Differing clinical features between Japanese and Caucasian patients with myelodysplastic syndromes:Analysis from the International Working Group for Prognosis of MDS

Clinical features of myelodysplastic syndromes (MDS) could be influenced by many factors, such as disease intrinsic factors (e.g., morphologic, cytogenetic, molecular), extrinsic factors (e.g, management, environment), and ethnicity. Several previous studies have suggested such differences between Asian and European/USA countries. In this study, to elucidate potential differences in primary untreated MDS between Japanese (JPN) and Caucasians (CAUC), we analyzed the data from a large international database collected by the International Working Group for Prognosis of MDS (300 and 5838 patients, respectively). JPN MDS were significantly younger with more severe cytopenias, and cytogenetic differences: less del(5q) and more +1/+1q, -1/del(1p), der(1;7), -9/del(9q), del(16q), and del(20q). Although differences in time to acute myeloid leukemia transformation did not occur, a significantly better survival in JPN was demonstrated, even after the adjustment for age and FAB subtypes, especially in lower, but not in higher prognostic risk categories. Certain clinical factors (cytopenias, blast percentage, cytogenetic risk) had different impact on survival and time to transformation to leukemia between the two groups. Although possible confounding events (e.g., environment, diet, and access to care) could not be excluded, our results indicated the existence of clinically relevant ethnic differences regarding survival in MDS between JPN and CAUC patients. The good performance of the IPSS-R in both CAUC and JP patients underlines that its common risk model is adequate for CAUC and JP

Multivariate analysis of febrile neutropenia occurrence in patients with non-Hodgkin lymphoma: data from the INC-EU Prospective Observational European Neutropenia Study

Myelosuppression, particularly febrile neutropenia (FN), are serious dose-limiting toxicities that occur frequently during the first cycle of chemotherapy. Identifying patients most at risk of developing FN might help physicians to target prophylactic treatment with colony-stimulating factor (CSF), in order to decrease the incidence, or duration, of myelosuppression and facilitate delivery of chemotherapy as planned. We present a risk model for FN occurrence in the first cycle of chemotherapy, based on a subgroup of 240 patients with non-Hodgkin lymphoma (NHL) enroled in our European prospective observational study. Eligible patients had an International Prognostic Index of 0–3, and were scheduled to receive a new myelosuppressive chemotherapy regimen with at least four cycles. Clinically relevant factors significantly associated with cycle 1 FN were older age, increasing planned cyclophosphamide dose, a history of previous chemotherapy, a history of recent infection, and low baseline albumin (<35 g/l). Prophylactic CSF use and higher weight were associated with a significant protective effect. The model had high sensitivity (81%) and specificity (80%). Our model, together with treatment guidelines, may rationalise the clinical decision of whether to support patients with CSF primary prophylaxis based on their risk factor profile. Further validation is required

Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma : Long-Term Results of the PRIMA Study

PURPOSE The PRIMA study (ClinicalTrials.gov identifier: NCT00140582) established that 2 years of rituximab maintenance after first-line immunochemotherapy significantly improved progression-free survival (PFS) in patients with follicular lymphoma compared with observation. Here, we report the final PFS and overall survival (OS) results from the PRIMA study after 9 years of follow-up and provide a final overview of safety. METHODS Patients (> 18 years of age) with previously untreated high-tumor-burden follicular lymphoma were nonrandomly assigned to receive one of three immunochemotherapy induction regimens. Responding patients were randomly assigned (stratified by induction regimen, response to induction treatment, treatment center, and geographic region) 1:1 to receive 2 years of rituximab maintenance (375 mg/m(2), once every 8 weeks), starting 8 weeks after the last induction treatment, or observation (no additional treatment). All patients in the extended follow-up provided their written informed consent (data cutoff: December 31, 2016). RESULTS In total, 1,018 patients completed induction treatment and were randomly assigned to rituximab maintenance (n = 505) or observation (n = 513). Consent for the extended follow-up was provided by 607 patients (59.6%) of 1,018 (rituximab maintenance, n = 309; observation, n = 298). After data cutoff, median PFS was 10.5 years in the rituximab maintenance arm compared with 4.1 years in the observation arm (hazard ratio, 0.61; 95% CI, 0.52 to 0.73; P <.001). No OS difference was seen in patients randomly assigned to rituximab maintenance or observation (hazard ratio, 1.04; 95% CI, 0.77 to 1.40; P = .7948); 10-year OS estimates were approximately 80% in both study arms. No new safety signals were observed. CONCLUSION Rituximab maintenance after induction immunochemotherapy provides a significant long-term PFS, but not OS, benefit over observation.Peer reviewe

Hepatitis B Surface Antigen Seropositivity and Low Body Weight Are Correlated with Asymptomatic Neutropenia In the Thai Population

Abstract Abstract 4751 Background The etiology of asymptomatic neutropenia is unknown. We have conducted a community-based study to determine predisposing factors for asymptomatic neutropenia in the Thai population. Method Blood specimens and self-report questionnaires (filled out with assistance from medical personnel) were collected from individuals in Bangkok and 4 surrounding provinces. Asymptomatic neutropenia was defined by an absolute neutrophil count of less than 1.5 × 109/liter, in the absence of any symptoms or known risk factors. Patients with a history of malignancy were excluded. Subjects that met this criterion for neutropenia were examined for the presence of anti-HIV and anti-hepatitis C virus (HCV) antibodies, hepatitis B surface antigen (HBsAg), antinuclear antibody (ANA), rheumatoid factor (RF), thyroid dysfunction, reduced serum ferritin, and reduced serum vitamin B12 and folate; this panel of laboratory tests was also done on control subjects (4 controls for every 1 neutropenic case – see below), which were picked at random from the normal population and were matched for age, sex, site of survey, and underlying disease. Odd ratios (OR) were then computed for significant risk factors. Results Overall, 7,180 individuals were included; 28 had neutropenia (0.39%, 95% CI 0.25–0.53). Based on answers to the questionnaire, the only factor correlating with neutropenia was low body weight (body mass index &lt; 18.5 kg/m2, p = 0.015); age, sex, site and period of survey, underlying disease, medications, herbal ingestion, food supplement, radiation exposure, family history of hematologic disease, alcohol consumption, history of drug abuse or exposure to chemical substance had no significant association with neutropenia. Additional tests on 25 of the neutropenic cases revealed positive findings for HBsAg (20%), anti-HCV antibody (12%), ANA (16%), RF (4%), hypothyroidism (4%), hyperthyroidism (14%) and hypoferritinemia (24%); none showed anti-HIV positivity, or low levels of serum vitamin B12 and folate. Of the 100 normal controls, 4% showed seropositive for HBsAg. HBsAg positivity was thus the significant risk factor associated with neutropenia (OR 6.0, 95%CI 1.48–24.34, p = 0.012). Conclusion HBsAg seropositivity is strongly associated with asymptomatic neutropenia in the Thai population. Low body weight is also correlated with the disorder, perhaps as a result of subtle nutritional deficiencies. Possible mechanisms that underlie neutropenia are currently being explored. Disclosures: No relevant conflicts of interest to declare. </jats:sec