The outcome of modi̇fi̇ed st. jude total xv protocol i̇n Turki̇sh chi̇ldren wi̇th newly di̇agnosed acute lymphoblasti̇c leukemi̇a

Childhood acute lymphoblastic leukemia (ALL) is the most frequent malignant disease of chilhood and nowadays, survival rates approach up to 90%. In this study, 183 pediatric patients (75 female/108 male, mean age 6,7±4,4 years) who were diagnosed with ALL in Hacettepe University Faculty of Medicine, Department of Pediatric Hematology between 01.01.2008 and 30.01.2016 were analyzed retrospectively, the survival and prognostic factors in this group of patients were evaluated. Moreover, in order to evaluate the effectivity of High Dose Methylprednisolon (HDMP) treatment, patients randomized consecutively at doses of 10 mg/kg/d (Group A (n=90)) or 20 mg/kg/d (Group B (n=65)) HDMP (maximum 1000 mg/day) during 7 days before Modified St. Jude Total XV protocol remission induction treatment. Absolute blast count (ABC) in peripheral blood and minimal residual disease (MRD) in bone marrow were recorded at the end of the HDMP treatment (day 7). HDMP doses were decreased at the beginning of the induction and continued for 7 days 5 mg/kg/d (Group A) and 10 mg/kg/d (Group B), respectively. Both groups were received 2 mg/kg/d methylprednisolon (MP) for the following 14 days. Of the patients receiving irregular dose MP (Group C (n = 28)) who were not included in the treatment efficacy comparison of different doses of HDMP, 26 patients were scheduled to start 20 mg/kg/day HDMP, while lower doses (1 mg/kg/day) MP were applied due to leukocytosis. On the other hand, 2 patients were started on HDMP at a dose of 10 mg/kg/day and MP dose was decreased because of bradycardia and hyperglycemia during the first 7 day. The most frequent complaint of patients at the initial presentation were high fever (45%) and bone-joint pain (40%); however hepatomegaly (86%) was the most frequent sign of the initial physical examination. At the time of diagnosis, there were 9 patients (5%) with CNS-3 and 8 patients (4%) with CNS-2. 88 of patients (49%) were classified as low, 72 were standard (41%) and 18 (10%) were high risk at the end of the induction treatment. When we compare Group A and B, age, gender, initial leucocyte count, CNS situation and immunophenotype at the time of diagnosis, risk groups, the rate of infections during induction and response to treatment based on ABC in peripheral blood on day 7 and MRD level in bone marrow on day 7 ,15 and 42 were similar (p>0.05). Patients who were steroid good responder, ABC<1000/mm3, on day 7 of HDMP comprised 88% of the group and 96% of patients had MRD<1% on day 15, 92% of patients had MRD<0,01% at the end of induction (day 42). 99% of all patients were in morphologically remission at the end of the induction. During the treatment period, 28% vincristine induced neuropathy, 24% osteonecrosis, 23% L-asparaginase hypersensitivity, 15% thrombosis, 3% PRESS, 2% acute pancreatitis were noted. During follow-up 16 (9%) patients, 9 (5%) isolated bone marrow, 7 (4%) isolated CNS had relapses and 13 out of 16 (81%) relapsed patients were died. Four relapsed, 4 t(9;22) positive and 1 MLL rearrangement patients, in total 9 (5%) patients underwent hematopoietic stem cell transplantation (HSCT). 25 out of 183 (13%) patients died. The five-year event-free survival (EFS) and overall survival (OS) were 85,6±2,6% and 89,2±2,3%, respectively. Univariate analysis revealed that 10-18 years of age at presentation, initial leucocyte count ≥50x109/L, t(1;19) positive ALL and presence of gram negatif infection during induction treatment were associated with lower EFS and OS. However irreguler MP treatment and CD20 positivity at the time of diagnosis were found to be only associated with lower EFS and OS, respectively. Multivariate analysis revealed that the risk of event and death were higher approximately 5 and 6,7 fold, respectively if the patient diagnosed ALL at the age of 10-18 years compared to at the age of 1-9,9 years. Patients whose initial leucocyte count was ≥50x109/L had approximately 6 fold higher event and 5,9 fold higher death risk when compared to patients whose initial leucocyte count was <50x109/L. Also, It was showed that CD20 positive patients at the time of diagnosis had 2,5 fold higher event and 3,8 fold higher death risk than CD20 negative ones. On the other hand, infection with gram negative bacteria during remission induction increased the risk of death 4,4 fold. There was no significant difference between survival rates of our study and the original protocol (St. Jude Total XV; EFS 85,6% (79,9-91,3%) and OS 93,5% (89,8-97,2%) (p>0,999 and p=0,183, respectively). Although we did not show any statistically significant difference between survival rates of groups who received different HDMP doses (10 and 20 mg/kg/d) given before induction, high response rates on day 7 and day 15 which were probably associated with HDMP were observed. Our encouraging EFS and OS results with modified St. Jude Total XV in childhood ALL patients is emphasizing early and high response effect of HDMP which will contribute to the literature.