• Progress in the treatment of acute lymphoblastic leukemia: 25 years of application of international protocols in the Department of Pediatric Hematology of the Western Ukrainian Specialized Children’s Medical Center
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Progress in the treatment of acute lymphoblastic leukemia: 25 years of application of international protocols in the Department of Pediatric Hematology of the Western Ukrainian Specialized Children’s Medical Center

SOVREMENNAYA PEDIATRIYA.2018.8(96):22-36; doi 10.15574/SP.2018.96.22

Dorosh O., Tsymbalyuk-Voloshyn I., Bodak Kh., Polishchuk R., Stepanyuk A., Vorobel O., Skoropad L., Troyanovska O., Kozlova O., Myh A., Seredych L., Hlynska O.
Lviv Regional Council Public Institution «Western Ukrainian Specialized Children's Medical Centre», Ukraine
D. Halytskyy Lviv National Medical University, Ukraine
Medical center of Saint Paraskevia, Lviv, Ukraine

The results of treatment for modified chemotherapy programs of the international BFM group from February 1993 to March 2018 in 370 patients with acute lymphoblastic leukemia (ALL) aged 0 to 18 years were analyzed. The event-free survival (EFS) indicator for the entire sample of patients is 73.2%. 143 (38.65%) patients received treatment based on programs ALL-BFM 90/95 (group 1); from November 2002 to June 2012 — 131 (35.41%) patients — ALL IC-BFM 2002 (group 2); from June 2012 — 88 (23.78%) patients — ALL IC-BFM2009 (group 3) correspondingly. Children under the age of 1 (8 persons) from August 2008 were treated according to INTERFANT'99/06 programs (group 4). EFS in group 1 is 68.0% with a median observation time (MO) for 220 months, in group 2 — 77.6% with MO 111 months, in group 3 — 85.2% with MO 39 months, in group 4 — 12.5% of MO 13.5 months. The statistically significant improvement of EFS indexes in group 3, the worst results in children under 1 year (p <0.05). The EFS for middle!risk group (MR) patients in the 1st group was 71.0%, in the 2nd group — 83.7%, and in the 3rd group — 90.6% (p = 0.04232). The EFS for the high-risk group (HR) patients in the 1st group was 50.0%, in the 2nd — 55.6% and in the 3rd group — 73.9% (p = 0.09653). The overall survival (OS) in the entire sample is 78.0%. Totally 73 died (18.7%). In 32 (43.8%) people, death was associated with the therapy of the 1st line of ALL, 11 of them (34.37%) died of toxic-septic complications until the remission of ALL during induction therapy; 19 children (59.37%) — from complications in 1st remission at different stages of intensive chemotherapy, 1 patient with HR — from post-transplant complications, 1 patient — for 160 months. after reaching a remission from the fulminant course of viral hepatitis B. The 39 (53.42%) patients, death occurred in the second acute period from the progression of leukemia and/or infectious complications. Relapse of ALL is diagnosed in 53 (16.21%) people. Disease-free survival (DFS) is 83.2%. A rare remote consequence of ALL treatment in children was secondary malignant diseases, which were registered in 5 (1.35%) children. Astrocytoma, meningioma, secondary acute myeloid leukemia (AML) have been successfully treated, oligodendroglioma and secondary myelodysplastic syndrome with transformation in to AML was a reason of lethal consequence. 8 persons from the HR-group in the 1st remission had allo-ВМТ (abroad), including 2 patients — for whom alloBMT was a second therapeutic line for treatment of secondary AML. The statistically significant improvement in the EFS indices in the application of program polychemotherapy ALL IC-BFM 2009 was revealed, the worst results of treatment in children under 1 year (p <0.05). Treatment of patients with high risk groups (HR) and in children of the first year of life requires further searching for ways to improve the effectiveness of therapy, and reduce its toxic effects.

Key words: children, acute lymphoblastic leukemia, treatment, international protocols.


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Article received: Aug 02, 2018. Accepted for publication: Dec 04, 2018.