Janakiram M, Tan CR, Mian H
… +18 more, Huang CY, Popat R, Martínez-Lopez J, Kastritis E, Chng WJ, Kapoor P, Dave M, Bal S, Garderet L, Corraes AMS, Riedhammer C, Steinbrunn T, Corona M, Nagarajan C, Einsele H, Martin T, Krishnan A, Lin Y
Am J Hematol
· 2026 Aug · PMID 42157444
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Talquetamab is a GPRC5D × CD3 bispecific antibody approved for relapsed/refractory multiple myeloma (RRMM). This is the first real-world study to comprehensively report muco-cutaneous toxicities, infections, and efficacy...Talquetamab is a GPRC5D × CD3 bispecific antibody approved for relapsed/refractory multiple myeloma (RRMM). This is the first real-world study to comprehensively report muco-cutaneous toxicities, infections, and efficacy of talquetamab in 151 patients across five countries with the longest follow-up reported enabling better efficacy and toxicity estimates. The median age was 64 years; high-risk cytogenetics were present in 42%; ECOG ≥ 2 in 22%; 12% had creatinine clearance < 30; and 55% would not have met MonumenTAL-1 eligibility. Patients received a median of 6 prior lines of therapy, 53% were penta-refractory, and 75% received prior BCMA therapy. Talquetamab was associated with skin toxicity in 39.7%, nail toxicity in 75.5%, dysgeusia in 60.4%, and oral toxicities in 62.9%, with grade ≥ 3 events uncommon (≤ 4%) and dose interruptions infrequent (9.6% for skin toxicity, 6.9% for dysgeusia, and 4.0% for oral toxicities). These findings underscore the need for improved supportive care for muco-cutaneous toxicities. In multivariate analysis, only platelet count < 50 (HR 1.8, 95% CI 1.15-2.83) was associated with inferior PFS, while penta-refractory status, absolute lymphocyte count < 0.4, and prior BCMA-targeted therapy were not statistically significant. With a median follow-up of 12.7 months, the overall response rate was 67.6%, median progression-free survival was 7 months, and 12-month overall survival was 65%. This study shows that talquetamab efficacy is maintained in a heavily pretreated real-world population with high prior BCMA exposure and notable comorbidity burden.
Am J Hematol
· 2026 Aug · PMID 42157378
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Age-related changes in human hematopoietic stem cells (HSCs) often form the basis for clonal hematopoiesis (CH), which presages the development of overt myeloid neoplasm with variable risk. CH can also arise after exposu...Age-related changes in human hematopoietic stem cells (HSCs) often form the basis for clonal hematopoiesis (CH), which presages the development of overt myeloid neoplasm with variable risk. CH can also arise after exposure to chemotherapy, radiotherapy, or immune interventions. In this study, we performed clinico-genomic profiling of therapy-related CH (t-CH) (n = 67) versus de novo CH (n = 123) from a multidisciplinary CHIP Clinic. The most enriched mutations in t-CH were TET2 (26.2%), DNMT3A (22.4%), and TP53 (8.4%). Median latency period from the time of initial exposure to the diagnosis of t-CH was 6.96 ± 1.10 years. Patients with t-CH had inferior event-free survival compared to de novo CH (median 29.9 months versus 122.1 months, p = 0.0045). Overall survival was also shorter in t-CH versus de novo CH (median 55.3 months vs. 129.2 months, p = 0.043). Genes that imparted significantly increased risk for progression from t-CH to overt therapy-related myeloid neoplasm (t-MN) included JAK2 (relative risk (RR) 9.42, p = 0.0001), RUNX1 (RR 7.11, p = 0.001), EZH2 (RR 7.11, p = 0.001), and TET2 (RR 13.4, p = 0.01). Clonal dynamic modeling of patients with t-CH who progressed to overt t-MN showed an increase in the relative clonal fraction and new clonal outgrowth. In the t-CH cohort, higher mean variant allele frequency was observed in progressors versus non-progressors (77.1% vs. 30.6%, p = 0.017). This study sheds light onto outcomes for CH based on differing clinical ontogeny and has implications for previvorship for secondary malignancies.
