This review aims to provide comprehensive and practical information on the once-nearly-forgotten but now resurgent roles and trends of autologous transplantation in leukemias. We seek to categorize when it is necessary as a first-line treatment (plasma cell leukemia) and to identify well-defined patient subgroups (such as certain types with intermediate prognosis in AML, APL second remission, etc.) in which autologous transplantation might be comparably or even slightly more effective than allogeneic transplantation, not only in frail patients. In some leukemias, such as CLL, autologous transplantation still does not play a role. Attempts to achieve anti-leukaemic effects in autologous settings have proven largely ineffective, but new approaches might be promising. Newer cell therapies (such as CAR-T) are significantly more effective, and the same applies to in vitro graft purging. However, this area has been investigated relatively recently in an innovative manner, using specific graft pretreatments that may also stimulate anti-leukemic immune responses in autologous cases.

Az idült mieloproliferatív betegségek lefolyásuk során állandóan fokozott vaszkuláris és az idő előrehaladtával emelkedő malignus transzformációs rizikót jelentenek, amelyek jelentősen befolyásolják a betegek morbiditását és mortalitását. Fontos olyan kezelés választása, ami mindkét rizikótényezőt a legjobban csökkenti. Az effektivitás mellett a terápiától további elvárás, hogy biztonságos, tolerálható legyen, hiszen az idült mieloproliferatív betegek többnyire idősek, több társbetegséggel rendelkeznek. A szerzők jelen retrospektív vizsgálatuk során a pegilált interferon terápia hatékonyságát és tolerálhatóságát vizsgálták hat magyar hematológiai centrum bevonásával. Etikai engedély birtokában, 153 beteg adatait elemzik deskriptív statisztikai módszereket alkalmazva. A vizsgált periódusban (átlag 39 hónap) a pegilált interferon terápia mellett artériás és/vagy vénás tromboembóliás esemény 4,57%, malignus transzformáció a betegek 1,93%-ánál jelentkezett. Túlnyomóan enyhe mellékhatást – amelyek nem tették szükségessé a terápia megszakítását – minden negyedik betegnél észleltek. Eredményeik – a nemzetközi szakirodalmi adatokkal összevetve – alátámasztják a pegilált interferon kezelés hatékonyságát és tolerálhatóságát krónikus mieloproliferatív betegségben szenvedőknél.

Bispecific antibodies represent a pivotal advancement in treating relapsed/refractory B-cell lymphomas, addressing unmet needs for patients with limited conventional options. This review examines CD20 × CD3 bispecific antibodies (BsAbs) like mosunetuzumab, epcoritamab, odronextamab, and glofitamab, which link malignant B-cells and T-cells, thus inducing targeted tumor lysis. These IgG-like molecules activate T-cells, triggering proliferation and cytotoxic molecule release, bypassing MHC presentation. These agents have received regulatory approval for the treatment of various B-cell lymphomas and exhibit substantial efficacy, with high overall and complete response rates in diffuse large B-cell lymphoma and follicular lymphoma. However, their use is associated with immune-related toxicities. Cytokine Release Syndrome, which is a systemic inflammatory response due to a cytokine surge, and Immune Effector Cell-Associated Neurotoxicity Syndrome, linked to endothelial activation and blood–brain barrier disruption, are critical concerns. This review details their mechanisms, grading, and management, including the use of tocilizumab and corticosteroids. Furthermore, BsAb therapy carries an elevated susceptibility to viral, bacterial, and opportunistic infections, often exacerbated by hypogammaglobulinemia. Expert recommendations for antimicrobial prophylaxis, including herpes and varicella zoster virus, pneumocystis, and immunoglobulin supplements are crucial for mitigating these risks. While BsAbs offer an “off-the-shelf” advantage, balancing their efficacy with comprehensive toxicity management is crucial for maximizing patient outcomes.

