Zhen S, Bandelita SN, Bhutani D
… +9 more, Maurer MS, Wats K, Brailovsky Y, Hughes MS, Radhakrishnan J, Coriu D, Mapara M, Lentzsch S, Chakraborty R
Am J Hematol
· 2026 Jun · PMID 42322078
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of baseline characteristics, treatment regimens, hematologic and cardiac responses, and survival outcomes among 51 patients with Mayo stage IIIb AL amyloidosis treated with daratumumab-based frontline therapy.of baseline characteristics, treatment regimens, hematologic and cardiac responses, and survival outcomes among 51 patients with Mayo stage IIIb AL amyloidosis treated with daratumumab-based frontline therapy.
Ludwig H, Terpos E, Gay F
… +23 more, van de Donk NWCJ, Bernhard S, Engelhardt M, Cook G, Schjesvold F, Einsele H, Jackson G, Pawlyn C, Mateos MV, Zweegman S, Schreder M, Beksaç M, Driessen C, Ocio EM, Popat R, Rasche L, Touzeau C, Musto P, Broijl A, Dimopoulos M, Hajek R, Boccadoro M, Sonneveld P
Am J Hematol
· 2026 Jun · PMID 42315477
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We performed a comprehensive review with meta- and network meta-analyzes of maintenance-therapy studies. Lenalidomide, proteasome inhibitors, and CD38 antibodies improved progression-free survival (PFS). However, overall...We performed a comprehensive review with meta- and network meta-analyzes of maintenance-therapy studies. Lenalidomide, proteasome inhibitors, and CD38 antibodies improved progression-free survival (PFS). However, overall survival (OS) benefit appeared only with lenalidomide in transplant-eligible (TE) patients, while CD38-directed therapy showed a trend toward improved OS not seen with proteasome inhibitors. The network meta-analysis ranked regimens against observation: daratumumab-lenalidomide (DR) yielded the greatest PFS benefit, followed by carfilzomib-lenalidomide-dexamethasone (KRd), KR in TE, and DRd in transplant-ineligible patients. Significant OS prolongation in TE patients occurred with KR, DR, and lenalidomide alone.
Am J Hematol
· 2026 Jun · PMID 42310859
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OVERVIEW: Systemic mastocytosis (SM) results from clonal proliferation of mast cells (MC) in extra-cutaneous organs. DIAGNOSIS: The major criterion is the presence of multifocal MC clusters in the bone marrow and/or extr...OVERVIEW: Systemic mastocytosis (SM) results from clonal proliferation of mast cells (MC) in extra-cutaneous organs. DIAGNOSIS: The major criterion is the presence of multifocal MC clusters in the bone marrow and/or extracutaneous organs. Minor diagnostic criteria include elevated serum tryptase level, MC CD25/CD2/CD30 expression, and the presence of activating KIT mutations. RISK STRATIFICATION: Establishing SM subtype as per the International Consensus Classification/World Health Organization classification systems is an important first step. Patients either have indolent/smoldering SM (ISM/SSM) or advanced SM, including aggressive SM (ASM), SM with associated myeloid neoplasm (SM-AMN), or mast cell leukemia. Identification of poor-risk mutations (i.e., ASXL1, RUNX1, SRSF2, NRAS) further refines the risk stratification. Several risk models are available to help assign prognosis in SM patients. MANAGEMENT: Treatment goals for ISM patients are primarily directed towards anaphylaxis prevention/symptom control/osteoporosis treatment. Patients with advanced SM frequently need MC cytoreductive therapy to reverse disease-related organ dysfunction. Tyrosine kinase inhibitors (TKI) (midostaurin, avapritinib) have changed the treatment landscape in SM. While deep biochemical, histological, and molecular responses have been documented with avapritinib treatment, its efficacy as monotherapy against a multimutated AMN disease component in SM-AMN patients remains unclear. Cladribine continues to have a role for MC debulking, whereas interferon-α has a diminishing role in the TKI era. Treatment of SM-AMN primarily targets the AMN component, particularly if an aggressive disease such as acute leukemia is present. Allogeneic stem cell transplant has a role in such patients. Imatinib has a therapeutic role only in the rare patient with an imatinib-sensitive KIT mutation.
