Acta Haematologica最新文献

Introduction: The accidental transmission of both malignant and non-malignant haematological diseases through allogeneic haematopoietic stem-cell transplantation (alloSCT) has been documented. Next-generation sequencing enables the detection of a broad spectrum of mutations associated with myeloid and other disorders.

Case presentations: We report two cases of donor-derived myeloid clonal haematopoiesis (M-CHIP) following alloSCT. In one case, donor-derived CHIP was stabilized through donor-lymphocyte infusions administered in response to declining donor chimerism.

Conclusion: The transfer of M-CHIP by alloSCT is not uncommon. The long-term relevance of these findings for patients and donors should be the subject of larger prospective trials. Furthermore, the transplantation of CHIP is not uncommon and presents significant medical and ethical challenges.

Introduction: Nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) often follows an indolent course but carries a risk of late recurrence and transformation. Given its rarity, there is significant variability in the treatment patterns at various healthcare centers.

Methods: This retrospective chart review aimed to compare the patient characteristics and outcomes of NLPHL patients >18 years of age diagnosed between January 1st, 2007, and December 31st, 2022, at Parkland Health, the safety-net system for uninsured/underinsured patients in Dallas County, with patients treated at the neighboring NCI-designated Harold C. Simmons Comprehensive Cancer Center (SCCC).

Results: Our cohort included 53 adult patients (25 at PH vs. 28 at SCCC). PH patients were more likely to belong to racial/ethnic minority groups (black non-Hispanic 84% at PH vs. 32% at SCCC, Hispanic 16% at PH vs. 0% at SCCC, p < 0.01) and to be uninsured (60% at PH vs. 0% at SCCC, p < 0.01). Site of care (PH vs. SCCC) or race/ethnicity did not impact the treatment choice. At a median follow-up of 60 months (IQR 21-83), 3 deaths occurred, resulting in an overall 5-year restricted mean overall survival of 57 months. Overall survival and progression-free survival were not statistically different between the two sites of treatment.

Conclusion: Despite health inequities that typically impact safety-net patients, we did not observe differences in treatment patterns or outcomes of Nodular lymphocyte-predominant Hodgkin's lymphoma between patients treated at PH compared to SCCC.

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) clones are frequently found in hypoplastic myelodysplastic syndromes (hMDS), though less commonly than in aplastic anemia. In contrast, the coexistence of hemolytic PNH with large clones and classical, hypercellular MDS (non-hMDS) is rare and likely underrecognized in clinical practice. Since 2014, 229 MDS patients have been seen at our department. Here, we report two cases with this association and discuss their particular diagnostic and treatment challenges.

Case presentations: The first case is a 68-year-old woman with a hemolytic PNH of 59 years duration. We first saw her in June 2021; she had pancytopenia, with values stable over the past 25 years. After a complete work-up, MDS with low blasts and SF3B1 mutation was diagnosed. She was subsequently diagnosed with symptomatic pulmonary hypertension, and in 2023, she started therapy with ravulizumab, achieving good disease control. The second case concerns a 76-year-old man diagnosed with MDS at age 74. One year later, his anemia worsened, and hemolytic PNH with large clones was diagnosed. The patient showed initial benefit from ravulizumab, and he was later switched to pegcetacoplan, which led to effective disease control.

Conclusion: We want to emphasize the importance of assessing PNH clones in the diagnosis of non-hMDS, especially in cases with significant anemia. Regarding PNH treatment in such patients, we found that they are underrepresented in studies investigating complement inhibitor. However, standard doses recommended for PNH appear effective and safe regardless of the underlying disease.

Introduction: Extramedullary involvement in multiple myeloma represents aggressive disease, with clinical stratification of primary extramedullary disease (EMD) remaining a challenge. In this study, we aimed to develop a credible nomogram utilizing routine laboratory variables to predict individual survival for primary EMD patients.

Methods: We retrospectively analyzed a cohort of 60 primary EMD patients, from January 2006 to December 2022. Independent risk factors were identified and subsequently incorporated to generate a nomogram using the Cox proportional hazard regression model. Then, we classified patients into two risk groups based on the nomogram model risk score and compared their survival time using the Kaplan-Meier method.