Background: This review aims to provide a comprehensive and practical overview of the evolving role of autologous transplantation in leukaemias, a strategy that was once largely abandoned but has recently regained interest in selected clinical settings. Methods: We reviewed the historical development of autologous transplantation in acute leukaemias, including the early period during which autologous transplantation was considered inferior to allogeneic approaches because of limited graft purification techniques and the inability to induce effective graft-versus-leukaemia (GVL)-like immune responses. We further summarise more recent experimental strategies aimed at improving stem cell purification and enhancing anti-leukaemic immune activity in autologous settings. In addition, we discuss how advances in measurable residual disease (MRD) assessment and molecular risk stratification have contributed to the renewed interest in autologous transplantation in selected subgroups of leukaemia patients. Results: This review identifies clinical situations in which autologous transplantation remains an important therapeutic option, including plasma cell leukaemia, where it continues to represent a standard first-line approach. We also discuss well-defined patient subgroups, particularly selected AML subtypes with intermediate-risk molecular profiles and acute promyelocytic leukaemia (APL) in second remission, in which outcomes following autologous transplantation may be comparable to, or occasionally superior to, those achieved with allogeneic transplantation. In contrast, autologous transplantation currently plays only a limited role in diseases such as chronic lymphocytic leukaemia (CLL) and chronic myeloid leukaemia (CML). Although attempts to induce potent anti-leukaemic immune effects in autologous settings have so far shown limited clinical efficacy, several emerging strategies appear promising and may further expand the role of autologous transplantation, particularly in elderly or frail patients. Discussion: Overall, current molecular and MRD-based risk stratification strategies, together with emerging immunological and graft-manipulation approaches, may redefine the role of autologous transplantation as a personalised therapeutic option in selected subgroups of leukaemia patients.

Trial registration: ClinicalTrials.gov number: NCT01777152

The phase 3 ENESTPath study investigated treatment-free remission (TFR) rates in patients with chronic Philadelphia chromosome-positive (Ph+) and/or BCR::ABL1+ chronic myeloid leukemia who had not achieved deep molecular response (DMR) after >2 years of imatinib treatment and were switched to nilotinib 300 mg twice daily (BID). After 24 months of treatment, patients with a stable DMR were randomized to either enter the TFR phase (Arm 1) or continue nilotinib consolidation for an additional 12 months and then enter the TFR phase if in stable DMR (Arm 2). The primary endpoint was the proportion of patients who remained in TFR (≥MR4.0 [BCR::ABL1IS ≤ 0.01

Immune checkpoint inhibitor-induced immune thrombocytopenia (ICI-ITP) is a rare but severe adverse event that may lead to bleeding complications and may require therapeutic changes or interventions. The clinical condition and interventions are highly complex; there are certainly tumour-type and combination-therapy differences, as well as individual ICI-agent factors that modify the risk of thrombocytopenia. ICI-ITP shares some common features, even though its pathogenesis differs markedly from that of traditional ITP. However, ICI-ITP is a clinically important complication; a deeper analysis of factors related to ICI–platelet interactions is also necessary. White blood cell–lymphocyte and platelet count ratios may have prognostic value in predicting the development of a low platelet count. Platelet counts themselves might influence the effectiveness of ICI-type anticancer interventions by facilitating T-cell-induced neoexpression of PD-1 on platelet surfaces. Baseline platelet counts and immunoglobulin levels may also modify treatment outcomes. Platelet activation can also promote immune-related adverse events. ICI-induced ITP-like syndrome’s prognostic factors are not only experimental facts but also clinically important. The connections among platelet counts, activation, immunoglobulins, and cell ratios are likely important factors influencing ICI-induced ITP risk reduction and the improvement of tumour-directed immune response by tailoring ICI selection to tumour type and specific baseline cellular characteristics.

