Lymphomatoid papulosis associated with myeloid neoplasm with eosinophilia and FIP1L1::PDGFRA rearrangement: Successful imatinib treatment in two cases.

Lymphomatoid papulosis (LyP) is a benign condition, listed among primary cutaneous CD30+ lymphoproliferative disorders. Its typical picture consists of relapsing-remitting papular lesions and it can be encountered in the course of a hematologic disease, at times representing its first manifestation. Hypereosinophilic syndromes are a heterogeneous group of disorders characterized by persistent peripheral blood hypereosinophilia that may lead to life-threatening organ damage. Among eosinophilic disorders, the subtype identified as myeloid/lymphoid neoplasm with eosinophilia and tyrosine kinase gene fusions has aroused particular interest due to its excellent response to tyrosine kinase inhibitors, including imatinib. Here, we described the case of two 33-year-old men presenting with LyP and myeloid neoplasm with eosinophilia and FIP1L1::PDGFRA rearrangement who achieved complete clinical and molecular remission of both conditions a few months after starting imatinib.

Pathological and genomic features of myeloproliferative neoplasms associated with splanchnic vein thrombosis in a single-center cohort.

Here, we reviewed clinical-morphological data and investigated mutational profiles by NGS in a single-center series of 58 consecutive MPN-SVT patients admitted to our hospital between January 1979 and November 2021. We identified 15.5% of PV, 13.8% of ET, 34.5% of PMF, 8.6% of SMF and 27.6% of MPN-U. Most cases (84.5%) carried JAK2V617F mutation, while seven patients were characterized by other molecular markers, namely MPL in four and CALR mutations in three cases. NGS was performed in 54 (93.1%) cases: the most frequent additional mutations were found in TET2 (27.8%) and DNMT3A (16.7%) genes, whereas 25 (46.3%) patients had no additional mutation. Cases with JAK2V617F homozygosity had a higher median number of additional mutations than those with low allele burden. More importantly, all cases of leukemic evolution were characterized by a higher median number of co-mutations, and a co-mutational pattern of high-risk lesions, such as truncating mutations of ASXL1, bi-allelic TP53 loss, and CSMD1 mutations. Nevertheless, no difference was found between cases with and without additional somatic mutations regarding fibrotic progression, SVT recurrence, other thrombo-hemorrhagic complications, or death. After a median follow-up of 7.1 years, ten deaths were recorded; fibrotic progression/leukemic evolution was ascertained in one (1.7%) and six (10.3%) patients, respectively, while 22 (37.9%) patients suffered from recurrent thrombosis. In conclusion, our data underline the importance of using NGS analysis in the management of MPN-related SVT as it can support the MPN diagnosis, particularly in "triple-negative" cases, and provide additional information with potential consequences on prognosis and therapeutic strategies.

Case report: Pleural effusion during tyrosine-kinase inhibitor treatment in chronic myeloid leukemia: Not only a dasatinib-related adverse event.

The spectrum of TKI-related adverse events (AEs) is variable. Pleural effusion (PE) is a frequent AE attributable to dasatinib treatment, while it is only rarely associated with nilotinib. The pathogenetic mechanism leading to PE during nilotinib therapy is still unknown and its management has not yet been defined. To the best of our knowledge, only a limited number of similar case reports have already been reported in the literature so far. Here, we describe the case of a 41-year-old CML patient who developed PE during first-line nilotinib, successfully treated with steroids and nilotinib permanent discontinuation. We highlight the differences among our patient and the others, proposing therapeutic strategies to solve this rare but still possible AE, of which physicians should be aware.

Complement Mediated Hemolytic Anemias in the COVID-19 Era: Case Series and Review of the Literature.

