Summary
In patients who do not meet the World Health Organization (WHO) criteria for overt polycythaemia vera (PV), a diagnosis of masked PV (mPV) can be determined. A fraction of mPV patients may ...display thrombocytosis, thus mimicking essential thrombocythaemia (ET). No previous studies have examined clinical outcomes of mPV among young JAK2‐mutated patients. We analysed a retrospective cohort of 538 JAK2‐mutated patients younger than 40 years, after a re‐assessment of the diagnosis according to the haemoglobin threshold for mPV. In this cohort of patients, 97 (18%) met the WHO criteria for PV, 66 patients (12%) were classified as mPV and 375 (70%) as JAK2‐mutated ET. Surprisingly, a significant difference in the incidence of thrombosis was found when comparing mPV versus overt PV patients (P = 0·04). In multivariate analysis, the only factor accounting for the difference in the risk of thrombosis was the less frequent use of phlebotomies and cytoreduction in mPV patients compared to those with overt PV. Thus, we emphasize the need for the identification of mPV in young JAK2‐mutated patients in order to optimize their treatments.
The hot and the cold Chevalier, Jacques M; Bain, Andrés Sánchez
The hot and the cold,
c2003, 20030321, 2003, 2000, 2003-01-01, 20030101, Volume:
24
eBook
Examines indigenous worldview and myth to challenge the prevailing notion that hot-cold reasoning of health and illness in Latin America is a product of the Hippocratic humoral doctrine brought by ...the Spaniards in the sixteenth century.
Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms with variable risk of evolution into post-PV and post-ET myelofibrosis, from now on referred to as secondary ...myelofibrosis (SMF). No specific tools have been defined for risk stratification in SMF. To develop a prognostic model for predicting survival, we studied 685 JAK2, CALR, and MPL annotated patients with SMF. Median survival of the whole cohort was 9.3 years (95% CI: 8-not reached-NR-). Through penalized Cox regressions we identified negative predictors of survival and according to beta risk coefficients we assigned 2 points to hemoglobin level <11 g/dl, to circulating blasts ⩾3%, and to CALR-unmutated genotype, 1 point to platelet count <150 × 10
/l and to constitutional symptoms, and 0.15 points to any year of age. Myelofibrosis Secondary to PV and ET-Prognostic Model (MYSEC-PM) allocated SMF patients into four risk categories with different survival (P<0.0001): low (median survival NR; 133 patients), intermediate-1 (9.3 years, 95% CI: 8.1-NR; 245 patients), intermediate-2 (4.4 years, 95% CI: 3.2-7.9; 126 patients), and high risk (2 years, 95% CI: 1.7-3.9; 75 patients). Finally, we found that the MYSEC-PM represents the most appropriate tool for SMF decision-making to be used in clinical and trial settings.
Polycythemia vera (PV) is a relatively indolent myeloid neoplasm with median survival that exceeds 35 years in young patients, but its natural history might be interrupted by thrombotic, fibrotic, or ...leukemic events, with respective 20-year rates of 26%, 16%, and 4%. Current treatment strategies in PV have not been shown to prolong survival or lessen the risk of leukemic or fibrotic progression and instead are directed at preventing thrombotic complications. In the latter regard, two risk categories are considered: high (age >60 years or thrombosis history) and low (absence of both risk factors). All patients require phlebotomy to keep hematocrit below 45% and once-daily low-dose aspirin, in the absence of contraindications. Cytoreductive therapy is recommended for high-risk or symptomatic low-risk disease; our first-line drug of choice in this regard is hydroxyurea but we consider pegylated interferon as an alternative in certain situations, including in young women of reproductive age, in patients manifesting intolerance or resistance to hydroxyurea therapy, and in situations where treatment is indicated for curbing phlebotomy requirement rather than preventing thrombosis. Additional treatment options include busulfan and ruxolitinib; the former is preferred in older patients and the latter in the presence of symptoms reminiscent of post-PV myelofibrosis or protracted pruritus. Our drug choices reflect our appreciation for long-term track record of safety, evidence for reduction of thrombosis risk, and broader suppression of myeloproliferation. Controlled studies are needed to clarify the added value of twice- vs once-daily aspirin dosing and direct oral anticoagulants. In this invited review, we discuss our current approach to diagnosis, prognostication, and treatment of PV in general, as well as during specific situations, including pregnancy and splanchnic vein thrombosis.
Aloe vera‐derived graphene (ADG) coupled system photocatalyst, mimicking natural photosynthesis, is one of the most promising ways for converting solar energy into ammonia (NH3) and nicotinamide ...adenine dinucleotide (NADH) that have been widely used to make the numerous chemicals such as fertilizer and fuel. In this study, we report the synthesis of the aloe vera‐derived graphene‐coupled phenosafranin (ADGCP) acting as a highly efficient photocatalyst for the generation of NH3 and regeneration of NADH from nitrogen (N2) and oxidized form of nicotinamide adenine dinucleotide (NAD+). The results show a benchmark instance for mimicking natural photosynthesis activity as well as the practical applications for the solar‐driven selective formation of NH3 and the regeneration of NADH by using the newly designed photocatalyst.
