Allogeneic-SCT in Patients with Hematological Malignancies Aged 60 Years or Older: Importance of HLA-Matching.

Despite the introduction of toxicity-reduced conditioning there is still much debate if patients aged 60 years or more should be considered as candidates for allogeneic stem cell transplantation (allo-SCT) and the experience with this patient group remains limited. This report summarizes our cumulative experience in a cohort of 31 consecutive elderly patients (age 60–69, median 61 years) with hematological malignancies treated with, depending on the underlying disease, a variety of toxicity-reduced conditioning regimens followed by allo-SCT. All but four patients received mobilized peripheral blood stem cells as graft and 12 patients had a sibling and 19 an unrelated donor (MUD), respectively. In the majority of patients the underlying disease was acute leukemia or progressive MDS (n=2) with only 25% being in complete remission at the time of transplant. The remaining 8 patients suffered from either chronic leukemia (CML, n=3; CLL, n=1), osteomyelofibrosis (n=3) and multiple myeloma (n=1). For this patient cohort the conditioning regimens applied were all myeloablative as evidenced by full donor chimerism at day +30 in all patients. The time to recovery of absolute neutrophil count >/=0.5 x 10(9)/l was 10-34 days (median 19 days). Despite the high relapse risk in the majority of patients we observed only 4 deaths because of recurrent leukemia. Severe acute GVHD (grade 3 and 4) occurred in 26% and the non relapse mortality was 39% with 5 patients dying from GVHD, 6 from infection and one from toxicity. With a median follow-up of 16 months (range 2 – 66m) for surviving patients the Kaplan-Meyer procedure estimates a 39% probability of survival at 4 y after transplantation. Interestingly, there is no difference what so ever in survival if patients had an identical sibling donor or a MUD. Patients with acute leukaemia had a trend to inferior survival as compared to the others; however, the remission status of these patients had no impact on survival. The most important risk factor for inferior survival was an incomplete HLA-match (8/8). None of the patients who received a mismatched graft survived more than 13 months, whereas in fully HLA-matched transplantations 56% of patients are currently alive and the Kaplan-Meier estimate for survival is 49% at 4 years. Our data support the notion that toxicity-reduced conditioning followed by allo-SCT may be still myeloablative in the elderly, nevertheless it can safely be applied and has excellent anti-leukemic efficacy. However, further efforts are needed for control of GVHD and infectious complications, especially in this high-risk population. A first step in that direction would be, to only accept fully HLA-matched donors.