BackgroundSickle cell anemia is an autosomal recessive disorder caused by abnormal hemoglobin S, which polymerizes when deoxygenated and distorts erythrocytes into sickle cells. This can lead to vaso-occlusive crises and multiorgan damage. Sickle cell patients often require blood transfusions for acute anemia, but 15-50% develop alloantibodies that complicate future transfusions. We present a sickle cell patient with rare complex alloimmunization.CaseA 45-year-old male with sickle cell disease presented to the emergency department with worsening pain in the ankles, back, and shoulders uncontrolled with his home pain regimen. Laboratory evaluation revealed severe normocytic anemia with hemoglobin of 5.4 g/dL. He was diagnosed with vaso-occlusive sickle cell crisis, but transfusion was deferred because compatible blood was unavailable after recent complex alloimmunization. He was managed with patient-controlled analgesia, intravenous immunoglobulin, intravenous steroids, and epoetin alfa. His hemoglobin stabilized, his pain improved, and he was discharged after eight days.SignificanceThis case highlights the challenges of managing severe anemia in an SCA patient with rare complex alloimmunization involving anti-Fy3, anti-Jsa, and anti-Doa, including anti-Fy3 formation with a homozygous FY*02N.01 GATA-associated Duffy-null genotype. Because this genotype abolishes erythrocyte Duffy expression while preserving non-erythroid expression, anti-Fy3 is a distinct and unusual immunohematologic event rather than the expected absence of anti-Fyb. Combined with hydroxyurea intolerance, this patient illustrates an underrecognized scenario in which standard first-line SCA therapies are simultaneously inaccessible. IVIG, corticosteroids, and epoetin alfa achieved hemoglobin stabilization without transfusion when compatible blood was unavailable.
BackgroundSickle cell disease (SCD) represents a significant global health burden and is characterized by hemolytic anemia, vaso-occlusive crises, end-organ damage, and early mortality. Red blood cells (RBCs) depend on glycolysis due to the virtual absence of mitochondria. RBC glycolysis generates adenosine triphosphate (ATP) and regulates levels of 2,3-diphosphoglycerate (2,3-DPG). Intracellular ATP is essential for numerous RBC functions, such as maintaining ion homeostasis, cell membrane integrity, redox protection, and RBC deformability. Sickle (SS) RBCs have reduced intracellular ATP compared to normal RBCs. RBCs also export ATP, which can modulate blood flow in response to hypoxia, inhibit intercellular adhesion, and prevent excess capillary permeability. We sought primarily to investigate a novel approach to augment ATP export from SS vs. healthy RBCs. Pyruvate kinase (PK) catalyzes the final step of glycolysis, generating RBC intracellular ATP. PK activators (PKAs), such as mitapivat (AG-348), are now approved in PK deficiency and are being studied in SCD patients. By increasing PKR (RBC PK) activity, they increase intracellular ATP while decreasing upstream 2,3-DPG. Our secondary aim was to compare the effects of a PKR activator (PKRA) on ATP export by RBCs in SCD vs. healthy (HC) individuals.MethodsWhole blood (WB) from SCD patients and healthy adults (IRB-approved) was incubated with AG-348 (10 µM) or vehicle (DMSO) at 4 °C for 18–24 h. RBCs were isolated, washed, and exposed to normoxic (21% O2) or hypoxic (1% O2) conditions. Supernatant and intracellular ATP was measured by luciferase assay, and hemoglobin was quantified to assess hemolysis. For adhesion assays, treated or control WB was perfused through laminin-coated microfluidic channels under increasing shear stress (0.3–10 dyn/cm²). Images were obtained after each shear increment, and adhesion was quantified as the percentage of cells remaining using ImageJ.ResultsWe obtained WB from pediatric SCD patients. PKRA treatment ex vivo raised intra-RBC ATP in HC blood, consistent with prior reports, but did not increase intra-RBC ATP significantly in SCD blood. Exported ATP was increased after HC RBC exposure to hypoxia (94.3 ± 24.3 nM (mean ± SEM) vs. 79.7 ± 20.6 nM in normoxia). ATP export from HC RBCs increased after treatment with the PKRA AG-348 in normoxia (80.3 ± 22.3 nM vs. 109.0 ± 30.2 nM) and hypoxia. ATP exported by SCD RBCs increased in hypoxia vs. normoxia. Exported ATP did not change significantly in SCD RBCs treated with the PKRA AG-348 (79.7 ± 20.6 nM vs. 77.1 ± 19.9 