Han W, Wang S, Zhang M
… +10 more, Fu S, Wu W, Zhao H, Wong KW, Yip SF, Cui J, Chang AH, Wei G, Huang H, Hu Y
Int J Hematol
· 2025 Dec · PMID 40931245
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Patients with primary plasma cell leukemia (pPCL), particularly those with extramedullary disease (EMD), face a poor prognosis even with chimeric antigen receptor (CAR)-T cell therapy. This case report describes a patien...Patients with primary plasma cell leukemia (pPCL), particularly those with extramedullary disease (EMD), face a poor prognosis even with chimeric antigen receptor (CAR)-T cell therapy. This case report describes a patient with relapsed/refractory pPCL and life-threatening malignant pleural effusion (PE) treated with intrapleural CAR-T cells targeting B-cell maturation antigens. CAR-T cell expansion within the PE was observed, along with a rapid reduction in leukemia cell count and PE volume. Subsequent lymphodepletion chemotherapy and intravenous CAR-T cell therapy induced complete remission with 9 months of progression-free survival. This case highlights the potential advantages of integrating local and systemic CAR-T cell therapy in managing complex EMD cases.
Sakai T, Shoji R, Tanaka R
… +7 more, Yukitaka K, Watanabe R, Sekiguchi Y, Sato K, Shimoyama-Ibuki S, Goto A, Konuma Y
Int J Hematol
· 2026 Jan · PMID 40920295
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INTRODUCTION: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) requires reliable vascular access for medication, transfusion, and blood sampling, which often involves painful venipuncture. This prospective...INTRODUCTION: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) requires reliable vascular access for medication, transfusion, and blood sampling, which often involves painful venipuncture. This prospective study evaluated a novel dual peripherally inserted central venous catheter (PICC) technique to reduce venipuncture frequency in allo-HSCT recipients. METHODS: The study enrolled 29 allo-HSCT recipients. Each patient received two single-lumen PICCs: Catheter A for tacrolimus infusion and Catheter B, positioned distally, for blood sampling. Tacrolimus concentrations from Catheter B and venipuncture were compared using Bland-Altman analysis. Catheter-related adverse events were also evaluated to assess safety. RESULTS: PICC placement was successful in all patients. During 1378 catheter-days, one catheter-related bloodstream infection and one catheter occlusion occurred. Tacrolimus concentrations from PICC samples were strongly correlated with those of venipuncture samples (r = 0.93). Bland-Altman analysis showed good agreement, with a mean difference of 0.064 ng/mL, limits of agreement within ± 2.0 ng/mL, and no fixed bias. CONCLUSION: Dual single-lumen PICCs provide a safe and accurate method for tacrolimus monitoring in allo-HSCT, and may improve patient experience by reducing the need for painful venipuncture. Further randomized-controlled trials are needed to confirm the benefits of this approach and assess its applicability to the monitoring of other therapeutic agents.
Schweneker K, Lenk M, Kern W
… +4 more, Haferlach C, Meggendorfer M, Pohlkamp C, Haferlach T
Int J Hematol
· 2025 Dec · PMID 40906032
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Chronic myeloid leukemia (CML) and BCR::ABL1-negative MPN were thought to be mutually exclusive, but synchronous and sequential cases have been reported. We screened 35,001 patients for BCR::ABL1 fusion or JAK2, CALR, or...Chronic myeloid leukemia (CML) and BCR::ABL1-negative MPN were thought to be mutually exclusive, but synchronous and sequential cases have been reported. We screened 35,001 patients for BCR::ABL1 fusion or JAK2, CALR, or MPL mutations to investigate the sequential development of CML and BCR::ABL1 negative-MPNs. We discovered that 5.6% had primary CML followed by BCR::ABL1-negative MPN, and 5.8% had the reverse sequence. Notably, we identified higher JAK2 variant allele frequencies (VAFs) in patients developing secondary CML. Previous MPN did not compromise the effectiveness of tyrosine kinase inhibitors (TKI) in treating secondary CML. The emergence of secondary MPN appeared to be unrelated to JAK2 VAF progression or BCR::ABL1 transcript levels. Our research indicates that newly detected leukocytosis or thrombocytosis should prompt consideration of secondary MPN. It also showed that secondary CML had no negative impact on response to therapy when patients were treated according to CML guidelines.