Background and Objectives: Autologous stem cell transplantation (ASCT) remains the standard of care for relapsed or refractory Hodgkin lymphoma (R/R HL), and an increasing proportion of patients receive programmed cell death protein 1 (PD-1) inhibitors prior to transplantation. Engraftment syndrome (ES) is a noninfectious inflammatory complication classically associated with neutrophil recovery; however, early peri-transplant inflammatory manifestations remain poorly characterized and may mimic infectious complications. We aimed to evaluate peri-transplant inflammatory events after ASCT, with particular emphasis on ES-compatible manifestations occurring before neutrophil engraftment and their association with prior PD-1 inhibitor exposure. Materials and Methods: In this single-center retrospective cohort study, 64 consecutive adult patients with HL undergoing ASCT between 2018 and 2025 were analyzed. ES was defined according to Spitzer and Maiolino criteria. Inflammatory manifestations fulfilling these criteria but occurring prior to neutrophil recovery were classified as pre-engraftment syndrome (pre-ES). Clinically significant events were defined by the requirement for systemic corticosteroid therapy. Clinical and laboratory parameters were compared using non-parametric statistical analyses. Results: No cases fulfilled the Spitzer criteria for classical ES, while three patients (4.7%) met the Maiolino criteria, none requiring corticosteroid therapy. Using the broader Maiolino definition, pre-ES was observed in 34 patients (53.1%) when the conventional engraftment time window was disregarded; however, only three patients required systemic corticosteroid therapy. Importantly, all three cases also fulfilled the Spitzer criteria outside the conventional time window, whereas the remaining Maiolino-defined pre-ES cases were self-limiting. All steroid-requiring pre-ES cases occurred exclusively in PD-1-exposed patients, and prior PD-1 therapy was significantly associated with severe pre-ES (p = 0.0007), although this finding is based on a very small number of events. These patients also demonstrated significantly higher early C-reactive protein (CRP) levels. Conclusions: While classical ES after ASCT was uncommon, clinically significant pre-ES occurred exclusively in PD-1-exposed patients. These early inflammatory events may represent a distinct phenotype and require prompt recognition and timely corticosteroid therapy after exclusion of infection. Prospective studies are warranted to validate these findings and refine risk stratification and monitoring strategies.

Introduction Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by elevated platelet counts, risk of vascular events and disease progression to myelofibrosis or acute leukemia. Most available therapies primarily focus on reducing platelet counts without any demonstrated impact on disease progression. Moreover, these treatments are often limited by intolerance, resistance or contraindications, leaving a substantial proportion of patients without satisfactory therapeutic options. Ropeginterferon alfa-2b (BESREMi®), a mono-pegylated, next-generation interferon alfa, approved globally for polycythemia vera with the potential to modify disease course, is being studied to address this unmet need. Methods This fully recruited, ongoing, phase 3, prospective, multicenter, single-arm study (ROP-ET; NCT06514807) enrolled adults with ET according to WHO 2016 criteria requiring cytoreduction, who were intolerant or resistant and/or ineligible for all locally approved cytoreductive therapies including hydroxyurea (HU), anagrelide (ANA), busulfan (BUS) and pipobroman (PB). A single-arm design was selected due to lack of an ethically acceptable comparator. Ropeginterferon alfa-2b is administered subcutaneously every two weeks starting at 125μg, with dose escalation to 250μg and 500μg if needed to achieve hematologic response. The primary endpoint is a composite durable hematologic and clinical response after 12 months based on modified European LeukemiaNet (ELN) criteria, including peripheral blood count remission, absence of thrombotic/hemorrhagic events and disease progression, and symptom improvement measured by the MPN-SAF Total Symptom Score (MPN-SAF TSS). The sample size was determined to ensure at least 93 evaluable patients for 12-month primary analysis (10% precision), with target enrollment of at least 117 to account for 20% dropout. The observed 12-month response rate will be statistically compared to a historical efficacy of 40%. Secondary endpoints include molecular response, quality of life, safety, and long-term outcomes. The total study duration is three years. Results A total of 132 ET patients received ropeginterferon alfa-2b. The study population had a median age of 56.5 years (range 22-87), included 58.3% females, and the median time from diagnosis was 3.3 years (range 0-25). Baseline median platelet count was 579 ×109/L (range 201-1958) and median white blood cell count was 7.3 ×109/L (range 3.2-20.5). At baseline, splenomegaly was present in 25.8% of patients and median MPN-SAF TSS was 8.0 (range 0-66). Driver mutations were distributed as follows: JAK2 (59.8%), CALR (27.9%), and MPL (1.6%). Risk stratification per revised IPSET-thrombosis criteria identified 43.8% patients as high, 13.8% as intermediate, 22.3% as low and 20% as very low risk. Of 132 patients 110 (83.3%) had prior cytoreductive therapy with either HU (32.6%), ANA (13.6%), HU and ANA (36.4%), or HU and PB (0.8%) but none received BUS. Among pre-treated patients, 107 (97.3%) patients were cytoreductive treatment resistant and/or intolerant with intolerance being most prominent (77.2% and 78.8% among HU and ANA pre-treated patients, respectively). All patients were interferon-naïve per inclusion criteria; 22 (16.7%) patients had not received any other cytoreductive therapy and were ineligible for all locally approved cytoreductive agents for ET. As of data cut-off (median exposure 301 days) treatment-emergent adverse events led to discontinuation in only 4 (3%) patients. The last patient 12-month visit will occur in Q3 2025 and primary endpoint results will be presented at the meeting. Conclusions Our study highlights the unmet need among ET patients of all risk levels for additional therapeutic options, since all patients enrolled required cytoreduction but were unable to receive locally approved agents. Aside reduction of thrombotic risk, ET patients, in particular younger individuals, have a significant lifetime risk of disease progression, requiring a disease modifying therapy. In this last-line population, treatment with ropeginterferon alfa-2b was well tolerated, with few discontinuations due to adverse events. The planned primary endpoint analysis will provide data on the efficacy of ropeginterferon alfa-2b in this underserved population.

