Activity of azacitidine in chronic myelomonocytic leukemia.

BACKGROUND: Hypomethylating drugs are useful in the management of myelodysplastic syndrome (MDS). Two of these drugs, azacitidine and decitabine, have received FDA approval for the treatment of MDS and chronic myelomonocytic leukemia (CMML). However, phase 2 and 3 studies that assessed these agents in MDS included only a small number of patients with CMML. The objective of this study was to evaluate the efficacy and safety of azacitidine in the treatment of CMML. METHODS: The records of thirty-eight patients diagnosed with CMML and treated with azacitidine at our institution were reviewed. Azacitidine was administered at 75 mg/m(2) /day for 7 days or 100 mg/m(2) /day for 5 days every 4 weeks. Patients who received at least 1 cycle of the drug were considered evaluable for response. RESULTS: Response was assessed by the modified International Working Group (IWG) criteria. The overall response rate was 39% (14 of 36); complete response (CR) rate was 11% (4 of 36); partial response (PR) rate was 3% (1 of 36); hematologic improvement (HI) was 25% (9 of 36). The median overall survival was 12 months. There was a statistically significant overall survival advantage in responders compared with nonresponders: 15.5 months versus 9 months, respectively (P = .04). Treatment was generally well tolerated. One of 2 patients had complete resolution of a skin rash that was due to monocytic infiltration. CONCLUSIONS: Azacitidine is active in the treatment of CMML. The therapy-associated toxicity is acceptable. Our results support further investigation of azacitidine in CMML, particularly in combination with other agents.

An examination of educational gaps in the diagnosis and treatment of myelodysplastic syndromes.

BACKGROUND: Myelodysplastic syndromes (MDS) comprise a heterogeneous group of hematologic malignancies, with an incidence rate of 3.4 cases per 100,000 in the United States. MDS affects patients predominantly over 60 years of age. As these syndromes are not well understood by many medical practitioner, patients with MDS may be underrecognized or underdiagnosed. The availability of new MDS treatment options further establishes the need to more closely assess gaps in clinical practice and underscores the necessity to develop educational activities to address those gaps. METHODS: A multidisciplinary panel was convened to examine current educational needs and gaps. A group consensus approach incorporating a modified nominal group technique was utilized to prioritize and review needs identified in the pre-meeting survey and to evaluate data provided by panelists prior to the meeting. RESULTS: The panel identified and prioritized seven educational areas of need: (1) MDS disease awareness, (2) diagnosis, (3) classification and risk stratification, (4) treatment issues, (5) referral to stem cell transplantation or new treatment protocols, (6) clinical monitoring and toxicity management, and (7) translation of new data into patient care. CONCLUSIONS: In-depth knowledge is critical to the timely diagnosis and optimal care of MDS patients. A number of key educational needs exist. Educational programs should be practical in orientation to integrate data into practice, and they should be tailored for the intended audience. In addition, an effective educational program must be easily applied by participants.

Recent advances in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal bone marrow disorders characterized by both bone marrow failure and a propensity for development of acute myeloid leukemia. The incidence of these conditions has risen sharply over the past several years, making them the most common malignant bone marrow disorders. While the majority of patients are diagnosed with low-grade disease, approximately two-thirds will succumb to complications of peripheral blood cytopenias or progression to acute leukemia. In recent years, there has been striking progress in our understanding of the pathogenesis of these disorders. For example, the recognition of the roles of angiogenesis and cytokine abnormalities in the development of these diseases led to clinical trials with agents such as thalidomide, which yielded encouraging erythroid responses. Subsequent work with the thalidomide derivative lenalidomide resulted in marked erythroid and cytogenetic responses in individuals with the 5q- abnormality. Additionally, the identification of hypermethylation as an important aspect in the pathogenesis of these and other hematological diseases led to clinical trials utilizing the demethylating agents azacitidine and decitibine. These agents are now known to result in trilineage responses in 30% to 50% of patients with MDS with as many as 20% achieving partial or complete remissions. These results have altered the natural history of these diseases in a significant number of patients. Investigators anticipate that further studies with tyrosine kinase, histone deacetylase, and farnesyl transferase inhibitors will contribute to already promising attempts to reverse or block the pathogenesis of these diseases. Other novel agents are being evaluated as investigators continue to make progress for patients affected by these disorders.

Treatment of acute myelogenous leukemia with outpatient azacitidine.

BACKGROUND: Patients older than 55 years of age with acute myelogenous leukemia (AML) are less likely to achieve complete remission and more likely to experience toxicity with conventional induction chemotherapy than younger patients. Azacitidine administered in the outpatient setting is well tolerated and can induce complete hematological remission in patients with myelodysplastic syndromes (MDS). At higher doses, azacitidine has activity in AML. METHODS: Twenty patients were retrospectively identified who had been treated with azacitidine with bone marrow blast counts between 21 and 38%. Patients with blast counts up to 29% were initially treated as MDS, but by WHO now meet criteria for AML. Patients with blast counts over 29% were treated with azacitidine after being deemed poor candidates for induction chemotherapy. Azacitidine 75 mg/m2/day was administered subcutaneously for 7 days every 4 weeks, which was defined as 1 cycle. RESULTS: The overall response rate was 60% (12/20): complete response (CR; n = 4; 20%); partial response (PR; n = 5; 25%); hematologic improvement (HI; n = 3; 15%). The median survival of responders was 15+ months compared with 2.5 months for nonresponders (P = .009). During therapy, responders had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or 0. The most common toxic event was infection (n = 8). Four patients were hospitalized during the first cycle of treatment. CONCLUSIONS: Azacitidine administered in the outpatient setting can induce remission in AML. The therapy is well tolerated and might be an alternative for patients unlikely to tolerate standard induction chemotherapy.