Occurrence of Secondary Malignancies in Chronic Myeloid Leukemia During Therapy With Imatinib Mesylate-Single Institution Experience

Abstract

IntroductionImatinib mesylate (IM) remains the treatment of choice for chronic myeloid leukemia (CML) showing a remarkable efficacy and offers a perspective for long disease-free survival. Due to prolonged administration of IM, the questions about the possible impact on the development of secondary malignancies (SM) are raised.ObjectiveTo investigate the incidence and clinical outcome of secondary malignancies during IM therapy for CML.Material and MethodsThe records of 221 CML patients treated with IM between 2003–2013 in a single institution were reviewed. The Poisson regression model was used to estimate the relative risks for SM and death in CML patients.ResultsSecondary malignancies developed in eight out of the 221 patients (3.6%) receiving IM for a median of 61 months (range, 10–137 months). Female/male ratio was 5/3. Two patients were diagnosed with their CML at accelerated phase whereas 6 had chronic phase. The median age at IM initiation was 58 years (range, 31–72 years). Five of these 8 SM patients received IM after other treatments failure: interferon α (n=5), hydroxyurea (n=4) and cytarabine (n=1). Three patients received IM as a frontline therapy. All patients were on IM at 400mg daily at SM occurrence. The therapy for SM included surgery (n=3), chemotherapy only (n=3), and chemotherapy followed by radiotherapy (n=1). One patient did not receive treatment due to disseminated disease. All CML patients were in hematologic and complete cytogenetic response (CCR) at the time of SM development. All of them also met the criteria for major molecular response (BCR-ABLIS ≤0.1%). They continued their IM while receiving treatment for SM. Among eight patients with SM, five patients are alive and remain in CCR on IM whereas three patients died due to SM. The risks for SM development as well as death due to SM in CML patients were not statistically increased if compared to age-adjusted population.ConclusionsThe association between IM therapy for CML and SM development has not been found.

Characterisation of clonal Philadelphia‐negative cytogenetic abnormalities in a large cohort of chronic myeloid leukaemia

“…The mechanism for CPCA is still unknown. Although the TKI and their intermediates are genotoxic at high concentration in vitro , some data reported that this phenomenon was not caused by TKI treatment because CPCA could be found in Ph‐negative cells prior to TKI treatment …”

Hodgkin lymphoma in a case of chronic myeloid leukemia treated with tyrosine kinase inhibitors

“…Similarly, Helbig et al found that a second malignancy developed in 8 patients (one case each of malignancy of endometrium, testis, skin melanoma, breast, bladder, prostate, large bowel and lung) out of 221 CML patients (3.6%) treated with Imatinib with a median interval of 61 months (10-137 months). However, the risks for second malignancy development as well as for related death in CML patients were not statistically increased if compared to age-adjusted population (9). There was no case of Hodgkin lymphoma detected in the above studies.…”

“…In August 2014, the BCR-ABL was found to be 27.38%. Chromosomal analysis revealed 46XY; t(9;10;22)(q34;p11.2;q11.2) (11)/46, XY (9). Mutation analysis showed E255V mutation in 100% of cells.…”

Molecular investigation of coexistent chronic myeloid leukaemia and peripheral T-cell lymphoma – a case report

“…Although secondary tumours have been described after imatinib therapy, the analyses of their frequency with respect to the age-adjusted general population yielded conflicting results 3 4 17 18 19 . Differences in cohort size, follow-up time and the interpretation of the term “secondary cancer” may have been responsible for this difference.…”