Therapy-Related Myeloid Leukemia

Department of Medicine and Cancer Research Center, University of Chicago, Chicago, IL 60637, USA. <>
Seminars in Oncology (Impact Factor: 3.9). 09/2008; 35(4):418-29. DOI: 10.1053/j.seminoncol.2008.04.012
Source: PubMed


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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    • "Numerous reports have related the effect of high-dose chemotherapy and the pathogenesis of second neoplasms. Treatment-related factors are presumed to be responsible for the elevated risk of myelodysplastic syndrome, lung cancer, non- Hodgkin's lymphoma and acute myeloid leukemia in patients treated with chemotherapy for distinct primary malignancies, such as hematologic and non-hematologic malignancies and Hodgkin's lymphoma (Swerdlow et al. 2011, Godley and Larson 2008, Leone et al. 2007). These studies show that there is a need for careful long-term monitoring of patients receiving chemotherapy for a primary condition, for the early detection and treatment of secondary cancers (Freeman et al. 2012, Papanikolaou et al. 2011, Swerdlow et al. 2011, Yamada et al. 1999). "
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    ABSTRACT: Mitotic recombination is a process involved in carcinogenesis which can lead to genetic loss through the loss of heterozygosity. The recombinogenic potentials of two anticancer drugs topoisomerase I inhibitors, camptothecin (CPT) and irinotecan (CPT-11), were evaluated in the present study. The homozygotization assay, which assess the induction of mitotic recombination and gene homozygosis, as well as the heterozygous A757//UT448 diploid strain of Aspergillus nidulans were employed. The three non-cytotoxic concentrations of CPT (3.5 ng mL-1, 10.5 ng mL-1 and 17.4 ng mL-1) were found to induce both mitotic recombination and gene homozygosis. CPT treatment produced three diploids homozygous, for nutritional and conidia color genes, and Homozygotization Indices (HI) significantly different from negative control. On the other hand, only the highest CPT-11 concentration tested (18 µg mL-1), corresponding to the maximal single chemotherapeutic dose, produced HI values higher than 2.0 and significantly different from negative control HI values. The recombinogenic effects of both topoisomerase I blockers were associated with the recombinational repair of DNA strand breaks induced by CPT and CPT-11. The anticancer drugs CPT and CPT-11 may be characterized as secondary malignancies promoters in cancer patients after chemotherapy treatment.
    Preview · Article · Oct 2014 · Anais da Academia Brasileira de Ciências
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    • "T-MDS is also occasionally found after treatment with topoisomerase II inhibitors, but more commonly the patient presents with full-blown AML after a latency period of just 1 to 3 years. Topoisomerase II inhibitors are associated with translocations involving chromosome bands 11q23 or 21q22.9) "
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    ABSTRACT: Myelodysplastic syndromes (MDS) are probably the most common hematologic malignancies in adults over the age of 60 and are a major source of morbidity and mortality among older age groups. Diagnosis and management of this chronic blood cancer has evolved significantly in recent years and there are Food and Drug Administration-approved therapies that can extend patients' life expectancy and improve quality of life. Primary care physicians (PCPs) are often involved in the process of diagnosis and follow-up of MDS patients, especially those in low-risk groups. They can therefore play an important role in improving patient care and quality of life by ensuring early referral and participating in supportive management. There is also a shortage of oncologists which increases the importance of the role of PCPs in management of MDS patients. In the face of limited resources, PCPs can improve access and quality of care in MDS patients. This article provides an overview of the common manifestations, diagnostic approaches, and therapeutic modalities of MDS for PCPs, with a focus on when to suspect MDS, when a referral is appropriate, and how to provide appropriate supportive care for patients diagnosed with MDS.
    Full-text · Article · May 2014 · Korean Journal of Family Medicine
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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.
    Full-text · Article · Mar 2013
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