Background/Objectives: Hodgkin lymphoma (HL) represents a rare but clinically significant complication in patients with Common Variable Immunodeficiency (CVID). Immune dysregulation, impaired viral control, and Epstein–Barr virus (EBV) infection may contribute to pathogenesis and adversely affect treatment tolerance. This case-based review aims to [...] Read more.

Background/Objectives: Hodgkin lymphoma (HL) represents a rare but clinically significant complication in patients with Common Variable Immunodeficiency (CVID). Immune dysregulation, impaired viral control, and Epstein–Barr virus (EBV) infection may contribute to pathogenesis and adversely affect treatment tolerance. This case-based review aims to highlight the impact of early CVID recognition and multidisciplinary management on outcomes in CVID-associated HL.Methods: A retrospective screening of 224 patients with HL treated at our institution between 2010 and 2023 identified two individuals with CVID and EBV-positive HL. These cases are presented in detail and contextualized within a structured review of the published literature.Results: The first patient, diagnosed with CVID prior to HL onset, received immunoglobulin replacement and a modified chemotherapy regimen substituting bleomycin with brentuximab vedotin, resulting in sustained complete remission. The second patient, in whom CVID was recognized only after HL relapse, experienced recurrent infections, intolerance to therapy, and fatal disease progression despite treatment with brentuximab vedotin, checkpoint inhibition, and rituximab. The literature review revealed only eight comparable cases, underscoring the rarity and complexity of this association.Conclusions: Early identification of CVID facilitates infection control and enhances tolerance to HL therapy, thereby improving clinical outcomes. Multidisciplinary, individualized management and incorporation of targeted agents are pivotal in optimizing care for this vulnerable population.Full article

Background and Clinical Significance: Mastocytosis and mast cell activation syndrome (MCAS) include conditions in which patients manifest signs, symptoms, and laboratory findings consistent with mast cell activation and can only be diagnosed in the presence of specific criteria. Mutations ofZRSR2, a [...] Read more.

Background and Clinical Significance: Mastocytosis and mast cell activation syndrome (MCAS) include conditions in which patients manifest signs, symptoms, and laboratory findings consistent with mast cell activation and can only be diagnosed in the presence of specific criteria. Mutations ofZRSR2, a gene involved in RNA splicing, are not closely associated with mast cell disorders, but rather with myelodysplastic syndromes development.Case Presentation: We report a case of a 37-year-old man who was referred to our institution for anaphylaxis after a bee sting and elevated serum tryptase levels (17.8 ng/mL in the first sample and 19.2 ng/mL in the second sample). Complete blood count was unremarkable. Bone marrow biopsy showed signs of dysplasia and some CD25+ mast cells. ASO-qPCR and targeted myeloid NGS analysis did not detect theKIT p.D816V mutation, but rather showed the presence of a pathogenetic variant of theZRSR2 gene (p.S447_R448del) with a variant allele frequency of 7.4%. Mastocytosis could not be diagnosed based on the established diagnostic criteria. The patient’s symptoms were not recurrent and tryptase release was not event-related; therefore, a diagnosis of MCAS could not be made either. Taken together, these findings led to the diagnosis of clonal hematopoiesis of indeterminate potential (CHIP). A watch and wait strategy consisting of clinical evaluations, blood tests, and cardiovascular risk assessment was initiated.Conclusions: This case report highlights the importance of combining clinical and laboratory findings, hematopathology, and molecular analyses to establish the most probable diagnosis in challenging cases. It also underscores the possible relevance of identifying predisposing conditions, such as CHIP, in order to guide counseling and follow-up strategy.Full article

Objective: To describe the epidemiology, survival rate, and prognostic factors of mucosal-associated lymphoid tissue (MALT) lymphoma.Patients and Methods: This investigation utilized the Thai Lymphoma Study Group (TLSG) registry to gather data on patients diagnosed with MALT lymphoma. The analysis included demographic details, [...] Read more.

