Blast Transformation of Chronic Myeloid Leukemia Driven by Acquisition of T(8;21)(q22;q22)/: Selecting Optimal Treatment Based on Clinical and Molecular Findings

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2024 Oct 26

PMID 39457651

Authors

Adolfo Fernandez-Sanchez

Alberto Hernandez-Sanchez

Cristina de Ramon

Maria-Carmen Chillon

Maria Belen Vidriales

Monica Baile-Gonzalez

Cristina-Teresa Fuentes-Morales

Magdalena Sierra-Pacho

Lucia Lopez-Corral

Fermin Sanchez-Guijo

Affiliations

Soon will be listed here.

Abstract

The advent of tyrosine kinase inhibitors (TKIs) has changed the natural history of chronic myeloid leukemia (CML), and the transformation from the chronic phase to the blast phase (BP) is currently an uncommon situation. However, it is one of the major remaining challenges in the management of this disease, as it is associated with dismal outcomes. We report the case of a 63-year-old woman with a history of CML with poor response to imatinib who progressed to myeloid BP-CML, driven by the acquisition of t(8;21)(q22;q22)/. The patient received intensive chemotherapy and dasatinib, followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, she suffered an early relapse after allo-HSCT with the acquisition of the T315I mutation in . Ponatinib and azacitidine were started as salvage treatment, allowing for the achievement of complete remission with deep molecular response after five cycles. Advances in the knowledge of disease biology and clonal evolution are crucial for optimal treatment selection, which ultimately translates into better patient outcomes.

References

Geelen I, Sandin F, Thielen N, Janssen J, Hoogendoorn M, Visser O . Validation of the EUTOS long-term survival score in a recent independent cohort of "real world" CML patients. Leukemia. 2018; 32(10):2299-2303. DOI: 10.1038/s41375-018-0136-7. View

Deau B, Nicolini F, Guilhot J, Huguet F, Guerci A, Legros L . The addition of daunorubicin to imatinib mesylate in combination with cytarabine improves the response rate and the survival of patients with myeloid blast crisis chronic myelogenous leukemia (AFR01 study). Leuk Res. 2010; 35(6):777-82. DOI: 10.1016/j.leukres.2010.11.004. View

Hochhaus A, Larson R, Guilhot F, Radich J, Branford S, Hughes T . Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia. N Engl J Med. 2017; 376(10):917-927. PMC: 5901965. DOI: 10.1056/NEJMoa1609324. View

Wadhwa J, Szydlo R, Apperley J, Chase A, Bua M, Marin D . Factors affecting duration of survival after onset of blastic transformation of chronic myeloid leukemia. Blood. 2002; 99(7):2304-9. DOI: 10.1182/blood.v99.7.2304. View

Haddad F, Sasaki K, Bidikian A, Issa G, Kadia T, Jain N . Characteristics and outcomes of patients with chronic myeloid leukemia and T315I mutation treated in the pre- and post-ponatinib era. Am J Hematol. 2023; 98(10):1619-1626. PMC: 11526380. DOI: 10.1002/ajh.27037. View

Fang B, Li N, Song Y, Han Q, Zhao R . Standard-dose imatinib plus low-dose homoharringtonine and granulocyte colony-stimulating factor is an effective induction therapy for patients with chronic myeloid leukemia in myeloid blast crisis who have failed prior single-agent therapy with.... Ann Hematol. 2010; 89(11):1099-105. DOI: 10.1007/s00277-010-0991-4. View

Abaza Y, Kantarjian H, Alwash Y, Borthakur G, Champlin R, Kadia T . Phase I/II study of dasatinib in combination with decitabine in patients with accelerated or blast phase chronic myeloid leukemia. Am J Hematol. 2020; 95(11):1288-1295. DOI: 10.1002/ajh.25939. View

Yanada M, Konuma T, Yamasaki S, Kondo T, Fukuda T, Shingai N . Relapse of acute myeloid leukemia after allogeneic hematopoietic cell transplantation: clinical features and outcomes. Bone Marrow Transplant. 2020; 56(5):1126-1133. DOI: 10.1038/s41409-020-01163-z. View

Saussele S, Richter J, Guilhot J, Gruber F, Hjorth-Hansen H, Almeida A . Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial. Lancet Oncol. 2018; 19(6):747-757. DOI: 10.1016/S1470-2045(18)30192-X. View

10.

