title: High-dose melphalan and allogeneic peripheral blood stem cell transplantation for treatment of early relapse after allogeneic transplant.
abstract: Patients with acute leukemias relapsing within 1 year of an allogeneic BMT have a poor prognosis. We studied the use of melphalan 180 mg/m2 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/m2 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 >0.5 x 10(9)/l and to a platelet count >20 x 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 short-term disease control to facilitate donor lymphocyte infusion-based immunotherapy or other measures to prevent disease recurrence.
authors.affiliation: Department of Blood and Marrow Transplantation, University of Texas MD Anderson Cancer Center, Houston 77030-4095, USA.
authors.forename: M
authors.initials: M
authors.lastname: de Lima
authors.forename: K
authors.initials: K
authors.lastname: van Besien
authors.forename: J
authors.initials: J
authors.lastname: Gajewski
authors.forename: I
authors.initials: I
authors.lastname: Khouri
authors.forename: B
authors.initials: B
authors.lastname: Andersson
authors.forename: M
authors.initials: M
authors.lastname: Korbling
authors.forename: R
authors.initials: R
authors.lastname: Champlin
authors.forename: S
authors.initials: S
authors.lastname: Giralt
mesh_terms: D000208:Acute Disease; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000276:immunology; D002648:Child; D002908:Chronic Disease; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D010865:Pilot Projects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000628:therapy*; D012074:Remission Induction; D018183:Transplantation Chimera
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan