A 42 éves fiatal férfinál 2019-ben leuko-thrombocytosis hátterében csontvelői vizsgálat alapján myelofibrosist igazoltunk. 30 hónap figyelmes várakozást követve betegségprogresszió igazolódott, első vonalban ruxolitinibkezelés indult. Emellett betegsége progrediált, ezért navtemadlin klinikai vizsgálatba vontuk be. Az MDM2 inhibitor mellett gasztrointesztinális mellékhatások jelentkeztek, mely miatt a klinikai vizsgálatból a beteget kivontuk. Ezt követően harmadvonalbeli terápiaként fedratinibet indítottunk, mellyel csökkenő splenomegaliát és javuló vérképet értünk el. Végül elektív splenectomiát követően allogén hemopoetikus őssejt-transzplantációt végeztünk, elhúzódó hematológiai felépülést követően 100% donor graftműködést és rendezett vérképet értünk el.

Zamtocabtagene autoleucel is an autologous, non-cryopreserved tandem CD20-CD19 directed CAR-T cell therapy produced on the fully automated CliniMACS® Prodigy System in 12 d and showed promising efficacy and safety in a Phase II trial in r/r DLBCL. We report primary analysis results of the pivotal DALY 2-EU trial (NCT04844866), which compares zamto-cel vs standard of care (SoC) as second-line (2L) therapy for r/r LBCL in non-transplant eligible (NTE) pts in a randomized, multicenter study.Adult NTE pts with r/r (≤ 24 m after start of first-line [1L] therapy) LBCL were assigned to receive zamto-cel or SoC (R-GemOx, n=78 or Pola-BR, n=8). Key inclusion criteria were LBCL, ECOG ≤ 2 or one NTE criterion. Pts in the zamto-cel arm started lymphodepletion (fludarabine + cyclophosphamide) during manufacturing, followed by infusion of zamto-cel, target dose 2.5 × 106 CAR-T cells/kg body weight. No chemoimmunotherapy bridging except steroids was allowed. The primary endpoint was event free survival (EFS) by blinded independent review committee comparing zamto-cel vs R-GemOx. Key secondary endpoints included remission rates, progression-free survival (PFS) and overall survival.In total, 168 pts were randomized (N=82 zamto-cel, N=86 SoC). Key baseline characteristics were balanced: 63% male pts, median age 74 y (range 19-87), 85% DLBCL, 57% refractory to 1L therapy, 57% IPI 3-5 pts and 66% stage III-IV. 76 pts (93%) received zamto-cel. Six pts did not receive zamto-cel (2 withdrawals, coronary artery stenosis, pneumonia, worsening condition, progressive disease). Median vein-to-vein time was 15 d (range 14-16). With a median follow-up of 17 m, median EFS was 6.2 m (95% CI 3.8-13.8) for zamto-cel and 2.5 m (95% CI 2.0-3.3) for R-GemOx (HR 0.39; 95% CI 0.27-0.58; p<0.0001) in the ITT population. Median PFS was significantly longer with zamto-cel vs R-GemOx (8.5 m [95% CI 3.8-16.8] vs 3.3 m [95% CI 2.0-3.8]; HR 0.43 [95% CI 0.28-0.65]; p<0.0001). ORR was 72% (61-81%) with a CR rate of 54% for zamto-cel vs 45% (34-57%) ORR and 14% CR rate for R-GemOx. Among all patients treated with zamto-cel in the experimental arm, ORR was 78%, with 58% achieving CR. In the zamto-cel arm, CRS Grade (G) ≥3 was reported in 4 pts (5.3%; 2 pts G3, 1 pt G4, 1 pt G5). Median time to onset of CRS was 2 d (1-14), median duration was 3 d (1-24). One pt (1.3%) had ICANS G3, no G4/5. For CRS, 29 (38%) pts received tocilizumab, 14 (18%) corticosteroids. Persisting neutropenia (≥ 28 d) of G4 was reported in 7 pts (9%). Within 90 d after start of treatment, 8 pts died in each arm; main reason was progression in 4 (50% zamto-cel) and 5 (63% R-GemOx) pts.Zamto-cel demonstrated significant and clinically meaningful superiority over R-GemOx in NTE pts. Zamto-cel was well tolerated in this vulnerable elderly population with low rates of severe CRS/ICANS. This favorable risk/benefit profile suggests the use of zamto-cel as preferred treatment option in 2L NTE pts with r/r LBCL.

