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Summary: Available data have proved insufficient to develop consensus recommendations on the prevention of thrombosis and bleeding in myelofibrosis (MF). We evaluated the incidence and risk factors of vascular complications in 1613 patients from the Spanish Myelofibrosis Registry. Over a total of 6981 patient‐years at risk, 6.4% of the study population had at least one thrombotic event after MF diagnosis, amounting to an incidence rate of 1.65 per 100 patient‐years. Prior history of thrombosis, the JAK2 mutation, and the intermediate‐2/high‐risk International Prognostic Scoring System (IPSS) categories conferred an increased thrombotic risk after adjustment for the risk‐modifying effect of anti‐thrombotic and cytoreductive treatments. History of thrombosis and the JAK2 mutation allowed us to pinpoint a group of patients at higher risk of early thrombosis. No decreased incidence of thrombosis was observed while patients were on anti‐thrombotic or cytoreductive treatment. An increased risk of venous thrombosis was found during treatment with immunomodulatory agents. A total of 5.3% of patients had at least one episode of major bleeding, resulting in an incidence rate of 1.5 events per 100 patient‐years. Patients in the intermediate‐2/high‐risk IPSS categories treated with anti‐coagulants had an almost sevenfold increased risk of major bleeding. These findings should prove useful for guiding decision‐making in clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: In patients with essential thrombocythemia (ET), after the JAK2V617F driver mutation, mutations in CALR are common (classified as type 1, 52‐bp deletion or type 2, 5‐bp insertion). CALR mutations have generally been associated with a lower risk of thrombosis. This study aimed to confirm the impact of CALR mutation type on thrombotic risk. Methods: We retrospectively investigated 983 ET patients diagnosed in Spanish and Polish hospitals. Results: With 7.5 years of median follow‐up from diagnosis, 155 patients (15.8%) had one or more thrombotic event. The 5‐year thrombosis‐free survival (TFS) rate was 83.8%, 91.6% and 93.9% for the JAK2V617F, CALR‐type 1 and CALR‐type 2 groups, respectively (P =.002). Comparing CALR‐type 1 and CALR‐type 2 groups, TFS for venous thrombosis was lower in CALR‐type 1 (P =.046), with no difference in TFS for arterial thrombosis observed. The cumulative incidence of thrombosis was significantly different comparing JAK2V617F vs CALR‐type 2 groups but not JAK2V617F vs CALR‐type 1 groups. Moreover, CALR‐type 2 mutation was a statistically significant protective factor for thrombosis with respect to JAK2V617F in multivariate logistic regression (OR: 0.45, P =.04) adjusted by age. Conclusions: Our results suggest that CALR mutation type has prognostic value for the stratification of thrombotic risk in ET patients. [ABSTRACT FROM AUTHOR]

Several studies have reported uneven results when evaluating the prognostic value of bone marrow biopsy ( BMB) and PET/ CT as part of the staging of diffuse large B-cell lymphoma ( DLBCL). The heterogeneity of the inclusion criteria and not taking into account selection and collinearity biases in the analysis models might explain part of these discrepancies. To address this issue we have carried a retrospective multicenter study including 268 DLBCL patients with a BMB and a PET/ CT available at diagnosis where we estimated both the prognosis impact and the diagnostic accuracy of each technique. Only patients treated with R- CHOP/21 as first line ( n = 203) were included in the survival analysis. With a median follow-up of 25 months the estimated 3-year progression-free survival ( PFS) and overall survival ( OS) were 76.3% and 82.7% respectively. In a multivariate analysis designed to avoid a collinearity bias with IPI categories, BMB- BMI [bone marrow involvement](+) ( HR: 3.6) and ECOG PS > 1 ( HR: 2.9) were independently associated with a shorter PFS and three factors, age >60 years old ( HR: 2.4), ECOG PS >1 ( HR: 2.4), and abnormally elevated B2-microglobulin levels ( HR: 2.2) were independently associated with a shorter OS. In our DLBCL cohort, treated with a uniform first-line chemotherapy regimen, BMI by BMB complemented performance status in predicting those patients with a higher risk for relapse or progression. In this cohort BMI by PET/ CT could not independently predict a shorter PFS and/or OS. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 35-year-old man who was diagnosed with ileocolonic Crohn's disease. The patient was placed on maintenance therapy with azathioprine (AZA) with no complications after surgery. Activated macrophages and erythrophagocytosis were revealed on bone marrow aspirate. Ganciclovir and intravenous corticosteroids treatment was initiated.

Competing Interests: The authors declare no conflict of interest.

Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) with heterogeneous clinical course. Allogeneic hematopoietic cell transplantation remains the only curative therapy, but its morbidity and mortality require careful candidate selection. Therefore, accurate disease risk prognostication is critical for treatment decision-making. We obtained registry data from patients diagnosed with MF in 60 Spanish institutions (N = 1386). These were randomly divided into a training set (80%) and a test set (20%). A machine learning (ML) technique (random forest) was used to model overall survival (OS) and leukemia-free survival (LFS) in the training set, and the results were validated in the test set. We derived the AIPSS-MF (Artificial Intelligence Prognostic Scoring System for Myelofibrosis) model, which was based on 8 clinical variables at diagnosis and achieved high accuracy in predicting OS (training set c-index, 0.750; test set c-index, 0.744) and LFS (training set c-index, 0.697; test set c-index, 0.703). No improvement was obtained with the inclusion of MPN driver mutations in the model. We were unable to adequately assess the potential benefit of including adverse cytogenetics or high-risk mutations due to the lack of these data in many patients. AIPSS-MF was superior to the IPSS regardless of MF subtype and age range and outperformed the MYSEC-PM in patients with secondary MF. In conclusion, we have developed a prediction model based exclusively on clinical variables that provides individualized prognostic estimates in patients with primary and secondary MF. The use of AIPSS-MF in combination with predictive models that incorporate genetic information may improve disease risk stratification., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

