Accelerated-phase CML: de novo and transformed

Author:

Shanmuganathan Naranie1234,Hughes Timothy P.123

Affiliation:

1. 1 Precision Cancer Medicine Theme, South Australian Health & Medical Research Institute (SAHMRI), Adelaide, Australia

2. 2 Department of Haematoloxgy, Royal Adelaide Hospital and SA Pathology, Adelaide, Australia

3. 3 Adelaide Medical School, University of Adelaide, Adelaide, Australia

4. 4 Department of Genetics and Molecular Pathology & Centre for Cancer Biology, SA Pathology, Adelaide, Australia

Abstract

Abstract Despite the dramatic improvements in outcomes for the majority of chronic myeloid leukemia (CML) patients over the past 2 decades, a similar improvement has not been observed in the more advanced stages of the disease. Blast phase CML (BP-CML), although infrequent, remains poorly understood and inadequately treated. Consequently, the key initial goal of therapy in a newly diagnosed patient with chronic phase CML continues to be prevention of disease progression. Advances in genomic investigation in CML, specifically related to BP-CML, clearly demonstrate we have only scratched the surface in our understanding of the disease biology, a prerequisite to devising more targeted and effective therapeutic approaches to prevention and treatment. Importantly, the introduction of the concept of “CML-like” acute lymphoblastic leukemia (ALL) has the potential to simplify the differentiation between BCR::ABL1-positive ALL from de novo lymphoid BP-CML, optimizing monitoring and therapeutics. The development of novel treatment strategies such as the MATCHPOINT approach for BP-CML, utilizing combination chemotherapy with fludarabine, cytarabine, and idarubicin in addition to dose-modified ponatinib, may also be an important step in improving treatment outcomes. However, identifying patients who are high risk of transformation remains a challenge, and the recent 2022 updates to the international guidelines may add further confusion to this area. Further work is required to clarify the identification and treatment strategy for the patients who require a more aggressive approach than standard chronic phase CML management.

Publisher

American Society of Hematology

Subject

Hematology

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