Influence of melphalan plus fludarabine-conditioning regimen in elderly patients aged ⩾55 years with hematological malignancies

Some recent clinical developments allow the extension of hematopoietic stem cell transplantation (HSCT) to elderly patients. Reduced-intensity conditioning (RIC) regimen-based HSCT was introduced for these patients. Although various RIC regimens have been used and subsequently reported, the high treatment-related toxicity, early mortality and lower survival rate of elderly recipients remain unresolved. Several groups have reported that conditioning regimens employing fludarabine plus melphalan (FM) are efficacious and well tolerated. We previously investigated the appropriate melphalan dose in combination with fludarabine in a prospective phase 1 study, and our findings led us to recommend a melphalan dose of ⩾ 135mg/m to induce initial full-donor chimerism. Although another group reported that melphalan administered to elderly patients at doses up to 180mg/m is safe and efficacious, most of these reports included a wide range of melphalan doses. The optimal melphalan dose combined with fludarabine for elderly patients is still unclear. We performed a retrospective, multicenter analysis. Data were provided by the Nagoya Blood and Marrow Transplantation Group, and the registry data were managed using the Transplant Registry Unified Management Program. Between April 2002 and March 2011, 371 elderly patients aged ⩾ 55 years underwent their first allogeneic HSCT at nine Nagoya Blood and Marrow Transplantation Group-affiliated hospitals. We included 113 patients with AML, ALL/lymphoblastic lymphoma and myelodysplastic syndrome who fulfilled the following criteria: the conditioning regimen included fludarabine (125 mg/m) and melphalan (130–180 mg/m; FM). GvHD prophylaxis was either cyclosporine or tacrolimus (Tac), which was combined with a short course of methotrexate (MTX). The grafts comprised either bone marrow or granulocyte CSF-mobilized PBSC. Patients receiving TBI or undergoing in vivo or ex vivo T-cell depletion were excluded. We compared two groups according to melphalan dose as follows: FM 160–180 (melphalan4140mg/m) and FM 130–140 (melphalan ⩽ 140mg/m) based on the Center for International Blood and Marrow Transplant Research criteria, which define melphalan ⩽ 140mg/m as RIC regimens. The disease risk was defined according to the disease risk index, which combined cytogenetic risk and stage risk. Acute GvHD was classified according to clinical criteria, and chronic GvHD was graded as limited or extensive. The Institutional Review Board approved this study, which was conducted in accordance with the Declaration of Helsinki.  In brief, FM 160–180 patients had higher disease risk, transplantation during the preceding year, and they were more likely to receive stem cells from unrelated donors, bone marrow transplantation and Tac-based GvHD prophylaxis. In contrast, FM 130–140 patients more frequently received stem cell transplants from HLA-matched donors. The median follow-up period for all survivors was 833 days (range, 104–1925 days), and the 2-year overall survival (OS) was 46.7%. OS was higher for FM 130–140 0.00 0.20 0.40 0.60 0.80 1.00