This single-institution retrospective study evaluated a measurable residual disease (MRD)-guided induction intensification strategy in transplant-eligible patients with newly diagnosed multiple myeloma treated in the anti-CD38 antibody era. Sixty patients undergoing autologous stem cell transplantation (ASCT) between 2020 and 2025 were included. Most received bortezomib, lenalidomide, and dexamethasone as initial therapy. Patients with persistent MRD by multiparameter flow cytometry underwent treatment intensification, commonly with daratumumab, carfilzomib, and dexamethasone before ASCT. Among 52 evaluable patients, 35 (67.3%) achieved MRD negativity before ASCT, and 30 of 32 (93.8%) were MRD-negative after ASCT. Stem cell mobilization and engraftment were successful. After median follow-up of 28.5 months, 2-year progression-free and overall survival were 87.3% and 98.0%. R-ISS stage III and extramedullary disease were associated with inferior progression-free survival. High-risk cytogenetics showed poorer outcomes. This MRD-adapted strategy was feasible, achieved deep responses, and preserved mobilization, but high-risk disease remained prone to relapse, supporting post-transplant intensification.
Invasive fungal infections (IFIs) cause substantial morbidity and mortality, yet optimal antifungal prophylaxis in adult acute lymphoblastic leukemia (ALL) remains uncertain given unclear incidence and drug interaction constraints. We performed a PRISMA 2020-compliant systematic review and meta-analysis (PROSPERO CRD420251048884) of PubMed, Embase, and Cochrane CENTRAL from inception through September 2025, including adults with ALL receiving antineoplastic therapy, excluding HSCT and pediatric cohorts. Primary outcome was IFI incidence per European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) criteria; invasive aspergillosis (IA) was secondary. Of 1,789 records, 36 studies met eligibility; 23 contributed to meta-analyses. Pooled incidence of proven/probable IFI was 9% (95% CI 7-11%; N = 3,316), proven/probable/possible IFI 16% (12-21%; N = 806), and IA 5% (4-8%; N = 3,190). IFIs remain clinically significant in adult ALL, supporting risk-adapted prophylaxis during higher-risk treatment phases. Heterogeneity reflected differences in prophylaxis, treatment, and limited comparative data on strategies across studies.
Classic Hodgkin lymphoma (cHL) generally has favorable outcomes with frontline ABVD chemotherapy; however, 15-30% of advanced-stage patients experience relapse. While PD-1 inhibitors like pembrolizumab have shown promise in relapsed/refractory cHL, immune-related adverse events remain incompletely characterized. We report a 56-year-old male with stage IV nodular sclerosis cHL who relapsed after multiple treatment lines including ABVD, DHAP, brentuximab vedotin, and ICE. Following pembrolizumab plus GVD (gemcitabine, vinorelbine, liposomal doxorubicin), he achieved complete metabolic response. Subsequently, he developed marked leukocytosis (WBC: 63,000/μL) with profound eosinophilia (53,000/μL), meeting criteria for hypereosinophilic syndrome (HES). Molecular workup revealed FIP1L1-PDGFRA rearrangement in 2% of cells. The patient required hospitalization for dehydration, renal dysfunction, and anasarca, and was managed with corticosteroids after hydroxyurea intolerance. This case uniquely documents HES as a rare complication of pembrolizumab/GVD in multiply relapsed cHL, occurring after extensive prior therapy that may have contributed to its development. The molecular findings suggest potential therapeutic avenues. Clinicians should maintain vigilance for eosinophilia during PD-1 inhibitor therapy, as HES management may take precedence over ongoing immunotherapy.
CD74, originally known as the invariant chain of Major Histocompatibility Complex Class II Molecules (MHC class II), has now been acknowledged as a versatile signaling nexus and a universal lymphoma antigen. It has a pivotal role in the maturation, stimulation, and viability of various immune cells, such as B cells, T cells, Regulatory T Cells (Tregs), monocytes, and macrophages. It is extensively and significantly expressed in a variety of hematologic cancers, encompassing acute and chronic leukemias, lymphomas, and multiple myeloma. Given its expression pattern, along with its swift internalization and limited expression in most normal tissues, CD74 emerges as a promising target for a wide array of therapeutic approaches like antibody-drug conjugates (ADCs), bispecific antibodies, and Chimeric Antigen Receptor T-cell (CAR-T) therapy. However, the downstream signaling network of CD74 is highly context-dependent, playing a dual role in physiological immune regulation and pathological pro-cancer survival.