The intestinal microbiome is a key regulator of immune homeostasis, metabolism, and epithelial barrier integrity. In patients with malignant hematological diseases, particularly those undergoing hematopoietic stem cell transplantation, microbiome perturbations by reduced diversity, pathobiont expansion, and loss of beneficial metabolites are common as a consequence of exposure to cytotoxic therapy and broad-spectrum antimicrobials. Accordingly, enteral microbiome manipulation has emerged as a promising strategy. We performed a narrative review of the literature in PubMed/MEDLINE, Embase, and the Web of Science from inception to October 2025. We focused on adult hematology and HSCT populations and synthesized evidence across microbiome-directed interventions, including fecal microbiota transplantation (FMT) and emerging standardized microbiota products, as well as adjunctive strategies such as pre-, pro-, and postbiotics, dietary modulation, and microbiome-sparing antimicrobial practices. Available clinical evidence, predominantly from case series, small cohorts and a limited number of randomized trials, suggests that FMT is feasible in selected immunocompromised patients and may be beneficial for recurrent Clostridioides difficile infection, multidrug-resistant organism decolonization and steroid-refractory gastrointestinal GvHD. Mechanistic data support pleiotropic effects of microbiome restoration, including replenishment of immunoregulatory metabolites, improved colonization resistance and reinforcement of mucosal function. While most reported adverse events are mild, rare transmission events and product variability necessitate for rigorous donor screening, standardized manufacturing and regulatory oversight. Key knowledge gaps include patient selection, optimal timing, dosing strategies, durability of benefit and integration with concurrent medications. In conclusion, microbiome-based interventions may transition from rescue therapy toward a structured component of supportive care in hematologic malignancy management.

Advanced age, comorbidities, and immunocompromised states remain major risk factors for severe or persistent COVID-19 despite vaccination and antivirals, underscoring the need for innovative treatments such as adoptive T-cell therapy (ATT). In this prospective single-center study, we evaluated the safety, feasibility, and efficacy of two ATT approaches in immunocompromised patients with high-risk or persistent SARS-CoV-2 infection: interferon-γ cytokine capture system virus-specific T cells (IFN-γ CCS VST, n = 12; median age 59) and CD45RA + T-cell depleted donor lymphocyte infusion (CD45RA+ TCD DLI, n = 11; median age 46). Most patients (73.9

Hereditary hematological malignancies (HHM) are characterized by genetic heterogeneity, variable penetrance, and expressivity. Although individual gene involvement is rare, germline pathogenic variants are estimated to be present in at least 5-10% of hematological malignancies. In cases diagnosed at young age, with positive family history, or with multiple malignancies (including myeloid neoplasms after cytotoxic treatments), the prevalence rises, reaching 13-21%. Germline-focused tumor analysis may suggest genetic predisposition even without clinical suspicion. Using larger gene panels or whole-exome sequencing can further increase the detection rate of pathogenic germline variants to over 20%. In HHM, peripheral blood/bone marrow samples may contain somatic and germline variants. Germline confirmation requires non-hematopoietic samples, such as hair follicles or fibroblast cultures. Identifying HHM has clinical implications, especially in the timing of allogeneic stem cell transplantation, donor selection, conditioning, and follow-up. Genetic screening and counseling are essential for predisposed patients and family members to provide interdisciplinary care.

