Treatment
Initially, all patients received the induction therapy referred to as an improved ALL-Berlin-Frankfurt–Münster (BFM) protocol, as described earlier [6, 7]. Briefly, the patients received a CODPL induction (cyclophosphamide and prednisone or dexamethasone, vincristine, daunorubicin/idarubicin, and L-asparaginase) followed by consolidation and maintenance therapy. Two courses of 4-week re-induction therapy were administered every 6 months during consolidation treatment. The consolidation treatment consisted of 15 courses of high-dose methotrexate with or without pegaspargase, 3 courses of high-dose cytarabine, 2 courses of 4-week re-induction therapy and a course of ifosfamide. Moreover, the patients received 22–25 rounds of methotrexate, cytarabine, and dexamethasone intrathecal therapy to prevent central nervous system leukemia (CNSL). The maintenance therapy consisted of oral 6-mercaptopurine daily and weekly intramuscular methotrexate administration. The whole treatment course lasted 3–3.5 years.
The patients who were BCR-ABL1 positive were stratified in high risk (HR) group and others were stratified in intermediate risk (IR) group when they began the induction therapy. Then risk stratification was further refined by MRD detection of BM samples at the 15th or 33rd day of induction chemotherapy [8]. IR patients with MRD ≥ 25% blast at the 15th day or MRD ≥ 1% blast at the 33rd day would be upstaged to HR group. The dose and intensity of anthracyclines and high-dose methotrexate differed by risk group.
Fourteen patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after several courses of consolidation treatment. Ten patients received allo-HSCT after a first complete remission (CR1), and four relapse patients chose allo-HSCT after achieving a second complete remission (CR2).
In addition to routine chemotherapy, the patients who were BCR-ABL1 positive also received a tyrosine kinase inhibitor (TKI) orally throughout the course, and some of the refractory/relapsed patients received TKIs irregularly. TKIs included the first-generation TKI imatinib mesylate (Novartis, Basel, Switzerland) (initial dose of 260–340 mg/m2/d) and a second-generation TKI dasatinib (Bristol-Myers Squibb Company, Mount Vernon, USA) (initial dose of 50 mg/m2/d).