Additional Cytogenetic Changes and Prior Genotoxic Exposure Predict Unfavorable Prognosis in Myelodysplastic Syndromes and Acute Myeloid Leukemia with der(1;7)(q10;p10).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4894-4894
Author(s):  
Kazuma Ohyashiki ◽  
Hui-Hua Hsiao ◽  
Goro Sashida ◽  
Yoshikazu Ito ◽  
Junko H. Ohyashiki

Abstract We analyzed 23 patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) showing der(1;7)(q10;p10) (hereafter der(1;7)), to identify the exact predictive factor of this cytogenetic change. Eight (34.8%) patients, including 6 MDS and 2 AML patients, had a prior history of genotoxic exposure, especially radiation and/or antimetabolites. Patients with der(1;7) consisted of three groups; one-third of patients had a prior history of genotoxic agents, one-third had additional cytogenetic changes at the time of MDS/AML diagnosis without prior exposure history, and the remaining one-third had neither prior exposure history nor additional cytogenetic changes. The current study demonstrated that the poor outcome of MDS/AML with der(1;7) is due to the high frequency of associated risk factors, i.e., prior history of genotoxic exposure, the presence of additional cytogenetic changes, or both. Identification of prognostic disadvantage might be required for appropriate strategy in managing MDS/AML patients with rare der(1;7) abnormality.

2013 ◽  
Vol 54 (6) ◽  
pp. 1235-1241 ◽  
Author(s):  
Courtney D. DiNardo ◽  
Alexis Ogdie ◽  
Elizabeth O. Hexner ◽  
Noelle V. Frey ◽  
Alison W. Loren ◽  
...  

Leukemia ◽  
2021 ◽  
Author(s):  
Uwe Platzbecker ◽  
Anne Sophie Kubasch ◽  
Collin Homer-Bouthiette ◽  
Thomas Prebet

AbstractMyelodysplastic syndromes (MDS) represent a heterogeneous group of myeloid neoplasms that are characterized by ineffective hematopoiesis, variable cytopenias, and a risk of progression to acute myeloid leukemia. Most patients with MDS are affected by anemia and anemia-related symptoms, which negatively impact their quality of life. While many patients with MDS have lower-risk disease and are managed by existing treatments, there currently is no clear standard of care for many patients. For patients with higher-risk disease, the treatment priority is changing the natural history of the disease by delaying disease progression to acute myeloid leukemia and improving overall survival. However, existing treatments for MDS are generally not curative and many patients experience relapse or resistance to first-line treatment. Thus, there remains an unmet need for new, more effective but tolerable strategies to manage MDS. Recent advances in molecular diagnostics have improved our understanding of the pathogenesis of MDS, and it is becoming clear that the diverse nature of genetic abnormalities that drive MDS demands a complex and personalized treatment approach. This review will discuss some of the challenges related to the current MDS treatment landscape, as well as new approaches currently in development.


2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110184
Author(s):  
Meifang Zhao ◽  
Jingnan Sun ◽  
Shanshan Liu ◽  
Hongqiong Fan ◽  
Yu Fu ◽  
...  

Myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are a heterogeneous group of hematologic malignancies characterized by dysplastic and myeloproliferative overlapping features in the bone marrow and blood. The occurrence of the disease is related to age, prior history of MPN or MDS, and recent cytotoxic or growth factor therapy, but it rarely develops after acute myeloid leukemia (AML). We report a rare case of a patient diagnosed with AML with t(8; 21)(q22; q22) who received systematic chemotherapy. After 4 years of follow-up, MDS/MPN-unclassifiable occurred without signs of primary AML recurrence.


Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. 2742-2751 ◽  
Author(s):  
Miriam Miesner ◽  
Claudia Haferlach ◽  
Ulrike Bacher ◽  
Tamara Weiss ◽  
Katja Macijewski ◽  
...  