Objective: To describe the epidemiology, survival rate, and prognostic factors of mucosal-associated lymphoid tissue (MALT) lymphoma.Patients and Methods: This investigation utilized the Thai Lymphoma Study Group (TLSG) registry to gather data on patients diagnosed with MALT lymphoma. The analysis included demographic details, therapeutic interventions, and survival statistics.Results: The TLSG registry prospectively included 8404 patients with lymphoma. Among them, marginal-zone lymphoma (MZL) was the second most common subtype, with 670 histologically confirmed cases, accounting for 8.0% of the total cohort. An analysis of the MZL subtypes showed that MALT lymphoma was the most common, accounting for 77.8% of the diagnoses. This was followed by nodal MZL at 17.5% and splenic MZL at 7.7%. The distribution of primary disease sites indicated that the ocular adnexa (49.2%), stomach (12.9%), and sinonasal region (12.5%) were the three most common locations. Three variables were found to be statistically significant predictors of survival in the multivariate analysis: ECOG performance status > 2, age exceeding 65 years, and involvement of more than two extranodal organs. These identified prognostic factors were further assessed for their effect on overall survival (OS) and progression-free survival (PFS). A risk classification was established: the low-risk group comprised patients with zero identified risk factors, whereas the high-risk group included patients who had any of the specified risk factors. A comparison of five-year survival rates showed significantly more favorable outcomes for low-risk patients who had a PFS of 83.3% (vs. 66.1%,p = 0.028) and an OS of 97.8% (vs. 76.7%,p < 0.001) compared to the high-risk group.Conclusions: In this cohort, where MZL was the second most common lymphoma and MALT lymphoma was the predominant subtype, our analysis revealed that patients with no risk factors experienced statistically significant improvements in both PFS and OS.Full article

Background: This study evaluated possible variations in classic blood coagulation parameters according to groups formed from the main erythrocyte antigen systems.Methods: Consecutive patients admitted to a transfusion hemotherapy service at a private hospital in the Brazilian Federal District were evaluated for coagulation [...] Read more.

Background: This study evaluated possible variations in classic blood coagulation parameters according to groups formed from the main erythrocyte antigen systems.Methods: Consecutive patients admitted to a transfusion hemotherapy service at a private hospital in the Brazilian Federal District were evaluated for coagulation profile and blood type according to routine laboratory practices. The international normalized ratio (INR), the activated partial thromboplastin time (APTT) and the prothrombin time (PT) were compared according to the ABO blood group and the Rh factor in analyses controlled for classic influencers such as age, sex and comorbidities.Results: No significant differences in coagulation were found between groups defined by the ABO antigen system, despite a body of evidence in favor of this correlation. Rh-positive individuals showed increased mean values in PT (13.7 vs. 12.6 s), in APTT (32.0 vs. 30.1 s) and in INR (1.23 vs. 1.15 s) when compared to the Rh-negative counterparts.Conclusions: Our results suggest a lowered rate of coagulation among Rh-positive individuals, possibly owing to inhibitory effects of the Rh(D) erythrocyte antigen on the coagulation pathway.Full article

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Background/Objectives: In children developing B-cell acute lymphoblastic leukemia (B-ALL), an immune evasion event takes place where otherwise “silent” preleukemic cells undergo a malignant transformation while escaping immune control, often through unknown mechanisms. Methods and Results: Here, we identify the upregulation of PD-1 expression [...] Read more.

Background/Objectives: In children developing B-cell acute lymphoblastic leukemia (B-ALL), an immune evasion event takes place where otherwise “silent” preleukemic cells undergo a malignant transformation while escaping immune control, often through unknown mechanisms. Methods and Results: Here, we identify the upregulation of PD-1 expression in preleukemic cells, triggered byPax5 inactivation in mice and correlating with the time of conversion to leukemia, as a novel marker that favors leukemia evasion. This increase in PD-1 expression is apparent across diverse molecular B-ALL subtypes, both in mice and humans. PD-1 is not required for B-cell leukemogenesis, but, in the absence of PD-1, tumor cells express NK cell inhibitory receptors, highlighting the necessity for leukemic cells to evade the host’s NK immune response in order to exit the bone marrow. PD-1 expression reduces natural antitumor immune responses, but it sensitizes leukemic cells to immune checkpoint blockade strategies in mice and humans. PD-1 targeting confers clinical benefits by restoring NK-mediated tumor cell killing in vitro and eliminating tumor cells in vivo in mice engrafted with B-ALL. Conclusions: These results identify PD-1 as a new therapeutic target against leukemic progression, providing new opportunities for the treatment and possibly also the prevention of childhood B-ALL.Full article

Background: The aim was to evaluate whether an artificial intelligence (AI)-based tool for the automated quantification of the total metabolic tumour volume (tMTV) in patients with Hodgkin lymphoma (HL) could support nuclear medicine specialists in lesion segmentation and thereby enhance inter-observer agreement. Methods: [...] Read more.

