Treatment Protocol
Our treatment protocol was adopted from the St. Jude Total XV therapy
with minor modifications [5, 6]. Remission induction therapy began
with prednisone, vincristine, daunorubicin, and asparaginase. Patients
with ≥ 1% MRD on day 15 received three additional doses of
asparaginase. The second part of Induction therapy consisted of
cyclophosphamide, mercaptopurine and cytarabine. Upon hematopoietic
recovery (between days 43 and 46), MRD was assessed, and consolidation
therapy initiated.
After induction, patients were stratified into three risk groups (low,
intermediate, high) and two protocol arms (low-risk and
intermediate/high-risk). The consolidation phase of 8 weeks consisted of
a 24-hr IV infusion of methotrexate at a dose of 2.5 g/m2 for low-risk
patients and 5 g/m2 for intermediate- /high-risk individuals every 2
weeks for four doses in combination with 6-MP 50 mg/m2 orally once
daily. The continuation phase consisted of 120 weeks for females and 146
weeks for males. A more intensive therapy termed “reinduction” was
given for both risk groups. Reinduction I and II phases last for 3 weeks
each and occur at weeks 7–9 and 17–19, respectively, during
continuation therapy. Low-risk patients received nine doses of IM
asparaginase (ASP) at 10,000 units/m2/dose in combination with
dexamethasone 8 mg/m2/day for 2 weeks in each reinduction phase.
Intermediate-/high-risk patients received an intensive once weekly IM
ASP treatment of 25,000 units/m2/dose for the first 20 weeks of
continuation in combination with once monthly dexamethasone pulses of 12
mg/m2/day over 5 days. During reinduction phases (weeks 7–9 and
17–19), intermediate-/high-risk patients receive twice-monthly
dexamethasone pulses at the same dose over 7 days; between 2015 and
2017, dexamethasone doses were decreased from
12mg/m2/dose to 8mg/m2/dose for
intermediate/high risk patients and from 8mg/m2/dose
to 6mg/m2/dose for low risk patients.
In case of allergy to Escherichia coli (E. coli ) ASP,
Erwinia-derived ASP was used at a dose of 20,000 units/m2 three times
weekly to replace the 10,000 units/m2 of E. coli ASP during
induction and reinductions 1 and 2 for low risk patients and 30,000
units/m2/dose twice weekly instead of e once weekly 25,000 units/m2 ofE. coli ASP for Int/high risk patients. In case of allergy to
both products, we used pegylated ASP at a dose of 2,500 units/m2 once
every other week. Low-risk patients are those aged 1– 9.9 years with
precursor B-cell ALL and presenting white blood count of less than
50,000/𝜇 l, DNA index of ≥ 1.16 or t (12, 21). Low-risk patients
must not have extramedullary disease, t (1, 19), or mixed- lineage
leukemia (MLL) rearrangement. High-risk patients are those with t (9,
22) or failure of induction (> 1% of leukemic
lymphoblasts at remission date). Intermediate-risk patients are all
T-cell patients and precursor B-cell patients who do not meet the
low-risk criteria [4].