Search Results (18,559)

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma characterized by the t(11;14)(q13;q32) cytogenetic abnormality and cyclin D1 overexpression. We have found evidence that Forkhead box M1 (FOXM1), a transcription factor with oncogenic potential, is important in the pathogenesis of MCL. Relatively high levels of FOXM1 proteins were detectable in all six MCL cell lines examined. By immunohistochemistry, we consistently found a subset of FOXM1-positive cells in MCL tumors. Analysis of two Gene Expression Omnibus (GEO) datasets from MCL patients showed that elevated FOXM1 levels significantly correlate with a worse clinical outcome. In MCL cell lines, inhibition of FOXM1 using thiostrepton or shRNA effectively triggered apoptosis and significantly reduced cell growth. FOXM1 forms a positive feedback loop with NFκB in MCL cells. Specifically, inhibition of FOXM1 dramatically decreased the protein level/transcription activity of p65, while enforced FOXM1 expression upregulated p65 and downregulated IκBα, a key NFκB inhibitor. Conversely, curcumin-mediated NFκB inhibition decreased the protein level/DNA binding of FOXM1, while transduction of a constitutively active IKKα construct into MCL cells significantly dampened the inhibitory effects of thiostrepton. Confocal microscopy revealed that FOXM1 and p65 colocalize with each other. In conclusion, FOXM1 and NFκB work collaboratively in promoting the growth and drug resistance of MCL, and FOXM1 may be a potentially useful therapeutic target. Full article

Background/Objectives: CD19-directed chimeric antigen receptor T (CAR-T) cell therapy induces profound immune remodeling. Nonetheless, biomarkers predicting complete remission (CR) remain poorly defined. We characterized longitudinal cytokine and immune-cell dynamics after CAR-T infusion and identified early immunological features associated with CR. Methods: Longitudinal immune profiling was performed in 18 patients with non-Hodgkin lymphoma, including 14 with relapsed/refractory diffuse large B-cell lymphoma treated with anti-CD19 CAR-T cells. Peripheral blood was collected at the baseline and days 7, 14, 21, 28, and 60 post-infusion. Multiparameter flow cytometry quantified lymphoid and myeloid subsets and Toll-like receptor (TLR)2 and TLR4 expression. Serum cytokines were measured by multiplex assays. Machine-learning-based feature selection identified variables associated with CR. Results: Two inflammatory waves were observed. The first, at day 7, featured elevated IL-6, IL-10, IFN-α, IFN-γ, and TNF-α, accompanied by increased CD4⁺ T cells, HLA-DR^high classical monocytes, and non-classical monocytes. The second, at days 21–28, showed increased IL-5, IL-6, IL-12, IFN-γ, and GM-CSF, with expansion of CD4⁺ and CD8⁺ T cells, regulatory T cells, NK-T cells, and non-classical monocytes. TLR2 expression was significantly upregulated at day 7 on T-cell subsets and on classical and intermediate monocytes. An exploratory feature-selection analysis identified baseline and day-7 TLR2 and TLR4 expression on lymphoid and myeloid cells, early IFN-γ levels, and monocyte frequencies as variables associated with CR. Conclusions: Together, these data show that anti-CD19 CAR-T therapy induces two coordinated waves of cytokine release and immune-cell activation. Moreover, the findings suggest that early modulation of innate immune features, particularly TLR2 expression, is associated with complete remission, although these biomarker relationships remain exploratory and require validation in larger cohorts. Full article

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by progressive bone marrow fibrosis, extramedullary hematopoiesis (particularly symptomatic splenomegaly), constitutional symptoms, progressive cytopenias, and, in a subset of patients, leukemic transformation. The advent of the JAK1/2 inhibitor ruxolitinib has revolutionized the management of MF, substantially improving splenomegaly, symptom burden, and, in some settings, overall survival. However, a substantial percentage of patients fail to achieve sustained benefit, are intolerant, or become refractory; real-world and clinical trial data indicate that approximately half of treated patients discontinue ruxolitinib treatment within 3 years and up to approximately 75% within 5 years, with poor outcomes after discontinuation (median survival in several series is approximately 12–14 months). In recent years, several new small molecules that act beyond the JAK-STAT axis have emerged in clinical development. These include agents targeting telomerase (imetelstat), epigenetic regulation via BET inhibition (pelabresib/CPI-0610), the MDM2-p53 axis (navtemadlin/KRT-232), erythroid maturation and the bone marrow microenvironment (luspatercept), PI3K signaling (parsaclisib), and PIM inhibitors (nuvisertib). Early clinical data show promising results for symptom and splenic control in specific settings and, importantly, suggest potential disease-modifying activity (improvements in marrow fibrosis and molecular responses) for some compounds. This review summarizes the biological rationale, key clinical data (efficacy and safety), ongoing randomized trials, and remaining knowledge gaps for these non-JAK small molecules in MF and offers practical considerations for integrating them into contemporary treatment algorithms. Full article