Takahashi H, Tanaka S, Yuza Y
… +15 more, Iijima-Yamashita Y, Hasegawa D, Moritake H, Terui K, Iwamoto S, Shimada A, Matsubayashi J, Deguchi T, Hashii Y, Kiyokawa N, Miyachi H, Saito AM, Taga T, Adachi S, Tomizawa D
Int J Hematol
· 2026 Jan · PMID 40906031
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Arsenic trioxide (ATO) in combination with all-trans retinoic acid (ATRA) has been shown to be effective in both adult and pediatric patients with acute promyelocytic leukemia (APL). Addition of ATO to conventional chemo...Arsenic trioxide (ATO) in combination with all-trans retinoic acid (ATRA) has been shown to be effective in both adult and pediatric patients with acute promyelocytic leukemia (APL). Addition of ATO to conventional chemotherapy could lead to a reduction in the doses of cytotoxic agents, but the long-term safety of ATO is not fully understood, especially in children. The Japan Children's Cancer Group conducted a risk-stratified prospective study to investigate safety and efficacy of ATO in children with newly diagnosed APL by replacing all three intensification phases with ATO. The 3-year event-free survival and overall survival rates in 27 children were 96.3% (95% CI 76.5%-99.5%) and 100% (95% CI 87.2%-100%), respectively. Prolonged QTc interval or other cardiac conduction disorders of any grade were observed in 20 out of the 63 intensification cycles. The durations of leukocytopenia, neutropenia, and G-CSF treatment were significantly shorter in this study than in a previous Japanese study that used conventional cytotoxic chemotherapy. Furthermore, no cardiac, metabolic, renal, cutaneous, or neurological symptoms were reported for up to 5 years after completion of the protocol therapy. The JPLSG AML-P13 study demonstrated excellent outcomes and safety of ATO in children with APL.
Hanyu Y, Kanda J, Sugimoto M
… +12 more, Iwasaki M, Watanabe M, Arai Y, Mizumoto C, Kitawaki T, Yamashita K, Yamagiwa T, Taniguchi R, Nakagawa S, Yonezawa A, Terada T, Takaori-Kondo A
Int J Hematol
· 2026 Jan · PMID 40900269
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We retrospectively analyzed the effectiveness of posaconazole (tablet and infusion formulations) and its correlation with blood concentration in preventing invasive fungal infections (IFIs) in 360 patients who underwent...We retrospectively analyzed the effectiveness of posaconazole (tablet and infusion formulations) and its correlation with blood concentration in preventing invasive fungal infections (IFIs) in 360 patients who underwent allogeneic hematopoietic stem cell transplant (allo-HSCT) between 2010 and 2023. A total of 61 patients received posaconazole, 102 received micafungin, and 197 received fluconazole for primary prophylaxis. By day 100 post-transplant, the cumulative incidence of IFIs was significantly lower with posaconazole (5.0%) compared with fluconazole (14.4%) or micafungin (16.9%). Multivariate analysis showed that the risk of IFIs was significantly higher with fluconazole/micafungin than with posaconazole (hazard ratio 4.04, 95% CI 1.17-13.94, P = 0.027). This difference was most notable among patients with lymphoid malignancies (P = 0.053) and those undergoing repeat transplantation (P = 0.024). There were no significant differences in overall survival, non-relapse mortality, or mortality from IFI. Mean blood levels of posaconazole dropped to 0.57 μg/mL two weeks after allo-HSCT, coinciding with the observation of most IFIs in the posaconazole group shortly after transplant. Posaconazole appears to be more effective than fluconazole or micafungin as primary prophylaxis against IFIs in allo-HSCT recipients.