nM). Post-assay lysis levels were 1% or lower under all conditions. These low levels of lysis in ATP export assays did not differ as a function of PKRA treatment or between HC and SCD RBCs. As compared to the effects of vehicle alone, SS RBC adhesion to laminin after WB exposure to AG-348 was decreased at the physiologically relevant shear stresses of 0.3, 1, and 3 dyne/cm2.ConclusionsTo our knowledge, our data show for the first time that ATP export from HC RBCs increases after treatment with a PKRA, which also increased HC intra-RBC ATP, confirming prior reports. In contrast, exposure of SCD RBCs to PKRA under identical conditions did not significantly increase intra-RBC or exported ATP in SCD in normoxia or hypoxia. ATP export from untreated SS RBCs rose in hypoxia. Ongoing work addresses the determinants of cellular and exported ATP in HC and SCD RBCs (basal and treated) and the basis of the antiadhesive effect of this PKRA on SS RBCs.
Acute myeloid leukemia (AML) is an aggressive blood cancer characterized by the accumulation of immature myeloid cells in the bone marrow. Despite advances in genomic profiling and targeted therapies, patient outcomes remain poor because of high relapse rates and the persistence of therapy-resistant leukemic stem cells. Growing evidence underscores the critical role of the bone marrow microenvironment in regulating leukemia progression, survival, and treatment response. Normally, the bone marrow niche supports hematopoietic stem cell function through balanced interactions among stromal, vascular, immune, and metabolic components. In AML, leukemic cells actively remodel this niche to create an environment that promotes leukemia. This review outlines key cellular and molecular mechanisms underlying AML–niche interactions and their role in chemoresistance. We examine how BM niche components, including mesenchymal stromal cells, endothelial cells, immune cells, osteolineage cells, and adipocytes, contribute to leukemic growth by releasing cytokines, chemokines, and growth factors. The review further highlights key signaling pathways, including the CXCL12–CXCR4 axis, JAK/STAT, and adhesion-related signaling, which are essential for leukemic cell homing, survival, and drug resistance. Additionally, the roles of extracellular vesicles, metabolic changes, hypoxia, and immunosuppression, which further enhance the protective bone marrow environment, support the maintenance of leukemic stem cells and help them evade chemotherapy, leading to minimal residual disease and relapse, have been described. Finally, we discuss emerging therapies targeting the AML niche, including CXCR4 inhibitors, immune-based treatments, and strategies that disrupt stromal and vascular signaling. Addressing both leukemic cells and their supportive microenvironment may lead to more effective approaches to overcome chemoresistance and improve long-term outcomes in AML.
Patients with hematologic malignancies are at increased risk of thrombotic complications, which most commonly occur during chemotherapy or in association with central venous catheter placement. Thrombotic events detected before systemic treatment initiation are uncommon, and intracardiac thrombosis represents a rare and diagnostically challenging manifestation. We report the case of a 21-year-old woman with newly diagnosed classical Hodgkin lymphoma in whom an asymptomatic right atrial mass was identified during pre-treatment assessment, 13 days after peripherally inserted central catheter placement. Staging PET-CT showed increased FDG uptake in the right pericardiac region, raising concern for possible cardiac or pericardiac disease involvement. Transthoracic echocardiography revealed a multilobulated right atrial mass, while cardiac magnetic resonance imaging supported its thrombotic nature and showed no evidence of neoplastic infiltration. Anticoagulation therapy was initiated and subsequently optimized, allowing the patient to complete chemotherapy without thromboembolic or hemorrhagic complications. End-of-treatment PET-CT demonstrated complete metabolic response, and follow-up echocardiography showed progressive reduction of the intracardiac lesion. This case highlights the importance of multimodality imaging in the differential diagnosis of right atrial masses in patients with lymphoma and underscores the need to consider both malignancy-related hypercoagulability and catheter-associated mechanisms.