Javorniczky N, Wehrle J, Ihorst G, Hupfer V, Aumann K, Pfeifer D . Prevalence and characteristics of myeloproliferative neoplasms with concomitant monoclonal gammopathy. Leuk Res. 2020; 98:106454. DOI: 10.1016/j.leukres.2020.106454. View

11.

Ruggiu M, Oberkampf F, Ghez D, Cony-Makhoul P, Beckeriche F, Cano I . Azacytidine in combination with tyrosine kinase inhibitors induced durable responses in patients with advanced phase chronic myelogenous leukemia. Leuk Lymphoma. 2017; 59(7):1659-1665. DOI: 10.1080/10428194.2017.1397666. View

12.

Kantarjian H, Cortes J . Complete cytogenetic response, not deep molecular response, is associated with survival in chronic myeloid leukemia. J Clin Oncol. 2014; 32(27):3077. DOI: 10.1200/JCO.2014.56.0904. View

13.

Dohner H, Wei A, Appelbaum F, Craddock C, DiNardo C, Dombret H . Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022; 140(12):1345-1377. DOI: 10.1182/blood.2022016867. View

14.

Oki Y, Kantarjian H, Gharibyan V, Jones D, OBrien S, Verstovsek S . Phase II study of low-dose decitabine in combination with imatinib mesylate in patients with accelerated or myeloid blastic phase of chronic myelogenous leukemia. Cancer. 2007; 109(5):899-906. DOI: 10.1002/cncr.22470. View

15.

Silver R, Cortes J, Waltzman R, Mone M, Kantarjian H . Sustained durability of responses and improved progression-free and overall survival with imatinib treatment for accelerated phase and blast crisis chronic myeloid leukemia: long-term follow-up of the STI571 0102 and 0109 trials. Haematologica. 2009; 94(5):743-4. PMC: 2675690. DOI: 10.3324/haematol.2009.006999. View

16.

Hochhaus A, Baccarani M, Silver R, Schiffer C, Apperley J, Cervantes F . European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020; 34(4):966-984. PMC: 7214240. DOI: 10.1038/s41375-020-0776-2. View

17.

Johansson B, Fioretos T, Mitelman F . Cytogenetic and molecular genetic evolution of chronic myeloid leukemia. Acta Haematol. 2002; 107(2):76-94. DOI: 10.1159/000046636. View

18.

Morita K, Jabbour E, Ravandi F, Borthakur G, Khoury J, Hu S . Clinical Outcomes of Patients With Chronic Myeloid Leukemia With Concurrent Core Binding Factor Rearrangement and Philadelphia Chromosome. Clin Lymphoma Myeloma Leuk. 2021; 21(5):338-344. PMC: 11513896. DOI: 10.1016/j.clml.2020.12.025. View

19.

Lauseker M, Bachl K, Turkina A, Faber E, Prejzner W, Olsson-Stromberg U . Prognosis of patients with chronic myeloid leukemia presenting in advanced phase is defined mainly by blast count, but also by age, chromosomal aberrations and hemoglobin. Am J Hematol. 2019; 94(11):1236-1243. DOI: 10.1002/ajh.25628. View

20.

Marcucci G, Mrozek K, Ruppert A, Maharry K, Kolitz J, Moore J . Prognostic factors and outcome of core binding factor acute myeloid leukemia patients with t(8;21) differ from those of patients with inv(16): a Cancer and Leukemia Group B study. J Clin Oncol. 2005; 23(24):5705-17. DOI: 10.1200/JCO.2005.15.610. View