Makiyama J, Ohno N, Jimbo K
… +15 more, Kawamata T, Yokoyama K, Konuma T, Kato S, Takemura T, Ito A, Tanaka T, Inamoto Y, Fuji S, Imai Y, Takahashi S, Nannya Y, Tojo A, Fukuda T, Uchimaru K
Int J Hematol
· 2026 Jan · PMID 40897990
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Adult T-cell leukemia-lymphoma (ATL) is one of the most intractable peripheral T-cell neoplasms caused by human T-cell leukemia virus type I (HTLV-1) infection. Recently, the incidence of HTLV-1 infection and ATL has inc...Adult T-cell leukemia-lymphoma (ATL) is one of the most intractable peripheral T-cell neoplasms caused by human T-cell leukemia virus type I (HTLV-1) infection. Recently, the incidence of HTLV-1 infection and ATL has increased in non-endemic metropolitan areas in Japan. This retrospective study evaluated the clinical features and outcomes of patients with aggressive ATL aged 70 years or younger treated at a core hospital in Tokyo between 2004 and 2016. The median follow-up was 124.4 months for survivors. Among the 71 patients, 46 (64.8%) underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). The 3 year overall survival rate was 45.7% in allo-HSCT group versus 0% in non-allo-HSCT group. Patients who achieved complete/partial remission before allo-HSCT had a significantly better survival rate than those with stable/progressive disease (51.4% vs 27.3%). The 2 year cumulative incidence of relapse/progression and non-relapse mortality after allo-HSCT was 41.3% and 21.7%, respectively. In this study, a large percentage of patients underwent allo-HSCT and achieved favorable outcomes. As cases continue to rise in metropolitan areas, core hospitals will play a critical role in ATL treatment.
Kusakabe S, Kurashige R, Fukushima K
… +13 more, Shimizu K, Yoshihara T, Motooka D, Nakamura S, Kurashige M, Nakata K, Hino A, Kasahara H, Ueda T, Fujita J, Hosen N, Takehara T, Oda J
Int J Hematol
· 2025 Nov · PMID 40866789
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Several cases of inflammatory bowel disease (or similar gastrointestinal lesions) arising after allogeneic hematopoietic stem cell transplantation have been reported, but the effect of intestinal dysbiosis on development...Several cases of inflammatory bowel disease (or similar gastrointestinal lesions) arising after allogeneic hematopoietic stem cell transplantation have been reported, but the effect of intestinal dysbiosis on development of these lesions remains unclear. We performed fecal microbiota transplantation (FMT) and 16S rRNA microbiome analysis in a patient who developed Crohn's disease-like lesions after allogeneic transplantation. A 62-year-old woman underwent haploidentical stem cell transplantation from her daughter to treat double-hit lymphoma relapsed after chimeric antigen receptor T-cell therapy, and achieved remission without developing acute graft-versus-host disease. Eight months later, she developed Crohn's disease-like intestinal lesions after cytomegalovirus enteritis. Her condition did not improve with the conventional treatment, so she underwent FMT from her daughter as part of a clinical trial. Diarrhea gradually improved, and follow-up endoscopy 4 months after the FMT showed ulcer healing and scarring. The 16S rRNA analysis revealed a reduction in the relative abundance of the Enterococcus genus after FMT, suggesting that dysbiosis may have contributed to lesion development. The patient is currently on a regular diet, with no symptom recurrence, and the primary disease remains in remission. Although this outcome suggests that FMT is effective, careful patient selection is required to reduce the risk of FMT-associated sepsis.
