1. Is salvage autologous stem cell transplantation still a viable treatment option in relapsed myeloma patients?Luka Čemažar, Matevž Škerget, Barbara Skopec, 2025, izvirni znanstveni članek Povzetek: Background and Objectives: The role of salvage autologous stem cell transplantation (SAT) in relapsed multiple myeloma (MM) has been increasingly questioned, particularly with the emergence of novel immunotherapies and cellular therapies. This study aimed to evaluate the efficacy of SAT in a cohort of patients with relapsed MM following their first autologous stem cell transplantation (ASCT). Materials and Methods: A retrospective analysis was conducted on 78 patients from our institutional registry who underwent SAT for relapsed MM between April 2008 and October 2023. The primary endpoint was the progression-free survival (PFS), with secondary endpoints including the overall survival (OS) and overall response rates (ORRs) on day +100 after SAT. Results: The median age of the patients was 62 years (range: 48–78), and 32% were female. Most patients (81%) received reinduction therapy before SAT. The median PFS and OS from SAT were 24 months (95% CI: 20–36) and 76 months (95% CI: 48-NR), respectively. The ORR was 85%, and 65% achieved at least a very good partial response (VGPR). No significant differences in the PFS were found between subgroups based on the maintenance following SAT (hazard ratio (HR) = 0.93, 95% CI: 0.48–1.8, p = 0.831), cytogenetic risk (standard vs. high-risk) (HR = 0.98, 95% CI: 0.49–1.99, p = 0.969), age (<60 years vs. ≥60 years) (HR = 0.96, 95% CI: 0.5–1.85, p = 0.912) or number of prior treatment lines (<3 vs. ≥3) (HR = 0.186, 95% CI: 0.95–3.61, p = 0.069). The duration of remission after the first ASCT did not influence the PFS or OS following SAT (HR = 1.63, 95% CI: 0.78–3.39, p = 0.193 and HR = 1.2, 95% CI: 0.46–3.09, p = 0.7130). Conclusions: Salvage autologous stem cell transplantation remains a viable treatment option for patients with relapsed MM, particularly in resource-limited countries or for patients who prefer short, fixed-duration therapy. However, as is known from previous studies, maintenance therapy is crucial for achieving longer PFS. In this study, no statistically significant factors were identified to predict the benefit, underscoring the need for further research to optimize patient selection.
Ključne besede: salvage autologous stem cell transplantation, relapsed multiple myeloma
Objavljeno v DiRROS: 09.03.2026; Ogledov: 51; Prenosov: 37
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2. Precursor dendritic cell proliferation in multiple myeloma : a precursor to acute myeloid leukemiaKatarina Reberšek, Saša Anžej Doma, Matevž Škerget, Helena Podgornik, 2026, drugi znanstveni članki Povzetek: Background: Dendritic cells (DCs) are heterogeneous antigen-presenting cells that bridge innate and adaptive immunity. Recent classifications of hematolymphoid neoplasms highlight the complex origins of DC-related neoplasms. DCs have also been associated with the progression of multiple myeloma (MM). This report presents the case of a patient with MM in whom bone marrow analysis revealed an unusual additional clonal population of immature cells, in addition to plasmacytoid DCs, that later evolved into plasmacytoid dendritic cell proliferation associated with acute myeloid leukemia (pDC-AML). Methods: The bone marrow of a 69-year-old man with neutropenia and thrombocytopenia was examined by morphology, immunohistochemistry, flow cytometry, cytogenetics, fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS). Serial assessments were performed before and during treatment with bortezomib and dexamethasone for MM, and later with daunorubicin/cytarabine for AML. Results: Initial bone marrow analysis revealed coexisting clonal plasma cells with t(11;14) and a population of CD34+/CD123+/CD45RA+ cells lacking lineage markers, in addition to pDCs, suggestive of precursor DCs rather than acute undifferentiated leukemia. Cytogenetic analysis identified a small clone with isolated del(20q), which corresponded in size to the clone of undifferentiated cells and to the clone with pathogenic variants detected by NGS in the BCOR, RUNX1, and SRSF2 genes. Myeloma therapy decreased both MM and undifferentiated cells; however, within four months, pDC-AML evolved with del(20q) and higher variant allele frequencies of the previously detected gene variants. Remission was achieved with standard AML chemotherapy. Conclusions: This case supports evidence that MM-associated immune dysfunction and bone marrow niche alterations may promote secondary myeloid malignancies independently of cytotoxic therapy. It demonstrates the earliest events in pDC-AML evolution. Furthermore, the immature immunophenotype raises the question of appropriate treatment, since a diagnosis of acute undifferentiated leukemia can be established.