BACKGROUNDWhether fixed-duration acalabrutinib-venetoclax (with or without obinutuzumab) would result in better progression-free survival than chemoimmunotherapy in patients with untreated chronic lymphocytic leukemia (CLL) is unknown.METHODSIn this phase 3, open-label trial, we included patients 18 years of age or older who had an Eastern Cooperative Oncology Group performance-status score of 0 to 2 (range, 0 to 5, with higher numbers indicating greater disability) and who did not have a 17p deletion or T P53 mutation. Patients were randomly assigned, in a 1:1:1 ratio, to receive acalabrutinib-venetoclax (acalabrutinib, cycles 1 to 14; venetoclax, cycles 3 to 14), acalabrutinib-venetoclax-obinutuzumab (as above, plus obinutuzumab, cycles 2 to 7), or chemoimmunotherapy with the investigator's choice of f ludarabine-cyclophospha-mide-rituximab or bendamustine-rituximab (cycles 1 to 6). The primary end point was progression-free survival (acalabrutinib-venetoclax vs. chemoimmunotherapy) in the intention-to-treat population, assessed by blinded independent central review.RESULTSA total of 867 patients underwent randomization: 291 were assigned to receive acalabrutinib-venetoclax, 286 acalabrutinib-venetoclax-obinutuzumab, and 290 che-moimmunotherapy (of whom 143 received f ludarabine-cyclophosphamide-rituximab and 147 bendamustine-rituximab). The median age of the patients was 61 years (range, 26 to 86), 64.5% were men, and 58.6% had unmutated IGHV. Estimated 36-month progression-free survival at a median follow-up of 40.8 months was 76.5% with acalabrutinib-venetoclax, 83.1% with acalabrutinib-venetoclax-obinutuzumab, and 66.5% with chemoimmunotherapy (hazard ratio for disease progression or death with acalabrutinib-venetoclax vs. chemoimmunotherapy, 0.65 [95% confidence in-terval {CI}, 0.49 to 0.87], P = 0.004; for the comparison of acalabrutinib-venetoclax-obinutuzumab with chemoimmunotherapy, P<0.001). Estimated 36-month overall survival was 94.1% with acalabrutinib-venetoclax, 87.7% with acalabrutinib-veneto-clax-obinutuzumab, and 85.9% with chemoimmunotherapy. Neutropenia, the most common adverse event of clinical interest of grade 3 or higher, was reported in 32.3%, 46.1%, and 43.2% in the three groups, respectively; death from coronavirus disease 2019 was reported in 10, 25, and 21 patients in the three groups.CONCLUSIONSAcalabrutinib-venetoclax with or without obinutuzumab significantly prolonged progression-free survival as compared with chemoimmunotherapy in fit patients with previously untreated CLL. (Funded by AstraZeneca; AMPLIFY ClinicalTrials.gov number, NCT03836261.)