Background: The aim was to evaluate whether an artificial intelligence (AI)-based tool for the automated quantification of the total metabolic tumour volume (tMTV) in patients with Hodgkin lymphoma (HL) could support nuclear medicine specialists in lesion segmentation and thereby enhance inter-observer agreement. Methods: Forty-eight consecutive patients who underwent staging with [18F]FDG PET/CT were included. Eight invited specialists from different hospitals were asked to manually segment lesions for tMTV calculations in 12 cases without AI advice, and to use automated AI segmentation in a further 12 cases, with editing as required, i.e., segmenting/adjusting 24 cases each. Each case was segmented by two specialists manually and by two different specialists using the AI tool, allowing for the pairwise comparison of inter-observer variability. Results: The median difference between two specialists performing manual tMTV segmentations was 26 cm³ (IQR 10–86 cm³) corresponding to 23% (IQR 7–50%) of the median tMTV in the dataset, while the median difference between two specialists tMTV adjustments using AI segmentations was 12 cm³ (IQR 4–39 cm³) corresponding to 9% (IQR 2–21%) (p = 0.023). The median difference in tMTV between measurements with and without AI was 3.3 cm³, corresponding to 2.3% of the median tMTV. Conclusions: An automated AI-based tool can significantly increase agreement among specialists quantifying tMTV in HL patients staged with [18F]FDG PET/CT, without markedly changing the measurements.Full article

Acute myeloid leukemia (AML) is an aggressive clonal hematopoietic malignancy, characterized by marked biological heterogeneity and variable clinical outcomes. Among its rarer genetic subsets is AML with rearrangements of theMDS1 andEVI1 complex locus (MECOM), occurring in fewer than 2% [...] Read more.

Acute myeloid leukemia (AML) is an aggressive clonal hematopoietic malignancy, characterized by marked biological heterogeneity and variable clinical outcomes. Among its rarer genetic subsets is AML with rearrangements of theMDS1 andEVI1 complex locus (MECOM), occurring in fewer than 2% of newly diagnosed cases. This review examines the biology and clinical significance ofMECOM-rearranged AML, with a focus on its diverse mechanisms of leukemogenesis, including chromosomal inversion and translocation involving 3q26. We discuss how aberrantEVI1/MECOM activity alters gene expression networks and drives malignant transformation. Current therapeutic approaches—including intensive chemotherapy, hypomethylating agents in combination with venetoclax, and allogeneic stem cell transplantation—are evaluated with particular emphasis on inv(3) and other t(3q26) subtypes. Despite these treatment strategies, outcomes remain poor, underscoring the urgent need for novel, more effective therapies for this high-risk form of AML.Full article

Myelodysplastic neoplasms represent a diverse group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and an inherent risk of progression to acute myeloid leukemia. Accurate risk assessment and patient stratification are critical to optimizing therapeutic approaches and clinical outcomes. [...] Read more.