Patients with accelerated-phase/blast-phase myeloproliferative neoplasms (AP/BP-MPN) experience poor clinical outcomes. A multicenter, retrospective cohort study was conducted to assess outcomes of patients with AP/BP-MPN treated with hypomethylating agent (HMA) regimens. Of 188 patients included, 94 patients received HMA +/- JAK inhibitor and 56 patients received HMA + venetoclax (HMA+ven) +/- JAK inhibitor. The primary endpoint of overall survival (OS) was 9.2 months in both groups (log-rank p = 0.569). The rates of CR/CRi and CR/CRi/MLFS were higher with HMA+ven (36% vs. 11%, p = 0.0002 and 52% vs. 16%, p < 0.0001), but the rate of allogeneic hematopoietic cell transplant (alloHCT) was not different (HMA vs. HMA+ven, 14% vs. 18%, p = 0.51). Multivariate cox regression identified age and receipt of an alloHCT as significant predictors of survival. This large, multicenter, real-world analysis demonstrated the addition of venetoclax to HMA therapy in patients with AP/BP-MPN improved response rates but did not translate into an improvement in OS.
Following the approval of inotuzumab ozogamicin (InO) monotherapy for the treatment of adults with relapsed/refractory CD22-positive acute lymphoblastic leukemia, the US Food and Drug Administration issued a post-marketing requirement study due to their concerns that the proposed dose of 1.8 mg/m2/cycle may not be optimal in balancing the safety and efficacy of InO. Here, we provide an overview of single-agent InO dose-optimization strategies, including the rationale for studying a fractionated InO dosing schedule and justification for the approved dosing regimen based on clinical safety and efficacy data, as well as comprehensive exposure-response analyses from InO clinical studies.
Soluble immune mediators, such as checkpoint and cytokine receptors and their ligands, are emerging as biomarkers and potential therapeutic targets in hematologic malignancies. We assessed pretreatment levels of soluble PD-L1 (sPD-L1) as a prognostic biomarker in a retrospective single-center cohort of 54 newly diagnosed acute myeloid leukemia (AML) patients. Higher sPD-L1 levels were significantly associated with a greater disease burden and with patients undergoing allogeneic transplantation. Interpretation of longitudinal sPD-L1 data suggests that marked declines may reflect treatment response, whereas persistently high levels may indicate ongoing disease activity. In non-transplanted patients, high sPD-L1 levels were independently associated with inferior overall survival. These results indicate that sPD-L1 may inherently reflect high-risk characteristics that could potentially help guide treatment decisions.
Chimeric antigen receptor T-cell therapy (CART) has changed treatment for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL), but most patients still die of their disease and may benefit from palliative care (PC) or hospice services. Whether CART availability has affected PC or hospice referral patterns and end-of-life outcomes remains unclear. We conducted a single-center retrospective study for deceased patients with r/r DLBCL to evaluate PC and hospice utilization before and after CART introduction (87 pre-CART, 95 post-CART). PC referral rates were similar between eras (57.5% vs 70.5%, p = 0.39), as were hospice referrals (79.3% vs 83.2%, p = 0.78). However, patients in the post-CART era had shorter time from last treatment to death (95 vs 51 days, p = 0.001), higher hospitalization rates in the last 30 days of life (57.5% vs 72.6%, p = 0.03), and more in-hospital deaths (19.5% vs 33.7%, p = 0.045). Overall, 20-30% of patients were never referred to PC or hospice.
Extramedullary hepatic involvement is particularly rare. Here, we summarize published reports of hepatic myeloma treatment achieving infrequent and short-lived responses. Approach to a newly diagnosed multiple myeloma patient who presented with diffuse intrahepatic infiltration and cholestasis under frontline quadruplet induction will be presented here to complement the review. Contrary to earlier reports, he achieved a rapid response in/outside or marrow with elranatamab monotherapy. Importantly, this response enabled subsequent high dose melphalan and autologous stem cell transplantation (ASCT), which, otherwise, would not have been feasible. Currently under the 11th month of elranatamab treatment, patient is still in measurable residual disease (MRD)(-) CR. To our knowledge there has been no cases or series achieving such deep and durable responses for hepatic EMD. Elranatamab can be an effective and safe drug for extensive cholestatic liver myeloma involvement. Our results are quite premature, necessitating additional reports confirming the efficacy and safety of anti-BCMA bispecifics.