Introduction: In patients undergoing allogeneic hematopoietic stem cell transplantation, a disease -specific biomarker is not always available. Such cases can be monitored with a "chimerism test", which provides information about relapse, engraftment and recipient -derived hematopoiesis. Determination of clinical chimerism can be performed by different methods. In case of hematopoietic stem cell transplantation, the detection of "short tandem repeats" (STR) by fragment analysis can detect up to 1-5% recipient ratio, while more sensitive and accurate techniques are capable of measuring microchimerism (< 1%). Objective: Introduction of a method based on the detection of deletion insertion polymorphisms (DIP) by droplet digital PCR (ddPCR) and comparison of results measured with STR and DIP methods. Method: The assay was set up with artificial, mixed chimera samples prepared from genomic DNA of volunteers (n = 6), and limit of blank and limit of detection values were calculated. We correlated STR results to those of DIP technique (n = 48 recipients, 146 samples). Informativity values were calculated by using 403 transplantation cases. We used 8 DIP markers and a Y chromosome specific marker in our study. Retrospective studies were performed for early relapse -detection. Results: The results achieved by ddPCR showed strong correlation with STR in the 1-100% mixed chimerism range (R2 = 0.988, n = 146 samples). The average informativity value was 96% in case of transplantation with one donor, i.e., we were able to detect the mixed chimerism state with at least 1 marker with a high probability. The new method shortened the turnaround time and limit of detection is improved by 1-1.5 orders of magnitude compared to STR. Conclusion: With regular ddPCR monitoring, disease relapse can be predicted in an early phase before the onset of clinical relapse. The potential applications of ddPCR-based high -sensitivity chimerism detection are the following: microchimerism during hematopoietic microtransplantation, early detection of graft rejection after solid organ transplantation, and microchimerism studies in autoimmune diseases or pregnancies.

Bevezetés: Az allogén haemopoeticusőssejt-transzplantáción átesett betegek esetében betegségspecifikus biomarker nem mindig áll rendelkezésre, ekkor a beteg állapota chimaerismusvizsgálattal monitorozható, amely tájékoztatást ad a relapsusról, a vérképző sejtek megtapadásáról és a recipienseredetű vérképzésről. A klinikai chimaerismus, vagyis két vagy több különböző egyén sejtjeinek egymás melletti jelenléte, többféle módszerrel mutatható ki. A „short tandem repeat”-ek (STR) detektálásán alapuló fragmensanalízis-módszerrel legkevesebb 1–5% recipiensarány, ezzel szemben az érzékenyebb és pontosabb módszerekkel már a microchimaerismus (<1%) is kimutatható. Célkitűzés: A microchimaerismus detektálására alkalmas deletiós insertiós polimorfizmusok (DIP) jelenlétén alapuló módszer bevezetése és beállítása droplet digitális PCR (ddPCR-) technikával, illetve az STR- és a DIP módszerrel mért eredmények összehasonlítása. Módszer: A beállítás önkéntesek (n = 6) genomiális DNS-éből, mesterséges, kevert chimaeraminták előállításával történt, melyek során vakpróba és kimutathatósági határértékeket (LoB, LoD) számítottunk. Az STR- és a DIP-módszer mérési eredményeit korreláltattuk egymással (n = 48 recipiens, 146 minta), és informativitási értéket számítottunk 403 transzplantációs esetet felhasználva. A rutinvizsgálatok elvégzéséhez és a számításokhoz 8 DIP- és egy további, Y-kromoszóma-specifikus markert használtunk. A relapsus korai kimutatására retrospektív vizsgálatot végeztünk. Eredmények: A bevezetett ddPCR-módszer megbízható, és kifejezett korrelációt mutatott az STR-vizsgálat eredményeivel az 1–100% kevert chimaerismustartományban (R 2 = 0,988; n = 146 minta). A gyakorlati alkalmazhatóságot jellemző informativitási érték egy donorral történt transzplantáció esetében 96%-os, vagyis igen nagy valószínűséggel, legalább 1 markerrel detektálni tudtuk a kevert chimaeraállapotot. Az új módszerrel lerövidült a mintaátfordulási idő, és 1–1,5 nagyságrenddel javult a kimutathatósági határ az STR-technikához képest. Következtetés: Rendszeres ddPCR-monitorozással bizonyos esetekben még a klinikai relapsus megjelenése előtt, korai szakaszban előre jelezhető a betegség kiújulása. A ddPCR-rel végzett, nagy érzékenységű chimaerismusvizsgálat lehetséges alkalmazási területei: haemopoeticusőssejt-mikrotranszplantáció, szolidszerv-transzplantáció után a graftkilökődés korai kimutatása, illetve autoimmun betegségek és várandósság alatt előforduló microchimaerismust célzó kutatások. Orv Hetil. 2024; 165(8): 297–308.

