Outcome of children with multiply relapsed B-cell acute lymphoblastic leukemia: a therapeutic advances in childhood leukemia & lymphoma study

Abstract

The survival of pediatric patients with multiply relapsed and/or refractory (R/R) B-cell acute lymphoblastic leukemia has historically been very poor; however, data are limited in the current era. We conducted a retrospective study to determine the outcome of multiply R/R childhood B-ALL treated at 24 TACL institutions between 2005 and 2013. Patient information, treatment, and response were collected. Prognostic factors influencing the complete remission (CR) rate and event-free survival (EFS) were analyzed. The analytic set included 578 salvage treatment attempts among 325 patients. CR rates (mean ± SE) were 51 ± 4% for patients with bone marrow R/R B-ALL who underwent a second salvage attempt, 37 ± 6% for a third attempt, and 31 ± 6% for the fourth through eighth attempts combined. For patients achieving a CR after their second, third, and fourth through eighth attempts, the 2 year EFS was 41 ± 6%, 13 ± 7%, and 27 ± 13% respectively. Our results showed slight improvement when compared to previous studies. This is the largest and most recent study to date that evaluates the outcome of this patient population. Our data will provide detailed reference for the evaluation of new agents being developed for childhood B-ALL.

Locally produced CD19 CAR T cells leading to clinical remissions in medullary and extramedullary relapsed acute lymphoblastic leukemia

“…Nevertheless, extramedullary (EM) relapse is well described in ALL, with specific sanctuary sites such as the testes and central nervous system (CNS) being less susceptible to systemic chemotherapy, requiring radiation or intrathecal therapy . Although isolated EM first relapse of ALL usually has a better outcome, prognosis of multiple relapsed ALL is poor …”

Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy

“…Since then, paediatric oncology cooperative group trials and pioneering work by E. Donnall Thomas on haematopoietic stem cell transplantation (HSCT) among patients with leukaemia have led to dramatic improve ments in the cure rates of childhood ALL 3,4 . Despite improvements in overall remission rates (ORRs) for children with ALL, until now, the cure rates for chil dren with relapsed and/or refractory disease remain disappointingly low 5,6 . In the 1970s, E. Donnall Thomas considered a 15% salvage rate after disease relapse to be a promising result among a patient population with previously even more dismal outcomes 7 .…”

Recurrent Gastrointestinal Hemorrhage in Children with Philadelphia-Positive B-Cell Acute Lymphoblastic Leukemia Treated with Dasatinib: Case Reports

“…Ph + B-ALL is a subtype of B-ALL in which blast cells are detected to have a translocation between BCR on chromosome 22 and the ABL1 oncogene on chromosome 9; this molecular subtype accounts for 2-4% of pediatric ALL cases and approximately 20% of adult ALL cases [1][2][3][4]. TKIs have been approved for the treatment of chronic myeloid leukemia (CML) and Ph + ALL [1], and the prognosis of Ph + B-ALL has improved since the introduction of combination treatments with TKIs and chemotherapy [2][3][4][5]. Imatinib and dasatinib are the most widely used TKIs in the Ph + B-ALL population.…”

“…Acute lymphoblastic leukemia (ALL) is the most common cancer in children, and precursor B-cell lymphoblastic leukemia (B-ALL) accounts for 70-75% of pediatric ALL cases [1]. Pediatric B-ALL with Philadelphia positivity (Ph + B-ALL) is relatively rare and accounts for less than 5% of childhood cases of B-ALL [2].…”