Allogeneic Transplantation in Septuagenarians Using Post-Transplant Cyclophosphamide (PTCy): Similar Outcomes to Younger Patients Except for Higher Late Non-Relapse Mortality (NRM)

Abstract

Advances in allogeneic blood and marrow transplantation (alloBMT), especially nonmyeloablative (NMA) conditioning and haploidentical donors, have made this therapy available to older people in whom it was historically contraindicated or not available. Since Jan 1, 2009, 108 consecutive patients older than 70 (Table 1) underwent alloBMT at Johns Hopkins (through March 31, 2018). The median age was 72 (range 70-78). Refined disease risk index (DRI) was low in 10 (9%), intermediate in 83 (77%), and high or very high in 14 (13%). All patients received NMA conditioning. Haplo donors were used in 94 (87%), including 80 children, 7 grandchildren, and 4 nieces or nephews; matched sibling donors were used in 7 patients and matched unrelated donors in 6. All patients received PTCy, MMF from day 5 to 35, and either tacro or siro from day 5 until day 60 - 180. With a median follow-up of 938 days, the 2 year overall survival is 49% (95% CI 40-61), and 2 year PFS was 41% (95% CI 32-53) (Figure 1). The 180 day cumulative incidence (CuI) of non-relapse mortality (NRM) is 14% (CI 8-21), but 2-year NRM was 29% (95% CI 20-39%), with many late deaths (Fig 1). The 2 year CuI of relapse was 30% (95% CI 20-39%). Graft failure was 6% (95% CI 1-10%) at 100 days and was not different between BM and PBSCT grafts (7.7% vs 6.1%). The CuI of grade III-IV acute GVHD was 7% (95% CI 2-12%), and cGVHD at 2 years was 8% (95% CI 3-14%) (Figure 2). In univariate analyses, there were no differences in NRM, OS, or PFS between bone marrow and peripheral blood grafts. HCT-CI (0, 1-2,or 3 or more) did not predict NRM. Of 78 patients who were alive and had a weight recorded on day 180, the median weight change was loss of 4.4 kg. NRM after day 180 was 10/39 (26%) in patients who lost more than 4.4kg and 3/39 (8%) in those who lost less than 4.4kg (p=0.035). In conclusion, alloBMT with PTCy is relatively safe and feasible in septuagenarians. Acute and chronic GVHD rates with PTCy are low and similar to those seen in younger patients. Relapse rates are also similar. Early (6 month) NRM is also low, but overall NRM is higher at least in part because of late deaths that appear to be in part age-related (e.g., secondary malignancy, dementia, fall, CVA). We are currently studying functional outcomes of older patients undergoing alloBMT in a prospective trial, as well as potential predictors of long-term outcomes.