Imahashi N, Konuma T, Kobayashi S
… +16 more, Watanabe M, Takahashi S, Nishida T, Kawakita T, Nakamae H, Doki N, Onishi Y, Sakata-Yanagimoto M, Kanda Y, Tanaka M, Eto T, Yoshinaga N, Ishimaru F, Ichinohe T, Atsuta Y, Kanda J
Outcomes of allogeneic hematopoietic stem cell transplantation are significantly influenced by conditioning regimens and graft-versus-host disease (GVHD) prophylaxis. Previous studies comparing matched-related donor (MRD...Outcomes of allogeneic hematopoietic stem cell transplantation are significantly influenced by conditioning regimens and graft-versus-host disease (GVHD) prophylaxis. Previous studies comparing matched-related donor (MRD) and umbilical cord blood (UCB) transplantation included patients with heterogeneous conditioning regimens and GVHD prophylaxis, potentially obscuring the true effects of donor type. We retrospectively compared outcomes of MRD (n = 1335) and UCB (n = 1097) transplantation performed with conditioning regimens and GVHD prophylaxis considered appropriate for cyclophosphamide/total body irradiation-based transplantation. Multivariable analysis revealed better relapse-free survival (RFS) for UCB than MRD in acute myeloid leukemia (hazard ratio [HR]: 0.80; 95% confidence interval [CI]: 0.65-0.99; P = 0.04) and lymphoma (HR: 0.61; 95% CI: 0.37-0.997; P = 0.04). In contrast, RFS was similar between MRD and UCB in acute lymphoblastic leukemia (HR: 0.97; 95% CI: 0.79-1.18; P = 0.74) and worse for UCB in myelodysplastic syndrome (HR: 1.66; 95% CI: 1.09-2.52; P = 0.01). These findings suggest that, when appropriate regimens are used, UCB may perform more favorably than MRD depending on disease type. Further validation in independent registry studies is warranted.
Int J Hematol
· 2026 Mar · PMID 41917309
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Following asciminib's initial approval in Japan for chronic myeloid leukemia (CML) resistant or intolerant to previous therapy, this all-patient, postmarketing surveillance study was initiated. Predefined safety specific...Following asciminib's initial approval in Japan for chronic myeloid leukemia (CML) resistant or intolerant to previous therapy, this all-patient, postmarketing surveillance study was initiated. Predefined safety specifications, overall safety, and effectiveness were assessed for 48 weeks from asciminib initiation (safety analysis set, n = 523). The approved daily dose of asciminib (80 mg [40 mg twice daily]) was most frequently used (63.9%) and not exceeded. Discontinuations (28.5%) were primarily due to adverse events (18.2%), including disease progression. Incidences of the safety specifications myelosuppression, pancreatitis, QT interval prolongation, infections, vascular occlusive events, and photosensitivity were 8.6%, 4.4%, 2.5%, 1.3%, 0.2%, and 0%, respectively, with low rates of treatment discontinuation for these events. There were no notable trends in the rates or types of adverse drug reactions in patients aged ≥ 65 years or with concurrent renal impairment, hepatic impairment, or cardiac dysfunction. The cumulative major molecular response rate was 61.2% by week 48 and was not affected by age (≥ 65 years) or comorbidities. Cumulative MR and MR rates by week 48 were 42.3% and 26.5%, respectively, with some patients harboring baseline BCR::ABL1 mutations showing these responses. These real-world outcomes support the safety and effectiveness of asciminib for patients with resistant/intolerant CML.
Yilmaz Kars M, Kars TU, Cayci M
… +6 more, Bagci M, Cirik S, Gunay A, Yılmaz S, Basturk A, Kizilarslanoglu MC
Int J Hematol
· 2026 Mar · PMID 41917308
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Changes in body composition, particularly sarcopenia and adipose tissue remodeling, have prognostic implications in multiple myeloma (MM). This retrospective study evaluated the prognostic value of PET/CT-derived muscle...Changes in body composition, particularly sarcopenia and adipose tissue remodeling, have prognostic implications in multiple myeloma (MM). This retrospective study evaluated the prognostic value of PET/CT-derived muscle indices and brown adipose tissue (BAT) activity in 75 MM patients aged ≥ 60 years treated between January 2023 and March 2025. Autologous stem cell transplantation (ASCT) was performed in 41.3% of patients. Median progression-free survival was 6.06 months, with a median follow-up of 25.70 months. ASCT was independently associated with improved overall survival (OR: 0.249, p = 0.060) and a reduced risk of final disease progression (OR: 0.260, p = 0.019). Higher Charlson Comorbidity Index scores independently predicted increased mortality (OR: 1.677, p = 0.017). Reduced skeletal muscle mass, particularly a lower pectoralis major index, was independently associated with disease progression (OR: 0.003, p = 0.012). Among ASCT recipients, higher BAT activity (SUVmean) showed a strong negative correlation with post-transplant progression-free survival (rho = -0.717, p < 0.05). PET/CT-based body composition analysis may provide additional prognostic value in MM.