Covalent Bruton tyrosine kinase inhibitors (BTKis) have shown clinical activity as monotherapy in relapsed or refractory (R/R) follicular lymphoma (FL); however, outcomes such as response rates and progression-free survival (PFS) have generally been limited. Nemtabrutinib, a potent, noncovalent, reversible BTKi taken by mouth (PO) once daily (QD), has shown promising antitumor activity in various B-cell malignancies. Nemtabrutinib has additional activity versus ibrutinib against Src family kinases and kinases related to ERK signaling, which may produce robust responses. Analysis of nemtabrutinib-treated cell lines using next-generation sequencing showed a lack of mutation in BTK and PLCG2 domains, which contrasts with other covalent and noncovalent BTKis such as ibrutinib and pirtobrutinib, respectively. Furthermore, nemtabrutinib has also showed preclinical efficacy in cell lines carrying BTK mutations derived from patients treated with pirtobrutinib. The phase 2 BELLWAVE-003 study (NCT04728893) was designed to assess nemtabrutinib in participants with various hematologic malignancies. Initial results for cohort G of BELLWAVE-003 (median study follow-up, 6.1 months) showed that nemtabrutinib had a manageable safety profile and promising antitumor efficacy at the recommended phase 2 dose (RP2D) of 65 mg QD in participants with R/R FL. We present results from cohort G of BELLWAVE-003 after additional follow-up. The multicenter, open-label, single-arm phase 2 BELLWAVE-003 study enrolled participants with R/R CLL/SLL, FL, mantle cell lymphoma, marginal zone lymphoma, Richter transformation, and Waldenström macroglobulinemia. Participants with FL whose disease was R/R to chemoimmunotherapy and immunomodulatory agents received nemtabrutinib at the RP2D of 65 mg PO QD until unacceptable toxicity, disease progression, or withdrawal. The primary end point was objective response rate (ORR). Secondary end points included duration of response (DOR) per Lugano 2014 criteria by BICR and safety. Exploratory end points included PFS per Lugano 2014 criteria by BICR and overall survival (OS). The data cutoff date was January 29, 2025. A total of 51 participants with R/R FL were treated with nemtabrutinib at the RP2D. The median study follow-up, defined as time from first dose to the data cutoff date, was 12.2 months (range, 0.7-23.2). The median age of participants was 59 years (range, 33-80); 23 participants (45%) were female, and 29 (57%) had Lugano stage IV disease. Participants had received a median of 4 (range, 1-11) prior lines of therapy. The median duration of treatment was 3.5 months (range, 0.2-15.6), with 11 participants (22%) remaining on treatment at the data cutoff date. The ORR was 43% (95% CI, 29-58); 3 participants (6%) had a complete response, and 19 (37%) had a partial response. At the time of analysis, the median DOR was 3.3 months (95% CI, 2.8-not reached), median PFS was 5.6 months (95% CI, 5.3-8.3), and median OS was not mature. All-cause adverse events (AEs) of any grade were reported in 49 participants (96%). The most common all-cause AEs (≥20%) were neutrophil count decreased (24%) and platelet count decreased (20%). Grade 3 or 4 all-cause AEs occurred in 21 participants (41%). The most common grade 3 or 4 all-cause AEs (≥5%) were neutrophil count decreased (10%), thrombocytopenia (8%), neutropenia (6%), and platelet count decreased (6%). Dose reduction due to an all-cause AE were reported in 3 participants (6%; 1 with asthenia and blood creatinine increased, 1 with platelet count decreased, and 1 with sepsis). Discontinuation due to an all-cause AE occurred in 7 participants (14%; 1 each with asthenia, congestive cardiac failure, COVID-19 pneumonia, traumatic subdural hemorrhage, thrombocytopenia, toxicity to various agents, and urticaria). Death due to an all-cause AE occurred in 3 participants (6%; 1 each from respiratory tract infection, traumatic subdural hemorrhage, and medical aid in dying). No treatment-related AE resulting in death was reported. With additional follow-up, nemtabrutinib continued to show promising antitumor efficacy in participants with FL who had received multiple prior lines of therapy and had progressed on both chemoimmunotherapy and immunomodulatory therapy. The safety profile remained manageable, with no unexpected AEs observed. These results support the ongoing clinical evaluation of nemtabrutinib in the R/R setting for FL.