Nishiwaki S, Sugiura I, Fujisawa S
… +20 more, Hatta Y, Atsuta Y, Doki N, Kurahashi S, Ueda Y, Dobashi N, Maeda T, Matsumura I, Tanaka M, Kako S, Ichinohe T, Fukuda T, Ohtake S, Ishikawa Y, Miyazaki Y, Sakaida E, Maeda Y, Yamauchi T, Kiyoi H, Japan Adult Leukemia Study Group
Int J Hematol
· 2026 Jan · PMID 40864405
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This study compared dasatinib and imatinib in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). Using pooled data from three JALSG prospective trials (Ph + ALL202, Ph + ALL208, Ph + ALL213),...This study compared dasatinib and imatinib in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). Using pooled data from three JALSG prospective trials (Ph + ALL202, Ph + ALL208, Ph + ALL213), we analyzed outcomes for 206 patients aged 15-64 years treated with dasatinib (n = 74) or imatinib (n = 132) in combination with chemotherapy. We applied propensity score matching (1:1) and inverse probability of treatment weighting to minimize selection bias and balance baseline characteristics. Dasatinib plus chemotherapy was associated with significantly higher complete molecular response rates after induction therapy compared with imatinib. In the propensity score-matched cohort (n = 68 patients per group), 3-year event-free survival (EFS) was significantly higher with dasatinib (73 vs. 49%, P = 0.01), as was 3-year overall survival (OS) (85 vs. 60%, P = 0.004). Multivariate analysis, incorporating allogeneic stem cell transplantation in first complete remission as a covariate, confirmed that dasatinib had an independent favorable prognostic impact on EFS (hazard ratio [HR], 0.54; P = 0.02) and OS (HR, 0.39; P = 0.003). Although the 3-year cumulative incidence of relapse tended to be lower with dasatinib (18 vs. 40%, P = 0.07), non-relapse mortality was comparable between groups (8.8 vs. 12%, P = 0.33). This analysis demonstrates improved survival with dasatinib-based therapy in adult Ph + ALL, informing tyrosine kinase inhibitor selection in treatment planning.
Miyazawa Y, Yokohama A, Ishizaki T
… +8 more, Saitoh T, Saito A, Toyama K, Mitsui T, Murayama K, Ogura H, Tsukamoto N, Handa H
Int J Hematol
· 2026 Jan · PMID 40859046
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OBJECTIVE: Central nervous system (CNS) prophylaxis is recommended for patients with diffuse large B-cell lymphoma (DLBCL) who are at high risk of CNS relapse. This study aimed to determine the impact of CNS prophylaxis...OBJECTIVE: Central nervous system (CNS) prophylaxis is recommended for patients with diffuse large B-cell lymphoma (DLBCL) who are at high risk of CNS relapse. This study aimed to determine the impact of CNS prophylaxis on CNS relapse rates and overall survival (OS) in this patient population, as well as the optimal method for CNS prophylaxis. METHODS: This was a retrospective analysis of 178 patients with DLBCL at high risk of CNS relapse who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) or its derivatives with (N = 60) or without (N = 118) CNS prophylaxis. RESULTS: The 2-year CNS relapse rate was 17.6% in the all-prophylaxis group (HD-MTX 17.4%, IT 48.1%, and HD-MTX + IT 6.2%) and 13.0% in the non-prophylaxis group, with no significant difference between groups. However, HD-MTX + IT decreased the risk of CNS relapse. After a median follow-up of 72.8 months, HD-MTX + IT addition significantly improved the 5-year OS (HD-MTX 73.5%, IT 44.4%, HD-MTX + IT 93.2%; non-prophylaxis group 58.0%; p = 0.013). This advantage was maintained in the multivariate analysis (hazard ratio: 0.160; 95% confidence interval: 0.039-0.663; p = 0.012). CONCLUSIONS: CNS prophylaxis with HD-MTX + IT improved the prognosis of patients with DLBCL at high risk of CNS relapse.
