Procedures
tumor, neutropenia, Central nervous system, neurotoxicity, demyelination
LYSIS, TUMOR, DEMYELINATION, NEUTROPENIA
The details of the regimen have been previously published [Rituximab was given on Days 1 and 11 of Courses 1 and 3, and on Days 1 and 8 of Courses 2 and 4 (total 8 doses) in patients with CD20 expression ≥ 20%. Central nervous system (CNS) prophylaxis consisted of intrathecal therapy with methotrexate and cytarabine given alternately on Days 2 and 7 (± 3 days) of each course for a total of 8 doses. The order of intrathecal chemotherapy was reversed with the even courses: cytarabine on Day 2 and methotrexate on Day 7 (to avoid simultaneous systemic and intrathecal methotrexate, which might rarely cause demyelination and neurotoxicity) [Maintenance therapy was given for 3 years with monthly vincristine 2 mg for 1 year, prednisone 50 mg daily for 5 days every month for 1 year, 6-mercaptopurine 50 mg twice daily for 3 years, and methotrexate 10 mg/mTo reduce the risk of SOS and improve outcome, the protocol was amended in February 2017 to use fractionated and lower doses of inotuzumab, reduce chemotherapy from 8 to 4 courses, and add sequentially 4 courses of blinatumomab, followed by blinatumomab every 3 months × 4 during POMP maintenance (Additional file Supportive care measures were according to the institutional standard guidelines. Monitoring for tumor lysis and prophylaxis with allopurinol, or alternatives such as rasburicase, and appropriate intravenous hydration were administered in the first course to all patients. All patients received prophylactic antimicrobial therapy (levofloxacin or cefpodoxime; azole; valacyclovir or acyclovir) during neutropenia, which began in induction. Azoles, usually voriconazole or posaconazole, were held on Day-1, Day 0, and Day+1 of the vincristine administration to avoid increased vincristine neurotoxicity. Pegfilgrastim 6 mg subcutaneously was administered on Day 4 (+ 2 days) of each of the induction/consolidation courses. Ursodiol 300 mg orally 3 × daily was given as SOS prophylaxis since the protocol was amended in September 2015.