title: Importance of marrow dose on posttransplant outcome in acute leukemia: models derived from patients autografted with mafosfamide-purged marrow at a single institution.
abstract: Several prospective randomized trials in acute myelocytic leukemia (AML) documented a lower relapse rate with autologous bone marrow transplantation (ABMT) than with conventional chemotherapy. However, they also identified some transplant difficulties, such as failure to collect sufficient numbers of stem cells, slow kinetics of engraftment, and a high transplant-related mortality that diminished or negated positive impact on overall survival. Data for ABMT are inconclusive in acute lymphocytic leukemia (ALL) in adults. We retrospectively analyzed patients with acute leukemia autografted with marrow purged with mafosfamide after January 1983 in our institution. The population comprised 229 consecutive patients; 165 with AML [123 in first remission (CR1), 32 in second remission (CR2)]; 61 with ALL (46 in CR1, 4 in CR2); and 3 with undifferentiated acute leukemia. All patients were autografted with marrow purged with mafosfamide. Mafosfamide was given at a constant dose of 50 microg/mL in 103 and adjusted individually to produce a CFU-GM LD 95 (5% residual CFU-GM post purging) in 126. The outcome was analyzed for correlation with patient characteristics, the disease including cytogenetics, and the graft itself. Prognostic factors identified by multivariate analysis were used to derive a prognostic classification. Patients receiving higher doses of marrow submitted to purging (>5.46 x 10(4) CFU-GM/kg) experienced a lower treatment-related mortality (RR = 0.11, p = 0.005) and a higher leukemia-free (RR = 0.5, p = 0.005) and overall survival (RR = 0.4, p = 0.001). Patients receiving <0.004% CFU-GM of marrow actually infused post purging had a lower relapse rate (RR = 0.51, p = 0.003). Modeling of prognostic groups identified good-, intermediate-, and poor-risk categories. Patients receiving a stem cell dose evaluated before purging of >5.46 x 10(4) CFU-GM/kg and doses actually infused post purging of < or =0.02 x 10(4)/kg had a treatment-related mortality of only 2+/-2%, a leukemia-free survival of 70%, and an overall survival of 77+/-7% at 10 years. In this study of autotransplantation for acute leukemia using mafosfamide-purged marrow, the stem cell dose used for purging and the intensity of purging were the most important factors predicting outcome.
authors.affiliation: Department of Hematology, Hôpital Saint-Antoine AP-HP, Centre de Recherche Claude-Bernard, Université Paris VI et Fontenay-aux-Roses, France. norbert.claude@sat.ap-hop-paris.fr
authors.forename: N C
authors.initials: NC
authors.lastname: Gorin
authors.forename: M
authors.initials: M
authors.lastname: Labopin
authors.forename: J P
authors.initials: JP
authors.lastname: Laporte
authors.forename: L
authors.initials: L
authors.lastname: Douay
authors.forename: M
authors.initials: M
authors.lastname: Lopez
authors.forename: S
authors.initials: S
authors.lastname: Lesage
authors.forename: L
authors.initials: L
authors.lastname: Fouillard
authors.forename: F
authors.initials: F
authors.lastname: Isnard
authors.forename: J P
authors.initials: JP
authors.lastname: Jouet
authors.forename: N
authors.initials: N
authors.lastname: Bellal
authors.forename: C
authors.initials: C
authors.lastname: Perot
authors.forename: J
authors.initials: J
authors.lastname: Van Den Akker
authors.forename: F
authors.initials: F
authors.lastname: Bauters
authors.forename: A
authors.initials: A
authors.lastname: Najman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D002452:Cell Count; D002648:Child; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006085:Graft Survival; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C048341:mafosfamide; D003520:Cyclophosphamide