We report a novel hemoglobin (Hb) variant found in a Spanish individual from Santa Cruz de Tenerife, the Canary Islands in Spain. The proband was a 39-year-old male. High performance liquid chromatography (HPLC) displayed an unknown peak (19.3%) at a retention time of 1.3 min. eluting before Hb A 0 . Capillary zone electrophoresis (CZE) showed an abnormal peak (20.0%) in zone 12. Direct DNA sequencing of the α-globin genes revealed heterozygosity for a nonsense mutation at codon 139 ( A AA> T AA), causing a lysine to stop codon substitution [α139(HC1)Lys→Stop; HBA1 : c.418A>T]. We decided to name the variant Hb Nivaria (Tenerife) for the place of birth and residence of the proband.

Background: Ruxolitinib is approved for patients with polycythemia vera (PV) who are resistant/intolerant to hydroxyurea, but its impact on preventing thrombosis or disease-progression is unknown., Methods: A retrospective, real-world analysis was performed on the outcomes of 377 patients with resistance/intolerance to hydroxyurea from the Spanish Registry of Polycythemia Vera according to subsequent treatment with ruxolitinib (n = 105) or the best available therapy (BAT; n = 272). Survival probabilities and rates of thrombosis, hemorrhage, acute myeloid leukemia, myelofibrosis, and second primary cancers were calculated according to treatment. To minimize biases in treatment allocation, all results were adjusted by a propensity score for receiving ruxolitinib or BAT., Results: Patients receiving ruxolitinib had a significantly lower rate of arterial thrombosis than those on BAT (0.4% vs 2.3% per year; P = .03), and this persisted as a trend after adjustment for the propensity to have received the drug (incidence rate ratio, 0.18; 95% confidence interval, 0.02-1.3; P = .09). There were no significant differences in the rates of venous thrombosis (0.8% and 1.1% for ruxolitinib and BAT, respectively; P = .7) and major bleeding (0.8% and 0.9%, respectively; P = .9). Ruxolitinib exposure was not associated with a higher rate of second primary cancers, including all types of neoplasia, noncutaneous cancers, and nonmelanoma skin cancers. After a median follow-up of 3.5 years, there were no differences in survival or progression to acute leukemia or myelofibrosis between the 2 groups., Conclusions: The results suggest that ruxolitinib treatment for PV patients with resistance/intolerance to hydroxyurea may reduce the incidence of arterial thrombosis., Lay Summary: Ruxolitinib is better than other available therapies in achieving hematocrit control and symptom relief in patients with polycythemia vera who are resistant/intolerant to hydroxyurea, but we still do not know whether ruxolitinib provides an additional benefit in preventing thrombosis or disease progression. We retrospectively studied the outcomes of 377 patients with resistance/intolerance to hydroxyurea from the Spanish Registry of Polycythemia Vera according to whether they subsequently received ruxolitinib (n = 105) or the best available therapy (n = 272). Our findings suggest that ruxolitinib could reduce the incidence of arterial thrombosis, but a disease-modifying effect could not be demonstrated for ruxolitinib in this patient population., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Hematocrit control below 45% is associated with a lower rate of thrombosis in polycythemia vera. In patients receiving hydroxyurea, this target can be achieved with hydroxyurea alone or with the combination of hydroxyurea plus phlebotomies. However, the clinical implications of phlebotomy requirement under hydroxyurea therapy are unknown. The aim of this study was to evaluate the need for additional phlebotomies during the first five years of hydroxyurea therapy in 533 patients with polycythemia vera. Patients requiring 3 or more phlebotomies per year (n=85, 16%) showed a worse hematocrit control than those requiring 2 or less phlebotomies per year (n=448, 84%). There were no significant differences between the two study groups regarding leukocyte and platelet counts. Patients requiring 3 or more phlebotomies per year received significantly higher doses of hydroxyurea than the remaining patients. A significant higher rate of thrombosis was found in patients treated with hydroxyurea plus 3 or more phlebotomies per year compared to hydroxyurea with 0-2 phlebotomies per year (20.5% vs. 5.3% at 3 years; P<0.0001). In multivariate analysis, independent risk factors for thrombosis were phlebotomy dependency (HR: 3.3, 95%CI: 1.5-6.9; P=0.002) and thrombosis at diagnosis (HR: 4.7, 95%CI: 2.3-9.8; P<0.0001). The proportion of patients fulfilling the European LeukemiaNet criteria of resistance/intolerance to hydroxyurea was significantly higher in the group requiring 3 or more phlebotomies per year (18.7% vs. 7.1%; P=0.001) mainly due to extrahematologic toxicity. In conclusion, phlebotomy requirement under hydroxyurea therapy identifies a subset of patients with increased proliferation of polycythemia vera and higher risk of thrombosis., (Copyright© Ferrata Storti Foundation.)