Philadelphia‐like acute lymphoblastic leukemia: Characterization in a pediatric cohort in a referral center in Colombia

Abstract

Background: Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a subtype of pediatric leukemia with high risk factors and poor outcome. There are few reports of its prevalence in Latin America.Aim: This study evaluated the frequency and clinical and biological characteristics of Ph-like ALL in a pediatric cancer center in Colombia. Methods:The Ph-like genetic profile was analyzed by a low-density array (LDA).Samples from patients with Ph-like ALL were analyzed by fluorescent in situ hybridization for cytokine receptor like factor 2 (CRLF2) and ABL proto-oncogene 1, nonreceptor tyrosine kinase (ABL1) rearrangements. Copy number variations were assessed by multiplex ligation probe amplification.Results: Data from 121 patients were analyzed. Fifteen patients (12.4%) had Ph-like ALL, and these patients had significantly higher leukocyte counts at diagnosis and higher levels of minimal residual disease on days 15 and 33 of induction than patients without the Ph-like subtype. There were no significant differences in sex, age, or response to prednisone at day 8 between the two groups. CRLF2 rearrangements were identified in eight patients, and ABL1 rearrangements were identified in two patients. Other genetic alterations alone or in combination were identified in 77% of patients, including deletions in cyclin dependent kinase inhibitor 2 A/B (46.2%), IKAROS family zinc finger 1 (38.3%), and paired box 5 (30.8%).Conclusions: Ph-like ALL had a 12.4% prevalence in our cohort of patients with pediatric ALL. The identification of this group of patients has importance for risk stratification and future targeted therapy.Adriana Linares and Luz Karime Yunis contributed equally as first authors.

Expert Recommendations for the Diagnosis, Treatment, and Management of Adult B-Cell Acute Lymphoblastic Leukemia in Latin America

“…21 A result of positive MRD indicates treatment resistance and, thus, the need for allo-HSCT or targeted therapy. 18 Only one targeted therapy, blinatumomab, is approved to eradicate MRD. 22 …”