How I treat relapsed acute lymphoblastic leukemia in the pediatric population

Abstract

Relapsed acute lymphoblastic leukemia (ALL) has remained challenging to treat in children with survival rates lagging well behind those observed at initial diagnosis. Although there have been some improvements in outcomes over the past few decades, only approximately 50% of children with first relapse of ALL survive long term, and outcome are much worse with second or later relapses. Recurrences that occur within three years of diagnosis and any T-ALL relapses are particularly difficult to salvage. Until recently, treatment options were limited to intensive cytotoxic chemotherapy with or without site-directed, radiotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). In the past decade, several promising immunotherapeutics have been developed, changing the treatment landscape for children with relapsed ALL. Current research in this field is focusing on how to best incorporate immunotherapeutics into salvage regimens and investigate long-term survival and side effects, and when these might replace HSCT. As more knowledge is gained about the biology of relapse through comprehensive genomic profiling, incorporation of molecularly targeted therapies is another area of active investigation. These advances in treatment offer real promise for less toxic and more effective therapy for children with relapsed ALL and we present several cases highlighting contemporary treatment decision-making.

Use of cardiac radiation therapy as bridging therapy to CAR‐T for relapsed pediatric B‐cell acute lymphoblastic leukemia

“…With increasing use of targeted therapies in B‐ALL, extramedullary relapses are becoming more common 23 . Our experience demonstrates the ability of BRT to effectively treat bulky symptomatic extramedullary leukemic disease in critical sites with minimal toxicity, in order to achieve disease control, and also to prevent potential CAR‐T‐associated organ toxicity.…”

“…Of note, our patient also received salvage RT to the posterior fossa after relapse and tolerated it well with an ongoing complete response, similar to a previous report of durable remissions in R/R lymphoma patients treated with RT after CAR-T. 22 With increasing use of targeted therapies in B-ALL, extramedullary relapses are becoming more common. 23 Our experience demonstrates the ability of BRT to effectively treat bulky symptomatic extramedullary leukemic disease in critical sites with minimal toxicity, in order to achieve disease control, and also to prevent potential CAR-T-associated organ toxicity. Similarly, BRT prior to and following CAR-T in another B-ALL patient provided local ocular disease control, permitting successful treatment.…”

Testicular involvement of acute lymphoblastic leukemia in children and adolescents: Diagnosis, biology, and management

“…Therefore, for patients with B‐ALL and early testicular relapse and for those with T‐ALL and relapse at any time, very aggressive treatment, including hematopoietic cell transplantation (HCT), has been recommended (Table 3). 70‐72 When total body irradiation (~12 Gy) is included in the conditioning regimen, a testicular boost (an additional ~12 Gy) is typically administered. Patients with combined bone marrow and testicular relapse are treated similarly to those with isolated bone marrow relapse.…”

Antibody–Drug Conjugates for the Treatment of Acute Pediatric Leukemia

“…The therapeutic approach for relapsed B-ALL varies but most pediatric patients with first relapse B-ALL are treated with a standard four-drug re-induction. Therapy following re-induction is dependent on risk stratification but typically consists of either blinatumomab and chemotherapy for lower-risk patients or chemotherapy followed by HSCT for higher-risk patients [37]. InO has demonstrated efficacy in second or greater relapse (or refractory disease) in both COG trial AALL1621 and the European ITCC trial and is a good option as a bridge to transplant in that patient population [16,17].…”