Ain NU, Bar N, Guo L
… +8 more, Klinger K, Gupta P, Rahman AU, Yang R, Deng Y, Neparidze N, Nair S, Mistry PK
Am J Hematol
· 2026 Jun · PMID 42309787
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Chronic antigenic stimulation is implicated in the pathogenesis of monoclonal gammopathy and multiple myeloma, yet longitudinal human evidence linking sustained antigen exposure to modifiable clonal plasma cell evolution...Chronic antigenic stimulation is implicated in the pathogenesis of monoclonal gammopathy and multiple myeloma, yet longitudinal human evidence linking sustained antigen exposure to modifiable clonal plasma cell evolution remains limited. Gaucher disease (GD), caused by biallelic GBA1 pathogenic variants, is characterized by accumulation of glucosylsphingosine (LysoGL1), the direct antigenic target of GD-associated clonal immunoglobulins and a pharmacologically suppressible stimulus. We conducted a longitudinal retrospective cohort study of 235 adults with GD (3628 person-years; 2662 clinical visits), with incident-only ascertainment from a confirmed gammopathy-free baseline. Thirty-one patients (13.2%) developed incident monoclonal gammopathy. GD conferred a ninefold excess risk relative to population expectations (SIR 9.04; 95% CI 5.79-13.45). Male sex independently increased hazard 3.3-fold (HR 3.30; 95% CI 1.55-7.03; p < 0.01), mirroring the established male predominance of plasma cell dyscrasias. GD-specific therapy, initiated solely for systemic disease indications, was associated with a dose-dependent reduction in incident risk. In univariate Cox regression with age as the time scale, each additional therapy year conferred a 9% lower hazard (HR 0.91; 95% CI 0.88-0.94; p < 0.001), extending mean MGUS-free time by 8.4 years between untreated and most-treated quartiles. Cumulative therapy progressively suppressed circulating LysoGL1, with eliglustat achieving substantially deeper reduction than enzyme replacement therapy alone. Propensity score-weighted analyses were directionally concordant (IPTW HR 0.19; 95% CI 0.11-0.30; p < 0.001). These findings establish GD as a tractable model of antigen-driven oncogenesis-and provide a precedent for investigating whether therapeutic reduction of a defined antigenic stimulus can modify oncogenic trajectory in other chronic inflammatory states.
Smith SD, Sundaram S, Giri S
… +10 more, Ness A, Wang Y, Gopal AK, Pang Y, Tatoian ET, Grossfeld T, Lynch RC, Warren EH, Nowakowski GS, Park SI
Am J Hematol
· 2026 Jun · PMID 42305039
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First-line therapy for mantle cell lymphoma (MCL) represents a critical opportunity for clinical benefit via sustained complete response. We conducted a phase 2 multicenter trial in the academic and community cancer rese...First-line therapy for mantle cell lymphoma (MCL) represents a critical opportunity for clinical benefit via sustained complete response. We conducted a phase 2 multicenter trial in the academic and community cancer research united (ACCRU) network, testing a multitargeted 1st line regimen. CARiBOU (ACCRU-LY-1804) employs alternating VR-CAP and R-cytarabine with continuous acalabrutinib, in six 21-day cycles, for previously untreated MCL. The primary endpoint was complete metabolic response (CMR) rate. Secondary endpoints included safety, feasibility of stem cell collection, proportion proceeding to ASCT, and progression-free (PFS) and overall survival (OS). Peripheral blood measurable residual disease (MRD) was tested using the ClonoSEQ assay (Adaptive Biotechnologies). Of 41 patients enrolled, 39 (95%) responded to therapy, including 37 patients achieving CMR (90%). Two nonresponders discontinued therapy for toxicity early, prior to study-defined restaging, and received alternate therapy. Undetectable MRD at a 10 threshold was achieved in 26/33 tested patients (79%), and 94% at 10. 18-month estimated PFS is 79% (95% CI 64%-97%), and OS is 96% (95% CI 88%-100%). Toxicities were primarily hematologic (grade 3 hematologic AE in 32 patients, [78%]). Twelve required platelet transfusions, and one grade 3 bleeding event occurred. Febrile neutropenia occurred in 4 patients, and 6 (14%) experienced SAEs. There were no treatment-related deaths. CARiBOU is an efficient, highly effective outpatient 1st line MCL regimen, employing intermediate-dose cytarabine and continuous acalabrutinib for 6 cycles. This multitargeted regimen addresses the biologic heterogeneity of MCL and permits flexible MRD-guided decisions on consolidation and maintenance. Trial Registration: ClinicalTrials.gov identifier: NCT04626791.
