title: Difference in kinetics of hematopoietic reconstitution between ALL and ANLL after autologous bone marrow transplantation with marrow treated in vitro with mafosfamide (ASTA Z 7557).
abstract: The kinetics of hematopoietic recovery after autologous bone marrow transplantation (ABMT) reflect the hematopoietic capacity of the infused marrow. In vitro treatment of marrow with high doses of mafosfamide (ASTA Z 7557) alters the hematopoietic regenerative capacity of the graft. Thirty-two patients with acute leukemia (12 acute lymphoblastic leukemia (ALL) and 20 acute non-lymphoblastic leukemia (ANLL] with 27 in complete remission and five in partial remission were consolidated with cyclophosphamide (60 mg/kg x 2) and total body irradiation (10 Gy), followed by reinfusion of autologous marrow treated in vitro with mafosfamide. The marrow of each patient had been incubated with the highest tolerable dose of mafosfamide, individually predetermined from a preincubation test. We report here that the kinetics of engraftment are strikingly different in ANLL and ALL patients. In the ANLL group recovery to 0.1% reticulocytes took a median of 20.5 days (range 14-32) versus 15 (11-28) in the ALL group; 33.5 days (18-45) versus 19 (15-30) for leukocytes to reach 1.0 x 10(9)/l; 35 (19-60) versus 20.5 (15-30) for neutrophils to reach 0.5 x 10(9)/l; 110+ (45-480+) versus 50 (23-90) for platelets to reach 50 x 10(9)/l (p less than 0.01 and p less than 0.05). Detection of granulocyte-macrophage progenitors (CFU-GM) regeneration in marrow aspirates post-ABMT was delayed in ANLL (p less than 0.05). Neither the nature of the previous induction therapy, nor the status of the blood or bone marrow at the time of collection (CFU-GM and erythroid burst-forming units/ml) nor the stem cell sensitivity to mafosfamide, nor the doses of progenitor cells infused could explain these differences. We interpreted these observations as suggesting that the engraftment potential has been more severely altered in ANLL than in ALL, which may reflect both the intensity of the in vitro treatment and the intrinsic fragility of the stem cell pool in ANLL.
authors.affiliation: Unité d'Hématologie, Hôpital Rothschild, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Douay
authors.forename: J P
authors.initials: JP
authors.lastname: Laporte
authors.forename: J Y
authors.initials: JY
authors.lastname: Mary
authors.forename: M
authors.initials: M
authors.lastname: Lopez
authors.forename: M P
authors.initials: MP
authors.lastname: Lemonnier
authors.forename: J
authors.initials: J
authors.lastname: Stachowiak
authors.forename: O
authors.initials: O
authors.lastname: Benitez
authors.forename: J
authors.initials: J
authors.lastname: Deloux
authors.forename: A
authors.initials: A
authors.lastname: Najman
authors.forename: C
authors.initials: C
authors.lastname: Salmon
mesh_terms: D001853:Bone Marrow / Q000187:drug effects; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D013997:Time Factors
chemical_list: C048341:mafosfamide; D003520:Cyclophosphamide