Purpose Myeloproliferative neoplasm (MPN) symptoms are troublesome to patients, and alleviation of this burden represents a paramount treatment objective in the development of MPN-directed therapies. We aimed to assess the utility of an abbreviated symptom score for the most pertinent and representative MPN symptoms for subsequent serial use in assessing response to therapy. Patients and Methods The Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (MPN-SAF TSS) was calculated as the mean score for 10 items from two previously validated scoring systems. Questions focus on fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. Results MPN-SAF TSS was calculable for 1,408 of 1,433 patients with MPNs who had a mean score of 21.2 (standard deviation [SD], 16.3). MPN-SAF TSS results significantly differed among MPN disease subtypes (P < .001), with a mean of 18.7 (SD, 15.3), 21.8 (SD, 16.3), and 25.3 (SD, 17.2) for patients with essential thrombocythemia, polycythemia vera, and myelofibrosis, respectively. The MPN-SAF TSS strongly correlated with overall quality of life (QOL; r = 0.59; P < .001) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) functional scales (all P < .001 and absolute r ≥ 0.50 except social functioning r = 0.48). No significant trends were present when comparing therapy subgroups. The MPN-SAF TSS had excellent internal consistency (Cronbach's α = .83). Factor analysis identified a single underlying construct, indicating that the MPN-SAF TSS is an appropriate, unified scoring method. Conclusion The MPN-SAF TSS is a concise, valid, and accurate assessment of MPN symptom burden with demonstrated clinical utility in the largest prospective MPN symptom study to date. This new prospective scoring method may be used to assess MPN symptom burden in both clinical practice and trial settings.
MABLE investigated the efficacy and safety of rituximab plus bendamustine or rituximab plus chlorambucil in fludarabine-ineligible patients with chronic lymphocytic leukemia. Patients received rituximab plus bendamustine or rituximab plus chlorambucil every four weeks for six cycles. Rituximab plus chlorambucil-treated patients without a complete response after Cycle 6 received chlorambucil monotherapy for at least six additional cycles or until complete response. The primary endpoint was complete response rate (confirmed by bone marrow biopsy) after Cycle 6 in first-line patients. Secondary endpoints included progression-free survival, overall survival, minimal residual disease, and safety. Overall, 357 patients were randomized (rituximab plus bendamustine, n=178; rituximab plus chlorambucil, n=179; intent-to-treat population), including 241 first-line patients (n=121 and n=120, respectively); 355 patients received treatment (n=177 and n=178, respectively; safety population). In first-line patients, complete response rate after Cycle 6 (rituximab plus bendamustine, 24%; rituximab plus chlorambucil, 9%; P=0.002) and median progression-free survival (rituximab plus bendamustine, 40 months; rituximab plus chlorambucil, 30 months; P=0.003) were higher with rituximab plus bendamustine than rituximab plus chlorambucil. Overall response rate and overall survival were not different. In first-line patients with a complete response, minimal residual disease-negativity was higher with rituximab plus bendamustine than rituximab plus chlorambucil (66% vs. 36%). Overall adverse event incidence was similar (rituximab plus bendamustine, 98%; rituximab plus chlorambucil, 97%). Rituximab plus bendamustine may be a valuable first-line option for fludarabine-ineligible patients with chronic lymphocytic leukemia.
Recently, a Jak2V617F mutation has been described in the vast majority of patients with polycythemia vera (PV) as well as in subsets of patients with essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). The question arises whether this mutation is observed in those patients with ET and IMF who have also displayed previously described molecular markers, notably the ability to form endogenous erythroid colonies (EECs), overexpression of polycythemia rubra vera 1 (PRV-1), and decreased c-Mpl expression. We therefore analyzed the Janus kinase 2 (Jak2) DNA sequence, EEC growth, PRV-1 expression, and c-Mpl (myeloproliferative) levels in a cohort of 78 myeloproliferative disorder (MPD) patients (42 ET, 22 PV, and 14 IMF). Presence of the Jak2V617F mutation was very highly correlated with PRV-1 overexpression and the ability to form EECs in all 3 subtypes of MPDs (P < .001 IntroductionIn 1951, Dameshek 1 coined the term myeloproliferative disorders (MPDs) for a group of 4 clinically related diseases. At the time, this included polycythemia vera (PV), essential thrombocythemia (ET), idiopathic myelofibrosis (IMF), and chronic myelogenous leukemia (CML). Today, CML is regarded as a separate entity, defined by the t(9;22)(q34;q11) translocation, the "Philadelphia (Ph Ϫ ) chromosome," which results in production of the breakpoint cluster region/Abelson (Bcr/Abl) fusion protein and is not found in the remaining 3 MPD subtypes. 2,3 Several aberrations have been described in patients with PV, ET, and IMF, but none appeared causally linked to the molecular pathogenesis. 4-7 However, 2 alterations, the growth of endogenous erythroid colonies (EECs) and overexpression of the polycythemia rubra vera 1 (PRV-1) mRNA, are highly correlated in individual patients with all 3 subtypes of MPD. 8,9 Therefore, we have proposed that EEC-positive, PRV-1-overexpressing MPD patients constitute a distinct molecular category. 10 In our model, EEC/PRV-1-positive ET and IMF patients are molecularly and clinically more similar to PV patients than to other patients who carry the same clinically defined diagnosis. [9][10][11] The recent description of a point mutation in the Janus kinase 2 (Jak2; Jak2V617F) in the majority of patients with PV as well as subgroups of patients with ET and IMF 12-14 allows us to correlate the presence of this mutation with the occurrence of other markers in individual patients. This analysis can refute or prove the hypothesis that EEC/PRV-1-positive MPD patients share a common molecular determinant of disease etiology. Study design PatientsPeripheral blood samples were obtained from 42 patients with essential thrombocythemia (ET), 22 patients with polycythemia vera (PV), and 14 patients with idiopathic myelofibrosis (IMF). The diagnosis of ET, PV, and IMF were made according to the World Health Organization (WHO) criteria. 15 Venous blood was anticoagulated with EDTA (ethylenediaminetetraacetic acid) or heparin and shipped by courier to the central laboratory without cooling. Maximum time interval between...
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