Castillo JJ, Beltrán BE, Florindez JA
… +2 more, Chavez JC, Malpica L
Am J Hematol
· 2026 Aug · PMID 42138287
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DISEASE OVERVIEW: Plasmablastic lymphoma (PBL) is a rare CD20-negative aggressive lymphoma with poor prognosis when treated with standard treatment options. Although PBL is associated with HIV infection and other immunos...DISEASE OVERVIEW: Plasmablastic lymphoma (PBL) is a rare CD20-negative aggressive lymphoma with poor prognosis when treated with standard treatment options. Although PBL is associated with HIV infection and other immunosuppressed states, it can also affect immunocompetent individuals. DIAGNOSIS: The diagnosis of PBL requires a high clinical suspicion and pathological confirmation. EBV-encoded RNA (EBER) expression and MYC gene rearrangements are frequently detected in the malignant cells. The differential diagnosis includes EBV+ diffuse large B-cell lymphoma (DLBCL), extracavitary primary effusion lymphoma, ALK+ DLBCL, and HHV8+ large B-cell lymphoma, among others. RISK STRATIFICATION: Age ≥ 60 years, advanced clinical stage, and high International Prognostic Index scores are associated with worse survival. MANAGEMENT: Combination chemotherapy regimens, such as infusional EPOCH, are recommended. The addition of bortezomib or daratumumab might improve outcomes. B-cell maturation antigen-targeted therapies have shown early efficacy. The participation of patients with PBL in prospective clinical trials is warranted.
Am J Hematol
· 2026 Aug · PMID 42135784
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Chronic anemia is observed in individuals with sickle cell disease (SCD) and thalassemia syndromes. It has been associated with a range of neurological complications, particularly progressive silent cerebral infarcts in...Chronic anemia is observed in individuals with sickle cell disease (SCD) and thalassemia syndromes. It has been associated with a range of neurological complications, particularly progressive silent cerebral infarcts in brain regions with high oxygen extraction-specifically in vascular watershed areas-suggesting that regional tissue hypoxia may play a causal role. However, recent work in sickle cell mice reveals widespread white matter demyelination and chronic neuroinflammation superimposed upon regional ischemia. In light of these findings, we utilized high-fidelity diffusion imaging and modeling techniques to identify predictors of white matter damage in human subjects diagnosed with SCD (n = 76) and thalassemia (n = 20) compared to healthy individuals (n = 32). Our results demonstrate that white matter damage extended beyond vascular watershed areas in chronically anemic subjects and had MRI changes characteristic of demyelination. These findings were proportional to hemoglobin levels and largely disappeared after controlling for anemia severity. However, patients with SCD exhibited small but significant residual white matter derangements not seen in those with thalassemia. These residual abnormalities disappeared after LDH or reticulocyte count were included as markers of hemolytic rate. From a functional perspective, neuropsychological processing speed was correlated with white matter integrity in chronic anemia subjects, with stronger associations seen in patients with SCD. Taken together, these results demonstrate that chronic anemia is associated with widespread white matter demyelination that cannot be explained by regional blood flow variation and is proportional to anemia severity. Patients with SCD may have more severe disease and functional consequences than patients with thalassemia.