Results: After a median follow-up of 25.4 months, the median progression-free survival (PFS) of primary EMD patients was 29.4 months. Three independent prognostic factors, namely Ki67, endothelial activation stress index (EASIX), and monocyte count, were identified and subsequently incorporated to generate a nomogram using the Cox proportional hazard regression model. Nomogram performance was assessed using various metrics. Then, we classified patients into two risk groups based on the nomogram model risk score, and the Kaplan-Meier curve showed that the median PFS was significantly longer in the low-risk group compared to the high-risk group (37.1 months versus 2.6 months, p < 0.001).

Conclusion: A predictive nomogram was developed and validated to evaluate the outcome of primary EMD patients.

Introduction: Despite adequate pharmacologic treatment and transfusion support for myelodysplastic syndromes (MDS), there is an ongoing need to explore non-pharmacologic approaches for managing MDS symptom burden. Yoga has proved effective in oncologic patients. The aim of this observational study was to explore the feasibility of an 8-week online Kundalini yoga program, including its impact on symptom burden in MDS patients.

Methods: All patients diagnosed with MDS in our medical center were offered an 8-week online program, in which a 1-h weekly kundalini yoga session was held live via Zoom. All segments included postures in the sitting position, specifically planned for this patient population. Symptom burden was assessed before and after each session and at a later timepoint - 8 weeks post-course completion, using the Edmonton Symptom Self-Assessment Scale - global distress score (ESAS-GDS).

Results: Fourteen patients participated in the program. The median number of sessions per patient was 4. The questionnaires were reasonably easy for the patients to complete. Mean GDSs significantly improved after yoga sessions. Patients consistently endorsed reduced fatigue (78%), increased alertness (65%), increased general well-being (60%), and reduced anxiety (42%) after practicing yoga. Furthermore, symptom burden remained significantly improved 8 weeks after course completion.

Conclusion: This Kundalini yoga program for MDS patients was feasible and resulted in significantly better patient-reported health outcomes, ongoing for at least 8 weeks after the last intervention. Longer follow-up within a longer practice program is planned.

Introduction: Primary immune thrombocytopenia (ITP) is an autoimmune condition marked by low platelet counts, leading to symptoms such as bleeding. Avatrombopag (AVA), a second-generation thrombopoietin receptor agonist, has shown efficacy in clinical trials but lacks extensive real-world data, particularly in Central and Eastern Europe (CEE). This study aims to evaluate the effectiveness and safety of AVA in routine clinical practice for ITP patients across CEE countries.

Methods: A multicenter, noninterventional, retrospective analysis was conducted in Slovenia, Croatia, and the Czech Republic, involving 41 patients treated with AVA for primary ITP. The primary endpoint was achieving a platelet response at week 8 (W8).

Results: AVA treatment resulted in a 68.3% platelet response rate by W8, with a significant increase in median platelet counts. Rescue medication use decreased post-AVA initiation, and many patients reduced or discontinued steroids. AVA was well-tolerated, with only one adverse event reported and no significant bleeding events.

Conclusion: AVA is effective in improving platelet counts and reducing medication dependency in ITP patients in CEE countries. It offers a viable treatment option with a favorable safety profile, supporting its use across different ITP stages and patient demographics.

Background: Hairy-cell leukemia (HCL) is a rare chronic hematologic malignancy, generally presenting with pancytopenia, relative lymphocytosis, monocytopenia, and splenomegaly. Diagnosis is based on typical bone marrow evaluation with the BRAF-V600E mutation being present in almost 100% of cases of classical HCL.

