Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative option for patients with AML. However, most of them are diagnosed over 60 years of age, limiting in part the possibility of intensive treatment. In addition, advanced age is frequently associated with less probability to identify an available matched related donor among siblings (MSD), decreasing again the access to curative treatment. Unrelated donor (UD) Allo-HSCT is an alternative but is associated with higher morbidity, especially related to higher incidence of graft-versus-host disease. More recently, haplo-identical related donor (HRD) Allo-HSCT was developed as a valid option in the absence of a matched donor; still, many investigators reluctantly consider this alternative in elderly patients, anticipating higher morbidity. We here report a single institution comparative evaluation of our HRD vs MSD or UD Allo-HSCT transplant program for patients >= 60.
Inclusion criteria were: age >= 60 years; first Allo-HSCT from 2011 to 2016 for AML in a single center; Allo-HSCT from MSD, UD or HRD. All types of conditioning regimens, GVHD prophylaxis and graft source were included.
We retrospectively analyzed 94 consecutive patients who matched inclusion criteria, with a median age of 65 years (range: 60-73). Cytogenetics was intermediate and unfavorable in 61 (65%) and 28 (30%) patients, respectively. Eighty patients (85%) were transplanted in complete remission (CR), mostly first CR (66/80). Hematopoietic cell transplantation comorbidity index (HCT-CI) was >= 3 in 52 patients (55%). Conditioning regimens varied from non-myeloablative (NMAC, low dose TBI, no busulfan), to reduced (RIC, busulfan total dose of 260 mg/m²) or myeloablative intensity (MAC, busulfan total dose >= 390 mg/m²) in 13 (14%), 71 (76%) and 10 (11%) patient, respectively. Patients were transplanted with MSD (N=31, 33%), UD (N=30, 32%, 27 HLA-10/10 UD and 3 HLA-9/10 UD) and HRD (N=33, 35%). Patients transplanted with a HRD had more frequently refractory disease (MSD vs. UD vs. HRD: 13% vs. 7% vs. 24%, p=0.037) and more frequently received NMAC regimen (MSD vs. UD vs. HRD: 13% vs. 0% vs. 27%, p=0.007). Post-transplantation cyclophosphamide was used as GVHD prophylaxis for all HRD Allo-HSCT while most of remaining patients were given 5 mg/kg total dose of ATG. Cytogenetics and HCT-CI were equally distributed across the donor groups. Median follow up was 26 months (range: 4-77).
The cumulative incidence of grade 3-4 acute GVHD was significantly higher after UD Allo-HSCT compared with MSD or HRD Allo-HSCT (day-100: MSD vs. UD vs. HRD: 3% vs. 33% vs. 6%, Gray-test p=0.006, Figure 1A). No difference was observed in the cumulative incidence of extensive chronic GVH (2-year: MSD vs. UD vs. HRD: 17% vs. 27% vs. 16%, Gray-test p=0.487). The cumulative incidence of non-relapse mortality (NRM) and relapse (CIR) at 2 years were not significantly different according to donor type (NRM: MSD vs. UD vs. HRD: 19% vs. 27% vs. 24%, Gray-test p=0.709; CIR: MSD vs. UD vs. HRD: 32% vs. 25% vs. 25%, Gray-test p=0.411). Finally, we found similar progression free survival (PFS) and overall survival (OS) in the 3 donor groups (PFS: MSD vs. UD vs. HRD: 48% vs.48% vs. 50%, Log rank-test p=0.865; OS: MSD vs. UD vs. HRD: 50% vs. 51% vs. 55%, Log rank-test p=0.960, Figure 1B). Interestingly, both HCT-CI (< 3 vs. >= 3) and age (< 65 vs. >= 65 years) failed to predict differential NRM.
We conclude that in the specific setting of patients >= 60 years transplanted for AML, the use of HRD is not associated with unfavorable outcome compared with MSD and UD, confirming that it is a valuable alternative for patients without HLA-matched donors. Moreover, Allo-HSCT from a familial donor (MSD or HRD) apparently results in a lower incidence of acute GVHD. Thus, we consider that there is no evidence for limiting the access to Haplo-SCT in elderly patients with AML who need transplantation, and that HRD favorably compares with UD in absence of MSD.
Charbonnier: Incyte: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau.
Asterisk with author names denotes non-ASH members.