Jp. Laporte et al., 125 ADULT PATIENTS WITH PRIMARY ACUTE-LEUKEMIA AUTOGRAFTED WITH MARROW PURGED BY MAFOSFAMIDE - A 10-YEAR SINGLE INSTITUTION EXPERIENCE, Blood, 84(11), 1994, pp. 3810-3818
A total of 125 acute leukemia adult patients were autografted with bon
e marrow (BM) purged by mafosfamide (ASTA Z) during the period of Janu
ary 1983 to January 1993. The median follow-up period was 64 months (r
ange, 3 to 126). There were 84 acute myeloblastic leukemias (AMLs) and
41 acute lymphoblastic leukemias (ALLs). At time of autologous BM tra
nsplantation (ABMT); 64 AMLs were in first complete remission (CR1), a
nd 20 were in second CR (CR2); 35 ALL were in CR1, and 6 were in CR2.
The median age of the patients was 33 years (range, 16 to 55). The med
ian interval between achieving CR and autografting was 5 months (range
, 1.3 to 23). The pretransplant regimen consisted of cyclophosphamide
(120 mg/kg) and total body irradiation. All patients were grafted with
autologous BM treated in vitro with mafosfamide used at levels indivi
dually adjusted in 95 patients and at a standard dose in 30 patients.
The initial richness in granulomacrophagic progenitors (CFU-GM) of the
harvested BMs was 5.16 x 10(4) CFU-GM/kg (range, 0.55 to 33). After m
afosfamide purging, the residual CFU-GM number was 0.021 x 10(4)/kg (r
ange, 0 to 1.78). The probability of successful engraftment was signif
icantly higher and the time to engraftment was significantly shorter i
n ALL, Of 33 patients grafted with BM containing no residual CFU-GM, t
hose with AML (n = 22) had platelet recoveries that were significantly
longer than those for AML patients receiving BM with residual CFU-GM.
At 8 years, patients autografted in CR1 for AML and ALL had a leukemi
a-free survival (LFS) of 58% and 56%, respectively, with a relapse inc
idence (RI) of 25% and 37%, respectively. Patients autografted in CR2
for AML had an LFS of 34% and an RI of 48% at 5 years. The incidence o
f late relapses was significantly higher in ALLs. By multivariate anal
ysis, four factors were found to influence favorably engraftment in ad
dition to a diagnosis of ALL, a younger age, ABMT performed in CR1, th
e adjusted dose technique of purging, and a shorter interval from CR t
o ABMT. Two factors were correlated with a better outcome. (1) The LFS
was significantly higher and the transplant-related mortality signifi
cantly lower in patients who received richer BM. (2) The RI was signif
icantly lower in patients autografted within 150 days from CR. Our res
ults reinforce the view that ABMT is one approach to improve the outco
me of adult patients with acute leukemia. The initial richness of the
BM at collection and the timing of the transplant are important predic
tive factors for the outcome. (C) 1994 by The American Society of Hema
tology.