Summary:Patients with acute leukemias relapsing within 1 year of an allogeneic BMT have a poor prognosis. We studied the use of melphalan 180 mg/m 2 followed by allogeneic peripheral blood stem cells (PBSC) as salvage treatment for patients relapsing after related (n = 7) or matched unrelated transplants (n = 3). Diagnoses were AML (n = 4), ALL (n = 3), biphenotypic acute leukemia (n = 2) and CML in blast crisis (n = 1). Eight patients were beyond first relapse and none were in remission. The median time from previous transplant to relapse was 146 days (range 66-206). The melphalan dose was 90 mg/m 2 intravenously on days −4 and −3 with PBSC infusion on day 0. GVHD prophylaxis consisted of cyclosporine and methylprednisolone. The median time to an absolute neutrophil count Ͼ0.5 × 10 9 /l and to a platelet count Ͼ20 × 10 9 /l was 11 and 13 days, respectively. All engrafting patients (n = 8) had 100% donor cells. Two patients died before day 30, but no other grade 3 or 4 toxicity occurred. Acute GVHD grades II-III occurred in two subjects, and chronic GVHD in four. Seven patients achieved CR, but relapsed at a median of 116 days (range 56-614). Leukemia was the cause of death in eight patients. Median survival was 149 days (range 6-614). This treatment produced responses in the majority of this poor prognosis group. However, durable remissions were not observed, and new treatments to consolidate the responses achieved in this setting are needed. This regimen could be considered for shortterm disease control to facilitate donor lymphocyte infusion-based immunotherapy or other measures to prevent disease recurrence. Bone Marrow Transplantation (2000) second myeloablative conditioning with allograft, 5 and enhancement of the graft-versus-leukemia effect by discontinuation of immunosuppressive therapy or addition of immunocompetent donor cells. [6][7][8][9][10][11][12][13][14][15][16][17][18] Other studies have involved stimulation of donor-derived immune responses or inhibition of the leukemic clone using cytokines such as interferon, G-CSF or interleukin-2. [19][20][21][22][23] Early relapses occurring during the first year post transplant carry an ominous prognosis with few patients responding to immune manipulation, chemotherapeutic maneuvers or second myeloablative therapies, which are associated with an extremely high risk of toxicity and treatment-related mortality.Immunological approaches such as interferon or donor lymphocyte infusion have been generally successful in chronic myelogenous leukemia (CML) relapsing in chronic phase, but not in acute leukemia or CML in transformed phases. The failure of immunological approaches in these diseases may be due in part to the proliferative rate of malignant cells and the long interval required for buffy coat infusions to exert an immune therapeutic effect. Cytoreduction with chemotherapy followed by reinfusion of both immunocompetent and hematopoietic progenitor cells could reinduce remissions in this setting. Cytoreduction with chemotherapy would allow donor-derive...