Treatment Outcome of Dasatinib in Combination with Less-Intensive Induction, Homobarringtonie, Cytarabine, G-SCF in Newly Diagnosed Patients with Ph+ALL

Unprecedented achievement has been made in the treatment of childhood ALL within the past decades. However, how to improve the outcome of Ph+ALL remains a conundrum for the care providers towards the cure of the disease. Using Auto-hematopoietic stem cell transplant (HSCT), after a negative BCR-ABL, or allo-HSCT has become the curative options for Ph+ALL cases although either relapse or life threatening transplant related complications could lead to treatment failure.

To determine the safety and efficiency of a dasatinib based mild induction with homobarringtonie, cytarabine, G-SCF (HAG) contained regimen, we enrolled 67 patients with de novo Ph+ALL from 2012-2017 for the trial. The medium follow-up time was 39 months (17 months to 65 months). In brief, the induction consisted of vincristine and prednisone, in addition to daily dasatinib (70mg; bid), followed by six cycles of HAG regimen (homobarringtonie 1mg/m2/days 1-14; G-CSF 5ug/kg on day one; Ara-C 10mg/q12h/days 1-14; every three month/cycle) plus daily dasatinib (70mg; bid). The maintenance included two cycles of HAG (every six months) in addition to daily dasatinib. The intrathecal injection was given 11 times along with the treatment to prevent CNS leukemia. A serial MRD detection of BCR-ABL by qPCR was performed every three months.

There were four patients eligible for the study. Among the 63 evaluated patients, 55 (88%) achieved CR in induction. There was no treatment related mortality during the induction. Good prednisone response was indicated among 51 patients (81%) on day eight. The day 30 MRD detection for those in CR indicated 43 (68%) reached ≤5 *10^-2 and four (7%) achieved 10^-3. The MRD detection at month three and six suggested that 38 (60%) vs 33 (52%) patients were within the level of ≤5 *10^-2 and six (10%) vs 10 (16%) achieved 10^-3, respectively. Relapse-related death occurred in 11 of 63 patients (16%), and four patients (6%) experienced treatment-related mortality. Grade 3-4 adverse events were observed among 10 cases (30%). The main toxicities were liver dysfunction and coagulation abnormality which can be solved by close monitoring and multi-disciplinary care. Four-year probability of event-free survival (pEFS) was found to be 58%. Those who went with hematopoietic stem cell transplantation (HSCT) after chemotherapy achieved significantly better pEFS than only chemotherapy (65.7% vs 50.5%,p=0.03). Our protocol can be used as an effective and less toxic treatment option to improve the outcome of Ph+ALL with promising survival and acceptable adverse effects shedding new light on treating Ph+ALL.