Myelodysplastic neoplasms represent a diverse group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and an inherent risk of progression to acute myeloid leukemia. Accurate risk assessment and patient stratification are critical to optimizing therapeutic approaches and clinical outcomes. In 2022, significant advancements reshaped both the classification and prognostic stratification of MDSs. The revised WHO Classification introduced crucial genetically defined subtypes, particularly those involving biallelicTP53 inactivation andSF3B1 mutations, shifting the emphasis from traditional morphology-based criteria to molecular ones. Simultaneously, morphological subtypes such as hypoplastic and hyperfibrotic MDSs were established as distinct entities with unique prognostic implications. At the same time, the introduction of the International Molecular Prognostic Scoring System (IPSS-M) provided a more precise prognostic stratification by integrating comprehensive molecular data alongside traditional clinical and cytogenetic parameters. Several validation studies have confirmed IPSS-M’s superior discriminative power compared to previous models, notably IPSS-R, improving predictions regarding overall survival and leukemia transformation. Nevertheless, practical considerations regarding the widespread application of IPSS-M have emerged, including concerns over economic feasibility and accessibility of advanced molecular testing methods, such as extensive Next-Generation Sequencing panels. This review synthesizes the recent literature and critical studies validating these classification and prognostic updates, discussing their clinical impact, practical considerations, and implications for targeted therapeutic strategies. By focusing on molecular pathogenesis, the latest classification systems and prognostic models promise significant advances in patient-specific management, setting the stage for future innovations in treatment and improved patient outcomes.Full article

Background/Objectives: The role of daratumumab, lenalidomide, and dexamethasone (DRd) in autologous stem cell transplantation (ASCT)-eligible patients with multiple myeloma (MM) after first-line bortezomib, cyclophosphamide, and dexamethasone (VCd) treatment is not yet established.Methods: We retrospectively evaluated ASCT-eligible patients with MM who received second-line [...] Read more.

Background/Objectives: The role of daratumumab, lenalidomide, and dexamethasone (DRd) in autologous stem cell transplantation (ASCT)-eligible patients with multiple myeloma (MM) after first-line bortezomib, cyclophosphamide, and dexamethasone (VCd) treatment is not yet established.Methods: We retrospectively evaluated ASCT-eligible patients with MM who received second-line therapy with DRd after initial induction therapy with VCd between 2017 and 2023 (salvage group). For comparison, patients who successfully underwent per-protocol treatment with VCd induction, followed by ASCT during the same period, were selected (control group).Results: Eight patients with a median age of 61 years (range, 36–68 years) were included in the salvage group. After a median of 5 DRd cycles, the best response was partial response (PR) in two patients (25%) and a very good partial response (VGPR) in six (75%). All patients underwent ASCT, resulting in PR in one (13%), VGPR in four (50%), and stringent complete response in three (38%). Measurable residual disease (MRD) assessed using multicolor flow cytometry was negative in four patients (50%). The controls included thirteen patients with a median age of 60 years (range, 44–64 years). While most patients in both groups received various post-ASCT therapies, the post-ASCT 2-year time to the next treatment rate was slightly better in the salvage group than in the control group (88% vs. 49%,p = 0.089). However, hypogammaglobulinemia was more common in the salvage group (75% vs. 15%,p = 0.018).Conclusions: This small case series suggests that DRd is promising for ASCT-eligible patients with MM after VCd failure.Full article

Multiple myeloma is a hematological cancer depicted by the proliferation of plasma cells within the bone marrow, causing immune dysfunction and other abnormalities. The gut microbiome, the microbial community in the gastrointestinal tract, was found to modulate systemic immunity, inflammation, and metabolism. Although [...] Read more.

Multiple myeloma is a hematological cancer depicted by the proliferation of plasma cells within the bone marrow, causing immune dysfunction and other abnormalities. The gut microbiome, the microbial community in the gastrointestinal tract, was found to modulate systemic immunity, inflammation, and metabolism. Although the interplay between gut microbiome and multiple myeloma has been found in recent research, there is a gap in knowledge linking the effect of the microbiome on the pathogenesis and treatment of multiple myeloma. The imbalance in the gut microbiome, dysbiosis, may influence multiple myeloma pathogenesis through immune modulation and inflammation. Certain microbial species have been associated with multiple myeloma progression, complications, and therapeutic responses to treatment. Moreover, microbiome-derived metabolites, short-chain fatty acids, can influence the immune circuits associated with multiple myeloma progression. Understanding the bidirectional relationship between multiple myeloma and gut microbiota may provide insights into enhanced treatment and the development of new microbiome-based interventions. The current review provides a comprehensive highlight of current evidence linking the gut microbiome with multiple myeloma, demonstrating its significant roles in the development, progression, and treatment of multiple myeloma. Additionally, it focuses on the therapeutic potential of modulating the gut microbiome as a novel adjunct strategy in multiple myeloma management.Full article

Background: Primary central nervous lymphoma (PCNSL) is a rare, aggressive, non-Hodgkin’s lymphoma. Outcomes are poor with standard induction of high-dose methotrexate (HD-MTX)-based regimens and consolidation. We present retrospective data from the Georgia Cancer Center.Methods: A single retrospective chart review was [...] Read more.