BackgroundReceiving a leukaemia diagnosis and undergoing treatment impact patients and their informal carers. Our objective was to explore and quantify the impact on the quality of life (QoL) of adult family members or partners of persons living with acute or chronic leukaemia.MethodsWe conducted a global, cross-sectional online study distributed via three leukaemia patient advocacy networks. Adult informal carers completed the Family Reported Outcome Measure (FROM-16) tool. Higher FROM-16 scores indicate poorer QoL, ranging from 0 to 32, with a critical threshold of 17 indicating a “very large effect”. We summarised the demographic variables and caregiving characteristics and assessed their relationships with the FROM-16 scores using Kruskal–Wallis tests with Bonferroni adjustment. Eta-squared (η2) was used to assess the effect size.ResultsA total of 511 respondents entered the dataset: 59% (299/511) supported someone with acute leukaemia (“acute group”), whilst 41% (212/511) supported someone with chronic leukaemia (“chronic group”). The mean age of all informal carer respondents was 48.1 years [standard deviation (SD) = 13.9]. The acute group tended to be younger (mean = 43.8 years, SD = 11.8) than the chronic group (mean = 54.2 years, SD = 14.4). The majority of informal carer respondents were women (73%, 353/485). The median FROM-16 score was 14, and 38% (195/511) of the respondents scored above the critical threshold of 17. The acute and chronic leukaemia groups differed (median = 16 vs. 8, respectively), with a moderate-to-large effect size (η2 = 0.122, p = 2.92E−15). Providing higher caregiving hours was associated with greater FROM-16 scores (i.e., lower QoL), with large effect sizes in both groups (acute: η2 = 0.130, p = 5.32E−6; chronic: η2 = 0.232, p = 5.65E−7). Giving medication was associated with moderate effect sizes (acute: η2 = 0.071, p = 3.98E−6; chronic: η2 = 0.094, p = 9.56E−6), whilst providing personal care showed small to moderate effects (acute: η2 = 0.036, p = 9.93E−4; chronic: η2 = 0.092, p = 1.17E−5).ConclusionOur findings highlight a need for tailored support to reflect the differing burdens faced by informal carers of people with acute and chronic leukaemia. Policymakers and clinicians could integrate informal carer wellbeing into leukaemia care strategies, promoting holistic, family-centred support services.
BackgroundRelapse is the main cause of treatment failure after allogeneic hematopoietic cell transplantation (allo-HCT). Therapeutic donor lymphocyte infusion (DLI) and second allo-HCT are common post-relapse options, but comparative evidence from the time of relapse is limited.MethodsWe retrospectively analyzed 85 adults with acute leukemia or myelodysplastic syndromes (MDS) who received therapeutic DLI or a second allo-HCT after relapse (2010–2022). DLI required hematologic or clinical relapse. Overall survival (OS) was assessed using Kaplan–Meier analysis, Cox regression, and propensity score matching (PSM). Competing risks models evaluated relapse-related mortality (RRM) and non-relapse mortality (NRM).Results60 patients received DLI and 25 underwent a second allo-HCT. No significant difference in OS was observed between groups (median OS 0.92 vs. 0.61 years, p=0.295). DLI showed higher RRM, while second allo-HCT showed a trend toward higher NRM. In the matched cohort (n = 36), OS remained numerically longer after second allo-HCT without significance.ConclusionOS did not differ between second allo-HCT and therapeutic DLI. Treatment should be individualized, and larger multicenter studies are needed to refine patient selection.