Abstract The World Health Organization classification of acute myeloid leukemia (AML) is hierarchically structured and integrates genetics, data on patients' history, and multilineage dysplasia (MLD). The category “AML with myelodysplastic syndrome (MDS)–related changes” (AML-MRC) is separated from “AML not otherwise specified” (AML-NOS) by presence of MLD, MDS-related cytogenetics, or history of MDS or MDS/myeloproliferative neoplasm (MPN). We analyzed 408 adult patients categorized as AML-MRC or AML-NOS. Three-year event-free survival (EFS; median, 13.8 vs 16.0 months) and 3-year overall survival (OS; 45.8% vs 53.9%) did not differ significantly between patients with MLD versus without. However, MLD correlated with preexisting MDS (P < .001) and MDS-related cytogenetics (P = .035). Patients with MLD as sole AML-MRC criterion (AML-MLD-sole; n = 90) had less frequently FLT3 internal tandem duplication (P = .032) and lower median age than AML-NOS (n = 232). Contrarily, patients with AML-NOS combined with AML-MLD-sole (n = 323) had better 3-year EFS (16.9 vs 10.7 months; P = .005) and 3-year OS (55.8% vs 32.5%; P = .001) than patients with history of MDS or MDS/MPN or MDS-related cytogenetics (n = 85). Gene expression analysis showed distinct clusters for AML-MLD-sole combined with AML-NOS versus AML with MDS-related cytogenetics or MDS history. Thus, MLD alone showed no independent clinical effect, whereas cytogenetics and MDS history were prognostically relevant.


2017 ◽  
pp. 1-7 ◽  
Author(s):  
Seth A. Wander ◽  
Robert P. Hasserjian ◽  
Kwadwo Oduro ◽  
Krzysztof Glomski ◽  
Valentina Nardi ◽  
...  

A 44-year-old woman with a prior history of myxoid liposarcoma who was previously treated with radiation, chemotherapy, and resection, was admitted with syncope and pancytopenia. She was diagnosed with a high-grade therapy-related myelodysplastic syndrome and treated with decitabine. Her disease soon progressed to overt acute myeloid leukemia (AML). She was treated with cytotoxic chemotherapy including cytarabine and topotecan, but she was not a candidate for further anthracycline exposure given her prior treatment for sarcoma and concern for cardiotoxicity. Her AML was refractory to two sequential induction regimens. Given that targeted genomic sequencing had revealed a BRAF V600E mutation with a high allelic fraction, she was then placed on combined targeted BRAF/MEK therapy with dabrafenib and trametinib for her refractory disease. This resulted in a dramatic response with clearance of circulating myeloblasts, restoration of normal hematopoiesis, a significant decrease in marrow leukemic burden, and a concordant decrease in the BRAF V600E allelic burden. The response was transient, however, with a rapid increase in circulating blasts a few weeks later. At the time of subsequent progression, four separate KRAS mutations were identified. She died approximately 4 months after her diagnosis from rapidly progressive AML.


Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 186
Author(s):  
Marcus Bauer ◽  
Christoforos Vaxevanis ◽  
Haifa Kathrin Al-Ali ◽  
Nadja Jaekel ◽  
Christin Le Hoa Naumann ◽  
...  

Background: Myelodysplastic syndromes (MDS) are caused by a stem cell failure and often include a dysfunction of the immune system. However, the relationship between spatial immune cell distribution within the bone marrow (BM), in relation to genetic features and the course of disease has not been analyzed in detail. Methods: Histotopography of immune cell subpopulations and their spatial distribution to CD34+ hematopoietic cells was determined by multispectral imaging (MSI) in 147 BM biopsies (BMB) from patients with MDS, secondary acute myeloid leukemia (sAML), and controls. Results: In MDS and sAML samples, a high inter-tumoral immune cell heterogeneity in spatial proximity to CD34+ blasts was found that was independent of genetic alterations, but correlated to blast counts. In controls, no CD8+ and FOXP3+ T cells and only single MUM1p+ B/plasma cells were detected in an area of ≤10 μm to CD34+ HSPC. Conclusions: CD8+ and FOXP3+ T cells are regularly seen in the 10 μm area around CD34+ blasts in MDS/sAML regardless of the course of the disease but lack in the surrounding of CD34+ HSPC in control samples. In addition, the frequencies of immune cell subsets in MDS and sAML BMB differ when compared to control BMB providing novel insights in immune deregulation.


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