Imatinib (IMA) plus chemotherapy followed by allogeneic hematopoietic cell transplantation (HCT) is established treatment for Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). We investigated the use of dasatinib (DASA) combined with intensive chemotherapy in ALL (18-55 years) first-line in a prospective, multicenter phase II trial by the GMALL study group. 140 mg DASA QD was used with a pediatric-based induction and consolidation chemotherapy according to GMALL 07/2003 protocol with recommended consecutive HCT. Nineteen of 20 planned patients were enrolled in 12 centers. The hematologic CR rate after induction was 79% with an overall MRD negativity rate of 62.5%. Six patients died during induction and two discontinued therapy. This regimen achieved deep molecular responses but was associated with a higher than expected early mortality (21%) and was stopped prematurely due to toxicities. The GMALL therefore adopted a combination of low intensity chemotherapy plus IMA as its current induction regimen.
Keywords: Acute lymphoblastic leukemia; BCR::ABL1; dasatinib.