Yoon SE, Cho J, Cho D
… +3 more, Kang ES, Kim SJ, Kim WS
Int J Hematol
· 2025 Oct · PMID 40847083
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Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment landscape for relapsed and refractory large B-cell lymphoma (RR-DLBCL). This study evaluated the real-world efficacy and toxicities of 96 patie...Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment landscape for relapsed and refractory large B-cell lymphoma (RR-DLBCL). This study evaluated the real-world efficacy and toxicities of 96 patients with RR-DLBCL who received tisagenlecleucel (tisa-cel) at a single institution. Among 81 patients who received bridging chemotherapy, most received a bendamustine and rituximab regimen (n = 48, 46.9%), and 31 (38.3%) responded to bridging chemotherapy (17.3% complete remission [CR] and 21.0% partial remission). Tisa-cel showed an overall response rate (ORR) of 71.9% at 1 month, which declined to 55.1% at 3 months. The median progression-free survival (PFS) was 4.5 months, with 1-year PFS at 33.3%. Median overall survival (OS) was 13.9 months, with a 1-year OS rate of 55.2%. Achieving CR at 3 months was correlated with significantly improved PFS and OS. Cytokine release syndrome occurred in 75% of patients (14.6% grade ≥ 3) and immune effector cell-associated neurotoxicity syndrome occurred in 22.9% of patients (7.3% grade ≥ 3). All adverse events were managed effectively. The results demonstrated significant survival benefits with manageable toxicities, supporting tisa-cel as a viable salvage therapy for RR-DLBCL.
Int J Hematol
· 2025 Dec · PMID 40820164
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BACKGROUND: Iron deficiency anemia (IDA) is the leading cause of nutritional anemia. In some cases, oral iron therapy (OIT) fails to achieve an optimal therapeutic response. Oral doses of iron acutely increase serum hepc...BACKGROUND: Iron deficiency anemia (IDA) is the leading cause of nutritional anemia. In some cases, oral iron therapy (OIT) fails to achieve an optimal therapeutic response. Oral doses of iron acutely increase serum hepcidin, resulting in decreased iron absorption and poor response treatment. OBJECTIVE: The primary objective was to assess the efficacy of alternate-day versus twice-daily OIT in children with IDA. The secondary objective was to study the effects of alternate versus twice-daily OIT on serum hepcidin levels and to compare gastrointestinal side effects between groups. METHODS: This was an RCT of 40 IDA patients, aged 6 months 10 years. The first group received twice-daily OIT, and the second group received alternate-day OIT. Serum hepcidin levels were measured at baseline and 48 h after starting OIT. Changes in hemoglobin level were noted after 30 days. RESULTS: Patients who received alternate-day OIT had increase hemoglobin (P = 0.002) and decrease serum hepcidin (P = 0.01). Four of twenty in the alternate-day group (20%) had gastrointestinal side effects (P = 0.01). CONCLUSION: Children who received alternate-day OIT had lower serum hepcidin levels, which resulted in better iron absorption and compliance, significant improvement in hemoglobin levels, and fewer gastrointestinal side effects.
Hosono N, Tomiyama Y, Emori N
… +2 more, Isogaya K, Yamauchi T
Int J Hematol
· 2025 Dec · PMID 40815417
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CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin. The safety of CPX-351 in Japanese patients was verified by comparing safety data from the Japanese phase 1/2 study and the global phase 3 stu...CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin. The safety of CPX-351 in Japanese patients was verified by comparing safety data from the Japanese phase 1/2 study and the global phase 3 study. This analysis included 47 patients in the safety analysis set of the Japanese study and 153 patients who received CPX-351 and were included in the intention-to-treat analysis for the global study. In both the Japanese and global studies, the most frequent adverse events were febrile neutropenia (FN) (Japanese: 85.1%, global: 70.0%) and pneumonia (25.5% and 24.2%). Median time to occurrence was 8 and 11 days for FN, and 17 and 23 days for pneumonia. Median time to hematologic recovery was 36 and 41 days for neutrophils (> 1000/μL), and 36 and 44 days for platelets (> 100,000/μL). In the global study, univariate analysis was performed after one cycle of induction therapy to investigate factors that delay neutrophil and platelet recovery, but no specific factors were identified. In these analyses, the pattern and frequency of adverse events were similar in Japanese and non-Japanese patients, with no need for race- or region-specific management.
