Case report: Efficacy of ponatinib in a case of chronic myeloid leukemia with a complicated clonal evolution including a myelodysplastic syndrome

Boli Fan,Denis Soulières,Harold J Olney,William Mccarvill,Xiaoduan Weng

doi:10.7243/2052-434x-6-3

Abstract

Abstract Chronic myeloid leukemia (CML) is characterised by the presence of the Philadelphia chromosome (Ph), which results in the production of the constitutively active tyrosine kinase BCR-ABL1, with tyrosine kinase inhibitors (TKI)

Highlights

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm characterized by dysregulated clonal proliferation of mainly myeloid and erythroid cells and platelets
clonal chromosomal abnormalities (CCAs) in Philadelphia chromosome (Ph)-negative cells arising during treatment for CML are rare and were initially described in patients exposed to chemotherapy and interferon-α but are increasingly reported in patients treated with imatinib, and more recently dasatinib and nilotinib, with cases reported in patients treatment naive before the use of tyrosine kinase inhibitors (TKI) [17-21]
This is an interesting case because this patient, over the course of her disease, developed secondary resistance to the three TKIs approved as first-line treatment for CML, as well as developing a poor prognosis myelodysplastic syndrome (MDS) according to revised International Prognostic Scoring System (R-IPSS)

Summary

Introduction

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm characterized by dysregulated clonal proliferation of mainly myeloid and erythroid cells and platelets. CCAs in Ph-negative cells arising during treatment for CML are rare and were initially described in patients exposed to chemotherapy and interferon-α but are increasingly reported in patients treated with imatinib, and more recently dasatinib and nilotinib, with cases reported in patients treatment naive before the use of TKIs [17-21] These anomalies have unclear clinical implications, with only a minority of patients eventually developing a secondary hematological neoplasm such as a myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML) [18,21-23]. Cytogenetic studies on a bone marrow specimen revealed a clonal population of Ph-negative cells in 15 metaphases harboring -7 as well as gain of chromosome 22 (+22), while the patient had a deep molecular response (defined as a BCR-ABL1 transcript level less than 0.0032%) of her CML with a BCR-ABL1 transcript level of 0.0014%. The molecular response is sustained with no recurrence of the MDS, and ponatinib is currently well tolerated at the adjusted doses

Findings

Discussion

Conclusion