Fludarabine and melphalan-based conditioning for patients with advanced hematological malignancies relapsing after a previous hematopoietic stem celltransplant

Severe regimen-related toxicity often complicates second transplant procedu res performed in patients with hematological malignancies that have relapse d after an initial hematopoietic stem cell (HSC) transplant. Therefore, we studied the safety and efficacy of a reduced-intensity fludarabine and melp halan based conditioning regimen in 11 patients who had relapsed following an autologous (n = 7) or allogeneic (n = 4) HSC transplant. All patients re ceived allogeneic peripheral blood HSC from either an HLA-identical (n = 7) or an HLA-mismatched (n = 4) relative. Diagnoses included AML (n = 9), ALL (n = 1), or Hodgkin's disease (n = 1). Only one patient was in complete re mission at the time of second transplant. The median interval between first transplant and relapse was 163 days (range 58-1885). Recipients of HLA-mis matched transplants received antithymocyte globulin in addition to fludarab ine and melphalan as part of the conditioning regimen. All 11 patients rece ived acute GVHD prophylaxis consisting of tacrolimus and methotrexate. Ten of 11 patients achieved hematopoietic engraftment with a median time to abs olute neutrophil count >0.5 x 10(9)/l and to platelet count of > 20 x 10(9) /l of 14 and 19 days, respectively. All engrafting patients achieved 100% d onor chimerism. on initial analysis, except for one with persistent leukemi a at day +19. Two patients experienced grade 3 regimen-related toxicity, ma nifesting as acute renal failure. Acute GVHD grades 2-4 occurred in two rec ipients and chronic GVHD in four. The 100-day mortality from all causes was 36%. Ten of 11 patients (91%) died a median of 140 days (range 9-996) afte r the second transplant. The causes of death included relapse (n = 5), seps is (n = 4), and idiopathic pneumonia syndrome (n = 1). One patient with AML survives in remission at 880 days post-transplant. We conclude that fludar abine- and melphalan-based conditioning promotes full donor chimerism, even following HLA-mismatched transplants. However, the regimen may be more ben eficial when applied to patients undergoing allogeneic HSC transplantation earlier in their disease course.