Ishikawa K, Mori N, Fushimi K
… +1 more, Ishikawa KB
Int J Hematol
· 2026 Jan · PMID 40815416
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The epidemiology of febrile neutropenia (FN) remains poorly understood. Although the Diagnosis Procedure Combination (DPC) database offers valuable clinical information, it lacks FN-specific diagnostic codes. This study...The epidemiology of febrile neutropenia (FN) remains poorly understood. Although the Diagnosis Procedure Combination (DPC) database offers valuable clinical information, it lacks FN-specific diagnostic codes. This study aimed to develop an algorithm to identify patients with FN using DPC data and to investigate the epidemiology of FN. Data from St. Luke's International Hospital were used to identify DPC-based FN cases in patients with hematological malignancies who underwent chemotherapy, blood culture collection, and antipseudomonal antibiotic therapy. True FN cases were confirmed through chart review, incorporating neutrophil counts and body temperature. The algorithm demonstrated a sensitivity of 79.6%, specificity of 94.1%, PPV of 81.9%, NPV of 93.2%, and an F-measure of 80.6%. A sensitivity analysis for 2015-2020 showed improved performance: sensitivity 98.9%, specificity 99.6%, PPV 82.4%, NPV 99.6%, and F-measure 89.9%. Among the 144,009 patients with hematological malignancies in the DPC database, 50,558 received chemotherapy, and 13,720 (27.1%) developed FN as indicated by the algorithm, with in-hospital mortality rates of 15.0%. Although 76.7% of patients with FN received guideline-recommended first-line antibiotics, 17.0% received carbapenem, suggesting a potential need for antimicrobial stewardship interventions. The algorithm represents a valuable tool for large-scale epidemiological studies and could help inform strategies for FN management in Japan.
Suzuki S, Hosoda Y, Umeda M
… +10 more, Maegaki M, Adachi K, Tajima F, Hatayama Y, Hosoda R, Hara K, Kawamura K, Yamashiro Y, Hattori Y, Fukuda T
Int J Hematol
· 2025 Dec · PMID 40804159
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A Japanese woman presented with a history of neonatal jaundice and recurrent episodes of severe fatigue and jaundice during viral infections in her late teens. Her mother, aunt, and grandmother had similar clinical histo...A Japanese woman presented with a history of neonatal jaundice and recurrent episodes of severe fatigue and jaundice during viral infections in her late teens. Her mother, aunt, and grandmother had similar clinical histories. During an admission for fever and fatigue, blood tests revealed acute hemolysis and an abnormal hemoglobin band on high-performance liquid chromatography. β-globin gene sequencing identified a codon 34 substitution from GTC (Val) to GAC (Asp), confirming the presence of the unstable hemoglobin variant Hb Santander. This very rare hemoglobinopathy was previously reported only in a single sporadic case involving a Spanish man; this is the first documented case in a Japanese family. Our observation of four affected individuals across three generations provided insight into the progression of Hb Santander from birth to old age. Unstable hemoglobin variants can lead to recurrent, severe episodes of acute hemolytic crisis. Chronic hemolysis in the steady state was compensated without anemia or polycythemia but was associated with an increased risk of gallstone formation. Hb Santander does not appear to be a life-shortening hemoglobinopathy; however, clinical vigilance is necessary for acute hemolysis triggered by drugs or infections and for gallstones at a younger age, particularly in patients with Gilbert syndrome.