At present, the detailed mechanisms of how cytotoxic chemotherapy routinely produces cure in a limited number of malignancies whilst causing only more modest effects on the majority of cancers and healthy normal cells are uncertain. In this article, we reviewed published information regarding the impact of chemotherapy exposure on the viability of the cells of origin of a number of chemotherapy-curable malignancies. In general, these cells are difficult to study as they are transient, challenging to study ex vivo, and anatomically relatively inaccessible. In B-cell and T-cell acute lymphoblastic leukaemia, it is apparent that exposure to DNA damaging chemotherapy or radiotherapy results in near total loss of the respective cells of origin of pro-B cells and double-positive (DP) thymocytes within 2 days. However, these cells are rapidly replaced from the chemotherapy-resistant bone marrow stem cells. In diffuse large B-cell lymphoma, the germinal centre cells of origin are naturally poised on the edge of apoptosis, with a half-life of approximately 6 h, making in vitro study impractical. The probable cell of origin of testicular cancer is the OCT4+ stem cell, which shows similar sensitivity to chemotherapy to that of malignant cells, with total loss of these stem cells upon exposure to BEP (bleomycin, etoposide, and platinum/cisplatin) combination chemotherapy. Overall, it appears that chemotherapy-curable malignancies do not acquire a high degree of sensitivity to chemotherapy on their change to the malignant phenotype; rather, they maintain the high sensitivity of their cells of origin. These findings are in keeping with our previous observations that the high degree of chemotherapy sensitivity follows the dramatic changes in apoptotic sensitivity that accompany the genetic manipulations of variable–diversity–joining (VDJ) recombination, somatic hypermutation, meiosis, and nuclear fusion occurring in these normal healthy but transient cells.
BackgroundHigh-risk acute promyelocytic leukemia (APL) [white blood cell (WBC) count >10 × 109/L) accounts for 20%–30% of cases with early mortality of 15%–25%. Optimal induction with reduced-intensity all-trans retinoic acid plus arsenic trioxide (ATRA+ATO) versus intensive chemotherapy remains debated.MethodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD420261293473), we searched PubMed and Cochrane Library (2000–2025). Reduced-intensity: ATRA+ATO with gemtuzumab ozogamicin (GO; 6–9 mg/m2), low-dose idarubicin (one to two doses of 12 mg/m2), or hydroxyurea; intensive: ATRA-based therapy with three or more anthracycline doses. Random-effects meta-analysis used logit transformation and inverse variance weighting. RoB 2 and ROBINS-I were used to assess risk of bias.ResultsA total of 17 studies (1,323 patients, 11 on the reduced-intensity arm and 14 on the intensive arm) were included. Complete remission (CR) was 92.3% (95%CI = 85.9–95.9%, I2 = 0%) versus 89.3% (82.6%–93.6%, I2 = 56%, p = 0.35). Early mortality was 8.8% versus 10.4% (p = 0.62). Event-free survival (EFS) from two randomized controlled trials (RCTs) favored reduced-intensity induction (HR = 0.23, 95%CI= 0.07–0.76, p = 0.015). Relapse was 3.9% versus 5.5% (p = 0.49). WBC-stratified CR remained stable at 91.6%–92.5% with reduced-intensity induction, while intensive CR declined from 96.0% to 86.6% at WBC ≥30 × 109/L.ConclusionsReduced-intensity ATRA+ATO-based induction achieves equivalent CR, comparable early mortality, superior EFS (HR = 0.23, p = 0.015), and lower relapse, supporting ATRA+ATO with GO or low-dose anthracycline as the preferred first-line therapy for high-risk APL.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420261293473.