Background: Primary central nervous lymphoma (PCNSL) is a rare, aggressive, non-Hodgkin’s lymphoma. Outcomes are poor with standard induction of high-dose methotrexate (HD-MTX)-based regimens and consolidation. We present retrospective data from the Georgia Cancer Center.Methods: A single retrospective chart review was conducted on all PCNSL patients from 2013 to 2023 to assess for various factors influencing care.Results: Of a total of 38 PCNSL patients, 6 died and 2 were lost to follow-up prior to therapy initiation, leading to a total of 30 patients for analysis. The median age was 62.3 (21–82 years). One patient had HIV/AIDS. Two patients were on immunosuppression for either kidney transplant or multiple sclerosis (MS). The HIV and MS cases were Epstein-Barr Virus (EBV)-positive. Completion of ≥six cycles of induction was predictive of response.Conclusions: PCNSL remains an area of high unmet need. Recent studies have shown that HD-MTX-based therapy and autologous stem cell transplantation afterwards leads to improved outcomes regardless of age; however, non-relapse mortality is important to consider. Our data from a primarily elderly and sub-rural cohort reiterate the efficacy of combination chemoimmunotherapy and impact of induction cycle number on response, regardless of age. A multidisciplinary approach and targeted agent maintenance should be considered to improve outcomes in the elderly.Full article

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Background: Clinical trials comparing novel oral anticoagulants (NOACs) with warfarin reported a lower mortality rate and a reduced incidence of bleeding with NOACs. However, these studies do not allow for final conclusions about safety. Moreover, direct comparisons among NOACs are not available. [...] Read more.

Background: Clinical trials comparing novel oral anticoagulants (NOACs) with warfarin reported a lower mortality rate and a reduced incidence of bleeding with NOACs. However, these studies do not allow for final conclusions about safety. Moreover, direct comparisons among NOACs are not available.Objectives: The aim of this study was to analyze data from EudraVigilance in order to compare OAC safety profiles.Methods: We searched for all suspected adverse drug reactions (ADRs) from OACs collected in the EudraVigilance up to March 2019. We calculated the reporting odds ratios (RORs) in order to assess the risk of reporting specific ADRs among drugs. Moreover, OAC safety profiles were investigated through correspondence analysis and visualized in contribution biplots.Results: A total of 244,149 individual case safety reports (ICSRs; 431,354 ADRs) related to OACs were retrieved from EudraVigilance. About 80% of ICSRs refer to NOACs, especially rivaroxaban. Gastrointestinal (Gastr) and central nervous system (Nerv) disorders were the most represented categories. More than 90% of ADRs were serious and almost 9% fatal, with the highest ROR reported for dabigatran. Both fatal and non-fatal ADRs reported for Vitamin K Antagonists (VKAs) differed from those reported for NOACs. Among the latter, dabigatran and rivaroxaban showed similar profiles, while apixaban differed from all other OACs, even in the case of fatal ADRs.Conclusions: As expected, data collected from EudraVigilance showed differences among drugs, probably related to their specific characteristics and/or the peculiar utilization in clinical practice. Further investigations are needed to better compare the safety profile of OACs.Full article

Objective: This study aimed to analyze pharmacokinetic and clinical parameters (bleeding rates and joint health) before and after switching from standard half-life (SHL) factor VIII (FVIII) to extended half-life (EHL) PEGylated turoctocog alfa pegol in patients with severe/moderate hemophilia A (HA) on prophylaxis, [...] Read more.