Background: Chronic hypoxemia in cyanotic congenital heart disease triggers well-recognized hematological adaptation; however, whether hypoxemia also drives systemic inflammatory activation remains uncertain. This study aimed to evaluate hematological parameters and inflammatory indices in cyanotic and acyanotic congenital heart disease (CHD) to better characterize the relationship between hypoxemia and systemic inflammatory status. Methods: In this single-center retrospective study, 260 children with congenital heart disease were classified as cyanotic (n = 158) or acyanotic (n = 102). Preoperative clinical data and laboratory parameters were analyzed, including oxygen saturation, hemoglobin, hematocrit, leukocyte indices, C-reactive protein (CRP), and procalcitonin (PCT). Inflammatory indices derived from complete blood counts were calculated, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune–inflammation index (SII). Results: Oxygen saturation was significantly lower in cyanotic patients than in acyanotic patients (75 ± 9% vs. 95 ± 4%, p < 0.001). Consistent with hypoxemia-driven hematological adaptation, hemoglobin and hematocrit levels were significantly higher in the cyanotic group (16.1 ± 2.9 g/dL vs. 13.1 ± 2.0 g/dL and 50.8 ± 9.7% vs. 39.7 ± 5.5%, respectively; p < 0.001). In contrast, inflammatory indices (NLR, PLR, and SII) were similar between cyanotic and acyanotic patients, and no significant associations were observed between oxygen saturation and these inflammatory indices. Conclusions: While cyanotic congenital heart disease demonstrates marked hematological adaptation secondary to chronic hypoxemia, systemic inflammatory indices appear similar in cyanotic and acyanotic patients. These findings suggest a relative dissociation between hypoxemia-driven hematological responses and the evaluated systemic inflammatory indices, indicating that inflammatory burden in congenital heart disease may not be solely explained by cyanosis and may reflect additional underlying mechanisms not captured by these markers. Full article

Background: Elevated anticardiolipin IgG (aCL IgG) has been reported in end-stage renal disease (ESRD), but its association with specific etiologies of kidney failure remains unexplored. The unique pathophysiology of diabetic–hypertensive nephropathy may be associated with a microenvironment that could potentially contribute to antiphospholipid antibody production and thrombotic complications. This study aimed to investigate whether aCL IgG elevation in hemodialysis (HD) patients is associated with combined diabetes–hypertension (DM + HTN) etiology and thrombocytopenia, thereby identifying a clinically distinct potential high-risk subgroup. In this hypothesis-generating study, we focused on within-HD patient comparisons rather than healthy controls. Methods: We enrolled 242 participants: 150 healthy controls (included only to establish local reference ranges) and 92 patients with maintenance HD. The study was conducted from 01 September to 20 November 2025 in Madinah, Saudi Arabia. Serum aCL IgG was measured by chemiluminescence immunoassay (positive ≥ 12 GPL units). Comprehensive hematological and biochemical parameters were analyzed. Multivariable logistic regression identified predictors of aCL positivity. Results: In the HD cohort, 21% demonstrated aCL positivity; this represents a substantially higher rate than the 2% observed in local healthy controls (p < 0.001). This elevation was not uniform across etiologies. Strikingly, 94.7% (18/19) of aCL-positive HD patients had DM + HTN aetiology, compared with only 17.8% of aCL-negative patients (p < 0.001). Thrombocytopenia was significantly more severe in aCL-positive patients (median platelets: 100 vs. 191 × 10⁹/L, p < 0.001). In multivariable analysis, DM + HTN etiology (HTN-alone vs. DM + HTN odds ratio [OR]: 0.0013, 95% confidence interval [CI]: 0.00002–0.0999, p = 0.003; confirmed by Firth’s penalized logistic regression sensitivity analysis, and lower platelet count (OR: 0.92 per 1 × 10⁹/L increase, 95% CI: 0.87–0.98, p = 0.006) independently predicted aCL positivity. Conclusions: These hypothesis-generating findings suggest a potential association between metabolic–vascular disease and antiphospholipid immunity in ESRD. Causality cannot be inferred from this cross-sectional design. At present, routine aCL screening is not recommended outside of research protocols; prospective studies are needed to confirm these associations. Full article

