Chronic Myeloid Leukemia Following Treatment for Primary Neoplasms or Other Medical Conditions

A Report of 21 Cases and Review of the Literature

Lian-He Yang, MD, PhD; Pu Su, MD, PhD; Catherine Luedke, MD; Chuanyi Mark Lu, MD; Abner Louissaint Jr, MD, PhD; Chad M. McCall, MD, PhD; Sarah Rapisardo, PhD; Bethany Vallangeon, MD; Endi Wang, MD, PhD

Disclosures

Am J Clin Pathol. 2018;150(3):246-258. 

In This Article

Abstract and Introduction

Abstract

Objectives: Therapy-related chronic myeloid leukemia (CML) has been reported, but its clinical presentation and pathologic features have not yet been well characterized.

Methods: Twenty-one cases of CML following treatment for primary diseases were collected and retrospectively analyzed.

Results: The clinical presentation, pathologic features, and cytogenetic profile were similar to de novo CML. In particular, those with an isolated Philadelphia chromosome constituted 88.9% of our cases, and additional aberrations characteristic of therapy-related acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) were not identified in this study. The patients responded to imatinib/derivatives and survived with limited follow-up.

Conclusions: Therapy-related CML has a clinical presentation, pathologic features, and cytogenetic profile akin to de novo CML. Absence of additional significant aberrations seems to suggest a pathogenesis different from therapy-related AML/MDS. Therapy-related CML exhibits a robust therapeutic response to imatinib/derivatives and favorable clinical outcomes similar to de novo CML.

Introduction

Chronic myeloid leukemia (CML) is a specific type of myeloproliferative neoplasm characterized by a hallmark genetic change, t(9;22)(q34;p11), also known as the Philadelphia chromosome.[1,2] At the molecular level, this particular translocation results in the fusion of the BCR gene on chromosome 22 to the ABL gene on chromosome 9. The incidence of CML is 1.7 per 100,000 population annually and represents 0.4% of all new cancer diagnoses in the United States.[3] While the vast majority of these cases arise de novo, CML, on rare occasions, occurs in association with other medical conditions, particularly after treatment for a primary malignancy.[4–64] Of hematolymphoid neoplasms related to prior treatment, the vast majority are myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), which have previously been well characterized.[65] Although a significant number of CML cases have been reported to be associated with chemotherapy, radiotherapy,[4–64] or immunosuppressive therapy,[66–69] the etiology behind the development of CML in this particular patient population is unclear, with opinions including coincidence, diminished immune surveillance due to impaired B-cell and T-cell function, and direct oncogenic effect of cytotoxic agents or irradiation. The literature is limited to single case reports and small case series,[2–63,66–95] and a comprehensive analysis of these cases has not been performed to determine their clinical outcome, particularly in the era of tyrosine kinase inhibitor therapy. Herein, we present original data of 21 cases of CML with a history of treatment for malignancy or other primary conditions. We also extensively review the literatures and analyze the reported cases.

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