Srinivasan M, Izquierdo AR, Tolosa P
… +20 more, García ÁVA, González-Medina J, García-Mosquera JJ, Iwase T, Desaraju N, Escobar JAP, Trinidad AP, Lamaj G, Benasutti R, Butterworth I, Castro-González C, Sánchez-Ferro Á, Bourquard A, Nasrazadani A, Martínez-Bueno A, Cuglievan B, Gil EMC, Sloan JM, Martinez-Lopez J, PointCheck Study Group
Am J Hematol
· 2026 Aug · PMID 42132420
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Tordjman M, Meribout A, Geahchan A
… +15 more, Bolger I, Yuce M, Zhuo X, Pavuluri S, Choe E, Restrepo F, Yu A, D'anna A, Lagana A, Crossley-Brown K, Petralia G, Jagannath S, Mei X, Parekh S, Taouli B
Am J Hematol
· 2026 Aug · PMID 42132247
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Extraosseous (EO) involvement in multiple myeloma (MM) is a critical marker of systemic clonal escape, but its spatial and temporal dynamics are largely omitted from current risk models like R2-ISS. In this cohort of 543...Extraosseous (EO) involvement in multiple myeloma (MM) is a critical marker of systemic clonal escape, but its spatial and temporal dynamics are largely omitted from current risk models like R2-ISS. In this cohort of 543 patients with longitudinal follow-up between 2010 and 2025, whole-body (WB) imaging including WB-MRI ± FDG-PET/CT was used to characterize EO disease. EO status was modeled as a time-varying covariate in multivariable Cox proportional hazards models including clinical, biological, and genetic covariates to assess impact on overall survival (OS). EO disease was identified in 24.6% of cases (n = 134). We identified a distinct prognostic hierarchy for OS based on the timing and pattern of dissemination: compared to marrow-confined disease, prognosis was increasingly worse for primary paraskeletal (PS) lesions present at diagnosis (HR = 2.22), secondary PS (HR = 3.33), and reaching an ultra-high-risk for secondary extramedullary disease (EMD) (HR = 8.14). Patients with initial PS lesions faced a 2.6-fold increased risk of evolving into secondary EMD (p = 0.002). While lesion volume and anatomical localization of EO lacked prognostic value, secondary EMD, R2-ISS stage IV, number of lines of treatment and TP53 mutation at time of EO diagnosis independently predicted lower post-EO survival. Thus, EO involvement defines an aggressive phenotype in which prognosis is driven by the timing and dissemination pattern rather than EO tumor burden. WB imaging accurately identifies patients transitioning into these high-risk groups. Integrating timing and spatial EO features into future risk frameworks is essential for better prognostication, as the adverse impact of EO disease persists even after adjusting for R2-ISS and cytogenetic status.
Zhao H, Lin Z, Zheng H
… +32 more, Wei G, Luo Y, Shi J, Cui Q, Zhao M, Liang A, Zhang Q, Yang J, Li X, Chen J, Song X, Jing H, Li Y, Hao S, Wu W, Yin ETS, Tan Y, Yu J, Zhao Y, Lai X, Wei Y, Li P, Huang J, Wang T, Blaise D, Xiao L, Chang AH, Nagler A, Leung G, Mohty M, Huang H, Hu Y
Am J Hematol
· 2026 Aug · PMID 42130055
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Sequential allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a critical approach to enhance the efficacy of chimeric antigen receptor T cell (CAR-T) therapy for relapsed/refractory acute lymphoblastic leu...Sequential allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a critical approach to enhance the efficacy of chimeric antigen receptor T cell (CAR-T) therapy for relapsed/refractory acute lymphoblastic leukemia (R/R ALL). The long-term survival rates following allo-HSCT after CAR-T cell therapy remain controversial. We previously reported the results of 122 patients with R/R B-ALL who achieved minimal residual disease negative (MRD-) complete remission (CR) after anti-CD19 CAR-T, including 67 patients without subsequent transplantation (non-transplant group) and 55 patients with subsequent haplo-HSCT (transplant group). Here, we present the extended follow-up of this cohort, with a median of 72.9 months. Compared with the non-transplant group, transplantation recipients had a higher 5-year LFS (50.5% vs. 25.7%; p < 0.001) and OS (53.5% vs. 25.6%; p < 0.001). Multivariable analysis identified MRD positivity at transplantation as an independent factor associated with worse LFS, OS, and a higher cumulative incidence rate of relapse (CIR). MRD-negative patients before transplant (MRD- group) had a lower 5-year CIR compared to MRD-positive patients (MRD+ group) (20.8% vs. 50.0%; p = 0.014). The 5-year LFS rates in the MRD+ and MRD- groups were 26.7% and 59.4%, respectively (p = 0.003). The 5-year OS of the MRD- group was higher than that of the MRD+ group (62.0% vs. 30.5%; p = 0.006). For patients who achieve CR after CAR-T therapy, haplo-HSCT with pre-transplant MRD negativity was associated with better long-term survival. However, infections emerged as a significant complication that may reduce the long-term survival benefits. Trial Registration: ClinicalTrials.gov identifier: ChiCTR1900023957.
