Study design
This was a retrospective medical records study of children (0-16 years) diagnosed with ALL at MTRH from January 2017 to December 2020. We included all children with a diagnosis of ALL, regardless of their clinical condition, before the initiation of treatment. Previous medical record data before (2010-2016) modification of induction therapy, with improved social and financial support and supportive care, was available for comparison.
Socio-demographic data, including age, gender, the distance of residence from MTRH, and duration of symptoms, had been collected at diagnosis for the current cohort (2017-2020) and was available. In addition, we obtained data on health insurance status and treatment outcomes from the medical records. We recorded treatment outcomes as abandonment, death, relapsed or progressive disease, and event-free. Additional clinical data for the current cohort (2017-2020) included: white blood cell (WBC) count at diagnosis, ALL immunophenotype, and central nervous system (CNS) disease status. We determined survival through induction and the survival estimates by WBC, sex, age at diagnosis, health insurance status (NHIF) at diagnosis, event-free and overall survival.
The children with ALL at MTRH were treated with a modification of the Dutch Oncology Group ALL-6 Study (1984-1988) therapy for non-high-risk ALL.14 All patients received the same standard protocol without risk stratification and consisted of induction (6 weeks), consolidation (2 weeks), methotrexate phase (7 weeks), re-induction (3 weeks), and maintenance therapy (83 weeks). For this cohort study (2017-2020), doxorubicin was dropped from the induction phase) as the supply of vincristine, prednisone, and especially L-asparaginase was improved. The additional modification included intensified L-asparaginase therapy and a fourth high-dose methotrexate. The duration of ALL treatment lasts for 104 weeks (supplementary material, TABLE S1).
The diagnosis of ALL was made based on a bone marrow examination by the pathologists. Due to financial constraints, the use of flow cytometry to further confirm the diagnosis and determine ALL immunophenotypes could only be done in some patients.
Refusal to start or continue with planned treatment for four or more weeks consecutively was considered treatment abandonment.9,15 Induction or early deaths were those that occurred before the start of treatment or during induction (<42 days from the start of treatment).3,9Deaths that occurred before the start of treatment or following relapsed/progressive leukemia were deemed to be disease-related. The deaths that occurred after treatment was initiated were deemed to be treatment-related. The clinical signs and symptoms and the presence of lymphoblasts on bone marrow aspirate or peripheral blood smear confirmed the relapsed disease). CNS involvement was evaluated through cerebral-spinal fluid examination, which was reported as positive or negative.
This study was approved by the Institutional research and ethics committee of MTRH and Moi University.