Background: Platelet concentrates (PCs) are vital for treating hematologic disorders and thrombocytopenia, yet their short shelf life (3–5 days) is limited by platelet storage lesion (PSL)—a process involving biochemical and structural deterioration that reduces post-transfusion efficacy. This study aimed to characterize alterations in platelet surface receptors and RNA content during storage to better understand PSL mechanisms. Methods: Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were prepared from healthy donors and stored PCs. Flow cytometry was used to assess the expression of GPIbα, GPVI, Integrin αIIbβ3, and CD9. Thiazole orange (TO) staining evaluated RNA content to distinguish young from aged platelets, while soluble GPVI (sGPVI) levels were quantified by ELISA. Data were analyzed using one-way ANOVA and Student’s t-test (p < 0.05). Results: Baseline receptor profiles were established from fresh donor platelets. Stored PCs showed a progressive decline in GPIbα and GPVI expression from day 6, with significant reductions by day 11 (p < 0.05). αIIbβ3 expression decreased early (day 6) and stabilized thereafter, whereas CD9 remained unchanged. TO staining indicated a gradual loss of RNA-rich platelets, signifying aging. ELISA revealed increased sGPVI levels from day 6 to day 14, inversely correlating with surface GPVI loss. Conclusions: Prolonged storage leads to receptor degradation and platelet senescence, notably affecting GPIbα, GPVI, and αIIbβ3. Elevated sGPVI levels and reduced RNA content reflect progressive PSL. Flow cytometry and ELISA offer reliable monitoring tools, and sGPVI may serve as a biomarker for platelet quality during storage. Full article

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, constituting an important public health problem. Although curable, it presents a widely variable prognosis. The main tool used for prognostic stratification in DLBCL is the International Prognostic Index (IPI), which does not consider crucial biological variables for understanding its prognostic heterogeneity. Cell adhesion molecules (CAMs) play a central role in cancer biology and can be evaluated in affected tissues or in plasma, in soluble forms (sCAMs). CAMs promote proliferation, survival, and dissemination of malignant cells. Although extensively studied in solid tumors, their role remains unclear in hematological malignancies, particularly in DLBCL. Methods: This is a prospective and longitudinal study involving 87 newly diagnosed DLBCL (ND-DLBCL) patients aiming to quantify plasma levels of sCAMs (sICAM-1, sVCAM-1, sP-selectin, and sE-cadherin) at diagnosis and assessing its potential prognostic impact, as well as establishing clinical-biological associations. Results: Plasma quantification of sICAM-1, sVCAM-1, and sP-selectin did not present prognostic impact in DLBCL. However, continuous increases in sE-cadherin levels, as well as sE-cadherin ≥ 126.55 ng/mL were associated with lower response rates to R-CHOP regimen, higher frequency of recurrence following first-line therapy, and shortened survival. Additionally, sE-cadherin concentration ≥ 126.55 ng/mL was an independent predictor related to decreased overall survival. Conclusion: sE-cadherin measured at diagnosis has emerged as a new prognostic biomarker able to predict response, relapse and survival in ND-DLBCL. Full article

