Improved Outcome in High Risk and Very High Risk ALL by Risk Adapted SCT and in Standard Risk ALL by Intensive Chemotherapy in 713 Adult ALL Patients Treated According to the Prospective GMALL Study 07/2003.

In 2003 the German Multicenter ALL Study Group (GMALL) initiated the trial GMALL 07/2003. Major aims were improvement of outcome by shortened, intensified induction, intensified consolidation, risk adapted and extended SCT indication and minimal residual disease (MRD) based treatment stratification. 8drug-induction was followed by uniform 1 st consolidation based on HDARAC and HDMTX. Further treatment was stratified according to the following risk factors (RF): WBC > 30.000 in B-prec. ALL, late CR (>3wks), proB-, earlyT and mature T-ALL, Ph/BCR-ABL and t(4;11)/ALL1-AF4. The risk groups were defined as follows: standard risk (SR, no RF), high risk (HR,>= 1RF) and very high risk (VHR,Ph/BCR-ABL). HR and VHR pts were scheduled for SCT in CR1 with the following priorities: allo sibling, allo matched unrelated and autologous. VHR pts mostly received Imatinib according to different schedules. SR pts received 5 consolidation cycles (HDMTX/ASPx3, VP16/ARAC, CYCLO/ARAC) and reinduction. SR pts with high MRD after consolidation I were allocated to SCT. In the remaining SR pts decision on maintenance therapy was based on MRD. Between 04/03-12/06 713 evaluable (15–55 yrs) pts were included. The median age was 34 yrs. The CR rate after induction was 89% with 5% early death and 6% failure. 50%, 33% and 17% were allocated to SR (N=353), HR (N=235) and VHR (N=117) with similar CR rates of 92%, 88% and 85%. CR rate was not different in pts 35 yrs (90% vs 89%). 5 year overall survival (OS) was 54% and survival of CR (S-CR) pts was 59%. HR and VHR pts obtained 55% and 49% S-CR at 3 yrs resp. HR subgroups showed different S-CR for early T (58%), mature T (70%), pro B (66%) and other B-lineage ALL (37%). 68% and 71% of HR and VHR pts received SCT in CR1 as scheduled which thus contributed substantially to improved outcome. In SR- ALL S-CR was 69% (68% c/preB, 66% thymicT). The CCR probability was 52% at 3 yrs. CNS prophylaxis was very effective since only 2% of the CR pts had CNS involvement at relapse. Univariate analysis confirmed a significant prognostic impact of immunphenotype, WBC in B-lin ALL, time to CR and Ph/BCR-ABL. WBC was no prognostic factor in T-lin-ALL. Age was highly significant for survival with 64% survival