The complex pathophysiologic interplay between SARS-CoV-2 infection and complement activation is the subject of active investigation. It is clinically mirrored by the occurrence of exacerbations of complement mediated diseases during COVID-19 infection. These include complement-mediated hemolytic anemias such as paroxysmal nocturnal hemoglobinuria (PNH), autoimmune hemolytic anemia (AIHA), particularly cold agglutinin disease (CAD), and hemolytic uremic syndrome (HUS). All these conditions may benefit from complement inhibitors that are also under study for COVID-19 disease. Hemolytic exacerbations in these conditions may occur upon several triggers including infections and vaccines and may require transfusions, treatment with complement inhibitors and/or immunosuppressors (i.e., steroids and rituximab for AIHA), and result in thrombotic complications. In this manuscript we describe four patients (2 with PNH and 2 with CAD) who experienced hemolytic flares after either COVID-19 infection or SARS-Cov2 vaccine and provide a review of the most recent literature. We report that most episodes occurred within the first 10 days after COVID-19 infection/vaccination and suggest laboratory monitoring (Hb and LDH levels) in that period. Moreover, in our experience and in the literature, hemolytic exacerbations occurring during COVID-19 infection were more severe, required greater therapeutic intervention, and carried more complications including fatalities, as compared to those developing after SARS-CoV-2 vaccine, suggesting the importance of vaccinating this patient population. Patient education remains pivotal to promptly recognize signs/symptoms of hemolytic flares and to refer to medical attention. Treatment choice should be based on the severity of the hemolytic exacerbation as well as of that of COVID-19 infection. Therapies include transfusions, complement inhibitor initiation/additional dose in the case of PNH, steroids/rituximab in patients with CAD and warm type AIHA, plasma exchange, hemodialysis and complement inhibitor in the case of atypical HUS. Finally, anti-thrombotic prophylaxis should be always considered in these settings, provided safe platelet counts.

Large Granular Lymphocyte Expansion in Myeloid Diseases and Bone Marrow Failure Syndromes: Whoever Seeks Finds.

Large granular lymphocytes (LGL) are lymphoid cells characterized by either a T-cell or a natural killer phenotype whose expansion may be reactive to toxic, infectious, and neoplastic conditions, or result from clonal selection. Recently, the higher attention to LGL clones led to their detection in many clinical conditions including myeloid neoplasms and bone marrow failures. In these contexts, it is still unclear whether LGL cells actively contribute to anti-stem cell autoimmunity or are only a reaction to dysplastic/leukemic myelopoiesis. Moreover, some evidence exists about a common clonal origin of LGL and myeloid clones, including the detection of STAT3 mutations, typical of LGL, in myeloid precursors from myelodysplastic patients. In this article we reviewed available literature regarding the association of LGL clones with myeloid neoplasms (myelodysplastic syndromes, myeloproliferative neoplasms, and acute myeloid leukemias) and bone marrow failures (aplastic anemia and pure red cell aplasia, PRCA) focusing on evidence of pathogenic, clinical, and prognostic relevance. It emerged that LGL clones may be found in up to one third of patients, particularly those with PRCA, and are associated with a more cytopenic phenotype and good response to immunosuppression. Pathogenically, LGL clones seem to expand after myeloid therapies, whilst immunosuppression leading to LGL depletion may favor leukemic escape and thus requires caution.

Inadvertent and minimal gluten intake has a negligible role in the onset of symptoms in patients with coeliac disease on a gluten-free diet.

Although the quantity of gluten that a well-instructed coeliac patient can involuntarily ingest is <10 mg of gluten/d which cannot induce significant villous damage, coeliac patients often attribute the origin of symptoms to the involuntary ingestion of trace quantities of gluten, either certain or hypothetical. Our aim was to evaluate whether the occurrence of symptoms in coeliac patients who histologically responded to a strict gluten-free diet was related to the involuntary consumption of minimal quantities of gluten. A case-control study to assess the association between gluten exposure and the occurrence of symptoms was designed. Between January 2017 and May 2018, coeliac patients attending our outpatient clinic were interviewed to detect the presence of symptoms. Based on a specifically designed form, patients were also divided into different risk groups of gluten exposure. A total of ninety-five coeliac patients on a strict gluten-free diet and with known histological recovery were enroled. Of them, fifty-two of them reported symptoms and they were enroled as cases; the remaining forty-three patients denied symptoms and were enroled as controls. Although this was not statistically significant, gluten exposure was more frequent in controls (Fisher's exact test, P=0·07). Our results show no relationship between exposure to minimal quantities of gluten and onset of symptoms in coeliac patients. Symptoms are more frequent in patients who have no risk of gluten exposure. It is possible that the presence of these symptoms leads the patients to avoid situations that may place them at risk of gluten exposure.