Treatment of aggressive B-cell lymphoma in elderly patients: influence of single nucleotide polymorphisms affecting pharmacodynamics of chemotherapeutics.

Clinical and/or biological risk factors are needed to identify elderly patients with aggressive B-cell lymphoma able to receive full-dose R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) treatment. We present a retrospective analysis of 83 patients≥75 years of age (range: 75-97) who were diagnosed with aggressive B cell lymphoma between 2004 and 2011 in our clinic. R-CHOP-like therapy was administered in 82% of these patients resulting in a median overall survival of 54 months. A median cumulative dose of 226 mg/m2 doxorubicin and a median of six cycles were applied in these patients. Two genotypes of the CBR3 and MLH1 genes affecting the metabolism of cytostatics identified a subgroup with a favorable prognosis (median overall survival not reached vs. 30 months, p=0.01). A treatment strategy aiming at full-dose R-CHOP was feasible and resulted in an encouraging treatment outcome in patients≥75 years. Pharmacogenetic parameters, if independently validated, may be helpful in elderly patients.

Complications of 5-azacytidine: Three cases of severe ischemic colitis in elderly patients with myelodysplastic syndrome.

5-Azacytidine (5-AZA) was the first drug to be approved for the treatment of high-risk myelodysplastic syndrome (MDS). The adverse event profile of this drug appears favorable compared with the conventional intensive chemotherapy that is used for MDS or acute myeloid leukemia. However, uncommon adverse events may have remained undetected in the limited number of patients that have been treated to date. The present study describes three cases/66.8 person-years (4,491 cases/100,000 person-years) of severe ischemic colitis in a single center cohort of 95 patients who were consecutively treated using subcutaneous 5-AZA. The results demonstrated a much higher incidence of colitis compared with the rates in the general population or in patients of greater ages and co-morbidities. The present study investigated whether the combination of anemia and constipation due to the co-medication of 5-HT3 receptor antagonists may explain the three cases of ischemic colitis.

Azacitidine in patients with WHO-defined AML - results of 155 patients from the Austrian Azacitidine Registry of the AGMT-Study Group.

OBJECTIVE: The Austrian Azacitidine Registry is a multi-center database (ClinicalTrials.gov: NCT01595295). The nature and intent of the registry was to gain a comprehensive view of the use, safety and efficacy of the drug in a broad range of AML-patients treated in real-life scenarios. PATIENTS AND METHODS: The sole inclusion criteria were the diagnosis of WHO-AML and treatment with at least one dose of azacitidine. No formal exclusion criteria existed. A total of 155 AML-patients who were mostly unfit/ineligible for intensive chemotherapy, or had progressed despite conventional treatment, were included. True ITT-analyses and exploratory analyses regarding the potential prognostic value of baseline-variables/performance-/comorbidity-/risk-scores on overall survival (OS), were performed. RESULTS: In this cohort of 155 pretreated (60%), and/or comorbid (87%), elderly (45% ≥75 years) AML-patients, azacitidine was well tolerated and efficacious, with an overall response rate (CR, mCR, PR, HI) of 45% in the total cohort (ITT) and 65% in patients evaluable according to IWG-criteria, respectively. Pre-treatment with conventional chemotherapy (P = .113), age ≤/>80 years (P = .853), number of comorbidities (P = .476), and bone marrow (BM) blast count (P = .663) did not influence OS. In multivariate analysis hematologic improvement alone (without the requirement of concomitant bone marrow blast reduction), although currently not regarded as a standard form of response assessment in AML, was sufficient to confer OS benefit (18.9 vs. 6.0 months; P = .0015). Further deepening of response after first response was associated with improved OS (24.7 vs. 13.7 months; P < .001). CONCLUSIONS: In this large cohort of AML-patients treated with azacitidine, age >80 years, number of comorbidities and/or BM-blasts >30% did not adversely impact OS.