The Outcome of Modified St. Jude Total XV Protocol in Turkish Children with Newly Diagnosed Acute Lymphoblastic Leukemia

Introduction: Childhood acute lymphoblastic leukemia (ALL) treatment with St. Jude Total therapies showed superior outcome with event-free and overall survival rates 85.6 ± 2.9% and 93.5 ± 1.9%, respectively. Here, we studied prognostic features and the outcome of Turkish children with newly diagnosed ALL treated with modified St. Jude Total Therapy XV Protocol.

Patients and methods: There were 182 newly diagnosed ALL patients aged 1-18 years old and treated with modified Total Therapy XV between 1 January 2008 and 30 January 2016. According to our previous successful results with high dose methylprednisolone (HDMP), each patient received 7 days of HDMP as an initial treatment and randomized at doses of 20 mg/kg/d or 10mg/kg/d HDMP, not exceeding at maximum 1000 mg MP. After the first 7-day steroid treatment, concomitant chemotherapy was given and the steroid doses were tapered to 10mg/kg/d and 5mg/kg/d during the next week in each group, respectively. Afterwards, the whole group received 2 mg/kg/d MP for the following two weeks. Also, there were a third group received lower doses (<10 mg/kg/d) of MP because of the hyperleukocytosis for the first 7 days.

Results: Out of 182 patients, 174 completed the treatment and 1 patient experienced induction failure, 4 patients died during remission induction, 3 patients abandoned treatment during maintenance. 97.2% of the children entered complete remission after remission induction. 16 patients (8.9%) had relapses during follow-up, 9 isolated bone marrow, 7 isolated CNS and 3 of 7 patients who had CNS relapse experienced a second relapse (bone marrow) afterwards. The five-year event-free survival (EFS) and overall survival (OS) were 85.6±2.6 % and 89.2±2.3%, respectively. There was no significant difference according to the survival rates between different MP doses (10 and 20mg/kg/d) which were given before induction. Moreover, difference in frequency of infection between patient groups treated with different steroid doses during induction period was not found statistically significant. Univarite analysis showed that age ≥ 10 years at the time of diagnosis, initial leukocyte count ≥50x10⁹/L, low MP doses (<10mg/kg/d) and infection with gram negative bacteria during remission induction were associated with inferior EFS. Multivariate analysis revealed lower EFS rates with an initial leukocyte count ≥50x10⁹/L [HR=5.58, 95% CI: 1.99-15.64, p<0.001], age ≥ 10 years at the time of diagnosis [HR=3.81, 95% CI: 1.65-8.81, p=0.002], infection with gram negative bacteria during remission induction [HR=3.71, 95% CI: 1.55-8.88, p=0.003] and CD20 positivity (>20%) at diagnosis [HR=2.49, 95% CI: 1.08-5.73, p=0.031]. Response to MP measured as <1000/mm³absolute blast count in peripheral blood sample after first 7 days did not have statistically significant influence on survival in comparison with poor MP response (<1000/mm³absolute blast count in peripheral blood).

Conclusion: Our encouraging EFS result with modified St. Jude Total XV in childhood ALL patients is comparable with the one in original protocol. Favorable effect of higher doses of MP (20 mg/kg/d) on survival could not be demonstrated when compared with 10mg/kg/d.