The potential role of hematocrit control on symptom burden among polycythemia vera patients: Insights from the CYTO-PV and MPN-SAF patient cohorts.

Current guidelines suggest that polycythemia vera (PV) patients maintain a strict hematocrit less than 45%. However, to date, little is known about the relationship between HCT control and PV- related symptom burden. In this study, PV patient data was analyzed from the CYTO PV trial (n = 224) and the MPN-SAF study cohort (n = 645). No significant differences in symptom burden were seen at the 6 and 12 month follow-up when evaluating prospective hematocrit control in the CYTO PV cohort. Patients in the MPN-SAF cohort with a worst item score of greater than 5/10 on the Myeloproliferative Neoplasm Symptom Total Symptom Score had a significantly lower mean hematocrit (p = .0376). These findings suggest a relationship between traditional aggressive therapy for PV and increased symptom burden with prolonged therapy. Thus, symptom burden should be considered when contemplating the choice of therapy in the second-line setting for PV.

Prognostic impact of metabolic syndrome in patients with chronic heart failure: data from GISSI-HF trial.

OBJECTIVES: The adverse prognostic impact of metabolic syndrome (METS) in unselected populations and in patients with coronary heart disease has been previously shown. The aim of the current analysis was to evaluate the impact of METS on prognosis in chronic heart failure (HF). METHODS: International Diabetes Federation criteria were used for the diagnosis of METS. Adjusted Cox regression models with all-cause and HF death as outcomes were fitted in 6648 patients enrolled in GISSI-HF trial with no missing values for the variables of interest. RESULTS: Risk of all-cause and HF death was significantly reduced in patients with METS compared to patients without METS (HR: 0.83, 95% CI: 0.72 to 0.95, p=0.005; HR: 0.76, 95% CI: 0.59 to 0.98, p=0.031; respectively). As compared with patients with no METS and no type 2 diabetes mellitus (DM), the risk of all-cause and HF death was significantly lower in patients with METS and no DM (HR: 0.76, 95% CI: 0.62 to 0.95, p=0.015; HR: 0.65, 95% CI: 0.42 to 0.99, p=0.046; respectively), whereas it was significantly increased in patients with DM and no METS (HR: 1.34, 95% CI: 1.21 to 1.48, p<0.001; HR: 1.44, 95% CI: 1.21 to 1.72, p<0.001; respectively). Patients with METS and DM showed no difference for risk of total and HF death compared with patients with no METS and no DM (HR: 1.03, 95% CI: 0.87 to 1.21, p=0.762; HR: 0.99; 95% CI: 0.73 to 1.35; p=0.963; respectively). CONCLUSIONS: METS is associated with reduced all-cause and HF mortality in patients with HF. HF patients with DM without METS are at the highest risk of mortality, whereas METS attenuates mortality risk in HF patients with DM.

Cardiovascular events and intensity of treatment in polycythemia vera.

BACKGROUND: Current treatment recommendations for patients with polycythemia vera call for maintaining a hematocrit of less than 45%, but this therapeutic strategy has not been tested in a randomized clinical trial. METHODS: We randomly assigned 365 adults with JAK2-positive polycythemia vera who were being treated with phlebotomy, hydroxyurea, or both to receive either more intensive treatment (target hematocrit, <45%) (low-hematocrit group) or less intensive treatment (target hematocrit, 45 to 50%) (high-hematocrit group). The primary composite end point was the time until death from cardiovascular causes or major thrombotic events. The secondary end points were cardiovascular events, cardiovascular hospitalizations, incidence of cancer, progression to myelofibrosis, myelodysplasia or leukemic transformation, and hemorrhage. An intention-to-treat analysis was performed. RESULTS: After a median follow-up of 31 months, the primary end point was recorded in 5 of 182 patients in the low-hematocrit group (2.7%) and 18 of 183 patients in the high-hematocrit group (9.8%) (hazard ratio in the high-hematocrit group, 3.91; 95% confidence interval [CI], 1.45 to 10.53; P=0.007). The primary end point plus superficial-vein thrombosis occurred in 4.4% of patients in the low-hematocrit group, as compared with 10.9% in the high-hematocrit group (hazard ratio, 2.69; 95% CI, 1.19 to 6.12; P=0.02). Progression to myelofibrosis, myelodysplasia or leukemic transformation, and bleeding were observed in 6, 2, and 2 patients, respectively, in the low-hematocrit group, as compared with 2, 1, and 5 patients, respectively, in the high-hematocrit group. There was no significant between-group difference in the rate of adverse events. CONCLUSIONS: In patients with polycythemia vera, those with a hematocrit target of less than 45% had a significantly lower rate of cardiovascular death and major thrombosis than did those with a hematocrit target of 45 to 50%. (Funded by the Italian Medicines Agency and others; ClinicalTrials.gov number, NCT01645124, and EudraCT number, 2007-006694-91.).

Validation of the Hematopoietic Cell Transplantation-Specific Comorbidity Index: a prospective, multicenter GITMO study.

The development of tools for the prediction of nonrelapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (HSCT) would offer a major guidance in the therapeutic decision. Recently, the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) has been associated with increased NRM risk in several retrospective studies, but its clinical utility has never been demonstrated prospectively in an adequately sized cohort. To this aim, we prospectively evaluated a consecutive cohort of 1937 patients receiving HSCT in Italy over 2 years. HCT-CI was strongly correlated with both 2-year NRM (14.7%, 21.3%, and 27.3% in patients having an HCT-CI score of 0, 1-2, and ≥ 3, respectively) and overall survival (56.4%, 54.5%, and 41.3%, respectively). There was an excellent calibration between the predicted and observed 2-year NRM in patients having an HCT-CI score of 0 and 1-2, whereas in the ≥ 3 group the predicted NRM overestimated the observed NRM (41% vs 27.3%). HCT-CI alone was the strongest predictor of NRM in patients with lymphoma, myelodysplastic syndrome, and acute myeloid leukemia in first remission (c-statistics 0.66, 064, and 0.59, respectively). We confirm the clinical utility of the HCT-CI score that could also identify patients at low NRM risk possibly benefiting from an HSCT-based treatment strategy.