Biological markers such as disease risk and mutation profile can predict survival outcomes of acute myeloid leukemia (AML) treated with first-line venetoclax (Ven) in combination with a hypomethylating agent. However, the impact of socioeconomic factors with this regimen is unclear. Using a widely validated metric of disadvantage, Area Deprivation Index (ADI), we investigated the influence of socioeconomic disparity on overall survival (OS) in seventy-nine newly diagnosed patients with AML who received Ven-based therapy at the University of Wisconsin. Median OS was 6.77 months (IQR 2.52-11.57) with a cumulative mortality rate of 75.9%. While previous reports demonstrated worse outcomes in disadvantaged patients treated with intensive therapy, we observed no statistically significant difference between State/National ADI and OS (p = 0.697 and p = 0.582 respectively) in our Ven cohort.
Diffuse large B-cell lymphoma (DLBCL) is a clinically and biologically heterogeneous malignancy, but the prognostic and biological significance of O-linked β-N-acetylglucosamine (O-GlcNAc) modification remains incompletely understood. We analyzed three microarray-based DLBCL cohorts obtained from the Gene Expression Omnibus (GSE87371, GSE117556, and GSE181063; total n = 2,090). Consensus clustering was used to characterize the expression patterns of glycosylation-related genes. The associations of these expression patterns and O-GlcNAc transferase (OGT) expression with overall survival were evaluated using Kaplan-Meier analysis and Cox regression. Differential expression, pathway enrichment, single-sample gene set enrichment, and correlation analyses were performed to characterize biological features associated with OGT expression. We also used OCI-LY3 and SU-DHL-4 cell lines to investigate the effects of OGT overexpression, shRNA-mediated knockdown, and pharmacological inhibition on cell proliferation and apoptosis. Co-immunoprecipitation and immunoblotting were performed to assess protein O-GlcNAcylation and phosphorylation, together with selected signaling proteins, anti-apoptotic factors, and epigenetic regulators. In result, Glycosylation-related genes displayed heterogeneous expression patterns across DLBCL samples that were associated with survival, with OGT emerging as a key prognostic candidate. High OGT expression was associated with shorter survival in all three cohorts, and patients with OGT overexpression and high International Prognostic Index scores had particularly poor outcomes. Increased levels of OGT expression co-varied with PI3K-AKT-MTOR signaling, MYC target signaling, and selected anti-apoptotic and epigenetic features. In both cell lines, OGT overexpression promoted proliferation and was accompanied by increased O-GlcNAcylation and activation-associated phosphorylation of PI3K, AKT, and Myc, together with increased protein levels of Bcl-2, Mcl-1, EZH2, and KMT2D. OGT knockdown or pharmacological inhibition produced opposite changes and increased apoptosis. These findings indicate that elevated OGT expression is associated with unfavorable survival and adverse signaling features in DLBCL. Further studies are required to establish the direct causal relationships and therapeutic significance of OGT-associated O-GlcNAcylation.
SRSF2/TET2 is a common co-mutation characterized by monocytosis across many myeloid neoplasms, including CMML. Myelodysplasia-related gene (MRG) mutations, including SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, and STAG2, are key contributors to leukemic transformation, though their interactions with other mutations are understudied. In this retrospective cohort study, we examined the clinical and prognostic impact of additional mutated MRGs in 412 patients with SRSF2/TET2 co-mutated neoplasms, identified from the Moffitt Next Gen Sequencing Database. The majority of patients (55%) had at least one additional MRG mutation, which was associated with decreased monocytosis, increased anemia, and poorer overall survival (10.941 vs. 23.787 months, p < 0.001). ASXL1 was the most common MRG mutation and independently predicted worse survival. Patients with additional MRGs were more likely to have AML arising from CMML (12.3% vs 5.9%, p = 0.029). These findings may be used in future clinical practice to provide better prognosis and treatment stratification.