IntroductionAcquired Hemophilia A (AHA) is a rare autoimmune disorder characterized by the emergence of inhibitors that specifically target coagulation Factor VIII, frequently resulting in severe bleeding episodes.MethodsWe conducted a retrospective analysis of the medical records of a 68-year-old male patient who presented with adalimumab-induced AHA.ResultsThe patient received adalimumab, a tumor necrosis factor inhibitor antibody, as part of his treatment for rheumatoid arthritis. The patient’s clinical journey, characterized by intense bleeding and coagulopathy, was effectively managed with the application of recombinant Factor VIIa (rFVIIa) and the CyDRi protocol.DiscussionThe case emphasizes the importance of prompt coagulation assessment in patients with bleeding symptoms receiving disease-modifying therapy for rheumatoid arthritis that includes adalimumab therapy, considering the rare yet life-threatening nature of AHA. Additionally, this report provides an extensive review of the existing literature on drug-induced AHA, with a special emphasis on cases linked to immunomodulatory medications. Through this two-pronged approach, our report aims to enhance understanding and awareness of this severe complication among healthcare providers, promoting timely diagnosis and intervention.

Thromboinflammation/immunothrombosis plays a role in several diseases including thrombotic thrombocytopenic purpura (TTP) and COVID-19. Unlike the extensive research that has been conducted on COVID-19 cytokine storms, the baseline and acute phase cytokine profiles of TTP are poorly characterized. Moreover, we compared the cytokine profiles of TTP and COVID-19 to identify the disease-specific/general characteristics of thromboinflammation/immunothrombosis. Plasma concentrations of 33 soluble mediators (SMs: cytokines, chemokines, soluble receptors, and growth factors) were measured by multiplex bead-based LEGENDplex™ immunoassay from 32 COVID-19 patients (32 non-vaccinated patients in three severity groups), 32 TTP patients (remission/acute phase pairs of 16 patients), and 15 control samples. Mainly, the levels of innate immunity-related SMs changed in both diseases. In TTP, ten SMs decreased in both remission and acute phases compared to the control, one decreased, and two increased only in the acute phase compared to remission, indicating mostly anti-inflammatory changes. In COVID-19, ten pro-inflammatory SMs increased, whereas one decreased with increasing severity compared to the control. In severe COVID-19, sixteen SMs exceeded acute TTP levels, with only one higher in TTP. PCA identified CXCL10, IL-1RA, and VEGF as the main discriminators among their cytokine profiles. The innate immune response is altered in both diseases. The cytokine profile of TTP suggests a distinct pathomechanism from COVID-19 and supports referring to TTP as thromboinflammatory rather than immunothrombotic, emphasizing thrombosis over inflammation as the driving force of the acute phase.

We report the case of long-term persisting rheumatoid arthritis (RA), treated with CD20-CD19 CAR-T when it became associated with diffuse large B cell lymphoma (DLBCL), resulting in a sustained drug-free remission of the preceding RA, as well as of the subsequent DLBCL that formed the indication of the CAR-T therapy using zamtocabtagene autoleucel, with a 1-year follow-up. According to our best knowledge, this is the first published clinical case report of long-term persisting RA treated with CAR-T cell therapy.

Grafikus absztraktA cytomegalovirus infekció megelőzése és kezelése allogén vérképző őssejt-transzplantáltakbanRövidítések: CMV: cytomegalovirus, HSCT: vérképző őssejt-transzplantáció, DLI: donor limfocita infúzió, NEAK: Nemzeti Egészségbiztosítási Alapkezelő, EMK: egyedi méltányossági kérelem, T-reg: regulátor T-limfocita, VST: vírus-specifikus T-sejt (terápia), ISU: immunszuppresszió, CRISPR/Cas-9: clustered regularly interspaced short palindromic repeats endonuclease (génszerkesztési eszköz), IL: interleukin, IVIG: intravénás immunglobulin (készítmény), Ig: immunglobulin, MoAt: monoklonális antitest

