David P. Steensma

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No abstract text is available yet for this article.

DNA methyltransferase inhibitors (DNMTIs) for patients with higher risk myelodysplastic syndromes (HR-MDS) have low complete remission rates and are not curative. Early DNMTI combination clinical trials in HR-MDS are often termed "promising", but many randomized trials subsequently failed to show benefit. Clearer understanding when a combination is likely to improve upon DNMTI monotherapy would inform randomized studies. We reviewed MDS azacitidine or decitabine monotherapy studies. We collected baseline demographics including IPSS risk, DNMTI, disease characteristics; and response variables including survival, marrow and hematologic responses...

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Clonal hematopoiesis (CH) - a biological state in which one or a small number of hematopoietic stem or progenitor cells contribute disproportionately to blood cell production, usually as a result of somatic gene mutations in the stem cells - is often considered to be a precursor to myeloid neoplasia, especially myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). However, the majority of people with CH never develop an overt myeloid neoplasm, and CH can be a precursor to lymphoid cancers as well as myeloid neoplasms...

Clonal hematopoiesis (CH) is associated with adverse outcomes in patients with non-Hodgkin lymphoma (NHL) and multiple myeloma undergoing autologous stem cell transplantation. Still, its implications for patients with indolent NHL have not been well studied. We report the prevalence of CH in patients with Waldenström macroglobulinemia (WM) and its association with clinical outcomes. To unambiguously differentiate CH mutations from those in the WM clone, CH was defined by the presence of somatic mutations in DNMT3A, TET2, or ASXL1 (DTA) and was detected in 14% of 587 patients with IgM monoclonal gammopathy of undetermined significance (MGUS), smoldering WM (SWM) or WM...

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Myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) is characterized by anemia, ring sideroblast erythroid precursors, and persistent thrombocytosis. Case reports suggest lenalidomide may be effective in treating MDS/MPN-RS-T. We evaluated a large series of patients with MDS/MPN-RS-T to compare hematological improvement (HI) response rates among different drug therapies including lenalidomide. We identified 167 patients with MDS/MPN-RS-T. Among the patients tested, 84% had SF3B1 mutations and 43% had JAK2 V617F mutations...

PURPOSE: Patients with myelodysplastic syndromes (MDS) have a survival that can range from months to decades. Prognostic systems that incorporate advanced analytics of clinical, pathologic, and molecular data have the potential to more accurately and dynamically predict survival in patients receiving various therapies. METHODS: A total of 1,471 MDS patients with comprehensively annotated clinical and molecular data were included in a training cohort and analyzed using machine learning techniques...

People who have advanced myelodysplastic syndromes (MDS) may live longer if they get a bone marrow transplant (BMT) instead of other therapies. However, only 15% of people with MDS actually get BMT. Experts say community physicians and transplant physicians should team up with insurance companies and patient advocacy groups to 1) spread this news about lifesaving advances in BMT, 2) ensure that everyone can afford health care, 3) provide emotional support for patients and families, 4) help patients and families get transportation and housing if they need to travel for transplant, and 5) improve care for people of under-represented racial and ethnic backgrounds...

PURPOSE: Chronic myelomonocytic leukemia (CMML) is a rare leukemia characterized by peripheral monocytosis with no disease-modifying therapies. CMML cells are uniquely hypersensitive to granulocyte-macrophage colony-stimulating factor (GM-CSF) and robustly engraft in immunocompromised mice that secrete human cytokines. To leverage these unique biological features, we conducted an integrated human and murine study evaluating ruxolitinib, a JAK1/2 inhibitor that potently downregulates intracellular GM-CSF signaling...

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We conducted a phase I clinical trial of H3B-8800, an oral small molecule that binds Splicing Factor 3B1 (SF3B1), in patients with MDS, CMML, or AML. Among 84 enrolled patients (42 MDS, 4 CMML and 38 AML), 62 were red blood cell (RBC) transfusion dependent at study entry. Dose escalation cohorts examined two once-daily dosing regimens: schedule I (5 days on/9 days off, range of doses studied 1-40 mg, n = 65) and schedule II (21 days on/7 days off, 7-20 mg, n = 19); 27 patients received treatment for ≥180 days...

Hypomethylating agents (HMAs) are the standard of care for higher risk MDS (HR-MDS) patients. The current dogma is to begin HMA therapy in all HR-MDS patients at the time of initial diagnosis. We investigated the impact of the timing of HMA initiation among HR-MDS patients presenting with adequate blood counts to discern the possible benefit of early treatment based solely on disease risk. We identified 320 HR-MDS patients with adequate hematopoiesis who were treated with HMA. The complete response rates were 21%, 26%, 23%, and 7% respectively for patients treated within 30, 31-60, 61-90, and more than 90 days from time of diagnosis ( p =...

Stamp Vignettes focus on biographical details and accomplishments related to science and medicine, and not individual views and prejudices except when they had a major impact on the subject's life. The authors of Stamp Vignettes do not intend to imply any endorsement of such views when discussing a Stamp Vignette on Medical Science.

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Patients with myelodysplastic syndromes (MDSs) display severe anemia but the mechanisms underlying this phenotype are incompletely understood. Right open-reading-frame kinase 2 (RIOK2) encodes a protein kinase located at 5q15, a region frequently lost in patients with MDS del(5q). Here we show that hematopoietic cell-specific haploinsufficient deletion of Riok2 (Riok2f/+ Vav1cre ) led to reduced erythroid precursor frequency leading to anemia. Proteomic analysis of Riok2f/+ Vav1cre erythroid precursors suggested immune system activation, and transcriptomic analysis revealed an increase in p53-dependent interleukin (IL)-22 in Riok2f/+ Vav1cre CD4+ T cells (TH 22)...