Acute Lymphoblastic Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Abstract

The NCCN Guidelines for Acute Lymphoblastic Leukemia (ALL) focus on the classification of ALL subtypes based on immunophenotype and cytogenetic/molecular markers; risk assessment and stratification for risk-adapted therapy; treatment strategies for Philadelphia chromosome (Ph)-positive and Ph-negative ALL for both adolescent and young adult and adult patients; and supportive care considerations. Given the complexity of ALL treatment regimens and the required supportive care measures, the NCCN ALL Panel recommends that patients be treated at a specialized cancer center with expertise in the management of ALL This portion of the Guidelines focuses on the management of Ph-positive and Ph-negative ALL in adolescents and young adults, and management in relapsed settings.

Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in Adults

“…In the setting of adult patients, two retrospective studies from Sasaki et al, including one propensity score analysis, suggested superiority of ponatinib + HCVAD over imatinib or dasatinib + HCVAD [ 167 , 168 ]. However, there is to date no prospective available data that compares different TKIs for adult Ph+ ALL patients and no specific guidelines [ 109 ]. Prospective randomized trials are currently ongoing ( Table 2 ).…”

“…Allo-HSCT is still standard of care for eligible patients in CR1 [ 109 ]. However, its role has become less clear with the advent of 2G/3G-TKIs with lower allo-HSCT rates in these trials.…”

“…The EBMT and the 2021 National Comprehensive Cancer Network (NCCN) guidelines recommend starting TKIs administration for all Ph+ ALL patients as soon as possible after full hematologic recovery from allo-HSCT. Recommended dosage is lower than in the pre-transplantation period in order to reduce toxicities (400 mg/d for Imatinib, 50–100 mg/d for Dasatinib, 200mg bid for Nilotinib and 15 mg/d for Ponatinib) [ 106 , 109 ]. Imatinib administration should be favored except in case of imatinib resistance in the pre-alloSCT period, pre-existing ABL kinase domain mutation or in the context of CNS involvement as imatinib poorly penetrates CNS, contrary to dasatinib or ponatinib [ 108 , 110 , 111 , 112 ].…”

“…Relapses are often due to BCR-ABL kinase domain resistance mutations, which are found in 70% to 80% of imatinib resistant patients and in 80% of 2G-TKIs resistant patients [ 123 , 124 , 125 ]. The NCCN recommend performing BCR-ABL mutation screening in R/R Ph+ ALL patients [ 109 ]. The most frequent mutation in Ph+ ALL patients is the T315I mutation, which is resistant to all TKIs except ponatinib [ 126 ], followed by the P-loop mutations E255K and Y253H.…”

Venetoclax-ponatinib for T315I/compound-mutated Ph+ acute lymphoblastic leukemia

“…Response assessments were performed according to the NCCN guidelines for acute lymphoblastic leukemia (version 2. 2021) [ 9 ]. Event-free survival (EFS) was defined as the time from complete remission (CR) after the VPD regimen until relapse, death, or last follow-up date, whichever occurred first.…”