The COVID-19 pandemic has exacerbated mortality rates among immunocompromised patients, accentuating the need for novel, targeted therapies. Transplant recipients, with their inherent immune vulnerabilities, represent a subgroup at significantly heightened risk. Current conventional therapies often demonstrate limited effectiveness in these patients, calling for innovative treatment approaches. In immunocompromised transplant recipients, several viral infections have been successfully treated by adoptive transfer of virus-specific T-cells (VST). This paper details the successful application of SARS-CoV-2-specific memory T-cell therapy, produced by an interferon-γ cytokine capture system (CliniMACS® Prodigy device), in three stem cell transplant recipients diagnosed with COVID-19 (case 1: alpha variant, cases 2 and 3: delta variants). These patients exhibited persistent SARS-CoV-2 PCR positivity accompanied by bilateral pulmonary infiltrates and demonstrated only partial response to standard treatments. Remarkably, all three patients recovered and achieved viral clearance within 3 to 9 weeks post-VST treatment. Laboratory follow-up investigations identified an increase in SARS-CoV-2-specific T-cells in two of the cases. A robust anti-SARS-CoV-2 S (S1/S2) IgG serological response was also recorded, albeit with varying titers. The induction of memory T-cells within the CD4 + compartment was confirmed, and previously elevated interleukin-6 (IL-6) and IL-8 levels normalized post-VST therapy. The treatment was well tolerated with no observed adverse effects. While the need for specialized equipment and costs associated with VST therapy present potential challenges, the limited treatment options currently available for COVID-19 within the allogeneic stem cell transplant population, combined with the risk posed by emerging SARS-CoV-2 mutations, underscore the potential of VST therapy in future clinical practice. This therapeutic approach may be particularly beneficial for elderly patients with multiple comorbidities and weakened immune systems.

Introduction: Acquired factor V inhibitor (AFVI) is a rare autoimmune bleeding disorder. The treatment of AFVI is challenging, and patients often require both bleeding control and inhibitor eradication.Methods: We conducted a retrospective analysis of the medical records of a 35-year-old Caucasian woman who presented with severe AFVI-induced bleeding and subsequent immunosuppressive therapy.Results: To provide haemostasis, rFVIIa was given with good efficacy. The patient was treated with various combinations of immunosuppressive regimens over the course of 2.5 years, including plasmapheresis plus immunoglobulins, dexamethasone + rituximab, cyclophosphamide + dexamethasone + rituximab + cyclosporine, cyclosporin + sirolimus + cyclophosphamide + dexamethasone, bortezomib + sirolimus + methylprednisolone, and sirolimus + mycophenolate mofetil. Although these treatment modalities resulted in intermittent partial reversals of AFVI over 2.5 years, eventually the inhibitor became therapy-resistant. However, following the discontinuation of all immunosuppressive therapy, the patient experienced a partial spontaneous remission, which was followed by a pregnancy. During the pregnancy, the FV activity increased to 54% and the coagulation parameters returned to normal levels. The patient underwent Caesarean section without any bleeding complications and delivered a healthy child.Discussion: The use of an activated bypassing agent for bleeding control is effective in patients with severe AFVI. The presented case is unique because the treatment regimens included multiple combinations of immunosuppressive agents. This demonstrates that AFVI patients may undergo spontaneous remission even after multiple courses of ineffective immunosuppressive protocols. Additionally, pregnancy-associated improvement of AFVI is an important finding that warrants further investigation.

Autologous stem cell transplantation (ASCT) is the standard treatment of primary refractory or relapsed Hodgkin-lymphoma, which can provide a cure rate of about 50%. The aim of our study was to analyze the data of 126 HL patients undergoing AHSCT in Hungary between 01/01/2016 and 31/12/2020. We assessed the progression-free and overall survival, the prognostic role of PET/CT performed before transplantation and effect of brentuximab vedotin (BV) treatment on survival outcomes. The median follow-up time from AHSCT was 39 (1-76) months. The 5-year OS comparing PET- and PET + patients was 90% v. 74% (p = 0.039), and 5-year PFS was 74% v. 40% (p = 0.001). There was no difference in either OS or PFS compared to those who did not receive BV before AHSCT. We compared BV treatments based on their indication (BV only after AHSCT as maintenance therapy, BV before and after AHSCT as maintenance treatment, BV only before AHSCT, no BV treatment). There was statistically significant difference in the 5-year PFS based on the inication of BV therapy. Recovery rates of our R/R HL patient population, who underwent AHSCT, improved significantly. Our positive results can be attributed to the PET/CT directed, response-adapted treatment approach, and the widespread use of BV.

IntroductionWhile complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood.MethodsWe therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome.ResultsWe show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p<0.0001) and COVID-19 severity. Despite this, genetic variations in MBL2 are not associated with susceptibility to SARS-CoV-2 infection or disease outcomes such as mortality and the development of Long COVID.ConclusionIn conclusion, activation of the MBL-LP only plays a minor role in COVID-19 pathogenesis, since no clinically meaningful, consistent associations with disease outcomes were noted.