Article

Therapy-Related Myeloid Leukemia

Department of Medicine and Cancer Research Center, University of Chicago, Chicago, IL 60637, USA. <>
Seminars in Oncology (Impact Factor: 3.94). 09/2008; 35(4):418-29. DOI: 10.1053/j.seminoncol.2008.04.012
Source: PubMed

ABSTRACT Therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/t-AML) are thought to be the direct consequence of mutational events induced by chemotherapy, radiation therapy, immunosuppressive therapy, or a combination of these modalities, given for a pre-existing condition. The outcomes for these patients have been poor historically compared to people who develop de novo AML. The spectrum of cytogenetic abnormalities in t-AML is similar to de novo AML, but the frequency of unfavorable cytogenetics, such as a complex karyotype or deletion or loss of chromosomes 5 and/or 7, is considerably higher in t-AML. Survival varies according to cytogenetic risk group in t-AML patients, with better outcomes being observed in those with favorable-risk karyotypes. Treatment recommendations should be based on performance status and karyotype. A deeper understanding of the factors that predispose patients to the development of therapy-related myeloid leukemia would help clinicians monitor patients more carefully after treatment for a primary condition. Ultimately, this knowledge could influence initial treatment strategies with the goal of decreasing the incidence of this serious complication.

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    • "Non-Hodgkin lymphoma is the most common malignancy that occurs after solid organ transplantation [3] [4], but t-MN has also been described [5] [6] [7] [8]. T-MN generally portends a poor prognosis despite treatment with induction chemotherapy and, more recently, allo-HCT [9]. Treatment of t-MN in solid organ transplant recipients is even more challenging as these patients require ongoing immunosuppression and often have multiple co-morbidities. "
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    ABSTRACT: Therapy-related myeloid neoplasm (t-MN) is a subtype of acute myeloid leukemia with adverse cytogenetics and poor overall prognosis despite intensive induction chemotherapy and allogeneic hematopoietic cell transplantation (allo-HCT). It is increasingly recognized as a late complication of chronic immunosuppression in patients who have received solid organ transplantation. In this paper, we describe a case of t-MN following orthotopic cardiac transplantation and its treatment with allo-HCT. We discuss molecular and biological challenges and considerations in double solid organ and bone marrow transplantation and review similar cases at our institution. Our experience suggests general feasibility and safety of allo-HCT in patients who have received solid organ transplantation.
    03/2013; 2013:140138. DOI:10.1155/2013/140138
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    • "It is reasonable to infer that when platinum therapy became the standard in adjuvant first-line treatment of EOC in the early 1980s and subsequently platinum/taxane based treatment supplanted platinum/cyclophosphamide in the mid 1990s [11], the overall risk of developing secondary leukemia has substantially decreased. This supports the previously reported notion that traditional alkylating agents, now rarely used in the treatment of EOC, have a higher leukemogenic potential than the current standard of care [1] [9] [12]. It has been shown in a previous case–control study of ovarian cancer patients that the use of melphalan carried a relative risk of developing secondary leukemia of 20.8 (95%CI 6.3–68.3) "
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    ABSTRACT: Therapy related acute myeloid leukemia (t-AML) is a potential late complication of cytotoxic therapy, and it is of particular concern in the treatment of patients with epithelial ovarian carcinoma (EOC) exposed to multiple courses of chemotherapy during the course of their disease. This study examines the incidence, characteristics and clinical outcomes of patients who developed secondary myeloid-type leukemia after a diagnosis of EOC. National Cancer Institute's Surveillance, Epidemiology and End Results database was pooled for diagnosis of secondary myeloid leukemia after an initial diagnosis of EOC. This group of patients was compared to patients with de novo AML, and to EOC patients who did not develop secondary myeloid leukemia. Demographic, cytopathological and survival data were recorded. Cox Proportional Hazards model was used to calculate hazard ratios (HR) for developing secondary leukemia and to determine the statistically significant variables impacting survival. Kaplan-Meier estimates of survival were obtained and comparisons between the groups were performed using log-rank test. One hundred and nine myeloid leukemia cases were identified among 63,359 patients with a prior diagnosis of EOC for an overall incidence of 0.17%. The median latency to development of leukemia was 4 years (range 0-27 years). Median survival from the time of secondary leukemia diagnosis was 3 months and significantly worse than the 6 month median survival in patients with de novo AML (p<0.001). Age at leukemia diagnosis greater than 65 and development of secondary vs. de novo leukemia had a statistically worse prognosis on multivariate analysis (HR of 2.69, 95%CI 2.60-2.78 and 1.81, 95%CI 1.49-2.20 respectively). The development of secondary leukemia was more common with EOC diagnosis made prior to the platinum/taxane era (HR 6.70, 95%CI 3.69-12.18). There was no difference in median survival between EOC patients who developed AML and those who did not. Development of t-AML is a rare but lethal event among EOC patients, and its incidence has decreased significantly since the use of platinum/taxane-based chemotherapy became the standard of care.
    Gynecologic Oncology 08/2011; 123(3):456-60. DOI:10.1016/j.ygyno.2011.07.097 · 3.69 Impact Factor
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    • "Mitoxantrone, a topoisomerase II inhibitor, was the conventional first-line chemotherapy for metastatic prostate cancer until recently [49]. Topoisomerase II inhibitors are known to induce AML [1] [2], which raises the possibility of mitoxantrone-related AML incidence in our study. However, no cases of mitoxantronerelated AML were documented in the literature until 2008 [50], which effectively excludes our study period. "
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    ABSTRACT: The effect of radiation therapy on acute myeloid leukemia incidence among prostate cancer patients has not been sufficiently elucidated despite evidence that acute myeloid leukemia is a consequence of therapeutic radiation in other primary malignancies. Therefore, we investigated the effect of definitive therapy with radiation therapy (external beam radiation therapy [EBRT] or brachytherapy) on acute myeloid leukemia incidence in a population-based cohort of patients with localized or locally advanced prostate cancer. We utilized the Surveillance, Epidemiology, and End Results database to identify a cohort of men (n=168,612) with newly diagnosed prostate adenocarcinoma between January 1988 and December 2003. Cox proportional hazard regression was used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of acute myeloid leukemia incidence following definitive therapy with EBRT alone, brachytherapy alone, or surgery alone compared to no definitive therapy (i.e. no EBRT, brachytherapy, or surgery). The cohort yielded 184 acute myeloid leukemia cases during 1,064,820 person-years of follow-up after prostate adenocarcinoma diagnosis. Patients treated with EBRT had a higher adjusted relative risk of developing acute myeloid leukemia than patients treated with brachytherapy or surgery when each therapy group was compared to patients who were not treated with definitive therapy (EBRT: HR=2.05, 95% CI 1.29, 3.26; brachytherapy: HR=1.22, 95% CI 0.46, 3.22; surgery: HR=1.24, 95% CI 0.77, 1.98). Our findings suggest that acute myeloid leukemia incidence is a greater concern for patients treated with EBRT than brachytherapy for localized or locally advanced prostate adenocarcinoma.
    06/2010; 34(3):274-8. DOI:10.1016/j.canep.2010.04.003
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