Summary: Treatment usually involves the use of purine analogs (PAs) as first-line therapy. Novel targeting therapies have recently been included in the treatment of therapy-naive HCL such as PA combination with anti-CD20, BRAF inhibitors alone, or combined with anti-CD20. In relapse/refractory disease, other novel agents were studied as BRAF and MEK inhibitors, Bruton tyrosine kinase, or BCL2 inhibitors: all showed encouraging results. Most clinical trials and guidelines do not specify what the optimal approach is for patients with HCL in special situations as elderly population above 80 years old, very young patients below 40 years old, pregnant women, and when leukemia is presented with other comorbidities as active infection or vasculitis.

Key messages: In this current manuscript, we summarized our approach to HCL in the era of novel agents with special emphasis on age and comorbidities.

Introduction: Congenital dyserythropoietic anemia type I (CDA-I) is a rare disorder of erythropoiesis. All CDA-I patients are expected to have iron overload and chronic hemolysis. Patients with severe anemia may undergo splenectomy. Hemochromatosis, chronic hemolysis, and splenectomy are all found to increase risk for thromboembolism in thalassemic patients. As CDA-I patients have similar findings, we sought to evaluate prevalence of thromboembolic events (TEEs) in these patients.

Methods: A retrospective case-control study was conducted, including 110 CDA-I patients (study group) and 326 age- and sex-matched iron deficiency anemia patients of the same ethnicity (control group). Patients were risk-stratified using Risk Assessment Models for thromboembolism.

Results: We identified 3 cases (2.7%) with TEEs in the CDA group and 1 case (0.3%) in the control group. All patients were females. VTE risk scores were low to moderate for CDA patients and higher for IDA patient. When compared to control group, CDA-I patients were nine times more likely to develop TEE (OR 9.11, 95% CI = 1.15-185.27, p = 0.057). All 3 CDA patients had a history of remarkable hemolysis and iron overload. Two underwent splenectomy.

Conclusion: These findings show that CDA patients appear to be at increased risk for TEEs.

Background: Chimeric antigen receptor (CAR)-natural killer (NK)/T-cells offer a new approach in immune therapy of haematological cancers. NK/T-cells bridge innate and adaptive immunity with strong anti-cancer effects. Unlike allogeneic CAR-T-cells, CAR-NK/T-cells do not require TCR genetic deletion to prevent major MHC recognition, have a lower risk of graft-versus-host disease, and can be used universally.

Summary: Pre-clinical studies report CAR-NK/T-cells effectively target antigens such as CD19 and B-cell maturation antigen in B-cell lymphomas and plasma cell myeloma. Compared with CAR-T-cells, CAR-NK/T-cells have faster immune responses, more cytotoxicity and better safety. Recent innovations increase efficacy of CAR-NK/T-cell therapies. Early clinical trials report promising safety and efficacy. Although still in the early phases of development, advances in NK/T-cell therapy are overcoming prior challenges.

Key messages: CAR-NK/T-cells may prove a safer, more flexible form of cell therapy of haematological cancers.

Introduction: Anemia can influence decisions regarding initiation, dosing, and discontinuation of Janus kinase inhibitor therapy for myelofibrosis. We evaluated the impact of new-onset or worsening anemia following ruxolitinib initiation on spleen response, symptom severity, and overall survival in patients with myelofibrosis.

Methods: This post hoc analysis used data from all patients enrolled in the phase 3b JUMP trial. Outcomes were stratified by presence or absence of new-onset or worsening anemia following ruxolitinib initiation, defined as hemoglobin decrease ≥15 g/L from baseline and hemoglobin <100 g/L (female)/<110 g/L (male) at Week 12, new transfusion requirement post-baseline until Week 12 (for baseline non-transfusion-dependent patients), or ≥50% increase from baseline in red blood cell transfusions through Week 12.

Results: Overall, 2,233 patients were included; 52.9% developed new-onset or worsening anemia up to Week 12. Ruxolitinib was associated with improvements in spleen length and myelofibrosis symptoms, regardless of the presence or absence of new-onset or worsening anemia or baseline anemia status. No differences in spleen response or overall survival were observed between patients with versus without new-onset or worsening anemia, regardless of baseline anemia status.

Conclusions: These results support the use of ruxolitinib in patients with myelofibrosis, regardless of baseline anemia or development of treatment-related anemia.