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).