ABSTRACT
Introduction: Upfront treatment of pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) and T-cell acute lymphoblastic leukemia (T-ALL) results in cure rates of 60-95%, depending on risk factors. However, patients with refractory or relapsed B-ALL or T-ALL have much worse outcomes with conventional chemotherapy, hence treatment of these cohorts with novel agents is a priority.Areas Covered: This paper reviews early phase clinical trials in pediatric leukemia. Investigational antibody therapy, chimeric antigen receptor T-cell (CAR-T), and other targeted therapies are examined. The authors discuss the mechanisms of action, side effects, trial designs, and outcomes and reflect on potential research directions. PubMed and Clinicaltrials.gov were searched from 2010 to present, using keywords 'lymphoblastic leukemia' with filters for pediatric age, Phase 1 clinical trial and Phase 2 clinical trial.Expert Opinion: Pediatric patients with relapsed or refractory leukemia often do not derive additional benefit from intensified conventional chemotherapy approaches which have arguably been maximized in the upfront setting. Therefore, novel approaches, such as immunotherapy and targeted agents should be prioritized. Progress will require commitment from pharmaceutical companies regarding these orphan diagnoses and acknowledgment from regulatory bodies that outcomes are suboptimal with conventional chemotherapy.
Subject(s)
Molecular Targeted Therapy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Child , Humans , Immunotherapy/methods , Immunotherapy, Adoptive/methods , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Recurrence , Therapies, Investigational/methodsABSTRACT
Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome (MDS)/myeloproliferative disorder most commonly seen in the elderly. We describe an adolescent with monosomy 7 CMML presenting as central diabetes insipidus (DI), who was treated with venetoclax and decitabine as a bridge to hematopoietic stem cell transplantation (HSCT). Central DI is a rare manifestation of monosomy 7-associated MDS including CMML, itself a rare manifestation of GATA2 deficiency, particularly in children. Venetoclax/decitabine was effective for treatment of CMML as a bridge to HSCT.