BackgroundAcute lymphoblastic leukemia (ALL) is the most common childhood malignancy in India, with survival rates (60%–70%) significantly lower than in high-income countries (85%–90%). Asparaginase, a cornerstone of ALL therapy, has a narrow therapeutic window with substantial interpatient pharmacokinetic variability. However, therapeutic drug monitoring is rarely performed in resource-limited settings.MethodsThe prospective pilot study assessed serum asparaginase activity during induction therapy in Indian children with high-risk B-cell ALL. Of 30 enrolled patients, nine high-risk cases (aged 1–12 years) received L-asparaginase according to the modified ICiCLe protocol. Serum asparaginase activity was measured using a spectrophotometric assay at pre-dose (trough) and 24-h post-dose (peak) time points. Treatment-related toxicities were monitored using standardized criteria.ResultsAmong the nine high-risk patients, five completed inductions, three died from treatment-related complications, and one was transferred. All evaluable patients (n = 5) had subtherapeutic trough asparaginase activity (<0.5 IU/mL; target ≥0.5 IU/mL). Peak levels showed marked interpatient variability (range: 0.52–1.97 IU/mL; median: 1.15 IU/mL). Higher enzyme activity correlated with biochemical toxicities: hepatotoxicity (5/5), elevated blood urea nitrogen (4/5), hypertriglyceridemia (3/5), and subclinical pancreatitis (2/5).ConclusionThis pilot study demonstrates consistently subtherapeutic trough asparaginase levels in a small cohort of Indian children with high-risk ALL, suggesting potential inadequate drug exposure during induction therapy. These findings highlight the potential role of therapeutic drug monitoring in optimizing dosing and minimizing toxicity in resource-limited settings. Larger, adequately powered studies are required to validate these observations and establish population-specific pharmacokinetic parameters and dosing strategies.
ObjectivesThe primary objective of this project was to explore the challenges related to the implementation of patient-reported outcome measures (PROMs) in myeloma, lymphoma and leukaemia patients undergoing chimeric antigen receptor T-cell (CAR-T) and T Cell engager bispecific antibody (BsAbs) therapies. The secondary aims focused on identifying and promoting opportunities to optimise PROM use for improved alignment, consistency, and interpretability of PROM data related to these innovative treatments.MethodsData was collected through online focus groups and interviews with patients, carers, representatives of patient organisations from myeloma, lymphoma, leukaemia communities, researchers, industry, regulatory and payer representatives. The information was transcribed for qualitative thematic analysis, using a deductive–inductive mixed approach.ResultsA total of 38 individuals participated; 14 interviews were conducted with 16 participants and two focus groups were conducted with 15 and 19 participants in each. Challenges reported included the unique complexities within trials of CAR-T and BsAbs in haematologic cancers such as the logistical challenges in the early post-infusion period for CAR-T and the wide variety of different BsAbs side-effects for patients occurring over different time periods. Further difficulties included balancing stakeholders’ expectations, and uncertainties about what to measure and when.ConclusionsCAR-T and BsAbs therapies present distinct challenges for PROM to capture treatment-related side effects and burden accurately. Use of generic and disease-specific instruments risk missing key elements of patients’ experiences and the use of ad-hoc strategies to complement these tools presents challenges for evidence synthesis. Clearer guidance, including early high-frequency assessments, systematic inclusion of patient-important domains currently under-captured, continued PRO data collection beyond clinical progression and transparent and comprehensive reporting of PRO findings will lead to substantial improvements in understanding the impact of CAR-T and BsAbs treatments.
Pancytopenia is a life-threatening condition necessitating a prompt, thorough workup to appropriately treat the underlying pathology. We describe a presentation of pancytopenia attributed to myelodysplastic syndrome (MDS)-associated immune-mediated hemolysis, which initially responded to immunotherapy, including steroids and the anti-CD20 monoclonal antibody rituximab. Cycles of relapse, followed by repeated clinical responses to immunotherapy over a two-year period, supported the diagnosis of immune-mediated cytopenias, substantially delaying identification of the true pathology. Subsequent investigations revealed pernicious anemia as the underlying diagnosis despite ostensibly normal vitamin B12 levels at presentation. This case highlights how the autoimmune features of pernicious anemia may confound the diagnostic workup of cytopenias by masking the detection of B12 deficiency, and, surprisingly, result in the sustained response of pernicious anemia to immunotherapy.
