Non-Intensive Continuous Treatment with a Tyrosine Kinase Inhibitor (TKI) Followed By Allo-HSCT Is an Effective Therapeutic Strategy for Adult Ph-Positive Acute Lymphoblastic Leukemia: Outcomes of the Russian Prospective Multicenter RALL Study

Introduction. As Ph-positive (Ph+) ALL in adults remains less favorable in prognosis than other ALL, and by expert opinion needs non-intensive chemotherapy protocols and new generation TKI with the majority of pts undergoing allo-HSCT, the results of treatment based on the different approach: de-escalated but continuous treatment with the change of TKI according to the molecular response and allo-HSCT may be of interest and provide new insights to the treatment of Ph+ ALL. Aim. To evaluate survival and outcomes in different risk groups in pts with Ph+ ALL in the RALL-study (Ph+ALL-2009, Ph+ALL-2012 and Ph+ALL-2012m protocols). Patients and methods. Between January 2010 and June 2021, 74 new Ph+ ALL cases were diagnosed in 6 centers of the RALL-group and 63 of them were evaluable for analysis (median age 37 years (17-73), m/f 32(43%)/42(57%), CNS disease in 13(21%) pts, WBC>30*10 9/l in 27(43%) pts, bcr/abl transcript p190/p210/p190+210 in 31(60%)/12(23%)/9(17%) cases). Standard cytogenetic was performed in all 63 pts, 1 had no mitosis, 6(10%) monosomy 7 and 2 (3%) complex karyotypes were detected. All pts were treated according to RALL protocols with continuous Imatinib. Ph+ALL-2009 protocol included 600 mg Imatinib with prednisone, VNCR, L-asp, Dauno, Cph, followed by 6-MP and MTX. Imatinib had to be changed to Dasatinib (140 mg) after non-achievement of molecular complete response (MolCR) on day 70. MolCR was defined as bcr/abl chimeric transcript