Children’s Oncology Group (COG) recently released a memo on new requirements for patients enrolled in the upcoming AALL17132 Acute Lymphoblastic Leukemia (ALL) High Risk Study. This phase III trial aims to determine how well inotuzumab ozogamicin and post-induction chemotherapy work in treating patients with high-risk B-cell lymphoblastic lymphoma (B-ALL), mixed phenotype acute leukemia, and B-lymphoblastic lymphoma (B-LLy). The purpose of this study is to develop a standard treatment for mixed phenotype acute leukemia. FISH analysis is now mandatory for the following rearrangements:
ABL1 non-BCR (New Requirement)
Besides its typical BCR fusion partner, ABL1 has also been shown to fuse with a variety of other genes in ALL, including ETV6, FOXP1, and SFPQ. click here
ABL2 (New Requirement)
A 2017 COG study of 1725 patients with B-ALL identified ABL2 fusions with both RCSD1 and ZC3HAV1.click here
PDGFRB (New Requirement)
PDGFRB has been shown to fuse with multiple genes in pediatric ALL, including EBF1, GTF21 and ATF7IP. Ph-like ALL cases with PDGFRB fusions have demonstrated excellent clinical response to dasatinib and imatinib. click here
BCR-ABL1
The overall survival of BCR-ABL1-positive pediatric ALL has significantly improved since the introduction of tyrosine kinase inhibitors (TKI) into treatment protocols. Despite this improvement, BCR-ABL1-positive ALL remains a high-risk subgroup with an unfavorable outcome. click here
ETV6-RUNX1
ETV6-RUNX1 is the most common genetic abnormality in childhood ALL, occurring in ∼25% of cases with a precursor-B phenotype. It was originally thought that this rearrangement was a favorable prognostic indicator, but later studies found that up to 20% of patients experience late relapse. click here
KMT2A
The frequency of KMT2A translocations in childhood B‐ALL differs significantly by age. About 75% of infants younger than 1 year old with ALL harbor somatic KMT2A rearrangements, and typically have poor overall survival (<50% at 4 years), despite intensive multiagent chemotherapy. click here
The intended purpose of adding these ABL-class genes to the panel is to identify patients with Ph-like ABL1 class aberrations as early as possible, allowing for the incorporation of tyrosine kinase inhibitors (TKIs) into their treatment regimens. Therefore, the expansion of this gene panel will allow for a more comprehensive analysis of pediatric ALL-associated aberrations, especially regarding their response to targeted therapies.
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