Ogasawara F, Minami Y, Chi S
… +3 more, Ueda T, Fukushima K, Kojima K
Int J Hematol
· 2026 Mar · PMID 41915141
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Mutant TP53 (mTP53) variants are diverse, and residual wild-type p53 function (functional, non-functional), gain-of-function (GOF) mTP53, and the number of mTP53 (single-hit, multi-hit) can affect prognosis. We used next...Mutant TP53 (mTP53) variants are diverse, and residual wild-type p53 function (functional, non-functional), gain-of-function (GOF) mTP53, and the number of mTP53 (single-hit, multi-hit) can affect prognosis. We used next-generation sequencing to evaluate the association between qualitative and quantitative mTP53 abnormalities and overall survival (OS) in 330 patients with acute myeloid leukemia (AML) enrolled in the Japanese multicenter study HM-SCREEN-JAPAN 01/02. Patients with single- and multi-hit mTP53 had a worse prognosis than patients with wild-type TP53 (median OS: 16.1 months vs. 7.5 months vs. 41.6 months). Patients with multi-hit mTP53 had a worse prognosis (P = 0.011). Patients with both mTP53 and complex karyotype (CK) had a worse prognosis than patients with either mTP53 or CK (median OS: 7.6 months vs. 15.0 months vs. 18.9 months; P = 0.03). Residual function did not affect prognosis in patients with single-hit mTP53 (median OS: 24.9 months vs. 16.1 months; P = 0.985), and prognosis did not differ between patients with GOF mTP53 and those with non-GOF mTP53 (median OS: 9.5 months vs. 9.8 months; P = 0.913). Quantitative abnormalities in the TP53 gene affected prognosis, suggesting that qualitative abnormalities did not.
Izumi A, Tachibana T, Miyazaki T
… +11 more, Takeda T, Konishi H, Abe M, Suzuki T, Sato S, Suzuki T, Yamazaki E, Bando K, Uemura Y, Tanaka M, Nakajima H
Int J Hematol
· 2026 Mar · PMID 41912754
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Previous studies have suggested that intensive chemotherapy to induce bone marrow hypoplasia before allogeneic hematopoietic stem cell transplantation (HSCT) may improve outcomes in relapsed/refractory acute lymphoblasti...Previous studies have suggested that intensive chemotherapy to induce bone marrow hypoplasia before allogeneic hematopoietic stem cell transplantation (HSCT) may improve outcomes in relapsed/refractory acute lymphoblastic leukemia. In this retrospective single-center study, we analyzed 14 patients who received clofarabine (CLO) as a preconditioning intervention (PCI) before HSCT between 2019 and 2024. PCI was defined as initiation of conditioning within 2 weeks after CLO. The median age was 34 years, and seven patients were not in remission at the time of CLO. CLO (30 mg/m for 5 days) was given in one or two cycles. WBC and bone marrow nucleated cells significantly decreased after CLO. The 1-year overall survival, relapse incidence, and non-relapse mortality rates were 67.5%, 32.2%, and 21.6%, respectively. Neutrophil engraftment was achieved in all patients. Acute and chronic graft-versus-host disease occurred in four and two patients, respectively. Bloodstream infections within 100 days after HSCT were observed in nine patients. Thrombotic microangiopathy (n = 2), sinusoidal obstruction syndrome/veno-occlusive disease (n = 2), drug-induced cardiomyopathy (n = 1), and organizing pneumonia (n = 1) were also observed but were clinically manageable. Considering the high-risk nature of this cohort, CLO-based PCI followed by HSCT appears to be a feasible treatment strategy with acceptable toxicity, warranting further investigation.