In classical Hodgkin lymphoma (HL), optimizing early risk stratification and response assessment are the cornerstones of therapy. The advanced interpretation of positron emission tomography - computed tomography (PET/CT) results can provide prognostic information beyond the Deauville score (DS). The aim of our study was to explore the prognostic value of the change in maximum standardized uptake value (ΔSUVmax) to predict disease progression during the first-line treatment of adult HL. All patients were treated with curative intent, standard therapy. PET/CT assessments were performed at baseline, interim and end-of-treatment timepoints. ΔSUVmax cut-off values were determined by the receiver operating characteristics (ROC) analysis. Overall- (OS) and progression-free survival (PFS) were determined as primary endpoints. Baseline SUVmax did not differ in patients who progressed during or after first-line therapy compared to patients in remission. However, patients with progressive disease had a higher mean SUVmax and lower ΔSUVmax at interim analysis. The presence of a ΔSUVmax > 88

In recent years, targeted therapies have become the standard of care for refractory/relapsed mantle cell lymphoma (MCL). Although the mutational profile of MCL has been extensively studied, there is a lack of understanding of resistance mechanisms and genetic factors that impact the response to novel treatments. Since patients relapsing on targeted treatment experience poor clinical outcomes, understanding the genetic foundation of resistance mechanisms in MCL is essential. In this study, we aimed to scrutinize the copy number profile and clonal dynamics of double-resistant MCL patients treated sequentially with Bruton's tyrosine kinase inhibitor (BTKi) and venetoclax using low-coverage whole genome sequencing (lcWGS). Samples obtained after systemic therapy showed more copy number alterations (CNAs) (p = 0.039; Wilcoxon) compared to samples collected before treatment initiation. Patients showing early progression on BTKi demonstrated CNAs affecting cytobands encompassing the coding regions of NOTCH1, TRAF2, BIRC2, BIRC3, and ATM. A deletion in chromosome 9p21.3 was identified in two out of three venetoclax-resistant patients. For patient MCL2, progressing on ibrutinib but showing venetoclax resistance, a 9p21.3 deletion was found throughout the disease course, with acquired SMARCA4-del(19)(p13.3-q13.11) and DLC1-del(8)(p23.2-q11.1) observed at relapse, highlighting their role in disease progression and therapy resistance. Using lcWGS, an innovative genome-wide approach, this study revealed novel putative primary and acquired resistance mechanisms in BTKi and venetoclax double-resistant MCL patients. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

