Treatment of young patients with Philadelphia chromosome‐positive acute lymphoblastic leukaemia using increased dose of imatinib and deintensified chemotherapy before allogeneic stem cell transplantation

Abstract

SummaryThe main outcomes of the Programa Español para Tratamiento de Hemopatías (PETHEMA)-acute lymphoblastic leukaemia (ALL)-Ph-08 trial were described and compared with those of the historical PETHEMA-CSTIBES02 trial. The trials differed in imatinib dose (600 vs. 400 mg/d) and amount of chemotherapy (one vs. two consolidation cycles) before stem cell transplantation (SCT). All patients (n = 29) enrolled in the ALL-Ph-08 trial achieved complete remission (CR) (vs. 90% in CSTIBES02), and SCT was performed in CR in 90% (vs. 78%). The reduction in early death, relapse before SCT and transplant-related mortality observed in the ALL-Ph-08 trial resulted in an improved 2-year event-free survival (63% vs. 37%, P = 0Á009).

A sequential approach with imatinib, chemotherapy and transplant for adult Ph+ acute lymphoblastic leukemia: final results of the GIMEMA LAL 0904 study

“…These results confirm the observations made in our previous study based on the use of dasatinib in induction, 16 and are in line with the current general knowledge on the prognostic impact of MRD. 12,19,[37][38][39][40][41][42][43] Furthermore, they strengthen the notion that MRD negativity should be regarded as a major goal in Ph + ALL treatment. Indeed, with few exceptions, 20,38 it is now well established that BCR-ABL1 transcript levels correlate with response.…”

“…5,6,10,12,13,15,[18][19][20][21]34,35 Furthermore, our schedule has the advantage that there are fewer deaths during induction treatment, in contrast to the majority of the combination studies in which, with few exceptions, 5 toxic deaths were recorded in 2%-7% of cases. 6,8,[12][13][14][18][19][20] Indeed, toxicity was recorded in the initial combination protocol (imatinib+chemotherapy) that led to the final amendment to a sequential strategy. These results indicate that the induction treatment for adult Ph + ALL can be effectively based on the administration of imatinib plus steroids, without systemic chemotherapy, which enables a CHR to be obtained in virtually all patients with no deaths in induction.…”

“…These results indicate that the induction treatment for adult Ph + ALL can be effectively based on the administration of imatinib plus steroids, without systemic chemotherapy, which enables a CHR to be obtained in virtually all patients with no deaths in induction. The toxicity of the combination of a tyrosine kinase inhibitor (TKI) with conventional chemotherapy has also been reported by the PETHEMA group, 19 and more recently by Chalandon et al 36 who have shown that imatinib can be effectively and more safely combined with reduced intensity chemotherapy.…”

“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] Prior to the introduction of TKI, prognosis was very poor, with virtually no adult patients (<5%) cured with standard chemotherapy; median survival was 8-10 months unless an allogeneic hematopoietic stem cell transplant (allo-SCT), the only potentially curative strategy, could be performed. [22][23][24][25] Today, treatment with TKI, with [5][6][7][8][9][10][12][13][14][15][18][19][20][21] or without 11,16,17 systemic chemotherapy, represents the most appropriate first-line management of patients with Ph + ALL in terms of rates of complete hematologic remission (CHR) and disease-free survival (DFS). Imatinib has been incorporated into different schedules either in induction [5][6][7]10,[12][13][14][18]…”

“…[22][23][24][25] Today, treatment with TKI, with [5][6][7][8][9][10][12][13][14][15][18][19][20][21] or without 11,16,17 systemic chemotherapy, represents the most appropriate first-line management of patients with Ph + ALL in terms of rates of complete hematologic remission (CHR) and disease-free survival (DFS). Imatinib has been incorporated into different schedules either in induction [5][6][7]10,[12][13][14][18][19][20][21] or following induction 8,10 in cohorts including also elderly patients, 8 with CHR rates varying from 72% to 96%. Moreover, the use of imatinib can also act as a "bridge" to an allo-SCT for those patients eligible.…”