The Outcome of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Experience from a Referral Center in South India

Abstract

Although improved survival in children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL) has been demonstrated in trials, the outcome appears to be inferior in low- and middle-income countries (LMIC). Methods A file review of children aged ≤ 15 years diagnosed with Ph-ALL from 2010 to 2019 was performed. Minimal residual disease (MRD) was assessed by flow-cytometry. Real-time polymerase chain reaction (qRT-PCR) was used to quantify the BCR::ABL1 transcripts during treatment. Results The mean age of the 20 patients in the study was 91 months. Of 19 patients in whom the BCR::ABL1 transcript was confirmed, 10(50%) had P210, 7(35%) had P190, and two showed dual expression. The mean dose of imatinib that was administered was 294 ± 41 mg/m²/day. qRT-PCR for BCR::ABL1 was < 0.01% in all patients who were in remission or had a late relapse and was ≥ 0.01% in patients who had an early relapse. Two patients underwent HSCT. The 3-year event-free survival (EFS) was 35.0 ± 10.7%. Patients with a good prednisolone response (GPR) and a negative end-of-induction MRD demonstrated a superior EFS to those who lacked either or both (80.0 ± 17.9% vs. 16.7 ± 15.2%, P = 0.034). Conclusion The 3-year EFS of 20 children with Ph-ALL treated with chemotherapy and TKI was < 50%. An unusually high proportion of patients with p210 transcript expression; sub-optimal TKI dosing and lesser intensity of chemotherapy, due to the concern of high treatment-related mortality in LMIC are possible reasons for the poor outcome. Conventional treatment response parameters such as GPR and MRD predict outcomes in Ph-ALL. qRT-PCR for BCR::ABL1 may have a role in predicting early relapse.

Supplementary information: The online version contains supplementary material available at 10.1007/s12288-023-01684-9.

Keywords: Allogeneic stem cell transplant; BCR-ABL; Minimal residual disease; Quantitative PCR; Relapsed leukemia.

Fig. 1

Flow diagram illustrating the inclusion of eligible patients for the study

Fig. 2

Illustration of the BCR::ABL1 transcript quantification performed in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia and the relation with conventional flow-cytometry-based MRD and outcome. Data for BCR::ABL1 transcript monitoring was available in 14 of the 20 patients. MRD: flow cytometry-based minimal residual disease (positive MRD ≥ 0.01%), qRT-PCR: quantitative real-time polymerase chain reaction (qRT-PCR) for BCR::ABL1 in the peripheral blood, TKI: tyrosine kinase inhibitor, BM: bone marrow, CNS: central nervous system

Fig. 3

Comparison of disease-free survival (DFS) of the patients with Philadelphia-chromosome positive acute lymphoblastic leukemia who were good risk (solid line) and poor risk (dotted line). Patients with a good risk (good prednisolone response and end of induction minimal residual disease negative) had a better 3-year DFS