In this study, the utilization of solar light irradiation enables the generation and regeneration of ammonia and NADH using an aloe vera‐derived graphene‐coupled phenosafranin (ADGCP) photocatalyst. The results show the remarkable efficiency and environmental friendly nature of the ADGCP system, offering the promising way to solve worldwide issues related to sustainable chemical synthesis and energy production.
Philadelphia-negative classical myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The 2016 revision of the WHO ...Classification of Tumours of Haematopoietic and Lymphoid Tissues includes new criteria for the diagnosis of these disorders. Somatic mutations in the 3 driver genes, that is, JAK2, CALR, and MPL, represent major diagnostic criteria in combination with hematologic and morphological abnormalities. PV is characterized by erythrocytosis with suppressed endogenous erythropoietin production, bone marrow panmyelosis, and JAK2 mutation. Thrombocytosis, bone marrow megakaryocytic proliferation, and presence of JAK2, CALR, or MPL mutation are the main diagnostic criteria for ET. PMF is characterized by bone marrow megakaryocytic proliferation, reticulin and/or collagen fibrosis, and presence of JAK2, CALR, or MPL mutation. Prefibrotic myelofibrosis represents an early phase of myelofibrosis, and is characterized by granulocytic/megakaryocytic proliferation and lack of reticulin fibrosis in the bone marrow. The genomic landscape of MPNs is more complex than initially thought and involves several mutant genes beyond the 3 drivers. Comutated, myeloid tumor-suppressor genes contribute to phenotypic variability, phenotypic shifts, and progression to more aggressive disorders. Patients with myeloid neoplasms are at variable risk of vascular complications, including arterial or venous thrombosis and bleeding. Current prognostic models are mainly based on clinical and hematologic parameters, but innovative models that include genetic data are being developed for both clinical and trial settings. In perspective, molecular profiling of MPNs might also allow for accurate evaluation and monitoring of response to innovative drugs that target the mutant clone.
Severe thrombocytopenia (platelets <50 × 109/L) is associated with very poor outcome of patients with myelofibrosis (MF). As patients with primary myelofibrosis (PMF) differ from patients with ...postessential thrombocythemia (PET‐MF) and postpolycythemia vera myelofibrosis (PPV‐MF), we aimed to evaluate the significance of low platelets among these patients. We present clinical characteristics and outcome of patients with either PMF, PPV‐MF, or PET‐MF, and thrombocytopenia who presented to our institution between 1984 and 2015. Of 1269 patients (877 PMF, 212 PPV‐MF, 180 PET‐MF), 11% and 14% had platelets either <50 × 109/L or between 50‐100 × 109/L, respectively. Patients with platelets <50 × 109/L were most anemic and transfusion dependent, had highest blast count and unfavorable karyotype. In general, their overall and leukemia‐free survival was the shortest with median time of 15 and 13 months, respectively; with incidence of acute leukemia almost twice as high as in the remaining patients (6.9 vs 3.6 cases per 100 person‐years). Nevertheless, this observation remains mostly significant for patients with PMF, as those with PEV/PVT‐MF have already significantly inferior prognosis with platelets <100 × 109/L.
Interferon-alpha (rIFNα) is the only disease-modifying treatment for polycythemia vera (PV), but whether or not it prolongs survival is unknown. This large single center retrospective study of 470 PV ...patients compares the myelofibrosis-free survival (MFS) and overall survival (OS) with rIFNα to two other primary treatments, hydroxyurea (HU) and phlebotomy-only (PHL-O). The median age at diagnosis was 54 years (range 20-94) and the median follow-up was 10 years (range 0-45). Two hundred and twenty-nine patients were women (49%) and 208 were high-risk (44%). The primary treatment was rIFNα in 93 (20%), HU in 189 (40%), PHL-O in 133 (28%) and other cytoreductive drugs in 55 (12%). The treatment groups differed by ELN risk score (p < 0.001). In low-risk patients, 20-year MFS for rIFNα, HU, and PHL-O was 84%, 65% and 55% respectively (p < 0.001) and 20-year OS was 100%, 85% and 80% respectively (p = 0.44). In high-risk patients, 20-year MFS for rIFNα, HU, and PHL-O was 89%, 41% and 36% respectively (p = 0.19) and 20-year OS was 66%, 40%, 14% respectively (p = 0.016). In multivariable analysis, longer time on rIFNα was associated with a lower risk of myelofibrosis (HR: 0.91, p < 0.001) and lower mortality (HR: 0.94, p = 0.012). In conclusion, this study supports treatment of PV with rIFNα to prevent myelofibrosis and potentially prolong survival.
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