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. 2021 Jul;2(4):326-337.
doi: 10.1158/2643-3230.BCD-20-0229.

Clinical significance of novel subtypes of acute lymphoblastic leukemia in the context of minimal residual disease-directed therapy

Sima Jeha #  1   2 , John Choi #  3 , Kathryn G Roberts #  3 , Deqing Pei  4 , Elaine Coustan-Smith  5 , Hiroto Inaba  1 , Jeffrey E Rubnitz  1 , Raul C Ribeiro  1 , Tanja A Gruber  1 , Susana C Raimondi  3 , Seth E Karol  1 , Chunxu Qu  3 , Samuel W Brady  6 , Zhaohui Gu  3 , Jun J Yang  7 , Cheng Cheng  4 , James R Downing  3 , Williams E Evans  7 , Mary V Relling  7 , Dario Campana  5 , Charles G Mullighan  8 , Ching-Hon Pui  9   2   3
Affiliations

Clinical significance of novel subtypes of acute lymphoblastic leukemia in the context of minimal residual disease-directed therapy

Sima Jeha et al. Blood Cancer Discov. 2021 Jul.

Abstract

We evaluate clinical significance of recently identified subtypes of acute lymphoblastic leukemia (ALL) in 598 children treated with minimal residual disease (MRD)-directed therapy. Among the 16 B-ALL and 8 T-ALL subtypes identified by next generation sequencing, ETV6-RUNX1, high-hyperdiploid and DUX4-rearranged B-ALL had the best five-year event-free survival rates (95% to 98.4%); TCF3-PBX1, PAX5alt, T-cell, ETP, iAMP21, and hypodiploid ALL intermediate rates (80.0% to 88.2%); and BCR-ABL1, BCR-ABL1-like and ETV6-RUNX1-like and KMT2A-rearranged ALL the worst rates (64.1% to 76.2%). All but three of the 142 patients with day-8 blood MRD <0.01% remained in remission. Among new subtypes, intensified therapy based on day-15 MRD≥1% improved outcome of DUX4-rearranged, BCR-ABL1-like, and ZNF384-rearranged ALL, and achievement of day-42 MRD<0.01% did not preclude relapse of PAX5alt, MEF2D-rearranged and ETV6-RUNX1-like ALL. Thus, new subtypes including DUX4-rearranged, PAX5alt, BCR-ABL1-like, ETV6-RUNX1-like, MEF2D-rearranged and ZNF384-rearranged ALL have important prognostic and therapeutic implications.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interests. C.G.M. has received research funding from Loxo Oncology, Pfizer and AbbVie; compensation from Amgen and Illumina, and holds stock in Amgen. C.-H..P. is on scientific advisory board of Adaptive Biotechnology, Inc and Data Monitoring Committee of Novartis, and received honorarium from Amgen.

Figures

Figure 1.
Figure 1.
Sequential levels of MRD in blood on day 8 (left column), in bone marrow on day 15 (middle column), and in bone marrow on day 42 (right column) of remission induction for individual leukemia subtypes. Results are not shown for some subtypes because of small number and not for “B other” because it represents heterogeneous disease.
Figure 2.
Figure 2.
Event-free survival for common leukemia subtypes. Note that there were only seven cases with ZNF384-rearranged ALL and nine with ETV6–RUNX1-rearranged cases. Results are not shown for some subtypes because of small number.
Figure 3.
Figure 3.
Treatment outcome based on leukemia cell subtype and MRD levels in bone marrow on day 15 (A) and day 42 (B). See Tables 2 and 3 for additional data. CRR, cumulative risk of any relapse; EFS, event-free survival; HD, hyperdiploidy; OS, overall survival.
See this image and copyright information in PMC

Comment in

References

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