Bloch C, Chhun S, Sritharan N
… +20 more, Gil M, Lhote R, Boubaya M, Lambotte O, Launay D, Larroche C, Lazaro E, Liffermann F, Michel M, Michot JM, Morel P, Terriou L, Urbansk G, Viallard JF, Cheminant M, Suarez F, Lepelletier Y, de Saint Basile G, Hermine O, French HLH Study Group
Am J Hematol
· 2026 Jun · PMID 42299056
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The predictive value of cytokines (CK) for malignancy-associated adult hemophagocytic lymphohistiocytosis (M-HLHa) remains uncertain. We evaluated a cytokine-based Risk Score (RS) and the IL-10/IL-6 Ratio to predict M-HL...The predictive value of cytokines (CK) for malignancy-associated adult hemophagocytic lymphohistiocytosis (M-HLHa) remains uncertain. We evaluated a cytokine-based Risk Score (RS) and the IL-10/IL-6 Ratio to predict M-HLHa. Adult patients (n = 112) from the French HLH cohort (NCT02113917) with complete data for nine key HLH related CK measured by Luminex were first analyzed. Logistic regression was performed, and a RS was subsequently derived and internally validated. In a post hoc analysis, the IL-10/IL-6 ratio obtained using the ELLA cytokine assay was evaluated in 75 patients, 54 of whom also had Luminex testing, plus 25 additional patients from the cohort. The RS and IL-10/IL-6 ratio were then jointly assessed in the 54 patients with results from both platforms. Among the 112 patients, 45 had M-HLHa and 67 non M-HLHa; median age was 48 years and 64 (57%) were male. Eight variables were associated with M-HLHa, of which four were retained in the logistic model: age > 48 years (2.9[1.12-7.33], p = 0.03), TNF-α ≤ 43 pg/mL (3.2[1.16-8.61], p = 0.02), IL-18 > 574 pg/mL (4.9[1.89-12.75], p = 0.001), and IL-10/IL-6 ≥ 1.5 (2.7[1.01-7.31], p = 0.04), with respective weights of 11, 12, 16, and 10. A RS ≥ 20 increased the odds of M-HLHa 17-fold (17.2 [5.4-54.5], p < 0.0001). The IL-10/IL-6 ratio alone (n = 75) showed good performance (AUC 0.83). In the 54 patients with both assays, the RS and IL-10/IL-6 ratio preserved their diagnostic performance (AUC 0.87 and 0.79, respectively). These data support the RS and IL-10/IL-6 Ratio as useful tools to improve the identification of M-HLHa in adults. Trial Registration: clinicaltrials.gov NCT02113917.
