Outcome of patients with low-risk and intermediate-1-risk myelodysplastic syndrome after hypomethylating agent failure: a report on behalf of the MDS Clinical Research Consortium.

Background: The hypomethylating agents (HMAs) azacitidine and decitabine are most commonly used to treat patients with higher-risk myelodysplastic syndromes (MDS). To the authors' knowledge, the prognosis of patients with low-risk and intermediate-1-risk MDS by the International Prognostic Scoring System (IPSS) after HMA failure has not been explored comprehensively.

Methods: The clinical characteristics and treatment outcome of 438 patients with low-risk and intermediate-1-risk MDS who were treated with HMAs were retrospectively analyzed.

Recent developments in myelodysplastic syndromes.

Once thought to be rare disorders, the myelodysplastic syndromes (MDS) are now recognized as among the most common hematological neoplasms, probably affecting >30 000 patients per year in the United States. US regulatory approval of azacitidine, decitabine, and lenalidomide between 2004 and 2006 seemed to herald a new era in the development of disease-modifying therapies for MDS, but there have been no further drug approvals for MDS indications in the United States in the last 8 years. The available drugs are not curative, and few of the compounds that are currently in development are likely to be approved in the near future.

TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients.

Only a minority of myelodysplastic syndrome (MDS) patients respond to hypomethylating agents (HMAs), but strong predictors of response are unknown. We sequenced 40 recurrently mutated myeloid malignancy genes in tumor DNA from 213 MDS patients collected before treatment with azacitidine (AZA) or decitabine (DEC). Mutations were examined for association with response and overall survival.

The leukemias: a half-century of discovery.

Studies of the leukemias in the laboratory and in the clinic have generated many new concepts and therapies that will undoubtedly continue to be rapidly applied to the other forms of systemic cancer, particularly the concept of narrowly targeted personalized therapy that has proven so effective in CML. It seems likely that other subtypes of leukemia will eventually approach the success achieved with APL, CML, and pediatric ALL.

Somatic mutations predict poor outcome in patients with myelodysplastic syndrome after hematopoietic stem-cell transplantation.

Purpose: Recurrently mutated genes in myelodysplastic syndrome (MDS) are pathogenic drivers and powerfully associated with clinical phenotype and prognosis. Whether these types of mutations predict outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) in patients with MDS is not known.

Patients And Methods: We used massively parallel sequencing to examine tumor samples collected from 87 patients with MDS before HSCT for coding mutations in 40 recurrently mutated MDS genes.

De novo acute myeloid leukemia with 20-29% blasts is less aggressive than acute myeloid leukemia with ≥30% blasts in older adults: a Bone Marrow Pathology Group study.

It is controversial whether acute myeloid leukemia (AML) patients with 20-29% bone marrow (BM) blasts, formerly referred to as refractory anemia with excess blasts in transformation (RAEBT), should be considered AML or myelodysplastic syndrome (MDS) for the purposes of treatment and prognostication. We retrospectively studied 571 de novo AML in patients aged >50 years, including 142 RAEBT and 429 with ≥30% blasts (AML30), as well as 151 patients with 10-19% BM blasts (RAEB2). RAEBT patients were older and had lower white blood count, but higher hemoglobin, platelet count, and karyotype risk scores compared to AML30, while these features were similar to RAEB2.

A phase 2, randomized, double-blind, multicenter study comparing siltuximab plus best supportive care (BSC) with placebo plus BSC in anemic patients with International Prognostic Scoring System low- or intermediate-1-risk myelodysplastic syndrome.

Interleukin-6 (IL-6) may play an important role in the pathophysiology of anemia of inflammation associated with myelodysplastic syndrome (MDS). This double-blind, placebo-controlled, phase 2 study assessed the efficacy and safety of siltuximab, a chimeric anti-IL-6 monoclonal antibody, in patients with low- and intermediate-1-risk MDS who require transfusions for MDS anemia. Patients were randomized in a 2:1 ratio to siltuximab 15 mg kg(-1) every 4 weeks + best supportive care (BSC) or placebo + BSC for 12 weeks.

Should the ASCO/ASH Guidelines for the use of intravenous iron in cancer- and chemotherapy-induced anemia be updated?

Coadministration of intravenous (IV) iron improves responses to erythropoiesis-stimulating agents (ESAs) in the treatment of cancer-associated (CAA) and chemotherapy-induced anemia (CIA). Twelve prospective studies have demonstrated synergy between parenteral iron and ESAs, with variable degrees of improved hemoglobin (Hgb) response rates, shorter times to target Hgb levels, and a lower ESA dose required for equivalent Hgb responses. Clinically significant adverse events (AEs) with currently available IV iron products are uncommon.

High cancer drug prices in the United States: reasons and proposed solutions.

The increase in cancer drug prices in the last 15 years has many contributing factors and is harming our patients and our health care system. It represents to many cancer experts a crossing of a moral line between reasonable profits and profiteering, in a situation involving a human catastrophe: patients who have developed cancer, and who may die because they cannot afford the treatment. With typical out-of-pocket expenses of 20% to 30%, the financial burden of cancer treatment would be $20,000 to 30,000 a year, nearly half of the average annual household income in the United States.

Disparity in perceptions of disease characteristics, treatment effectiveness, and factors influencing treatment adherence between physicians and patients with myelodysplastic syndromes.

Background: Previous studies have suggested that many patients with myelodysplastic syndromes (MDS) have an incomplete understanding of their disease, which may influence adherence to prescribed regimens and outcomes.

Methods: To better understand physician and patient perceptions about MDS and MDS therapy, the authors conducted 2 surveys in February 2012: 1 for patients with MDS and 1 for health care professionals (HCPs) who cared for patients with MDS. Patient and HCP surveys consisted of 57 and 49 questions, respectively, assessing understanding of MDS, perceptions of specific treatments, barriers to treatment adherence, and treatment experience.

NOTCH2 and FLT3 gene mis-splicings are common events in patients with acute myeloid leukemia (AML): new potential targets in AML.

Our previous studies revealed an increase in alternative splicing of multiple RNAs in cells from patients with acute myeloid leukemia (AML) compared with CD34(+) bone marrow cells from normal donors. Aberrantly spliced genes included a number of oncogenes, tumor suppressor genes, and genes involved in regulation of apoptosis, cell cycle, and cell differentiation. Among the most commonly mis-spliced genes (>70% of AML patients) were 2, NOTCH2 and FLT3, that encode myeloid cell surface proteins.

When is iron overload deleterious, and when and how should iron chelation therapy be administered in myelodysplastic syndromes?

Iron overload in MDS starts even before patients become red-blood cell transfusion dependent, because disease-associated ineffective erythropoiesis suppresses hepcidin production in the liver and thus causes unrestrained iron absorption in the duodenum. However, the main cause of iron overload is regular transfusion therapy, which in MDS is associated with a risk of unclear magnitude for iron-related complications. Iron deposition in tissues can now be detected with non-invasive techniques such as T2* MRI.

Biomedical system dynamics to improve anemia control with darbepoetin alfa in long-term hemodialysis patients.

Objective: To determine the value of a biomedical system dynamics (BMSD) approach for optimization of anemia management in long-term hemodialysis patients because elevated hemoglobin levels and high doses of erythropoiesis-stimulating agents (ESAs) may negatively affect survival in this population.

Patients And Methods: A model of erythropoiesis and its response to ESAs on the basis of a BMSD method (Mayo Clinic Anemia Management System [MCAMS]) was developed. Thereafter, an open-label, prospective, nonrandomized practice quality improvement project was performed with retrospective analysis in 8 community-based outpatient hemodialysis facilities.