# Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in Children: A Retrospective Cohort Study at a Pediatric Oncology Center

## TL;DR

This study examines treatment outcomes for a rare type of childhood leukemia at a Portuguese hospital, showing improved survival with updated treatment protocols.

## Contribution

The study provides real-world evidence of evolving treatment strategies and outcomes for pediatric Philadelphia chromosome-positive ALL.

## Key findings

- Patients treated with EsPhALL 2015 had 100% five-year overall survival but all showed disease progression.
- Allogeneic stem cell transplantation was reserved for relapsed or refractory cases after 2015.
- Cranial irradiation was discontinued in the latest treatment protocol.

## Abstract

Background and objective

Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL Ph+) is quite rare among pediatric patients. Its management has undergone significant changes in the past few years, leading to some variability in how it is approached. At the Portuguese Oncology Institute of Porto (IPOP), a tertiary oncological center, the standard of care has been aligned with the guidelines proposed by the European intergroup study of post-induction treatment of ALL Ph+ (EsPhALL). In this study, we aimed to examine the experience and outcomes related to the treatment of pediatric patients with ALL Ph+ at IPOP.

Methods

This retrospective cohort study involved pediatric patients diagnosed with ALL Ph+ at IPOP between January 2008 and December 2022 and analyzed their outcomes.

Results

A total of 14 patients were included. IKFZ1 was altered in five patients (out of nine in whom it was searched). Five patients were treated according to EsPhALL 2004, which involved starting imatinib later in a discontinuous manner [resulting in both five-year overall survival (OS) and progression-free survival (PFS) of 60%]. The EsPhALL 2010 (preconizing a continuous imatinib regimen instead) was employed in three patients, with a five-year OS and PFS of 66.7%. All children mentioned above received cranial irradiation therapy (CRT). Finally, six were treated according to the EsPhALL 2015, which stopped including CRT in its backbone. The five-year OS was 100%, whereas every patient progressed with an increase in BCR::ABL1 levels greater than 1-log. Moreover, until 2015, all patients had been recommended to undergo allogeneic hematopoietic stem cell transplantation (alloHSCT). However, since 2015, alloHSCT has been exclusively reserved for relapsed/refractory (R/R) disease or poor responders with positive measurable residual disease (MRD). In total, alloHSCT was performed in nine patients.

Conclusions

Although initially associated with a poor prognosis, the ALL Ph+ paradigm is drastically shifting. Further studies will hopefully clarify the outcomes in this population and help understand the role of central nervous system (CNS) prophylaxis, alloHSCT, and MRD quantification.