[Waldenström's macroglobulinemia and its individualized therapy options]. / A Waldenström-macroglobulinaemia és betegségre szabott kezelése.

Waldenström's macroglobulinaemia is a form of lymphoplasmocytic lymphoma that preferentially localizes to the bone marrow and causes a special syndrome characterized by monoclonal IgM hypersecretion. Recent results point to the fact that this disease has at least three different pathobiological forms with different clinical presentation. While mutations of MYD88 occur in 95-97% of the cases, there are CXCR4 mutations in 30-40%, ARID1A mutations in 17% and CD79B mutations in approximately 10% of afflicted individuals. CXCR pathway signaling is able to transcriptionally silence tumor suppressors induced by MYD88 activation. Patients with mutated MYD88 and CXCR4 present with higher tumor burden, slower developing and less deep response upon therapy with more frequent resistance. In this review, based on the most recent data, a treatment selection advice is provided for the therapy of symptomatic patients. Orv Hetil. 2017; 158(41): 1604-1614.

Case Report: Effective management of adalimumab-induced acquired hemophilia A with the CyDRI protocol.

Introduction: Acquired 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. Methods: We conducted a retrospective analysis of the medical records of a 68-year-old male patient who presented with adalimumab-induced AHA. Results: The 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. Discussion: The 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.

Effective venetoclax-based treatment in relapsed/refractory multiple myeloma patients with translocation t(6;14).

Introduction: The selective Bcl-2 inhibitor venetoclax has shown promising therapeutic potential in multiple myeloma, particularly in cases associated with t(11;14) IGH::CCND1 translocation. However, the efficacy of venetoclax in myeloma patients with the t(6;14) IGH::CCND3 translocation remains less investigated. Methods: In this study, we conducted a retrospective analysis to investigate the efficacy of venetoclax-based therapy in relapsed/refractory myeloma patients with t(6;14) translocation. The treatment courses of three patients, that included previous therapies and responses to venetoclax, were assessed. Clinical data, laboratory results, and adverse events were analyzed to evaluate treatment outcomes. Results: Our findings demonstrated remarkable therapeutic responses in three consecutive patients with t(6;14) translocation-associated myeloma who received venetoclax-based therapy. Patient 1, a lenalidomide-bortezomib-daratumumab and alkylator treatment refractory patient, achieved sustained stringent complete remission (sCR) after combining carfilzomib-dexamethasone with venetoclax, which was his best response ever. Similarly, Patient 2, refractory to frontline bortezomib-thalidomide-dexamethasone therapy, attained CR following a transition to bortezomib-dexamethason-venetoclax treatment. Patient 3, who was immunomodulatory (IMID)-intolerant, showed a highly favorable response to venetoclax-dexamethasone therapy after his first relapse following autologous stem cell transplantation. No significant adverse effects were observed in any of the patients. Discussion: Our study provides compelling preliminary evidence for the efficacy of venetoclax in t(6;14) translocation-associated myeloma. The outcomes observed in our patients suggest that venetoclax-based therapy holds substantial promise as an effective treatment option for this specific genetic subgroup. Furthermore, the similarities in treatment response between t(11;14) and t(6;14) translocation subgroups highlight the importance of personalized approaches targeting specific genetic abnormalities to optimize therapeutic outcomes.

Correlation between DNA ploidy, metaphase high-resolution comparative genomic hybridization results and clinical outcome of synovial sarcoma.

BACKGROUND: Although synovial sarcoma is the 3rd most commonly occurring mesenchymal tumor in young adults, usually with a highly aggressive clinical course; remarkable differences can be seen regarding the clinical outcome. According to comparative genomic hybridization (CGH) data published in the literature, the simple and complex karyotypes show a correlation between the prognosis and clinical outcome. In addition, the connection between DNA ploidy and clinical course is controversial. The aim of this study was using a fine-tuning interpretation of our DNA ploidy results and to compare these with metaphase high-resolution CGH (HR-CGH) results. METHODS: DNA ploidy was determined on Feulgen-stained smears in 56 synovial sarcoma cases by image cytometry; follow up was available in 46 cases (average: 78 months). In 9 cases HR-CGH analysis was also available. RESULTS: 10 cases were found DNA-aneuploid, 46 were DNA-diploid by image cytometry. With fine-tuning of the diploid cases according to the 5c exceeding events (single cell aneuploidy), 33 cases were so called "simple-diploid" (without 5c exceeding events) and 13 cases were "complex-diploid"; containing 5c exceeding events (any number). Aneuploid tumors contained large numbers of genetic alterations with the sum gain of at least 2 chromosomes (A-, B- or C-group) detected by HR-CGH. In the "simple-diploid" cases no or few genetic alterations could be detected, whereas the "complex-diploid" samples numerous aberrations (equal or more than 3) could be found. CONCLUSIONS: Our results show a correlation between the DNA-ploidy, a fine-tuned DNA-ploidy and the HR-CGH results. Furthermore, we found significant correlation between the different ploidy groups and the clinical outcome (p < 0.05).