McElwee J, Elsey G, Gonzalez R
… +22 more, Julian K, Snyder J, Granger K, Rice M, Nachar VR, Atrash S, Hansen DK, Grajales-Cruz A, Cahoon C, Bryan B, Sborov D, Mahmoudjafari Z, Warrick M, Dominick A, Rudoni J, Kissam J, Vince M, Khouri J, Ahmed I, Pianko M, Moore DC, Davis JA
Am J Hematol
· 2026 Jun · PMID 42298354
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Franke M, Kirchner R, Barredo B
… +14 more, Zaidan A, Torres-Esquius S, Acha P, Novoa-Jáuregui S, Montoro MJ, Churpek JE, Babushok DV, Lasho T, Kewan T, Ogbue O, Mangaonkar A, Jerez A, Ferrer A, Patnaik MM
Am J Hematol
· 2026 Jun · PMID 42290596
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Chavez JC, Bastos-Oreiro M, Diefenbach C
… +15 more, Lossos IS, Shah N, Assouline S, Olszewski AJ, Naik S, Ghosh N, Pham S, Wei MC, Batlevi C, To I, Ead W, Makadia S, Penuel E, Jing J, Budde LE
Am J Hematol
· 2026 Jun · PMID 42283231
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Mosunetuzumab plus polatuzumab vedotin has shown promising activity versus rituximab plus polatuzumab vedotin (R-Pola) in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL; NCT03671018). We present resu...Mosunetuzumab plus polatuzumab vedotin has shown promising activity versus rituximab plus polatuzumab vedotin (R-Pola) in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL; NCT03671018). We present results from the Phase II randomized cohort, evaluating subcutaneous mosunetuzumab plus polatuzumab vedotin (Mosun-Pola), with > 2 years of follow-up. Patients with R/R LBCL and ≥ 1 prior line of therapy were randomized to receive Mosun-Pola or R-Pola. Mosunetuzumab was administered subcutaneously with Cycle (C) 1 step-up dosing (5/45/45 mg) then 45 mg on C2 Day (D) 1-C8D1 (21-day cycles). Polatuzumab vedotin (1.8 mg/kg) was given intravenously (IV) on D1 of C1-6. Rituximab IV (375 mg/m) was given on D1 of C1-8. Primary endpoint was best objective response rate (ORR). As of November 15, 2024, 80 patients had been enrolled (Mosun-Pola, n = 40; R-Pola, n = 40). Best ORR was 77.5% (95% confidence interval [CI] 61.6-89.2) for Mosun-Pola and 50.0% (95% CI: 33.8-66.2) for R-Pola; complete response (CR) rates were 55.0% (95% CI: 38.5-70.7) and 35.0% (95% CI: 20.6-51.7), respectively. Median progression-free survival was 25.4 months for Mosun-Pola and 6.4 months for R-Pola (hazard ratio [HR] 0.47); median overall survival was not reached and 25.5 months (HR: 0.78), respectively. Cytokine release syndrome occurred in 12.5% of Mosun-Pola-treated patients (all Grade 1/2). Fixed-duration Mosun-Pola demonstrated benefit across all efficacy endpoints compared with R-Pola in patients with R/R LBCL. These findings are consistent with the observed benefit of Mosun-Pola for patients with R/R LBCL in the global Phase III SUNMO study (NCT05171647). Trial Registration: Clinicaltrials.gov number: NCT03671018.
Ciavarella A, Baronciani L, Seidizadeh O
… +8 more, Colpani P, Ingenito E, Cattaneo D, Pagliari MT, Truma A, Iurlo A, Siboni SM, Peyvandi F
Am J Hematol
· 2026 Jun · PMID 42272198
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Acquired von Willebrand Syndrome (AVWS) is a rare bleeding disorder characterized by quantitative or qualitative defects of von Willebrand factor (VWF) in patients without a personal or family history of bleeding. It is...Acquired von Willebrand Syndrome (AVWS) is a rare bleeding disorder characterized by quantitative or qualitative defects of von Willebrand factor (VWF) in patients without a personal or family history of bleeding. It is frequently associated with systemic diseases, particularly lymphoproliferative disorders (LPDs) and myeloproliferative neoplasms (MPNs). In this single-center, retrospective cross-sectional study, we included patients diagnosed with AVWS at the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center between April 2014 and March 2025. Bleeding severity was assessed using the ISTH-BAT score. Laboratory tests included FVIII:C, VWF:Ag, VWF:GPIbR, VWF:RCo, VWF:CB, VWFpp, and multimer analysis. Among 140 patients, 106 (76%) had MPNs and 26 (19%) LPDs. At least one bleeding symptom was observed in 70% of patients, with clinically significant bleeding occurring in 24% of the cohort. Clinically relevant bleeding (mainly mucocutaneous and gastrointestinal) was more frequent and severe in LPDs (58%) than in MPNs (13%). LPDs showed severe VWF functional defects, marked HMWM loss, and elevated VWFpp/VWF:Ag ratios (median 6.7), consistent with accelerated clearance. MPNs displayed mild HMWM reduction, normal clearance (median VWFpp/VWF:Ag ratio 1.0), and an inverse correlation between platelet count and the degree of HMWM depletion (ρ = -0.48, p < 0.001). Bleeding severity correlated inversely with VWF:GPIbR in LPDs (ρ = -0.50, p = 0.02) and with VWF:RCo in MPNs. Anti-VWF antibodies were found in 30% of tested LPDs or autoimmune cases. The two main phenotypes presented in AVWS were immune-mediated in LPDs and platelet-mediated in MPNs. Understanding the underlying mechanism is crucial for accurate diagnosis and targeted treatment to reduce bleeding risk and improve outcomes.