Chimeric antigen receptor (CAR) T-cell therapy is an effective treatment for hematologic malignancies. However, it is limited by high costs, risk of severe toxicities such as cytokine release syndrome and neurotoxicity, and heterogeneous patient responses. The current therapy monitoring depends largely on subjective symptom assessment, routine laboratory tests, and basic vital signs, without real-time, quantitative evaluation of CAR T-cell expansion or activation in clinical practice. This lack of timely immune monitoring hampers individualized care and contributes to increased treatment costs. To address this need, we present a proof-of-concept, label-free rapid optical imaging (ROI) biosensor with automated machine learning analysis for direct quantification of CAR T-cells from whole blood. This microfluidic platform integrates red blood cell (RBC) removal, CAR T-cell capture, and imaging-based quantification on a single chip, eliminating the need for centrifugation, staining, and operator-dependent interpretation. For validation, 50 μL whole blood samples spiked with Jurkat cells expressing CD19 CARs underwent RBC depletion by agglutination and microfiltration. The remaining blood components were then incubated on a sensor chip functionalized with recombinant CD19 protein. Captured CAR T-cells were imaged by brightfield microscopy and automatically enumerated using a machine learning algorithm trained on fluorescence-validated cells. The CD-19 cells’ capture performance was validated by flow cytometry and fluorescence imaging. The trained machine learning model validated at 88% sensitivity and 96% specificity. Buffer and whole blood calibration curves were established across clinically relevant concentrations (1–1000 cells/µL) with triple replicates. The results showed high correlation (0.975 and 0.990 R²) between the spiked concentration and the detected CAR T-cells, with a 95% certainty limit of detection (LOD) and quantification (LOQ) of 0.6 and 1.1 cells/µL for spiked buffer, and 14 and 67 cells/µL for spiked whole-blood, respectively. Full article

Background: Acute myeloid leukemia with extramedullary disease (EMD-AML) represents a distinct clinical entity associated with diagnostic and therapeutic challenges, and its prognostic significance remains uncertain. Methods: A retrospective study of 617 adults with newly diagnosed AML (2005–2018) was conducted, analyzing 246 patients with EMD-AML and 371 without EMD involvement. The clinical characteristics and treatment outcomes were analyzed. Propensity score matching (PSM) was applied to adjust for baseline confounders. Results: Patients with isolated EMD-AML and those with concurrent bone marrow involvement had comparable clinical outcomes. NPM1 mutations (48% vs. 25%, p = 0.0002) and t(8;21) translocation (23.2% vs. 3.7%, p < 0.001) were enriched in the EMD-AML cohort. After PSM, EMD-AML patients achieved a higher overall response rate compared with non-EMD-AML (88.1% vs. 72.0%, p = 0.0002) but experienced significantly higher relapse rates (35.7% vs. 15.5%, p < 0.0001). Despite the achievement of a higher response rate, EMD-AML was associated with shorter median overall survival (OS) (14.2 vs. 64.1 months, p < 0.0001) and event-free survival (EFS) (9.5 vs. 55.9 months, p < 0.0001). In a multivariable analysis, EMD-AML remained independently associated with worse OS and EFS (OS HR 1.79, p = 0.01; EFS HR 1.95, p = 0.001). Allogeneic hematopoietic stem cell transplantation did not confer a survival advantage in EMD-AML patients. Conclusions: EMD-AML, whether isolated or concurrent with bone marrow disease, represents a high-risk entity characterized by poor long-term outcomes despite strong initial response rates. Obtaining tissue biopsies for molecular profiling may help improve risk stratification, identify targetable mutations and guide individualized treatment. Full article

Glucose-6-phosphate dehydrogenase (G6PD) deficiency impairs NADPH generation through the pentose phosphate pathway, resulting in reduced glutathione regeneration and increased vulnerability to oxidative stress. While its clinical significance is well described in hemolytic disorders, its impact on tumor biology and chemosensitivity remains poorly characterized. Cisplatin, a backbone agent in the management of nasopharyngeal carcinoma (NPC), exerts its cytotoxicity through the formation of DNA adducts and the robust induction of reactive oxygen species (ROS) activity. We report a patient with non-keratinizing NPC and a G6PD variant, a (class III) deficiency, who demonstrated a rapid and pronounced objective response to cisplatin-based induction and concurrent chemoradiotherapy. Unfortunately, the patient also exhibited signs of rapid and persistent hematologic (platelets and white cells) toxicity. Notably, no hemolytic events occurred. A narrative review of the available literature indicates that G6PD-deficient cells exhibit a reduced antioxidant reserve, increased cisplatin-induced DNA damage, and impaired activation of ROS-detoxifying pathways. A few clinical observations similarly report enhanced tumor responsiveness in G6PD-deficient individuals, although the evidence is sparse and heterogeneous. Preclinical data support the notion that diminished NADPH availability amplifies cisplatin-triggered oxidative injury, thereby increasing tumor susceptibility. This case adds to emerging evidence that G6PD deficiency may potentiate cisplatin efficacy in NPC by exploiting intrinsic redox vulnerabilities. While preliminary, these findings suggest the potential utility of metabolic phenotyping in treatment stratification. Prospective studies are needed to define the predictive value, safety, and therapeutic implications of G6PD status in cisplatin-based regimens. Full article