Chediak–Higashi syndrome (CHS) is a rare autosomal recessive condition marked by lysosomal dysfunction, partial albinism, neurological impairment, and marked immunodeficiency. Patients with CHS exhibit increased susceptibility to aggressive malignancies, notably lymphoproliferative disorders. This report describes a 25-year-old man with CHS, complicated by an inborn error of immunity (IEI)-associated lymphoproliferative disorder (IEI-LPD). His initial symptoms presented were severe lower back pain, weight loss, and constitutional symptoms, alongside classic phenotypic features of CHS, including hypopigmentation, neurological abnormalities, and ocular manifestations. Laboratory findings revealed leucopenia, decreased immunoglobulins (IgA, IgM), and impaired natural killer cell function, confirming severe immune dysfunction. Imaging studies identified vertebral fractures, a retroaortic mass, and splenomegaly; histopathology confirmed IEI-LPD. Treatment comprised six cycles of dose-adjusted EPOCH chemotherapy with pegfilgrastim prophylaxis, achieving an initial complete response. Nevertheless, progressive neurological deterioration, recurrent infections, and institutional limitations contributed to this patient’s eventual demise. Genetic sequencing identified a homozygous LYST mutation variant c.9464G>A (p.R3155Q), classified as a variant of uncertain significance. This report underscores the diagnostic and therapeutic challenges in rare hematologic malignancies, emphasizing the importance of genetic characterization through next-generation sequencing and advocating for improved awareness, early diagnosis, and multidisciplinary management strategies for optimal outcomes in CHS-associated malignancies.
Polycythemia Vera (PV) and related myeloproliferative neoplasms (MPNs) require long-term management to minimize thrombotic complications, disease progression, and improve quality of life. While interferon-alpha (IFN-α) offers disease-modifying potential, disease symptoms and side effects often persist, necessitating the exploration of complementary therapeutic strategies. This review examines established drugs and lifestyle interventions for their potential to improve PV/MPN outcomes. We synthesize evidence from preclinical models, clinical trials in non-MPN populations, and observational studies in MPN patients, focusing on interventions targeting MPN-related pathways like JAK/STAT signaling, inflammation, and oxidative stress. We highlight the potential benefits of cardiovascular drugs like ACE inhibitors and statins; anti-diabetic medications such as metformin and pioglitazone; and readily available agents like colchicine, rapamycin, leukotriene modifiers, and N-acetylcysteine (NAC). Additionally, we review the evidence supporting natural compounds like green tea, curcumin, fish oil, alpha-ketoglutarate, beta-alanine, vitamin C, vitamin D3, and probiotics like Clostridium butyricum, to identify their potential for symptom management and disease control. We review evidence supporting lifestyle interventions like the Mediterranean diet, weight management, yoga and exercise. We share two case studies that highlight the potential for combination therapies. Finally, we suggest a two-pronged approach: incorporate readily applicable interventions into clinical practice based on biomarkers, while conducting rigorous research to validate emerging combination strategies. The combination therapy approach aims to improve both survival and quality of life for PV and MPNs.
Burkitt’s lymphoma is a highly aggressive B-cell lymphoma associated with human immunodeficiency virus (HIV) infection. Despite antiretroviral therapy (ART), Burkitt’s lymphoma remains diagnostically and therapeutically challenging, especially with concurrent infections. We describe a 50-year-old man presenting with constitutional symptoms and Salmonella bacteremia, found to have newly diagnosed HIV, stage IV Burkitt’s lymphoma with central nervous system (CNS) and marrow involvement, and cytomegalovirus (CMV) viremia. His management required coordination of ART, chemotherapy, and infection treatment, complicated by CMV encephalitis and adherence barriers. This case highlights the challenges of managing overlapping malignancy and infection, emphasizing early HIV testing and patient-centered multidisciplinary care.