Sheng L, Hu H, Lai Y
… +14 more, Wang S, Wang D, Tang S, Xu K, Sun Y, Zhang P, Lai B, Hu L, Chen L, Pan Y, Nie S, Gao X, Fan L, Ouyang G
Am J Hematol
· 2026 Jun · PMID 42265756
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This prospective biomarker study evaluated serial CSF ctDNA monitoring in newly diagnosed PCNSL treated with R-MO induction therapy. Mid-treatment ctDNA clearance was significantly associated with complete response and s...This prospective biomarker study evaluated serial CSF ctDNA monitoring in newly diagnosed PCNSL treated with R-MO induction therapy. Mid-treatment ctDNA clearance was significantly associated with complete response and superior progression-free survival, showing stronger predictive value than interim PET-CT in this cohort. These findings support CSF ctDNA clearance as a promising molecular biomarker for early response assessment in PCNSL.
Fathima S, Wong MM, Gonzalez-Lugo J
… +46 more, Geyer SM, Alsugair A, Sirenko M, Langer KJ, Lasho TL, Finke C, Choi J, Abdul-Hay M, Ho G, Litzow MR, Matin A, Durani U, Hefazi M, Hogan WJ, Shah MV, Al-Kali A, Begna KH, Gangat N, Saliba AN, Go RS, Kewan T, Bartoo G, Kutzke J, McCullough K, Warrington KJ, Sullivan M, Reichard KK, Olteanu H, Murthy H, Badar T, Kusne Y, Palmer J, Chhabra S, Punwani N, Riwes M, McGuirk JP, Krakow EF, Langston A, Kourelis T, Dingli D, Foran J, Koster MJ, Patnaik MM, Beck DB, Alkhateeb HB, Mangaonkar AA
Am J Hematol
· 2026 Jun · PMID 42260942
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Hypomethylating agents (HMA) and allogeneic hematopoietic stem cell transplantation (alloHSCT) have both demonstrated remissions in VEXAS; however, comparative data is lacking. We conducted a multicenter, retrospective a...Hypomethylating agents (HMA) and allogeneic hematopoietic stem cell transplantation (alloHSCT) have both demonstrated remissions in VEXAS; however, comparative data is lacking. We conducted a multicenter, retrospective analysis of 66 patients diagnosed with VEXAS syndrome treated with HMA (n = 35) or alloHSCT (n = 31). Baseline characteristics such as genetics, co-morbidities, and performance status were balanced between the groups, except older age in the HMA group. Median follow-up from therapy initiation was 18 months (95% CI: 11-26), and 14 (21%) deaths were reported (alloHSCT n = 3; HMA n = 11). Among all evaluable patients within the alloHSCT cohort, all patients achieved molecular remission, and a substantial proportion of patients discontinued glucocorticoids (58%). In contrast, HMA therapy was associated with lower but meaningful rates of molecular remission (22%) and glucocorticoid discontinuation (6%). In a real-world setting, HMA therapy was associated with a high discontinuation rate related to toxicity or lack of response. On multivariable analysis adjusted for age and Charlson Comorbidity Index, alloHSCT was associated with improved overall survival (HR = 0.20, 95% CI: 0.05-0.81; p = 0.024). This association remained consistent across multiple ancillary sensitivity analyses, including restriction to transplant-eligible patients, patients aged ≤ 75 years, 1:1 matching, and propensity score-based weighted analyses. Although limited by retrospective design, these findings suggest that alloHSCT remains an attractive and potentially curative strategy in selected patients with VEXAS. Prospective validation of these findings is warranted.
