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This article discusses the comparison between indolent systemic mastocytosis (ISM) and clonal mast cell disease that does not meet the World Health Organization (WHO) diagnostic criteria. ISM is a rare neoplasm characterized by abnormal mast cell proliferation, while clonal mast cell disease refers to cases with clonal markers but not all diagnostic criteria for ISM. The study collected data from 530 patients diagnosed with ISM or clonal mast cell disease and compared their clinical features, outcomes, and therapeutic needs. The results showed that the two groups had similar symptom burden, outcomes, and treatment requirements, suggesting that clonal criteria in the appropriate clinical context may be sufficient for diagnosing a "low-burden SM." The authors recommend similar management for both groups to prevent severe complications. [Extracted from the article]

Background: Incorporating real‐world data in the drug development process allows the improvement of health outcomes by providing better representation of actual patterns of drug safety and efficacy. Aims and Methods: Here, we present the results of a retroprospective, observational real‐life study of 154 patients with myelofibrosis treated with ruxolitinib in a real‐life setting in seven Italian centers of the MYNERVA project. Results: Median drug exposure was 29 (range, 3–98) months. Discontinuation rate was 27% after a median time of 13 (range, 3–61). While hematological toxicities were in line with previous findings, infections occurred frequently, representing a not negligible cause of discontinuation and death. Anemia, symptoms, and spleen responses were obtained at any time in 23%, 91%, and 68% of patients, respectively; most patients achieved their responses by week 24. Larger splenomegaly and delayed treatment initiation correlated with lower spleen response at 24 weeks. Spleen response was associated with a superior overall survival, regardless of DIPSS. Of interest, both achievement and loss of spleen response had prognostic implications. Discussion and Conclusion: Overall, our findings provide insights on the efficacy and safety of ruxolitinib in a real‐world, multicenter cohort of Italian MF patients. [ABSTRACT FROM AUTHOR]

Keywords: familial occurrence; systemic mastocytosis; cutaneous mastocytosis; adult patients; predisposition EN familial occurrence systemic mastocytosis cutaneous mastocytosis adult patients predisposition 845 848 4 05/17/21 20210515 NES 210515 Mastocytosis represents a group of clonal disorders characterized by abnormal proliferation and infiltration of mast cells in various tissues, particularly skin and haematopoietic organs, ranging from skin-limited diseases to systemic and more aggressive variants.1 Its clonal nature relies on somatic, gain-of-function mutations in exon 17, causing constitutive activation of the I c- i KIT proto-oncogene and detected in most patients.2 More than 80% of adult patients with a systemic disease carry a somatic aspartate-to-valine substitution in codon 816 (D816V) of the I KIT i gene.1 Although it is a putative, non-hereditary disease, familial cases have been reported in paediatric series, with an estimated frequency of 11-13%.3,4 However, data about the familial occurrence in adults are still lacking. Our cohort included 1541 adult patients followed by eight Italian Institutions, diagnosed with systemic or cutaneous mastocytosis, according to 2016 WHO criteria.5 All patients were asked about the occurrence of mastocytosis in relatives. Among SM patients, the I KIT i D816V mutation rate was of 93-3% and 42-9% in index cases and relatives, respectively; however, this mutation was not documented in any tested CM cases. [Extracted from the article]

The association of systemic mastocytosis with another hematologic neoplasia of myeloid or lymphoid origin is recognized as an advanced subvariant of mastocytosis. Here, we report the association of indolent or smoldering systemic mastocytosis with three cases of myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis, a recently recognized disease characterized by SF3B1 mutations. The hierarchical pattern of KIT, SF3B1, JAK2, and additional mutations was studied in whole and fractionated subpopulations of peripheral blood cells and whole bone marrow. In two cases, we could demonstrate a multilineage D816V KIT mutation, involving all myeloid lineages in one patient and also the lymphoid series in the other. Two patients displaying both SF3B1 and V617F JAK2 mutations had a very poor prognosis. Another patient bearing SF3B1, but not V617F JAK2 mutation, had a favorable response to erythropoietin treatment and long survival. [ABSTRACT FROM AUTHOR]

