Treatment:
Standard protocol:
All T-ALL patients were treated per modified St Jude total XV protocol. Treatment consisted of remission induction, consolidation, and continuation. Remission induction comprised of dexamethasone, vincristine, daunorubicin, and asparaginase. Patients with a level of minimal residual disease (MRD) of 0.1% or more on day 15-19 received three additional doses of asparaginase or one dose of peg asparaginase. Subsequent induction therapy consisted of cyclophosphamide, mercaptopurine, and cytarabine (Appendix Table 1A). On hematopoietic recovery (between days 43 and 46), the minimal residual disease was assessed, and consolidation therapy was begun with four doses of High dose methotrexate (HD-MTX) at dose of 5gm/m2 and daily mercaptopurine (Appendix Table 1C). During initial continuation therapy, patients received intensive schedule of asparaginase chemotherapy, daily mercaptopurine interrupted with pulses of doxorubicin plus vincristine plus dexamethasone and two reinduction cycles, followed by three rotating drug pairs. Continuation treatment lasted 120 weeks in girls and 146 weeks in boys (Appendix Table 1E).
Augmented regimen:
In September 2014, we modified our regimen for T-ALL by adding two blocks of chemotherapy to all patients; including FLAG and re-intensification. FLAG as (fludarabine 15 mg/m2 x 4 days, high dose cytarabine as 2 gm/m2 X4 days) in patients with negative MRD or MRD>=0.01% and <1%, and FLAG as (fludarabine 30 mg/m2 x4, high dose Cytarabine as 2 gm/m2 X4) if MRD >=1% (Appendix Table 1B). Re-Intensification (high dose cytarabine, dexamethasone, VP16, peg-asparaginase) was given to all patients (Appendix Table 1D); re-induction II was omitted in the augmented therapy group (Appendix Table 1E).
CNS directed therapy:
All patients received triple intrathecal therapy (IT) on days 1 and 15 of induction with additional doses on days 8 and 22 in patients with peripheral blood leukocyte count (Wbc) >=50,000/µL at presentation and continued through the consolidation and continuation therapy (total number,21-23). Cranial radiation (CRT) was given to patients at increased risk of CNS relapse, including patients with Wbc count >= 100,000/µL at presentation (CRT dose of 12Gy) and patients with CNS-2 or CNS-3 status at diagnosis or those who had a traumatic lumbar puncture with blasts (CRT dose of 18Gy).