INTRODUCTION: The major cause of failure after ASCT for AML in 1st remission is relapse. The collection/ infusion of more CD 34 + cells results in earlier engraftment, but its effect on relapse rates is unknown.

METHODS: Between 2/95 and 9/03, 87 patients with AML in 1st CR underwent ASCT on two sequential IRB-approved trials. Patients with APL, high-risk cytogenetics, or intermediate-risk cytogenetics and a sibling donor were preferentially treated on alternative protocols. Patients received two cycles of ara C (3 g/m2/12h x 8) and idarubicin 12mg/m2/d x 3 (one cycle ara C 2g/m2/12h x 8 if age 55–60). (Nine patients did not receive idarubicin).The 2nd cycle, followed by GCSF 10ug/kg, served as mobilization. All collected cells were infused. Conditioning utilized TBI/VP-16/cyclophosphamide (n = 47) or (AUC-targeted) busulfan/TBI/VP-16 (n = 40). Remission status (morphology; flow cytometry; normal cytogenetics) was confirmed in bone marrow samples prior to mobilization.

RESULTS: 5- year survival rates were 72% (95% CI 62–81%) overall and 68% (95% CI 56–77%) event-free (figure). Mobilization yielded 4.07 x 106 CD 34+ cells/kg (median; range 1.1– 45.08 x 106). Engraftment to ANC 500/ul occurred at 11 days (median; range 8–22), and to (non-transfused) platelet count of 20,000/ul at 22 days (median; range 7–183). In multivariable Cox regression analysis (model fit p-value 0.0007), earlier engraftment was associated with high versus standard dose ara C induction (1.77 times faster; p = 0.02), and graft CD 34+ cell content (1.06 times faster per 106 /kg; p = 0.001). By multivariable Cox proportional-hazards regression, (model fit p-value = 0.01) the number of CD 34+ cells collected/ infused and the time between remission and consolidation were both predictive of shorter event-free survival. An increase of 106 in the number of CD34+ cells was associated with a 1.06 factor increase in the probability of death or relapse (95% CI 1, 1.11, p = 0.04). Each month’s delay between remission and consolidation increased the probability of death or relapse by a factor of 1.22 (95% CI 1.02, 1.47, p = 0.03). The leukocyte count at diagnosis was associated with longer event-free survival (0.98 times per 1000 cells/ul), (95% CI 0.96, 1.00, p = 0.05). Age, sex, the presence of extramedullary disease, FAB subtype, cytogenetic risk group, type (high versus conventional dose ara-C) and number of induction cycles, use of idarubicin in consolidation, conditioning regimen, and IL-2 administration after transplant were not correlated with survival or event-free survival.

CONCLUSION: In this study, the collection and infusion of more CD 34+ cells resulted in shortened relapse-free survival, despite an initial favorable impact on engraftment times. Longer time between remission and consolidation also adversely influenced relapse-free survival.

Figure
View largeDownload slide

Figure

Topics:
adverse effects, autologous stem cell transplant, disease remission, cytarabine, idarubicin, etoposide, infusion procedures, aldesleukin, bone marrow specimen, busulfan

Author notes

Corresponding author

2005, The American Society of Hematology
2005
Sign in via your Institution