Chen GL, Bassett R, Mehta RS
… +13 more, Oran B, Khawaja F, Ariza-Heredia EJ, Aljawai Y, Olson A, Daher M, Smallbone P, Rezvani K, Kebriaei P, Popat U, Champlin R, Chemaly RF, Shpall EJ
Am J Hematol
· 2026 Aug · PMID 42128671
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Graft versus host disease (GVHD) prophylaxis with posttransplant cyclophosphamide (ptCY) and cytomegalovirus (CMV) prophylaxis with letermovir have changed the clinical epidemiology of CMV infection. We studied the incid...Graft versus host disease (GVHD) prophylaxis with posttransplant cyclophosphamide (ptCY) and cytomegalovirus (CMV) prophylaxis with letermovir have changed the clinical epidemiology of CMV infection. We studied the incidence, risk factors for, and outcomes of CMV infection after Day + 90 of allogeneic hematopoietic cell transplant (alloHCT). The patient cohort consisted of 2106 alloHCT patients treated from 2015 to 2022 with a single alloHCT. Fifty-seven percent of patients received ptCY. Forty-three percent of patients received letermovir. We performed landmark analysis of the cumulative incidence of CMV-emia with the competing risk of death from Day + 0 to +360 in 90-day intervals. Regression analyses of baseline and time-dependent covariates for CMV-emia and survival were performed for each interval. The cumulative incidence of CMV-emia (≥ 500 IU CMV DNA/mL) was associated with donor/recipient CMV serostatus. In the highest risk CMV serostatus donor negative and recipient positive (D-R+) group, the cumulative incidence was 24.3 (95% confidence interval [CI] 21.3-27.3), 9 (95% CI: 6.9-11.1), 5 (95% CI: 3.3-6.7), and 2.1 (95% CI: 0.9-3.3) from Day 0 to 90, 91 to 180, 181 to 270, and 271 to 360, respectively. The primary risk factors associated with CMV incidence were related to acute GVHD. PtCY was associated with a decreased risk of CMV infection. Letermovir prophylaxis did not associate with decreased CMV infection after Day + 90. In conclusion, the risk of CMV infection remains clinically significant until Day + 180, although this is affected by the GVHD status of the patient. Discontinuation of letermovir may be considered after Day + 180.
Li C, Lei T, Xu X
… +9 more, Lu J, Zhu X, Chen Z, Weng X, Yu H, Chen X, Peng S, Han S, Yang H
Am J Hematol
· 2026 May · PMID 42124356
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Relapsed/refractory (r/r) angioimmunoblastic T-cell lymphoma (AITL) is associated with a dismal prognosis, with historical overall survival (OS) < 6 months, underscoring the urgent need for novel therapies. We conducted...Relapsed/refractory (r/r) angioimmunoblastic T-cell lymphoma (AITL) is associated with a dismal prognosis, with historical overall survival (OS) < 6 months, underscoring the urgent need for novel therapies. We conducted the RCLARITY trial to evaluate the efficacy and safety of a chemotherapy-free regimen in this patient population. This single-arm, multicenter, prospective Phase II trial enrolled adult patients with r/r AITL. Patients received rituximab (375 mg/m intravenously on Day 1), lenalidomide (15 mg orally on Days 1-21), and chidamide (30 mg orally twice weekly) in 28-day cycles for up to 6 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints included the overall response rate (ORR), OS, duration of response (DoR), and safety. In total, 28 patients were enrolled between August 2019 and June 2024. The median age was 64 years (range, 44-70), and 71.4% had refractory disease. The ORR was 71.4% (complete remission: 32.1%), median PFS was 5.5 months (95% confidence interval [CI], 3.5-7.6), median OS was 17.6 months (95% CI, 10.3-24.8), and median DoR among responders was 10.7 months (95% CI, 2.7-16.0). Notably, 50% of patients with clonal Ig heavy- or light-chain rearrangements achieved PFS > 16 months. All nine patients with baseline serum EBV-DNA positivity converted to undetectable levels after two cycles. No Grade 5 adverse events or venous thromboembolic events occurred. The most common hematological adverse events per cycle were leukopenia (14.3%), thrombocytopenia (12.4%), and neutropenia (11.4%). Overall, the RLC regimen induced clinically meaningful anti-tumor activity with manageable toxicity in patients with r/r AITL. Trial Registration: ClinicalTrials.gov identifier: NCT04319601.