Uchino K, Nakagami Y, Enomoto M
… +14 more, Shimizu N, Kondo K, Yamamoto T, Sugita Y, Isaji Y, Saigusa S, Iida Y, Shinohara S, Horio T, Murakami S, Mizuno S, Ikegame K, Hanamura I, Takami A
Int J Hematol
· 2025 Dec · PMID 40794124
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Functional hyposplenism, defined as impaired splenic function in the absence of splenectomy, increases susceptibility to life-threatening infections. Although Howell-Jolly bodies (HJBs) are well-established markers for t...Functional hyposplenism, defined as impaired splenic function in the absence of splenectomy, increases susceptibility to life-threatening infections. Although Howell-Jolly bodies (HJBs) are well-established markers for this condition, the predictive value of spleen volume for infection risk remains unclear. We retrospectively analyzed 95 non-splenectomized patients with HJBs from 2014 to 2024. We measured spleen volume by computed tomography and compared results with ideal values. We evaluated the associations between splenic volume and infections using univariate and multivariate logistic regression analyses. The median patient age was 66 years (range, 16-95); 72% were male. The median spleen volume was 34 mL, lower than the ideal median of 210 mL. Forty-eight percent of patients experienced at least one infection. Univariate analysis identified age ≥ 65 years and spleen volume < 34 mL as significantly associated with sepsis. Both factors remained independent predictors in multivariate analysis (age ≥ 65: odds ratio [OR], p = 0.039; spleen volume < 34 mL: OR 3.0, p = 0.047). Age ≥ 65 also predicted any infection (OR 3.1, p = 0.013), while low spleen volume demonstrated a trend toward significance (OR 2.2, p = 0.064). In non-splenectomized patients with HJBs, reduced spleen volume and older age independently increase susceptibility to sepsis. Computed tomography-based measurements may help identify functional hyposplenism and guide targeted prophylactic measures.
Int J Hematol
· 2025 Sep · PMID 40773119
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Clonal hematopoiesis (CH) is defined as the age-associated expansion of hematopoietic stem and progenitor cells harboring somatic mutations, most frequently in epigenetic regulators such as DNMT3A, TET2, and ASXL1. Altho...Clonal hematopoiesis (CH) is defined as the age-associated expansion of hematopoietic stem and progenitor cells harboring somatic mutations, most frequently in epigenetic regulators such as DNMT3A, TET2, and ASXL1. Although CH was initially recognized as a precursor to hematological malignancies, accumulating evidence has led to its broad recognition as a relevant factor in various age-related nonmalignant diseases, particularly those with inflammatory components, such as cardiovascular disease, autoimmune disorders, and solid tumors. Notably, the increased overall mortality associated with CH is primarily driven by cardiovascular complications rather than hematological malignancies. Among CH-associated genes, ASXL1 mutations are distinguished by their strong associations with adverse clinical outcomes and pro-inflammatory signatures. However, compared to TET2 and DNMT3A, the molecular and pathological implications of ASXL1-mutated CH remain underexplored. Recent studies have expanded the disease spectrum of ASXL1 mutations beyond hematological malignancies, implicating them in clonal expansion and systemic inflammation. This review aims to summarize the current epidemiological and experimental insights into ASXL1-mutated CH, focusing on its potential contributions to inflammation-associated diseases. By integrating clinical observations and emerging mechanistic data, we highlight the urgent need for deeper investigation into ASXL1-driven CH and its systemic consequences beyond hematological transformation.
Tanaka K, Kikuchi H, Umezawa Y
… +3 more, Mori T, Fushimi K, Yamamoto M
Int J Hematol
· 2025 Dec · PMID 40770123
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Chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable efficacy in treating relapsed/refractory B-cell malignancies, as supported by real-world evidence (RWE). However, limited RWE exists on the management...Chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable efficacy in treating relapsed/refractory B-cell malignancies, as supported by real-world evidence (RWE). However, limited RWE exists on the management of adverse events during the perioperative period following CAR-T infusion. This study was conducted to obtain RWE on perioperative management using the Japanese Diagnosis Procedure Combination database, a comprehensive repository of Japanese health and medical service data. Between November 2019 and March 2022, 388 patients received CAR-T therapy. Of these, 312 had large B-cell lymphoma (LBCL) and 76 had B-cell acute lymphoblastic leukemia (B-ALL). The number of CAR-T infusions increased every 6-month interval, correlating with the rise in LBCL cases. Tocilizumab was administered for cytokine release syndrome in 56.1% of LBCL and 42.1% of B-ALL patients. Steroids were used for 22.9% and 81.3%, respectively. Prophylaxis for fungal infections was administered during CAR-T infusion in most LBCL and B-ALL patients. Treatment intensity was escalated in 2.8% of LBCL and 7.0% of B-ALL patients, and treatment for cytomegalovirus infection was initiated in approximately 7% of patients. This analysis elucidated perioperative management strategies based on patients' medication histories.