Background: Non-transfusion-dependent thalassemia (NTDT) can result in a range of clinical complications that can substantially reduce patient quality of life. To date, real-world studies on the clinical burden of the disease have focused on Europe and Asia and have been limited to beta-NTDT. Aim: To assess the complications and treatment patterns in patients with alpha- or beta-NTDT vs. matched controls in the United States (US). Methods: This retrospective observational study used data from US claims databases (January 1, 2013-June 30, 2021). Adult patients (>= 18 years) with >= 1 inpatient or >= 2 outpatient claims for alpha- or beta-thalassemia were included from Merative (TM) MarketScan (R) Commercial/Medicare and Multi-State Medicaid databases. Patients were classified as NTDT if they had <8 blood transfusions or >= 6 weeks between any two adjacent transfusions during the 12 months post-index date (date of first observed alpha- or beta-thalassemia diagnosis code). Patients were matched with controls (1:5 ratio). Primary analysis focused on patients from the Commercial/Medicare database with mean hemoglobin <10 g/dL during follow-up, to minimize inclusion of patients with thalassemia trait. Complications and treatment patterns were assessed during >= 12 months post-index. Comparisons between patients with NTDT vs. controls were performed using Chi-square tests (categorical variables) and t-tests (continuous variables) (two-sided significance level of 0.05). Analyses for the alpha- and beta-NTDT subgroups were also performed.Results In the Commercial/Medicare database, 149 patients with NTDT and hemoglobin <10 g/dL were matched with 745 controls (mean follow-up approximately 3 years). A significantly higher percentage of patients with NTDT had complications vs. controls, including malignancy (17.4% vs. 7.1%; p < 0.001), cardiovascular disease (15.4% vs. 7.8%; p = 0.003), liver disease (6.7% vs. 0.5%; p < 0.001), and gallstones (6.7% vs. 2.1%; p = 0.002). Overall, 18.8% of patients with NTDT had >= 1 transfusion; 4.0% received oral chelators. Similar trends across outcomes were observed for NTD alpha- and beta-thalassemia subgroups vs. controls. Conclusions: Patients with NTDT had a high disease burden and experienced a range of serious complications, with significantly higher rates compared with controls. Additional effective and well-tolerated treatments are needed to address the underlying causes of NTDT and prevent complications.
Castleman disease (CD) is a rare lymphoproliferative disorder with heterogeneous clinical manifestations, particularly in its idiopathic multicentric form (iMCD), which is driven by cytokine dysregulation rather than classical autoimmunity. Owing to overlapping features such as fever, lymphadenopathy, cytopenias, renal involvement, and elevated inflammatory markers, iMCD may closely mimic systemic lupus erythematosus (SLE). This resemblance is further complicated by the presence of autoantibodies in a subset of iMCD patients, increasing the risk of misclassification and delayed diagnosis. In this Perspective, we highlight key clinical scenarios in which CD presents as a lupus-like syndrome, including cases that initially fulfill SLE classification criteria but fail to respond to conventional immunosuppressive therapy. We emphasize the limitations of serologic testing in distinguishing these entities and underscore the central role of lymph node histopathology in establishing the correct diagnosis. Recognizing Castleman disease as an important mimic of SLE has critical therapeutic implications, as iMCD requires cytokine-directed treatment rather than immune suppression alone. These observations also suggest that CD and SLE may share a cytokine-driven inflammatory spectrum in selected patients; however, distinguishing between them remains essential because their therapeutic strategies differ fundamentally. Increased awareness of this diagnostic overlap may help clinicians avoid inappropriate treatment strategies and improve outcomes in patients presenting with atypical or refractory lupus-like disease.
