TY - JOUR

T1 - Management of CNS Disease in Pediatric Acute Lymphoblastic Leukemia

AU - McNeer, Jennifer L.

AU - Schmiegelow, Kjeld

PY - 2022

Y1 - 2022

N2 - Purpose of Review The treatment of acute lymphoblastic leukemia (ALL) is one of the success stories of pediatric oncology, but challenges and questions remain, including the optimal approach to the treatment of central nervous system (CNS) leukemia. It is unclear why some children with ALL develop CNS leukemia and others do not, and there remains debate regarding optimal regimens for prophylaxis, upfront treatment, and the treatment of CNS relapses. These topics are especially important since both cranial radiation therapy (CRT) and intensive intrathecal therapy carry risks of both short- and long-term adverse effects. In this review, we aim to identify areas of ongoing debate on this topic, review the biology of CNS leukemia, and summarize clinical trial data that address some of these questions. Recent Findings Both retrospective and meta-analyses have demonstrated that few patients with ALL benefit from CRT as a component of CNS-directed treatment for de novo disease, allowing cooperative groups to greatly limit the number of patients undergoing CRT as part of their initial ALL regimens. More recent efforts are focusing on how best to assay for low levels of CNS disease at the time of diagnosis, as well as the biological drivers that may result in CNS leukemia in certain patients. Progress remains to be made in the identification and treatment of CNS leukemia in pediatric ALL. Advancements have occurred to limit the number of children undergoing CRT, but much has yet to be learned to better understand the biology of and risk factors for CNS leukemia, and novel approaches are required to approach CNS relapse of ALL.

AB - Purpose of Review The treatment of acute lymphoblastic leukemia (ALL) is one of the success stories of pediatric oncology, but challenges and questions remain, including the optimal approach to the treatment of central nervous system (CNS) leukemia. It is unclear why some children with ALL develop CNS leukemia and others do not, and there remains debate regarding optimal regimens for prophylaxis, upfront treatment, and the treatment of CNS relapses. These topics are especially important since both cranial radiation therapy (CRT) and intensive intrathecal therapy carry risks of both short- and long-term adverse effects. In this review, we aim to identify areas of ongoing debate on this topic, review the biology of CNS leukemia, and summarize clinical trial data that address some of these questions. Recent Findings Both retrospective and meta-analyses have demonstrated that few patients with ALL benefit from CRT as a component of CNS-directed treatment for de novo disease, allowing cooperative groups to greatly limit the number of patients undergoing CRT as part of their initial ALL regimens. More recent efforts are focusing on how best to assay for low levels of CNS disease at the time of diagnosis, as well as the biological drivers that may result in CNS leukemia in certain patients. Progress remains to be made in the identification and treatment of CNS leukemia in pediatric ALL. Advancements have occurred to limit the number of children undergoing CRT, but much has yet to be learned to better understand the biology of and risk factors for CNS leukemia, and novel approaches are required to approach CNS relapse of ALL.

KW - Pediatric acute lymphoblastic leukemia

KW - Central nervous system leukemia

KW - Cranial radiation therapy

KW - Intrathecal chemotherapy

KW - NERVOUS-SYSTEM INVOLVEMENT

KW - INTRATHECAL LIPOSOMAL CYTARABINE

KW - TRAUMATIC LUMBAR PUNCTURE

KW - LOW LEUKOCYTE COUNTS

KW - CEREBROSPINAL-FLUID

KW - CANCER-INSTITUTE

KW - RECURRENT CNS

KW - CHILDREN

KW - CHILDHOOD

KW - RISK

U2 - 10.1007/s11899-021-00640-6

DO - 10.1007/s11899-021-00640-6

M3 - Review

C2 - 35025035

VL - 17

SP - 1

EP - 14

JO - Current Hematologic Malignancy Reports

JF - Current Hematologic Malignancy Reports

SN - 1558-8211

IS - 1

ER -