Objective: This study aimed to analyze pharmacokinetic and clinical parameters (bleeding rates and joint health) before and after switching from standard half-life (SHL) factor VIII (FVIII) to extended half-life (EHL) PEGylated turoctocog alfa pegol in patients with severe/moderate hemophilia A (HA) on prophylaxis, one year prior to and following the switch in a real-world setting.Methods: A single-center, comparative, observational, sequential, retrospective, multidisciplinary study was designed. The population pharmacokinetic parameters were estimated using the WAPPS-Hemo^® platform. The annualized bleeding rate (including total and joint bleeds), joint health (Hemophilia Joint Health Score), FVIII consumption, administration frequency, and treatment costs were analyzed.Results: Eight patients with severe (n = 7) or moderate (n = 1) HA on prophylaxis were included after switching to turoctocog alfa pegol. With this regimen, the median FVIII half-life was 16.8 (15.2–19.1) hours, the area under the curve (AUC) was 18,182 (12,879–21,214) IU·h/dL, and the incremental recovery was 2.2 IU/dL per (1.6–2.4) IU/kg. The patients required a median of 2.0 infusions per week (2.0–2.0), corresponding to a weekly consumption of 57.8 (54.2–61.1) IU/kg. Clinically, the prophylactic regimen was associated with fewer infusions per week, stable joint health, and a reduction in overall treatment costs.Conclusions: Prophylaxis with turoctocog alfa pegol provided the expected pharmacokinetic profile of an EHL-FVIII concentrate, enabled a lower infusion frequency, and was linked to a decreased treatment burden and cost while maintaining joint health.Full article

Background and Clinical Significance: Acquired hemophilia A (AHA) and acquired von Willebrand syndrome (AVWS) are rare bleeding disorders that do not often present concurrently. Here, we report a coexisting AHA and AVWS case due to underlying autoantibodies to factor VIII (FVIII) and von [...] Read more.

Background and Clinical Significance: Acquired hemophilia A (AHA) and acquired von Willebrand syndrome (AVWS) are rare bleeding disorders that do not often present concurrently. Here, we report a coexisting AHA and AVWS case due to underlying autoantibodies to factor VIII (FVIII) and von Willebrand factor (VWF).Case Presentation: A patient with gastrointestinal bleeding and prolonged aPTT was diagnosed with AHA and AVWS. The patient was started on immunosuppression with prednisone, cyclophosphamide, and intravenous immunoglobulin, alongside recombinant porcine FVIII replacement, susoctocog alfa. AVWS reduced the half-life of susoctocog alfa, requiring more frequent dosing and laboratory monitoring until AVWS resolved. The patient had two further relapses; the most recent was treated with Rituximab, following which remission has been maintained.Conclusions: Given the potential therapeutic implications, VWF testing should be considered as part of the diagnostic workup for AHA.Full article

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Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) survivors exhibit increased rates of psychological comorbidities, cognitive impairment (CI), and reduced health-related quality of life (HRQoL). This cross-sectional study investigated the prevalence of CI and its association with reduced HRQoL and depression among iTTP survivors. [...] Read more.

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) survivors exhibit increased rates of psychological comorbidities, cognitive impairment (CI), and reduced health-related quality of life (HRQoL). This cross-sectional study investigated the prevalence of CI and its association with reduced HRQoL and depression among iTTP survivors.Methods: iTTP survivors completed the Beck Depression Inventory (BDI-II), the SF-36 for evaluation of HRQoL, and the NIH Toolbox Cognition Battery. SF-36 scores and fluid cognition and crystallized cognition composite scores from the cognition battery were compared to the reference population. We examined associations of cognitive impairment with depression and HRQoL.Results: We enrolled 47 patients with iTTP; 76.6% were female, the median age was 51 (IQR 39, 60), and the median number of episodes was 2 (1, 3.5). Compared to the reference, iTTP survivors had significantly lower mean scores in seven SF-36 domains (physical function, physical limitation, general, mental health, vitality, social functioning, and emotional limitation) as well as the mental component score (MCS) (p < 0.0001) and physical component scores (PCS) (p < 0.0001). A lower physical HRQoL score was observed in those with mild (49.3 vs. 37.7,p = 0.005) and major (49.3 vs. 38.4,p = 0.007) CI compared to no CI. The fluid cognition composite score correlated strongly with the SF-36 Physical Component Summary (r = 0.548,p = 0.0002) but not the Mental Component Summary (r = 0.113,p = 0.489).Conclusions: Cognitive impairment in iTTP survivors is associated with reduced physical HRQoL. Identifying and addressing cognitive deficits in iTTP may improve HRQoL. Given that 40% of participants had depressive symptoms, which were associated with reduced mental HRQoL, iTTP survivors may also benefit from routine mental health screening t.Full article

