Helbig Grzegorz, Bober Grażyna, Seweryn Marek, Wichary Ryszard, Tukiendorf Andrzej, Sedlak Lech, Oleksy Tomasz, Kyrcz-Krzemień Sławomira
Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Poland.
Department of Statistics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
Mediterr J Hematol Infect Dis. 2015 Jan 1;7(1):e2015003. doi: 10.4084/MJHID.2015.003. eCollection 2015.
Imatinib 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.
To investigate the incidence and clinical outcome of secondary malignancies during IM therapy for CML.
The 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.
Secondary 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-ABL(IS) ≤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.
The association between IM therapy for CML and SM development has not been found.
甲磺酸伊马替尼（IM）仍是慢性髓性白血病（CML）的首选治疗药物，疗效显著，并为长期无病生存提供了希望。由于长期使用IM，引发了关于其对继发性恶性肿瘤（SM）发生可能影响的问题。
研究CML患者接受IM治疗期间继发性恶性肿瘤的发生率和临床结局。
回顾了2003年至2013年在单一机构接受IM治疗的221例CML患者的记录。采用泊松回归模型估计CML患者发生SM和死亡的相对风险。
221例接受IM治疗的患者中有8例（3.6%）发生继发性恶性肿瘤，中位治疗时间为61个月（范围10 - 137个月）。女性/男性比例为5/3。2例患者在加速期被诊断为CML，6例为慢性期。开始使用IM时的中位年龄为58岁（范围31 - 72岁）。这8例SM患者中有5例在其他治疗失败后接受IM治疗：干扰素α（n = 5）、羟基脲（n = 4）和阿糖胞苷（n = 1）。3例患者接受IM作为一线治疗。所有患者在发生SM时均接受每日400mg的IM治疗。SM的治疗包括手术（n = 3）、单纯化疗（n = 3）以及化疗后放疗（n = 1）。1例患者因疾病播散未接受治疗。所有CML患者在发生SM时均处于血液学和完全细胞遗传学缓解（CCR）状态。他们均符合主要分子反应标准（BCR-ABL(IS)≤0.1%）。他们在接受SM治疗的同时继续使用IM。8例SM患者中，5例存活并在接受IM治疗时仍处于CCR状态，3例因SM死亡。与年龄调整后的人群相比，CML患者发生SM以及因SM死亡的风险在统计学上没有增加。
未发现CML的IM治疗与SM发生之间存在关联。