Scheen M, Isnard P, Buob D
… +14 more, Schurder J, Frémeaux-Bacchi V, El Sissy C, Doreille A, Abbas A, Chauvet S, Luque Y, Vigneron C, Lazareth H, Rabant M, Duong JP, Ortoli CC, Karras A, Rafat C
Am J Hematol
· 2026 Aug · PMID 42124351
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Hao W, Stocker N, Gaugler B
… +2 more, Mohty M, Malard F
Am J Hematol
· 2026 Aug · PMID 42117718
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Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective treatment for patients with high-risk hematologic malignancies. Over the last decade, gut microbiota composition during allo-HCT has been associate...Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective treatment for patients with high-risk hematologic malignancies. Over the last decade, gut microbiota composition during allo-HCT has been associated with patients' outcomes. Treatment-related factors, in particular the use of broad-spectrum antibiotics and the conditioning regimen, frequently induce gut dysbiosis, which is associated with immune dysregulation, toxicity, and adverse outcomes, particularly after allo-HCT. Microbial metabolites further modulate immune responses and therapeutic efficacy. Emerging microbiota-targeted strategies-including antibiotic stewardship, nutritional interventions, probiotics, fecal microbiota transplantation, and postbiotics-show promise in reducing graft-versus-host disease, controlling inflammation, and improving treatment responses.
Torchio F, Lecalvez B, Garelli E
… +17 more, Mallebranche C, Carando A, Castex MP, Garnier N, Zecca M, Aladjidi N, Bertoni E, Sterin A, Licciardello M, Sirvent A, Sau A, Marie I, Bruno B, Da Costa LM, Fagioli F, Quarello P, Leblanc T
Am J Hematol
· 2026 Aug · PMID 42108919
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Diamond-Blackfan Anemia Syndrome (DBAS) is a rare congenital anemia often requiring chronic red blood cell transfusions from infancy. Without appropriate chelation, iron overload develops early and may be severe; however...Diamond-Blackfan Anemia Syndrome (DBAS) is a rare congenital anemia often requiring chronic red blood cell transfusions from infancy. Without appropriate chelation, iron overload develops early and may be severe; however, no data are available on chelation in patients under 3 years of age. To address this, we conducted a retrospective, multicenter study collecting data from the French and Italian DBAS national registries. A total of 167 transfused DBAS patients were screened. Of these, 64 (38%) initiated chelation before the age of three (median: 18 months). Indications for chelation were a serum ferritin ≥ 500 ng/mL (median: 1340 ng/mL) and more than 10 transfusions. Deferasirox was the most frequently used chelator (63%), followed by deferoxamine (35%). Chelation was associated with a significant reduction in serum ferritin levels (-11% per year; p < 0.001). At 5-6 years of age, ferritin level was available for 28 patients: 43% had levels < 500 ng/mL, and none exceeded 2000 ng/mL. Liver iron concentration was assessed in 31/64 patients (48%) at a median age of 3.2 years; 45% showed severe overload at first evaluation. Among 22 patients who underwent cardiac magnetic resonance, no myocardial iron overload was detected. These real-world data support the feasibility, tolerability, and effectiveness of chelation in transfusion-dependent DBAS patients under 3 years, allowing prevention of cardiac iron overload. Although derived from DBAS, these findings may inform the management of iron overload in infants and toddlers with other transfusion-dependent anemias and support development of age-specific chelation strategies.