Horigome Y, Kamata H, Ehata K
… +3 more, Tadera N, Hayama K, Suzuki T
Int J Hematol
· 2026 Mar · PMID 41910932
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Severe renal impairment (RI) is a major contributor to early morbidity and mortality in transplant-ineligible newly diagnosed multiple myeloma (Ti-NDMM). Although daratumumab, lenalidomide, and dexamethasone (DRd) is an...Severe renal impairment (RI) is a major contributor to early morbidity and mortality in transplant-ineligible newly diagnosed multiple myeloma (Ti-NDMM). Although daratumumab, lenalidomide, and dexamethasone (DRd) is an established frontline regimen, patients with creatinine clearance ≤ 30 mL/min were excluded from the MAIA trial, leaving evidence in this high-risk population limited. We retrospectively analyzed Ti-NDMM patients with severe RI, defined as estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m, treated with frontline DRd between 2019 and 2024 at our institution. Ten patients met inclusion criteria, all classified as stage III according to the Second Revision of the International Staging System. The overall hematologic response rate was 80%, including very good partial response or better in 50%. Complete renal response occurred in 40% and was associated with deeper hematologic response and significantly prolonged progression-free survival and time to next treatment. Median eGFR improved from 21 to 50.5 mL/min/1.73 m. These findings suggest that DRd is feasible and may provide clinically meaningful renal recovery and disease control in Ti-NDMM patients with severe RI, supporting its potential role as a frontline therapeutic option in this underrepresented population.
Yae H, Nishimoto M, Okamura H
… +5 more, Miyagawa H, Nakamae M, Nakashima Y, Hino M, Nakamae H
Int J Hematol
· 2026 Mar · PMID 41904780
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Infections are a major complication after allogeneic hematopoietic cell transplantation (allo-HCT). Although humoral immunity is essential, the phase-specific role of IgG remains unclear. We analyzed 579 allo-HCT recipie...Infections are a major complication after allogeneic hematopoietic cell transplantation (allo-HCT). Although humoral immunity is essential, the phase-specific role of IgG remains unclear. We analyzed 579 allo-HCT recipients, stratified into early, intermediate, and late post-transplant phases. The incidence of bacterial infections during the intermediate phase decreased with increasing IgG trough levels (incidence rate ratio [IRR], 0.85; 95% confidence interval [CI]: 0.78-0.94, p < 0.01), whereas no association was observed in the early or late phases. During the intermediate phase, multivariable analyses demonstrated that hypogammaglobulinemia (IRR, 1.70; 95% CI: 1.11-2.62, p = 0.02) and acute graft-versus-host disease with grade II-IV (IRR, 2.10; 95% CI: 1.39-3.18, p < 0.01) were associated with bacterial infections. In models including high-dose steroid exposure, steroid therapy was independently associated with bacterial infections, whereas the effect of hypogammaglobulinemia was attenuated. There was a trend toward an interaction between hypogammaglobulinemia and high-dose steroid exposure. A stratified analysis suggested that hypogammaglobulinemia had a more pronounced impact among patients without high-dose steroids (IRR 1.86; 95% CI: 1.09-3.16; p = 0.02). These findings suggest the clinical relevance of hypogammaglobulinemia is phase-specific and influenced by the intensity of immunosuppressive therapy. Monitoring IgG during this period may help identify candidates for targeted immunoglobulin replacement therapy.
Suzuki K, Matsumoto M, Takamatsu H
… +12 more, Kosugi H, Kondo T, Fujisaki T, Facon T, Zweegman S, Ito M, Sakai C, Kanai S, Nakatogawa T, Rowe M, Carson R, Usmani SZ
Int J Hematol
· 2026 Jul · PMID 41894094
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The phase 3 CEPHEUS trial was conducted in 13 countries starting December 11, 2018 in patients with newly diagnosed multiple myeloma (NDMM) who were transplant-ineligible or for whom transplantation was not planned as in...The phase 3 CEPHEUS trial was conducted in 13 countries starting December 11, 2018 in patients with newly diagnosed multiple myeloma (NDMM) who were transplant-ineligible or for whom transplantation was not planned as initial therapy. Bortezomib, lenalidomide, and dexamethasone (VRd) with daratumumab (D-VRd) provided deeper, more durable responses and lowered the risk of disease progression or death compared with VRd. This analysis evaluated the efficacy and safety of D-VRd specifically in the Japanese subpopulation of the CEPHEUS trial (D-VRd: n = 9; VRd: n = 13). At a median follow-up of 59.0 months, the overall minimal residual disease (MRD) negativity rate was 77.8% with D-VRd and 46.2% with VRd (odds ratio: 4.08 [95% confidence interval: 0.60, 27.65]). The complete response or better rate was 88.9% with D-VRd and 76.9% with VRd. Median progression-free survival was not reached in either group, with a hazard ratio of 0.34 favoring D-VRd. The sustained (≥ 12 months) MRD negativity rate was 55.6% with D-VRd and 38.5% with VRd. Efficacy and safety results were similar to those observed in the global CEPHEUS population, supporting the use of D-VRd in Japanese patients with NDMM.
