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.