engleski

Allogeneic transplantation for adult acute lymphoblastic leukemia: Intention to treat analysis of the EORTC ALL-4 phase III trial

Results of the EORTC ALL-3 reveal that the policy to perform allo-SCT in a case when a sibling donor is available does not result in a significantly better outcome than to offer auto-SCT or continuous maintenance. We also analysed the outcome of allografted patients in EORTC ALL-4. In this trial patients were randomized to receive either dexamethasone (10 mg/m2/day) or 6-methyl-prednisolone (60 mg/m2/day) on days 1-8 and 15-22 with standard induction chemotherapy (cyclophosphamide, daunorubicin, vincristine and MTX i.t.). After induction all patients had to receive a HAM consolidation course (HD-AraC 3 g/m2 every 12 hours, days 1-4 ; mitoxantrone 10 mg/m2, days 5-7 and MTX i.t.). Patients in CR received two courses of MA consolidation (MTX 1.5 g/m2 day 1 and L-asparaginase 104 IU/m2 day 2), and then underwent allo-SCT or patients without a donor were randomized either to receive autologous stem cells from peripheral blood or high maintenance therapy. The median follow-up was 4.9 years. Between 1998 and 2003, a total of 325 pts entered the study. The median age was 32 yrs range 15-72 yrs. In 248 (76%) patients CR1 was reached and 227 of them were HLA typed ; 100 had an identical sibling donor and 127 had no sibling donor. Allo-SCT was performed in 69 (69%) pts and auto-SCT or high maintenance therapy in 58 (46%). The 5-year DFS of pts with a donor vs pts without a donor was 41.8% vs. 35.5%, P = .40, hazard ratio 0.86, 95% CI 0.61-1.22). The relapse incidence was significantly lower (37.3% vs. 58.8% P = .004) and treatment related mortality (TRM) was significantly higher (20.9% vs. 5.7%, P = .0005) in the donor group compared to the no donor group. Five-year survival in pts with and without the donor was 43.0% and 36.9% respectively. For pts ≤ 50 years of age 199 of them were HLA-typed ; 91 had a donor and 108 had no sibling donor. The 5-yr DFS rate in the donor vs no donor group was 42.2% vs. 36.2%, P = .36, hazard ratio 0.84 95% CI 0.58-1.22). Relapse rate was significantly lower and TRM was significantly higher in the donor versus no donor group. Five-year survival for patients with and without a donor was 43.9% and 37.4% respectively (P = .58), hazard ratio 0.90 (95% CI 0.61-1.32). In conclusion, in the EORTC ALL-4 trial, the intention to treat analysis shows that DFS and survival rate for allografted pts younger than 50 years of age were not significantly different compared to those receiving auto-SCT or high maintenance. High TRM (∼ 20%) remains the main problem of allografting.

EORTC

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