Ponatinib induces a sustained deep molecular response in a chronic myeloid leukaemia patient with an early relapse with a T315I mutation following allogeneic hematopoietic stem cell transplantation: a case report
Nuno Cerveira,
Rosa Branca Ferreira,
Susana Bizarro,
Cecília Correia,
Lurdes Torres,
Susana Lisboa,
Joana Vieira,
Rui Santos,
Fernando Campilho,
Carlos Pinho Vaz,
Luís Leite,
Manuel R. Teixeira,
António Campos
Affiliations
Nuno Cerveira
Department of Genetics, Portuguese Oncology Institute
Rosa Branca Ferreira
Department of Bone Marrow Transplantation, Portuguese Oncology Institute
Susana Bizarro
Department of Genetics, Portuguese Oncology Institute
Cecília Correia
Department of Genetics, Portuguese Oncology Institute
Lurdes Torres
Department of Genetics, Portuguese Oncology Institute
Susana Lisboa
Department of Genetics, Portuguese Oncology Institute
Joana Vieira
Department of Genetics, Portuguese Oncology Institute
Rui Santos
Department of Genetics, Portuguese Oncology Institute
Fernando Campilho
Department of Bone Marrow Transplantation, Portuguese Oncology Institute
Carlos Pinho Vaz
Department of Bone Marrow Transplantation, Portuguese Oncology Institute
Luís Leite
Department of Bone Marrow Transplantation, Portuguese Oncology Institute
Manuel R. Teixeira
Department of Genetics, Portuguese Oncology Institute
António Campos
Department of Bone Marrow Transplantation, Portuguese Oncology Institute
Abstract Background Atypical BCR-ABL1 transcripts are detected in less than 5% of patients diagnosed with chronic myeloid leukaemia (CML), of which e19a2 is the most frequently observed, with breakpoints in the micro breakpoint cluster region (μ-BCR) and coding for the p230 BCR-ABL1 protein. p230 CML is associated with various clinical presentations and courses with variable responses to first-line imatinib. Case presentation Here we report a case of imatinib resistance due to an E255V mutation, followed by early post-transplant relapse with a T315I mutation that achieved a persistent negative deep molecular response (MR5.0) after treatment with single-agent ponatinib. Using CastPCR, we could trace back the presence of the T315I mutation to all the RNA samples up to the detection of T315 mutation by Sanger sequencing shortly after allogeneic hematopoietic stem cell transplantation (HSCT). Conclusion This case illustrates the major interest of ponatinib as a valid treatment option for e19a2 CML patients who present a T315I mutation following relapse after HSCT.