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome characterized by uncontrolled macrophage activation. Secondary HLH is more common in adults and may be triggered by infection, malignancy, or autoimmune disease. Dyslipidemia, particularly hypolipoproteinemia, has been described but remains underexplored. Methods: We [...] Read more.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome characterized by uncontrolled macrophage activation. Secondary HLH is more common in adults and may be triggered by infection, malignancy, or autoimmune disease. Dyslipidemia, particularly hypolipoproteinemia, has been described but remains underexplored. Methods: We retrospectively reviewed 18 adult HLH cases diagnosed between 2012 and 2020 at two institutions where complete lipid profiles were obtained at or near diagnosis. HLH was defined according to HLH-2004 criteria. Results: Among 18 patients, 17 (94%) had secondary HLH, most commonly idiopathic (n = 5, 28%) or Epstein–Barr virus-associated (n = 3, 17%). Hypolipidemia was nearly universal: all (18/18) had HDL-C < 30 mg/dL, 15/18 (83%) had HDL-C < 20 mg/dL, and 12/18 (67%) had HDL-C < 10 mg/dL. LDL-C was <100 mg/dL in 12/18 (67%), with 6/18 (33%) undetectable. Triglycerides were variably elevated (median 279 mg/dL, range 96–1658 mg/dL). Three representative cases with profound hypolipoproteinemia demonstrated lipid normalization after HLH-directed therapy. Conclusions: Severe reductions in HDL-C and LDL-C appear to accompany HLH and may contribute to its pathophysiology by impairing antioxidant defenses, destabilizing membranes, and potentiating macrophage activation. This case series highlights a consistent association between hypolipoproteinemia and HLH, suggesting potential diagnostic value. However, the observational design and small cohort limit generalizability. Larger prospective studies are needed to clarify mechanisms and evaluate whether full lipid profiling should be incorporated into diagnostic algorithms.Full article

Background and Clinical Significance: Common Variable Immunodeficiency (CVID) is a prevalent manifestation of primary immunodeficiency disorder. The current mainstay of treatment is immunoglobulin replacement therapy; however, in patients with severe complications or refractory disease, hematopoietic stem cell transplant (HSCT) is indicated. Despite this, [...] Read more.

Background and Clinical Significance: Common Variable Immunodeficiency (CVID) is a prevalent manifestation of primary immunodeficiency disorder. The current mainstay of treatment is immunoglobulin replacement therapy; however, in patients with severe complications or refractory disease, hematopoietic stem cell transplant (HSCT) is indicated. Despite this, there has been little research regarding HSCT as a treatment for CVID, with few case reports demonstrating clinical benefit.Case presentation: We present a unique case of common variable immunodeficiency Type XII (CVID12) with rare NFKB mutation and its management. A 20-year-old female with autoimmune alopecia, eczema, and a congenital atrophic right kidney presented to the emergency department with a three-month history of intermittent fever, malaise, lymphadenopathy, mouth sores, diarrhea, and odynophagia, accompanied by a 5 lb. unintentional weight loss and night sweats. Previously, she received multiple steroid prescriptions for these symptoms, providing only temporary relief with each course. Lab findings revealed severe neutropenia and imaging demonstrated hepatosplenomegaly and lymphadenopathy. Flow cytometry revealed a slightly atypical CD8-positive T-cell population and bone marrow biopsy revealed variable cellular marrow with trilineage hematopoiesis. Genetic testing confirmed the diagnosis of Autosomal Dominant Common Variable Immunodeficiency Type XII with an NFKB1 mutation. Pre-transplant treatments included monthly IVIG, weekly rituximab, and daily filgrastim, all of which failed to improve her autoimmune neutropenia and hypogammaglobulinemia and failed to reduce her symptomatic burden. Given the patient’s young age and refractory autoimmune neutropenia, it was decided to manage them definitively with hematopoietic stem cell transplantation (HSCT). She ultimately underwent allogenic stem cell transplantation (haploidentical, donor was the mother) with 3.96 × 10⁸/kg TNC without immediate post-transplant complications.Conclusions: This article demonstrates a rare case of NFKB1-positive CVID that was successfully treated with HSCT and highlights the importance of considering transplant therapy in younger patients with clinically significant, refractory autoimmune cytopenia.Full article