Systemic mastocytosis (SM) is a hematological malignancy characterized by extracutaneous infiltration by atypical mast cells. Together with indolent SM, aggressive SM, and mast cell leukemia, the World Health Organization (WHO) recognizes another major disease subgroup: SM with an associated hematological neoplasm, which is characterized by the presence of a concurrent neoplasm, more commonly, a chronic myelomonocytic leukemia. While KIT D816V is commonly regarded as the driver mutation, the clinical presentation of SM is extremely varied. Treatment of SM might not be simple, but now more specific therapies tailored toward prognostic subgroups of patients have been developed. Here, we report a detailed description of clinical management and biological features of a systemic mastocytocis case associated with multiple hematologic non-mast cell lineage diseases. [ABSTRACT FROM AUTHOR]

A case study of 68-year-old man is presented with the previous unremarkable medical history was referred to Institution for hyperferritinimemia. Topics include examines physical examination revealed splenomegaly with spleen palpable at several cm from the left costal margin and considered laboratory tests showed normal blood count, a mild increase of total bilirubin and serum lactate dehydrogenase.

Although several parameters are useful for risk stratification of patients with acute myeloid leukaemia (AML), there are no firm criteria for predicting response to induction treatment of individual patients. Daily flow cytometry (FC) analysis, carried out during induction treatment in 30 AML patients, showed that the clearance of blasts from peripheral blood (PBC) correlated closely with response, as assessed by bone marrow FC on day 14, and by morphologic analysis at haematopoietic recovery. Therefore, a major treatment outcome can be predicted very early in AML patients, thus providing an opportunity for tailoring treatment modalities from the outset. [ABSTRACT FROM AUTHOR]

Ruxolitinib is a potent Janus kinase (JAK) 1/JAK2 inhibitor approved for the treatment of myelofibrosis (MF). Ruxolitinib was assessed in JUMP, a large (N = 2233), phase 3b, expanded-access study in MF in countries without access to ruxolitinib outside a clinical trial, which included patients with low platelet counts (<100 × 10 9 /l) and patients without splenomegaly - populations that have not been extensively studied. The most common adverse events (AEs) were anaemia and thrombocytopenia, but they rarely led to discontinuation (overall, 5·4%; low-platelet cohort, 12·3%). As expected, rates of worsening thrombocytopenia were higher in the low-platelet cohort (all grades, 73·2% vs. 53·5% overall); rates of anaemia were similar (all grades, 52·9% vs. 59·5%). Non-haematologic AEs, including infections, were mainly grade 1/2. Overall, ruxolitinib led to meaningful reductions in spleen length and symptoms, including in patients with low platelet counts, and symptom improvements in patients without splenomegaly. In this trial, the largest study of ruxolitinib in patients with MF to date, the safety profile was consistent with previous reports, with no new safety concerns identified. This study confirms findings from the COMFORT studies and supports the use of ruxolitinib in patients with platelet counts of 50-100 × 10 9 /l. (ClinicalTrials.gov identifier NCT01493414)., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Myeloproliferative Neoplasms (MPN) course can be complicated by thrombosis involving unusual sites as the splanchnic veins (SVT). Their management is challenging, given their composite vascular risk. We performed a retrospective, cohort study in the framework of the International Working Group for MPN Research and Treatment (IWG-MRT), and AIRC-Gruppo Italiano Malattie Mieloproliferative (AGIMM). A total of 518 MPN-SVT cases were collected and compared with 1628 unselected, control MPN population, matched for disease subtype. Those with MPN-SVT were younger (median 44 years) and enriched in females compared to controls; PV (37.1%) and ET (34.4%) were the most frequent diagnoses. JAK2V617F mutation was highly prevalent (90.2%), and 38.6% of cases had an additional hypercoagulable disorder. SVT recurrence rate was 1.6 per 100 patient-years. Vitamin K-antagonists (VKA) halved the incidence of recurrence (OR 0.48), unlike cytoreduction (OR 0.96), and were not associated with overall or gastrointestinal bleeding in multivariable analysis. Esophageal varices were the only independent predictor for major bleeding (OR 17.4). Among MPN-SVT, risk of subsequent vascular events was skewed towards venous thromboses compared to controls. However, MPN-SVT clinical course was overall benign: SVT were enriched in PMF with lower IPSS, resulting in significantly longer survival than controls; survival was not affected in PV and slightly reduced in ET. MPN-U with SVT (n = 55) showed a particularly indolent phenotype, with no signs of disease evolution. In the to-date largest, contemporary cohort of MPN-SVT, VKA were confirmed effective in preventing recurrence, unlike cytoreduction, and safe; the major risk factor for bleeding was esophageal varices that therefore represent a major therapeutic target., (© 2019 Wiley Periodicals, Inc.)