BackgroundChronic Lymphocytic Leukaemia (CLL) is a slow-progressing condition often managed through active monitoring (“watch and wait”) strategies, which can lead to uncertainty for patients about prognosis, symptom management, and immunity-related risks. We studied the diagnostic and active monitoring pathway experiences of patients with CLL, and the impact of immunity-related knowledge on their quality of life (QoL).MethodsWe analysed data from 846 patients with CLL who responded to the cross-sectional 2023 Global Leukaemia Experience Survey, which included the Haematological Malignancy Specific Patient-reported Outcome (HM-PRO) instrument. Higher HM-PRO scores represent worse QoL. We used descriptive statistics and Kruskal-Wallis tests to quantify the impact on QoL.ResultsMost respondents (69%, 582/841) reported experiencing symptoms before diagnosis, although the majority (89%, 509/571) did not recognise these as signs of leukaemia. A large proportion (84%, 701/831) were placed on active monitoring, amongst whom 25% (172/689) reported being “very concerned/worried” about this approach. Fewer than half felt fully confident recognising signs of progression. QoL did not differ significantly by current active monitoring status but was associated with immunity-related knowledge: respondents unaware of their immunity status had worse QoL (median HM-PRO Part A “No”: 13 vs “Yes”: 11). Respondents who had not spoken to a healthcare professional about immunisation strategies reported higher HM-PRO Part-A scores (“No”: 13 vs “Yes, completely”: 10).ConclusionOur study highlights key challenges faced by individuals with CLL, including lack of symptom awareness, lack of association of those symptoms with cancer, inadequate understanding of active monitoring, and the impact of immunity-related education on QoL. Addressing these challenges through coordinated efforts amongst clinicians, advocacy groups, and policymakers may contribute to improved disease management and QoL for individuals living with CLL. Future research could seek to account for potential confounders to enhance the robustness of conclusions and build on these global findings by examining country-level differences.
IntroductionNephrotic syndrome caused by membranoproliferative glomerulonephritis (MPGN) related to chronic lymphocytic leukemia (CLL) is a rare condition. Due to the rarity, no standard of care has been established yet. The combination of rituximab, chlorambucil and fludarabin was described as an effective therapeutic regimen. However, the efficacy of the novel therapeutic options in CLL-induced nephrotic syndrome are rarely reported so far.Materials and methodsWe report two cases of patients with CLL suffering from concomitant nephrotic syndrome with significant proteinuria. The patients have consented to the evaluation and publication of their data. The patients received their initial diagnosis at our clinic and were followed for approximately 3 years.ResultsThe first patient, a 44-year old female with B-CLL, Binet A, and a low risk CLL-IPI score. Initially lupus nephritis was suspected to be associated with MPGN. However, despite the immunosuppressive treatment with mycophenolate mofetil and prednisolone no disease control was achieved. Consequently, CLL-associated nephrotic syndrome was assumed, and treatment with obinutuzumab and venetoclax was initiated. Six weeks after therapy initiation, the patient showed complete clinical resolution of nephrotic syndrome, accompanied by a marked reduction in proteinuria. The second patient, a 73-year old man, diagnosed with B-CLL, Binet C, CLL-IPI score intermediate risk presenting with concomitant MPGN. Treatment with obinutuzumab and venetoclax was initiated. Clinically, the nephrotic syndrome resolved within a few weeks after the initiation of therapy. Final assessment after completion of treatment by computed tomography and flow cytometry demonstrated complete remission of CLL. In addition, proteinuria completely resolved. At the last follow-up, the patient remains in sustained remission, with proteinuria persistently below the nephrotic range.ConclusionIn this report, we present two cases of CLL-related nephrotic syndromes, successfully treated with obinutuzumab and venetoclax. Furthermore, we emphasize the importance of awareness of this rare complication in patients with CLL.
