Yacoub et al report excellent responses to pegylated interferon alfa-2a in patients with hydroxyurea-resistant/intolerant polycythemia vera or essential thrombocythemia.

OBJECTIVES To measure short-term changes in physical and cognitive function and emotional well-being of older adults receiving intensive chemotherapy for acute myeloid leukemia (AML). DESIGN Prospective observational study. SETTING Single academic institution. PARTICIPANTS Individuals aged 60 and older with newly diagnosed AML who received induction chemotherapy (N = 49, mean age 70 ± 6.2, 56% male). MEASUREMENTS Geriatric assessment (GA) was performed during inpatient examination for AML and within 8 weeks after hospital discharge after induction chemotherapy. Measures were the Pepper Assessment Tool for Disability (activity of daily living, instrumental activity of daily living (IADL), mobility questions), Short Physical Performance Battery (SPPB), grip strength, Modified Mini-Mental State examination, Center for Epidemiologic Studies Depression Scale, and the Distress Thermometer. Changes in GA measures were assessed using paired t-tests. Analysis of variance models were used to evaluate relationships between GA variables and change in function over time. RESULTS After chemotherapy, IADL dependence worsened (mean 1.4 baseline vs 2.1 follow-up, P < .001), as did mean SPPB scores (7.5 vs 5.9, P = .02 for total). Grip strength also declined (38.9 ± 7.7 vs 34.2 ± 10.3 kg, P < .001 for men; 24.5 ± 4.8 vs 21.8 ± 4.7 kg, P = .007 for women). No significant changes in cognitive function (mean 84.7 vs 85.1, P = .72) or depressive symptoms (14.0 vs. 11.3, P = .11) were detected, but symptoms of distress declined (5.0 vs 3.2, P < .001). Participants with depressive symptoms at baseline and follow-up had greater declines in SPPB scores those without at both time points. CONCLUSIONS Short-term survivors of intensive chemotherapy for AML had clinically meaningful declines in physical function. These data support the importance of interventions to maintain physical function during and after chemotherapy. Depressive symptoms before and during chemotherapy may be linked to potentially modifiable physical function declines.

Objective Interferon α (IFNα) therapy leads to hematological remissions and a reduction of the JAK2V617F allele burden in patients with polycythemia vera (PV). In this study, the cellular target by which IFNα affects hematopoiesis in PV patients was evaluated. Materials and Methods CD34+ cells were isolated from normal bone marrow and the peripheral blood of patients with PV and were treated in vitro with each of the three commercially available forms of IFNα: IFNα 2b, pegylated IFN α 2a (Peg-IFNα 2a) and pegylated IFN α 2b (Peg-IFNα 2b). Results Each form of IFNα was equally potent in suppressing hematopoietic colony formation by normal CD34+ cells, but Peg-IFNα 2a and IFNα 2b were more effective than Peg-IFNα 2b in inhibiting BFU-E derived colony formation by PV CD34+ cells. In addition, exposure of PV CD34+ cells to equal doses of Peg-IFNα 2a and IFNα 2b resulted in a 38–40% reduction in the proportion of JAK2V617F-positive hematopoietic progenitor cells (HPC), while equivalent doses of Peg-IFNα 2b did not reduce the number of malignant HPC. Further studies explored the mechanism by which IFNα induced PV HPC growth inhibition. Treatment of Peg-IFNα 2a increased the rate of apoptosis of PV CD34+ cells and the phosphorylation/activation of p38 MAPK in PV CD34+ cells, while the p38-specific inhibitor SB203580 reversed the growth inhibition and apoptosis induced by Peg-IFNα 2a. Conclusion These data suggest that low doses of IFNα selectively and directly suppress PV JAK2V617F HPC and that these agents act through the p38 MAP kinase pathway.

The goal of therapy for essential thrombocythemia (ET) and polycythemia vera (PV) patients is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) are the most frequently used cytoreductive options for ET and PV patients at high-risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment naïve, high-risk ET/PV patients. The primary endpoint was complete response (CR) rate at 12 months. A total of 168 patients were treated for a median of 81.0 weeks. CR for HU was 37% and 35% for PEG (p=0.80) at 12 months. At 24/36 months, CR was 20%/17% for HU and 29%/33% for PEG. PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU. Thrombotic events and disease progression were infrequent in both arms, while grade 3/4 adverse events were more frequent with PEG (46% vs. 28%). At 12 months of treatment there was no significant difference in CR rates between HU and PEG. This study indicates that PEG and HU are both effective treatments for PV and ET. With longer treatment PEG was more effective in normalizing blood counts and reducing driver mutation burden, while HU produced more histopathologic responses. Despite these differences, both agents did not differ in limiting thrombotic events and disease progression in high-risk ET/PV patients. (Funded by the National Cancer Institute, 5P01CA108671-09; clinicaltrials.gov number (NCT01259856)