Hemato, Volume 5, Issue 3 (September 2024) – 4 articles

Refractoriness to standard first-line therapy in immune thrombocytopenia (ITP) should foster additional diagnostic work-up to exclude hematological clonal disease, mostly myelodysplatic syndrome (MDS) or clonal cytopenia of unknown significance (CCUS), which may present with isolated thrombocytopenia of immune or non-immune origin. We herein report on a patient who showed a transient leukoerythroblastic reaction (LEB) associated with bone marrow myelofibrosis upon rompilostim treatment, challenging a diagnosis of primary ITP and requiring additional investigations. RUNX-1-mutated myelodysplastic syndrome was eventually diagnosed. Even though LEB and marrow fibrosis have already been rarely reported during romiplostim treatment for ITP, this is the first case to our knowledge in which a background clonal hematopoiesis was diagnosed and deemed potentially involved in the abnormal response to this thrombopoietin receptor agonist (TPO-RA). Full article

We present a case of adult-onset systemic chronic active EBV disease (CAEBV) in a 40-year-old woman with chronic HBV hepatitis. Initial symptoms resembled a viral illness, progressing to recurrent fever, transaminitis, and anasarca. Investigations revealed high-level EBV viremia and an abnormal T-cell population in the liver and bone marrow, indicative of CAEBV. The liver biopsy showed CD3+ T-cells lacking TCRbeta and displaying dim/negative CD5, with elevated EBV-infected T-cells. Next-generation sequencing identified rare variants in CREBBP, SPEN, TP73, and PLCG2, suggesting potential contributions to disease pathogenesis. This case underscores the diagnostic challenges and management complexities of adult-onset CAEBV, particularly with underlying chronic HBV infection. Genomic profiling offers crucial insights into the molecular landscape of rare lymphoid malignancies, highlighting the importance of personalized treatment strategies. The distinct immunophenotypic features underscore the heterogeneity in EBV-associated T-cell LPDs, urging further research for optimized clinical management. Full article

Diagnosis of myeloid neoplasm is currently performed according to the presence of a predetermined set of clinical, morphological, and molecular diagnostic criteria agreed upon by a consensus of experts. Even strictly adhering to these criteria, it is possible to encounter patients who present features that are not easily ascribable to a single disease category. This is the case, e.g., of patients with de novo myeloid neoplasms with features intermediate between primary myelofibrosis (PMF) and chronic myelomonocytic leukemia (CMML). In this study, we retrospectively searched the pathological database of IRCCS Humanitas Research Hospital to identify cases of chronic myeloid neoplasm with monocytosis with a driver mutation of classic myeloproliferative neoplasms (MPN) and showing morphological MPN features. For each case, we assessed all epidemiological, clinical, histopathological, and molecular data. Then, we carried out a literature review, searching for cases with features similar to those of our patients. We retrieved a total of 13 cases presenting such criteria (9 from the literature review and 4 from our institution); in all of them, there was a coexistence of clinical, histopathological, and molecular myelodysplastic and myeloproliferative features. To date, according to current classifications (World Health Organization and International Consensus Classification), given the presence/absence of essential features for PMF or CMML, these patients should be formally diagnosed as myelodysplastic/myeloproliferative neoplasm unclassified/not otherwise specified (U/NOS). This review aims to summarize the features of these difficult cases and discuss their differential diagnosis and their classification according to the novel classifications and the existing literature on overlapping myeloid neoplasms. Full article

Monoclonal antibody (MoAb) therapy has been increasingly used in recent years for hematologic malignancies. The MoAbs anti-CD38 and anti-CD47 are immunoglobulins directed against epitopes that are highly expressed not only on cancer cells, but also on red blood cells (RBCs), as well as platelets. Additionally, producing an off-target effect interferes in pre-transfusion testing, having the potential to unchain hemolytic anemia. Blood banks must assure the availability and safety of blood products for patients in need. Thus, MoAbs have become a challenge for blood banks, since methods to overcome interferences must be adopted. Several strategies have been proposed to mitigate pan-reactivity in pre-transfusion indirect antiglobulin tests, such as the treatment of reagent RBCs with enzymes or reducing agents, allogeneic RBC adsorptions, and drug-specific neutralization assays. All of these have some kind of limitation. This review summarizes the interferences of MoAbs in pre-transfusion testing, focusing on the available strategies to mitigate them in order to provide a safe transfusion. Full article