After the first year, toxicity led to treatment discontinuation in 6 additional patients, including liver toxicity (n = 1), occurrence of biologic markers of autoimmunity (n = 1), muscular pain (n = 2), peripheral neurologic toxicity (n = 1), and fatigue (n = 1).
Slightly low hematocrit and hemoglobin skin#
Causes of treatment discontinuation for toxicity during the first year (n = 3) were: the only observed case of recurring grade 2 neutropenia that impeded weekly peg-IFN-α-2a administration resulting in nonsatisfactory control of Hct in this JAK2 unmutated patient, grade 3 skin toxicity after 6 months (n = 1), and grade 2 fatigue and headaches after 9 months (n = 1). Figure 1B shows time to treatment discontinuation, distinguishing between discontinuation because of AEs and other causes. Pretreatment evaluation also included patient history, physical examination, complete blood count and differential, serum chemistries, including liver and renal function studies, thyroid function tests, and molecular study for JAK2V617F mutation.ĭuring the whole study period, treatment was stopped in 13 patients, including 9 (24.3%) for toxicity (3%-8.1% during the first year).
![slightly low hematocrit and hemoglobin slightly low hematocrit and hemoglobin](https://images.agoramedia.com/ugcphotoservice/100/2019/3/22/83618921/7e5caaea-2f55-449d-a9b4-9cc91229aa24.jpg)
Bone marrow biopsy and cytogenetic analyses (not required by the PVSG criteria used for inclusion in this study) were performed in 11 (confirming PV diagnosis in all cases) and in 14 (all normal) patients, respectively. PV diagnosis workup included red cell mass measurement (performed in all cases), exclusion of secondary causes, spleen size assessment (clinically and by ultrasound, performed in all cases), serum erythropoietin (Epo) level measurement (performed in 37 cases), and search for endogenous erythroid colony formation (performed in 35 cases). Inclusion criteria were as follows: PV diagnosis according to Polycythemia Vera Study Group (PVSG) criteria, age 18 to 65 years, and no previous treatment or only phlebotomies or cytoreductive treatment for less than 2 years. Summary of the PVN1 study was registered at as #NCT00241241. These results show that pegylated IFN-α-2a yields high rates of hematologic and molecular response in PV with limited toxicity, and could even eliminate the JAK2 mutated clone in selected cases. Molecular CR (JAK2V617F undetectable) was achieved in 7 patients, lasting from 6 + to 18 + months, and persisted after pegylated IFN-α-2a discontinuation in 5. Sequential samples for %V617F monitoring, available in 29 patients, showed %V617F decrease in 26 (89.6%). After the first year, 35 patients remained in hematologic CR, including 5 who had stopped pegylated IFN-α-2a. Only 3 patients (8%) had stopped treatment. At 12 months, all 37 evaluable patients had hematologic response, including 94.6% complete responses (CRs).
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Objectives included evaluation of efficacy, safety, and monitoring of residual disease using JAK2V617F quantification (%V617F). We completed a phase 2 multicenter study of pegylated IFN-α-2a in 40 PV patients. Its use is limited by toxicity, leading to treatment discontinuation in approximately 20% of patients. Interferon-α (IFN-α) is a nonleukemogenic treatment of polycythemia vera (PV) able to induce cytogenetic remissions.