Sheth S, Corbacioglu S, de la Fuente J
… +23 more, Algeri M, Rupprecht J, Kuo KHM, Shah AJ, Lang P, Merkeley H, Carpenter B, Mapara MY, Liem RI, Grupp S, Chopra Y, Li AM, Kwiatkowski JL, Kirby-Allen M, Cappellini MD, Kattamis A, Zairis S, Liu T, Hobbs W, Frangoul H, Locatelli F, Meisel R, CLIMB THAL‐111 and CLIMB‐131 Study Groups
Am J Hematol
· 2026 Aug · PMID 42252696
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Exagamglogene autotemcel (exa-cel) is a one-time, ex vivo, CRISPR-Cas9 gene edited cell therapy approved for patients with transfusion dependent β-thalassemia (TDT) aged 12-35 years. In a Phase 3 study (CLIMB THAL-111),...Exagamglogene autotemcel (exa-cel) is a one-time, ex vivo, CRISPR-Cas9 gene edited cell therapy approved for patients with transfusion dependent β-thalassemia (TDT) aged 12-35 years. In a Phase 3 study (CLIMB THAL-111), exa-cel treatment resulted in reactivation of fetal hemoglobin and increases in total hemoglobin, leading to transfusion independence in 91% of participants. Here, we report on the impact of exa-cel treatment on measures of ineffective erythropoiesis and iron homeostasis, which were secondary and exploratory endpoints in CLIMB THAL-111 and the CLIMB-131 long-term follow-up study. Prior to exa-cel infusion, all participants were receiving regular red blood cell transfusions and iron chelation therapy. At time of data cut (April 2025), 98% of participants (55 of 56) had been transfusion independent for ≥ 12 months and 38 (68%) had discontinued iron removal therapy (mean duration off iron removal therapy 19.4 months). Following transfusion independence and cessation of iron removal therapy, erythroferrone concentrations decreased and hepcidin levels normalized in all participants, indicating correction of ineffective erythropoiesis and restoration of iron homeostasis. Further supporting this finding, improvements and trends toward normalization were seen in key erythropoiesis biomarkers, including erythropoietin levels, reticulocyte counts, and soluble transferrin receptor concentrations. Iron overload biomarkers, including ferritin, liver iron concentration, and cardiac T2*, decreased and then remained stable throughout follow-up, even after cessation of iron removal therapy. These results demonstrate restoration of effective erythropoiesis and iron homeostasis after exa-cel infusion in the setting of transfusion independence following reactivation of fetal hemoglobin. (CLIMB THAL-111 and CLIMB-131; Clinical Trials.gov numbers NCT03655678 and NCT04208529).
Yuan X, Luo Q, Huang Y
… +13 more, Li C, Yu T, Guo S, Guo Q, Jin X, Tong J, Zhao A, Lei W, Li X, Li B, Wei S, Qian W, Liang Y
Am J Hematol
· 2026 Jun · PMID 42252624
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Current prognostic models fail to capture the biological complexity of primary central nervous system lymphoma (PCNSL). We integrated whole-genome sequencing and multiplex immunofluorescence in 68 treatment-naïve patient...Current prognostic models fail to capture the biological complexity of primary central nervous system lymphoma (PCNSL). We integrated whole-genome sequencing and multiplex immunofluorescence in 68 treatment-naïve patients to define four genomic subtypes (C1, C2, C3, and C4) with divergent survival (C4 worst: median overall survival [OS], 26 months). In parallel, a novel tumor microenvironment (TME) classification based on CD8T/M2 macrophage ratio stratified patients into High (> 1.5), Intermediate (0.8-1.5), and Low (< 0.8) groups. Unexpectedly, the Intermediate TME group showed the poorest outcomes (5-year OS: 10%). Integration revealed a lethal subgroup (C4 + Intermediate TME; 9.8% of cohort) with a median OS of 3.0 months (hazard ratio = 7.24, p = 0.006). Prognostic nomograms incorporating these subtypes showed promising discriminative performance in internal validation (C-index > 0.78), but external validation is needed. Together, these findings identify a high-risk biological subset and provide a hypothesis-generating framework for future biomarker-driven risk stratification and therapeutic discovery in PCNSL.