IntroductionDue to risk and response-adapted treatment strategies, more than 80% of newly diagnosed adult classical Hodgkin lymphoma (HL) patients at any stage can be cured and become long-term survivors. A well-known side effect is cognitive dysfunction that appears in HL patients after chemotherapy (chemobrain). In the present longitudinal study, we measured cognitive function in our HL patients, in search of potential correlations between patient-related factors, the signs and symptoms of their diseases, and therapeutic factors.MethodsPatients underwent a computer-assisted assessment (CANTAB) of cognitive function (especially domains of visual memory, attention, working memory, and planning) and filled out psychological questionnaires (standardized, self-administered and validated for Hungarian language) before treatment (n=30, T1) and after the first-line treatment (n=25, T2), and 8.6 years after the end of chemotherapy (n=19, T3).ResultsThe median age of 16 females and 14 males was 35 years (20-69), 35 years (21-63) after chemotherapy, and 43 years (29-70) at the end of the long-term follow-up, when the study was completed. 77% of all patients showed cognitive impairment before treatment. A close correlation was found between attention and unfavorable prognostic factors (III-IV. stage, age, bulky) baseline comorbidities (T2DM, psoriasis, HTN) and place of residence. Visual memory was affected by comorbidities and the place of residence. Working memory and planning was influenced by single marital status, and bulk disease. Post-treatment cognitive impairment was evaluated in 77% of the HL patients. In the working memory and planning domain, the Stockings of Cambridge (SOC) subtest significantly improved after treatment, while visual memory and attention remained unchanged. The cumulative dose of bleomycin associated with SOC.ConclusionThe study highlights the fact that cognitive functions of HL patients were already impaired before treatment, especially attention, working memory, and planning. Long-term improvement in cognitive function was observed post-treatment. Employment status, place of residence and unfavorable prognosis have an impact on cognitive domains. Early diagnosis and intervention are essential to maintain patients’ quality of life throughout and after treatment.

Background: Hereditary hemorrhagic telangiectasia (HHT) is an inherited vascular bleeding disorder. The most common symptoms are recurrent, severe nosebleeds that occasionally necessitate intervention by an ENT (Ear, Nose, and Throat) specialist, as well as iron-deficiency anemia. Telangiectasia is typically located in the nasal cavity, lips, tongue, fingertips, and the gastrointestinal mucosa. Arteriovenous malformations (AVMs) are located in internal organs (brain, lungs, liver, etc.). The family history is positive for HHT. The diagnosis is based on the Curacao criteria. The endoglin and activin receptor-like kinase 1 genes (ENG and ACVRL1) are the most common mutation sites, leading to elevated endothelial growth factor (VEGF) levels. Methods: We conducted a retrospective analysis in the Department of Internal Medicine, Division of Hematology, and Center of Expertise for Rare Diseases at the University of Debrecen, spanning the period from 2010 to 2025. Records of patients referred with HHT were reviewed concerning demographic data, clinical presentations, laboratory findings, and treatment approaches. To evaluate management options, epistaxis severity was assessed using the Epistaxis Severity Score (ESS). Results: 48 HHT patients (21 male and 27 female) were included in this retrospective study. Genetic testing was positive in each case, showing mutations in the ENG (HHT1 subgroup) or ACVRL1 (HHT2 subgroup) genes. Most of the patients are followed-up with in our department. ESS was calculated at baseline and 6 months after antiangiogenic treatment by two independent physicians. Detailed computed tomography (CT) was performed in all patients. Seven patients were administered desmopressin, a synthetic analog of antidiuretic hormone (ADH), based on our previous experience in reducing bleeding in von Willebrand disease. Antiangiogenic therapy with thalidomide (50 mg oral tablets) was used in 24 patients, while bevacizumab was administered to 5 patients. Most patients experienced a remarkable decrease in epistaxis severity and a reduction in the need for transfusions (ESS before treatment: HHT1 patients, 4.15 ± 1.91 vs. ESS after treatment, 2.62 ± 0.99; HHT2 patients, 3.79 ± 3.19 vs. 2.02 ± 1.91). Subgroup analysis using paired ESS data showed a significant reduction in ESS in both HHT1 and HHT2 patients (p = 0.003 and p = 0.043, respectively). Bevacizumab further reduced the ESS, but the few cases were not suitable for statistical analysis. Serum iron levels significantly increased after antiangiogenic treatment in the HHT2 group (p = 0.01). Conclusions: HHT is a rare vascular bleeding disorder. Daily nosebleeds impair the patients' quality of life and sometimes lead to severe transfusion-dependent iron-deficient anemia. Frequent hospitalization places a significant burden on the healthcare system. Thus, we have used treatment options for HHT patients that primarily act by inhibiting VEGF, and these treatment modalities have yielded successful results in our hands.