Background: Higher-risk myelodysplastic neoplasms ( HR-MDS) are associated with poor survival and a substantial risk of leukemic transformation. Although azacitidine is a standard treatment in this setting, comparative real-world data remain limited. We evaluated the association between azacitidine exposure and clinical outcomes in patients with HR-MDS. Methods: We performed a retrospective single-center cohort study including 72 adults with HR-MDS, defined by the Revised International Prognostic Scoring System(IPSS-R) as High or Very High risk. Patients were categorized as azacitidine-treated (Aza, n = 44) or managed with best supportive care alone (No Aza, n = 28). Overall survival (OS) was defined from diagnosis to death from any cause. Progression-free survival (PFS) was defined as the time to acute myeloid leukemia transformation or death. Leukemic transformation (LT) was analyzed using Kaplan–Meier estimates and competing-risk cumulative incidence, with death without prior LT treated as a competing event. Univariable and multivariable Cox regression models were applied. Results: Azacitidine exposure was associated with longer OS compared with best supportive care, with a median OS of 13 vs.10 months and 24-month OS rates of 27% vs. 14% (p = 0.0239). PFS was also prolonged in the Aza group, with a median of 11 vs. 7 months (p = 0.0406). LT-related outcomes similarly favored azacitidine. In multivariable analyses, azacitidine remained independently associated with improved OS, PFS, and LT-related outcomes. IPSS-R Very High risk remained an adverse prognostic factor across endpoints, while a higher baseline bone marrow blast percentage independently predicted leukemic transformation. Conclusions: In this real-world HR-MDS cohort, azacitidine exposure was associated with improved survival outcomes and delayed leukemic transformation compared with best supportive care alone. Full article

Background/Objectives: Nursing assessment frameworks play a critical role in guiding holistic patient evaluations, standardizing documentation, and supporting organizational quality and safety initiatives. Among these, Gordon’s Functional Health Patterns (FHPs) offer a comprehensive and widely used framework for nursing assessment. However, no review has synthesized evidence on their association with outcomes. This scoping review aimed to map evidence on the use of FHPs in relation to patient and organizational outcomes, and to examine their integration into electronic health records (EHRs) and the analytical methods employed. Method: A scoping review was conducted following Joanna Briggs Institute methodology and PRISMA-ScR guidelines. PubMed, CINAHL, and Scopus were searched for quantitative primary studies reporting associations between FHPs and outcomes, and the final search was conducted on 22 March 2024. Three reviewers independently screened abstracts and full texts and extracted data. Results: Seven studies met the inclusion criteria. FHPs’ use was associated with improvements in several patient outcomes, including quality of life, psychological well-being, clinical parameters, self-management, dependency level, and functional performance. Organizational outcomes included reduced hospital readmission rates and a positive association between FHP-derived nursing diagnoses and nursing workload. Most studies used standardized nursing terminologies such as NANDA-I, NOC, or NIC, in conjunction with FHPs. Over half of the studies used EHR-based nursing documentation, reflecting increasing digital integration and enabling more structured and interoperable nursing data. Methodological approaches varied widely: most studies used associative analyses, two employed experimental designs, and one investigated the predictive utility of FHP-based assessment data. Conclusions: FHPs provide a structured framework for nursing practice with potential benefits for patient and organizational outcomes. Their increasing integration into EHRs supports standardized documentation and data-driven nursing practice, enhancing assessment quality, diagnostic accuracy, and the availability of structured data for clinical and managerial decision-making in health information systems. Further experimental and longitudinal research is needed to strengthen causal evidence and guide implementation. Full article