Zhou J, Wang C, You T
… +9 more, Wang Y, Zong X, Wang Q, Chen W, Sheng K, Ma X, Chen J, Wu D, Huang H
Am J Hematol
· 2026 May · PMID 42108795
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Glofitamab, a CD20 × CD3 bispecific antibody, has demonstrated significant efficacy in relapsed or refractory (R/R) B-cell lymphomas. However, real-world evidence on its clinical performance and immunologic correlates, p...Glofitamab, a CD20 × CD3 bispecific antibody, has demonstrated significant efficacy in relapsed or refractory (R/R) B-cell lymphomas. However, real-world evidence on its clinical performance and immunologic correlates, particularly in the context of chimeric antigen receptor T-cell (CAR-T) therapy, remains limited. This observational study included 64 patients with R/R aggressive B-cell lymphoma who received glofitamab-based therapy between February 2024 and December 2025 at the First Affiliated Hospital of Soochow University. The primary endpoint was complete response (CR) rate, whereas secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. We also analyzed the impact of prior bispecific antibody (BsAb) exposure on CAR-T cell manufacturing and efficacy and assessed the relationship between peripheral T-cell subsets and treatment outcomes. Among 56 evaluable patients, the CR and ORR were 41.1% and 78.7%, respectively. Median PFS and OS were not reached, with estimated 1-year PFS and OS rates of 61.3% and 67.7%. Patients with non-germinal center B-cell (non-GCB) subtype had significantly higher PFS than those with GCB subtype (p = 0.029), whereas prior CAR-T therapy was associated with poorer PFS (p = 0.022). Prior BsAb exposure did not affect CAR-T manufacture or efficacy. Immunophenotyping revealed that patients achieving CR had higher baseline CD4 effector T-cell counts (p = 0.04) and higher early CD8 T-cell expansion (p = 0.02). Overall, glofitamab demonstrated durable efficacy and a manageable safety profile in R/R aggressive B-cell lymphoma, with treatment outcomes closely associated with T-cell functional status, supporting its potential as an effective bridging strategy before CAR-T therapy.
Zhang C, Wu H, Cao T
… +8 more, Wu C, Yan C, Qi W, Zhang Y, Ji X, Jing H, Peng Q, Zhang W
Am J Hematol
· 2026 Aug · PMID 42086512
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Chimeric Antigen Receptor T-cell Immunotherapy represents a breakthrough in treating relapsed/refractory hematologic malignancies, yet immune-related adverse events, particularly hemophagocytic lymphohistiocytosis (HLH),...Chimeric Antigen Receptor T-cell Immunotherapy represents a breakthrough in treating relapsed/refractory hematologic malignancies, yet immune-related adverse events, particularly hemophagocytic lymphohistiocytosis (HLH), also known as immune effector cell-associated HLH-like syndrome (IEC-HS), are rapid-progressing and life-threatening. This systematic review and meta-analysis searched PubMed, Embase, and Cochrane CENTRAL up to August 20, 2025. Nineteen studies were analyzed using a random-effects model, covering 2780 patients, 47 HLH cases, and 20 HLH-related deaths. The pooled incidence of HLH was 1.6% at a median follow-up of 12.9 months, with an associated HLH mortality of 0.7%. The incidence of HLH differed markedly by disease entity (p = 0.0008), highest in B-cell acute lymphoblastic leukemia (B-ALL: 6.9%). CAR T-cell product was also a significant determinant (p = 0.0036), with tisagenlecleucel (Tisa-cel) showing the highest incidence (4.3%). Subgroup analyses confirmed that Tisa-cel had a significantly higher HLH incidence than axicabtagene ciloleucel (Axi-cel) in large B-cell lymphoma (2.4% vs. 0.6%, p = 0.038), and ciltacabtagene autoleucel (Cilta-cel) had a higher incidence than idecabtagene vicleucel (Ide-cel) in multiple myeloma (2.6% vs. 0.7%, p = 0.022). Higher-grade cytokine release syndrome (CRS) was positively correlated with HLH incidence, particularly in MM. Overall HLH incidence was significantly positively correlated with mortality. In conclusion, HLH risk after CAR T-cell therapy is primarily driven by underlying disease type and specific CAR T-cell product, with additional contribution from severe CRS. Enhanced surveillance and early intervention are strongly recommended for high-risk groups, particularly B-ALL patients and recipients of Tisa-cel or Cilta-cel.