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,Rui Santos,Susana Lisboa,Rosa Branca Ferreira,Carlos Pinho Vaz,Susana Bizarro,Cecília Correia,Lurdes Torres,Fernando Campilho,Manuel R Teixeira,Joana Vieira,António Campos,Luís Leite

doi:10.1186/s12885-018-5100-4

Nuno Cerveira, Rui Santos + Show 11 more

Open Access

https://doi.org/10.1186/s12885-018-5100-4

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Abstract

BackgroundAtypical 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 presentationHere 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).ConclusionThis 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.

Highlights

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 posttransplant relapse with a T315I mutation that achieved a persistent negative deep molecular response (MR5.0) after treatment with single-agent ponatinib
Cerveira et al BMC Cancer (2018) 18:1229 with p230 CML that was successfully treated with the third-generation tyrosine kinase inhibitor (TKI) ponatinib, following an early relapse with a T315I mutation after allogeneic stem cell transplantation
The patient rapidly achieved an haematological response and, after 3 months of treatment, a partial cytogenetic response (PCyR) was observed (28% Ph + metaphases), corresponding to an optimal response according to the ELN guidelines [8]

Summary

Introduction

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 posttransplant relapse with a T315I mutation that achieved a persistent negative deep molecular response (MR5.0) after treatment with single-agent ponatinib. After 6 months of imatinib therapy, he lost his cytogenetic response (CyR), with all the metaphases analysed showing the same karyotype detected at diagnosis, which suggested treatment failure [8]. After 4 months of therapy, he was in haematological remission, but karyotype analysis showed only a minimal cytogenetic response (75% Ph + metaphases).

Results

Conclusion