Ključne besede: dendritic cells, multiple myeloma, acute undifferentiated leukemia
Objavljeno v DiRROS: 05.01.2026; Ogledov: 398; Prenosov: 154
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3. High burden of clonal mast cell disorders and hereditary ▫$α-tryptasemia$▫ in patients who need Hymenoptera venom immunotherapyPeter Korošec, Gunter Sturm, Jonathan J. Lyons, Tinkara Pirc Marolt, Manca Svetina, Mitja Košnik, Mihaela Zidarn, Mark Kačar, Nina Frelih, Nika Lalek, Ajda Demšar Luzar, Samo Zver, Matevž Škerget, Ewa Czarnobilska, Wojciech Dyga, Sanja Popović-Grle, Miroslav Samaržija, Lisa Arzt-Gradwohl, Urban Čerpes, Grzegorz Porebski, Branko Pevec, Eva Schadelbauer, Peter Kopač, Julij Šelb, Matija Rijavec, 2024, izvirni znanstveni članek Povzetek: Background
In patients who require venom immunotherapy (VIT), there is a need to identify underlying mast cell (MC) disorders since these may affect the risk and severity of future sting reactions and the long-term effectiveness of VIT.
Methods
1319 individuals with Hymenoptera venom allergy (HVA) who needed VIT from referral centers in Slovenia, Austria, Croatia, and Poland underwent examination for KIT p.D816V in peripheral blood leukocytes (PBL) using a highly sensitive PCR test and tryptase genotyping by digital droplet PCR. We also included 183 control individuals with large local reactions (LLRs) to Hymenoptera stings and with asymptomatic sensitization to Hymenoptera venoms.
Results
285 of 1319 individuals recommended for VIT (21.6%) were positive for KIT p.D816V in PBL, preferably those who present with severe reaction (33.9% [n = 207 of 610] with Ring-Messmer grade 3–4 vs. 11% [n = 78 of 709] with Grade 1–2; p < .0001), whereas only 1.3% (n = 2 of 152) of controls with LLR and none with asymptomatic sensitization (n = 31) had KIT p.D816V. KIT p.D816V allelic burden was higher in those with severe reaction (median 0.018% [n = 207] in Grade 3–4 vs. 0.001% [n = 78] in Grade 1–2; p < .0001), and the majority had normal baseline serum tryptase levels (69% [n = 196 of 285]). All KIT p.D816V-positive individuals (n = 41) who underwent bone marrow (BM) biopsy were found to have underlying clonal diseases, principally BM mastocytosis. HαT was also associated with severe HVA and symptoms (p < .01), and remarkably, 31.0% (n = 31 of 100) were found to have concomitant KIT p.D816V. Concomitant HαT and KIT p.D816V showed an additive effect, and having both was associated with the highest risk for severe HVA, even higher than having either HαT or KIT p.D816V alone (OR = 3.8; p < .01).
Conclusions
By employing prospective universal tryptase genotyping and examination for KIT p.D816V in PBL in large HVA populations, we have demonstrated a high burden of clonal MC disorders and HαT in patients who require VIT.
Ključne besede: anaphylaxis, hereditary α-tryptasemia, hypersensitivity, immunotherapy, mast cell, mastocytosis, venom
Objavljeno v DiRROS: 17.06.2024; Ogledov: 1369; Prenosov: 816
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