Steinhardt MJ, Hegenbart U, Hellou T
… +21 more, Oubari S, Roussel M, Schwotzer R, Buadi F, Dingli D, Binder M, Kourelis T, Zanwar SS, Rieger MJ, Morbach C, Cejka V, Gerber B, Störk S, Einsele H, Kumar S, Gertz M, Carpinteiro A, Kortum KM, Muchtar E, Dispenzieri A, Schönland S
Am J Hematol
· 2026 Aug · PMID 42252535
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High dose melphalan (HDM) with autologous stem cell transplant is an established treatment for systemic light chain amyloidosis, but its incremental benefit in the era of effective standard intensity therapy is unknown....High dose melphalan (HDM) with autologous stem cell transplant is an established treatment for systemic light chain amyloidosis, but its incremental benefit in the era of effective standard intensity therapy is unknown. We retrospectively analyzed 475 transplant-eligible patients who completed standard intensity treatment with or without HDM within 12 months at six centers in Europe and the United States between 2010 and 2024 to evaluate outcomes by baseline risk factors, hematologic response, and receipt of HDM. Death was an equally competing risk after the 12-month landmark chosen to address early non-proportional hazards and to ensure completion of first-line therapy. BMPC > 20% was associated with inferior outcomes (HR 1.7), and gain/amp 1q with shorter TTP (HR 2.15), whereas other high-risk FISH abnormalities were not. In multivariable models, VGPR/CR after standard intensity therapy was associated with longer TTP (HR 0.49/0.29), while gain/amp 1q remained independently associated with shorter TTP (HR 2.18). Receipt of daratumumab and HDM were associated with longer TTP (HR 0.44/0.61). HDM benefited patients who had not achieved CR after standard intensity therapy (mTTP 21.0 vs. 5.7 months without HDM), whereas patients already in CR did not benefit. Higher BMPC at diagnosis was associated with earlier progression in patients not receiving HDM (HR 1.9 for 5%-20% and 4.09 for > 20%), a risk attenuated in the HDM cohort. Gain/amp 1q remained associated with shorter TTP regardless of HDM exposure. These findings support a selective role for HDM, primarily benefiting patients with residual disease after standard intensity therapy or higher BMPC burden at diagnosis.
Young G, von Drygalski A, Pipe S
… +1 more, Sidonio R
Am J Hematol
· 2026 Aug · PMID 42252525
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Despite major advances in hemophilia care, many patients continue to experience breakthrough bleeding, progressive joint morbidity, inhibitor development, and substantial treatment burden. To help more individuals achiev...Despite major advances in hemophilia care, many patients continue to experience breakthrough bleeding, progressive joint morbidity, inhibitor development, and substantial treatment burden. To help more individuals achieve active, unrestricted lives, health care professionals must move beyond traditional prophylaxis targets by applying evolving evidence on factor VIII (FVIII) levels, optimizing prophylaxis to provide sustained bleed protection, and individualizing therapy to meet patients' needs, preferences, and real-world considerations. This 3-segment podcast features expert discussions on optimizing joint health across the lifespan, including subclinical bleeding and imaging-based monitoring; applying current and emerging guidance on FVIII targets and factor-based strategies; and integrating rebalancing agents into practice, with a focus on clinical outcomes, safety and risk mitigation, treatment burden, patient selection, and individualized hemophilia management. To view this activity and obtain CME/CE credit, visit http://www.cmeologyce.org/ajhhemophiliapodcast.