Outcomes of pediatric patients transplanted for B-ALL with high-risk cytogenetics- a 20-year experience from LMIC setting

Abstract

Abstract Introduction Cytogenetics are increasingly utilized in guiding risk stratification and treatment in pediatric ALL. However, they still pose a clinical challenge to physicians regarding the choice of therapy, especially in low-resource settings, where cost effectiveness plays a vital role. In this study, we reviewed the King Hussein Cancer Center's (KHCC) experience in transplant outcomes of a subset of B-ALL children with high risk cytogenetic features. Methods Retrospective chart review of pediatric patients who underwent allogeneic hematopoietic cell transplant (HCT) for B-ALL with high risk cytogeneitcs. The cytogenetic features included were BCR/ABL1 fusion gene, intrachromosomal amplification of chromosome 21 (iAMP21), and KMT2A rearrangement. Study period was 2004-2024. Data were extracted from electronic medical records including demographic, disease characteristics, transplant regimens, and clinical outcomes. OS was defined as the time from transplant to death from any cause. Descriptive statistics were used in addition to the Kaplan-Meier method for survival analysis. Results Eighty-two patients were diagnosed with B-cell ALL at a median age of 4.8 years (0.2-17.8, range) throughout the study period. The most common genetic abnormality was KMT2A rearrangement in 41 patients (50%), followed by BCR/ABL1 in 28 (34%), and iAMP21 in 13 (16%). Thirty-eight (46%) patients underwent HCT at a median age of 9.5 years (2.3-18.1, range). Disease status at transplant was mostly CR2 (53%, n=20), followed by CR1 (45%, n=17), and CR3 (3%, n=1). Only 2 patients had positive MRD at the time of transplant. Thirty-seven patients (97%) received myeloablative conditioning regimens of which 36 (97%) were TBI-based. Grafts (71% peripheral blood) were collected from matched related donors in 29 cases (76%), haplo-identical donors in 7 (18%), and unrelated cord blood in 2 (5%). All patients experienced successful neutrophil engraftment within 28 days of stem cell infusion. After a median duration of 8.7 years (1.3-20, range), 7 patients died resulting an overall mortality rate of 18%. Six deaths occurred within 2 years of HCT and were due to disease relapse, while one patient developed secondary malignancy and died 6 years after HCT. Conclusion High-risk cytogenetic are a major poor prognostic factor in pediatric B-ALL, and allogeneic HCT offers a good chance of cure. Most patients in our cohort underwent HCT due to relapsed disease. More comparative studies are needed to elucidate the most affordable treatment modalities that offer the best cure chances.