 year | 5 | 17.5 | 3.5 | 0.002 | |
Median PLT units | 100 days | 3.5 | 10 | 3 | 0.008 |
1 year | 5 | 15 | 4 | 0.013 | |
Median days to engraftment | RBC | 11 | 29 | 9 | <0.0001 |
PLT | 11 | 14 | 11 | 0.003 | |
PMN | 18 | 19 | 16 | 0.091 | |
* Bidirectional ABO mismatches (n=5) were not included in the analysis | |||||