Natural killer/T-cell lymphoma (NKTCL) is a rare and aggressive Epstein–Barr virus (EBV)-associated lymphoma characterized by intrinsic chemoresistance and an immunosuppressive tumor immune microenvironment (TIME). EBV-driven immune dysregulation provides a biological rationale for immunotherapy. This review summarizes current advances in immunotherapeutic strategies for NKTCL, integrating molecular mechanisms, clinical evidence, and resistance mechanisms within the context of TIME remodeling and immune reprogramming. We synthesize evidence from clinical trials, translational studies, and preclinical investigations evaluating immune checkpoint inhibitors, antibody-based therapies, adoptive cellular therapies, immune engagers, EBV-directed immunotherapies, and multimodal combination strategies in NKTCL. Among these strategies, PD-1/PD-L1 inhibitors are the most extensively studied immunotherapies in NKTCL and demonstrate clinically meaningful activity across different clinical settings. However, therapeutic responses remain heterogeneous, and primary or acquired resistance is common, driven by EBV-associated immune suppression, defective antigen presentation, metabolic reprogramming, and multi-checkpoint co-expression. Beyond immune checkpoint blockade, emerging approaches—including dual-checkpoint inhibition, epigenetic and metabolic combinations, antibody–drug conjugates, EBV-specific cytotoxic T lymphocytes, chimeric antigen receptor (CAR)-based platforms, immune engagers, and EBV vaccines—have shown encouraging signals in early-phase studies. Increasing evidence also supports multimodal strategies integrating immunotherapy with radiotherapy and other immune-modulatory interventions to enhance immune reprogramming and improve response durability. Overall, immunotherapy has substantially expanded the therapeutic landscape of NKTCL but remains constrained by complex EBV–TIME interactions and interpatient heterogeneity. Future progress will rely on biologically informed patient stratification, rational multimodal combination strategies, and integration of innovative immune platforms to establish a durable, immune-reprogramming-centered treatment paradigm for EBV-driven NKTCL. Full article

Background: Bloodstream infections (BSIs) represent a severe complication among patients with solid tumors (STs), contributing substantially to morbidity and mortality, especially in the context of increasing antimicrobial resistance (AMR). Evidence in STs remains limited compared to hematologic malignancies. Methods: We conducted a two-center observational study including 282 hospitalized adults with solid malignancies and documented infections; 66 patients (23.4%) had confirmed BSIs. Clinical characteristics, microbiological profiles, resistance patterns, and outcomes were evaluated. Results: Patients had a mean age of 66.4 ± 11.8 years, and 63.6% were male. The majority (84.8%) had stage IV disease and were receiving chemotherapy (95.5%). Gram-negative bacteria predominated (51.5%), mainly Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Multidrug resistance (MDR) was detected in 45.5% of isolates, while 28.8% of BSIs were polymicrobial; both were associated with worse outcomes and increased infection-related mortality (p = 0.041 and p = 0.032, respectively). Overall infection-related mortality reached 28.8%. In multivariable analysis, poor functional status (ECOG PS ≥ 2), prior hospitalization, and concurrent radiotherapy were independently associated with unfavorable outcomes. Conclusions: BSIs remain a significant cause of morbidity and mortality in patients with STs. The high burden of Gram-negative and MDR pathogens, along with the impact of polymicrobial infections and impaired performance status, highlights the need for early risk stratification and locally adapted empirical antimicrobial strategies. Prospective multicenter studies are warranted to validate these findings and optimize management strategies in this vulnerable population. Full article

Background and Clinical Significance: Chromothripsis represents a catastrophic genomic event in plasma cell myeloma (PCM) associated with poor prognosis. We report a case of newly diagnosed PCM with complex cytogenetic abnormalities indicative of genomic instability. Case Presentation: A 67-year-old man presented with acute dyspnea and was found to have severe acute kidney injury, anemia, hypercalcemia, and IgG lambda monoclonal gammopathy. Bone marrow biopsy revealed plasma cell infiltration. Comprehensive FISH analysis demonstrated a complex pattern with gain of 1q, monosomy 13, and multiple numeric and structural abnormalities affecting chromosomes 5, 9, and 15, suggestive of a chromothripsis-like pattern. Despite requiring hemodialysis, the patient achieved complete renal recovery and >99% reduction in serum-free light chains after one cycle of CyBorD plus daratumumab, which was continued for four cycles. Follow-up bone marrow evaluation at three months confirmed complete histologic, flow cytometric, and cytogenetic remission, allowing for preparation for autologous stem cell transplantation. Conclusions: This case demonstrates that exceptional clinical responses can be achieved in high-risk disease with contemporary quadruplet regimens. While the long-term durability of such responses in genomically unstable cases remains uncertain, this case highlights the importance of comprehensive cytogenetic characterization to identify and monitor genomic instability in PCM. Full article