Background/Objectives: In haematology, a wide range of blood disorders are hereditary. The thalassaemias are hereditary anaemias characterised by a high burden of disease at the public health level, challenging the resources of many health systems. This review focuses on thalassaemias for which [...] Read more.

Background/Objectives: In haematology, a wide range of blood disorders are hereditary. The thalassaemias are hereditary anaemias characterised by a high burden of disease at the public health level, challenging the resources of many health systems. This review focuses on thalassaemias for which many countries have developed screening and prevention programmes. To manage this heavy burden, two approaches were introduced over the years. The first one focused on reducing the annual affected births consequent to appropriate non-directive genetic counselling, offering to the parents the chance to make an informed choice concerning their reproductive lives. The second approach was related to the development of curative treatments such as haematopoietic stem cell transplantation (HSCT) in the early years, with continued ongoing efforts for improvements, followed by successful advances in gene-based holistic cures in more recent years. Genetic counselling is a vital component in successful prevention, aiming at informing individuals who are found to be carriers and couples who are both carriers with a 25% risk at every pregnancy of having an affected child in the case of recessive, Mendelian inheritance. The issues are many, and that may have to be discussed, highlighting the level of skills which a genetic counsellor is expected to possess and utilise appropriately in every counselling session. The concern is that such trained and skilled professionals are few in number and not well integrated into the multidisciplinary groups addressing the control of these complex disorders. It is our experience that for blood disorders, counselling is rarely in the hands of qualified scientists. It is our firm belief that it is necessary to incorporate genetic counselling as an integral part of haematology services.Methods: To investigate current practices we have drawn on the experience of existing programmes, as well as published literature.Results: Currently, in almost all haemoglobinopathy prevention programmes, counselling is offered by the clinicians in charge of clinical care or, in some settings, by the nurse of the clinic or the screening laboratory scientist.Conclusions: The Thalassaemia International Federation suggests and is in the process of developing special training in counselling as part of haematology training, as well as professional development modules for those already in practice. Considering the complexity of the issues that must be discussed, a multidisciplinary approach to counselling should be considered where possible.Full article

Background and Clinical Significance: Chronic Myeloid Leukemia (CML) management has been revolutionized by tyrosine kinase inhibitors (TKIs), though cardiovascular and thrombotic complications remain a concern, especially in patients with underlying risk factors. Inherited thrombophilia, including protein S deficiency and Factor V Leiden mutation, [...] Read more.

Background and Clinical Significance: Chronic Myeloid Leukemia (CML) management has been revolutionized by tyrosine kinase inhibitors (TKIs), though cardiovascular and thrombotic complications remain a concern, especially in patients with underlying risk factors. Inherited thrombophilia, including protein S deficiency and Factor V Leiden mutation, poses a substantial risk for venous thromboembolism (VTE). Managing CML in patients with such prothrombotic predispositions presents complex therapeutic challenges, particularly in selecting an appropriate TKI and managing anticoagulation.Case Presentation: A 33-year-old woman with congenital thrombophilia (type I protein S deficiency and heterozygous Factor V Leiden mutation) and a history of VTE on long-term anticoagulation with acenocoumarol presented with CML. She exhibited primary resistance to first-line imatinib and poor tolerance with suboptimal response to second-line bosutinib. Third-line treatment with asciminib led to a rapid and sustained major molecular response (MR4.5) without bleeding or thrombotic complications.Conclusions: This case highlights the importance of individualized, multidisciplinary management in CML patients with coexisting thrombophilia. Asciminib, with its favorable cardiovascular safety profile, represents a promising therapeutic option in high-risk patients where other TKIs may be contraindicated due to resistance, intolerance, or thrombotic risk.Full article