Yoshinari H, Kawahara Y, Niijima H
… +12 more, Aoki S, Ishihara A, Horiuchi T, Hirata Y, Sanada Y, Onishi Y, Sakuma Y, Tsuji K, Tanaka Y, Kumagai H, Osaka H, Shimada A
Int J Hematol
· 2026 Jun · PMID 41874820
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Acute liver failure in the neonatal period is commonly caused by infections, metabolic disorders, immune disorders, or neonatal hepatitis-like diseases of unknown etiology; however, malignant diseases are rarely included...Acute liver failure in the neonatal period is commonly caused by infections, metabolic disorders, immune disorders, or neonatal hepatitis-like diseases of unknown etiology; however, malignant diseases are rarely included in the differential diagnosis, and leukemia may be overlooked. We report a case of neonatal acute liver failure that required living-donor liver transplantation from the patient's father, which was later diagnosed as acute megakaryoblastic leukemia (AMKL) harboring an RBM15::MKL1 fusion transcript. After liver transplantation, leukemic blasts infiltrated the transplanted liver, necessitating the initiation of chemotherapy. The patient achieved remission and has survived for four years after completion of reduced-intensity AML-type chemotherapy. RBM15::MKL1-positive AMKL is characteristically associated with both myelofibrosis and hepatic fibrosis. Congenital cases have also been reported, suggesting that RBM15::MKL1 AMKL may originate in the intrauterine fetal liver. A literature search for "acute liver failure" and "acute megakaryoblastic leukemia" revealed five cases reported since 2000. All patients had an RBM15::MKL1 fusion transcript and all died. In contrast, survival has been reported in patients with RBM15::MKL1-AMKL who did not present with acute liver failure. We speculate that our patient survived because acute liver failure was successfully managed with living-donor liver transplantation.
T-cell lymphomas represent a heterogeneous group of lymphoid malignancies characterized by marked biological diversity and generally poor clinical outcomes. Recent updates to the fifth edition of the World Health Organiz...T-cell lymphomas represent a heterogeneous group of lymphoid malignancies characterized by marked biological diversity and generally poor clinical outcomes. Recent updates to the fifth edition of the World Health Organization Classification and the 2022 International Consensus Classification have refined the disease entities based on transcription factor profiles, cytokine signatures, and molecular features. Comprehensive genomic and epigenomic analyses have revealed recurrent alterations affecting T-cell receptor signaling, epigenetic regulation, cell-cycle control, and immune pathways, thereby facilitating the development of molecularly targeted therapies. Viral oncogenesis plays a central role in selected subtypes, particularly adult T-cell leukemia-lymphoma and Epstein-Barr virus-associated natural killer/T-cell lymphomas. The accelerated development of molecularly targeted therapies has led to the introduction of several novel agents, while hematopoietic stem cell transplantation also continues to provide an important potentially curative strategy. This issue of Progress in Hematology provides a comprehensive overview of recent advances in molecular pathogenesis, viral biology, therapeutic developments, and transplantation strategies in T-cell lymphomas.
Fujii F, Onozawa M, Yoshida S
… +19 more, Miyashita N, Hidaka D, Ogasawara R, Takahata M, Hashiguchi J, Yokoyama S, Chiba M, Saga T, Shimizu T, Kasahara I, Shigematsu A, Fujimoto K, Iyama S, Igarashi T, Ito S, Haseyama Y, Kosugi-Kanaya M, Kondo T, Teshima T
Int J Hematol
· 2026 Mar · PMID 41857430
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Venetoclax (VEN), a BCL-2 inhibitor, was approved in Japan in March 2021, for acute myeloid leukemia (AML). We retrospectively analyzed the impact of VEN approval on treatment patterns and outcomes in older AML patients...Venetoclax (VEN), a BCL-2 inhibitor, was approved in Japan in March 2021, for acute myeloid leukemia (AML). We retrospectively analyzed the impact of VEN approval on treatment patterns and outcomes in older AML patients aged 65-74 years unfit for intensive chemotherapy in Japan. Using the Hokkaido Leukemia Net database, we categorized 101 patients into pre-VEN (n = 46) and post-VEN (n = 55) cohorts, excluding those who had acute promyelocytic leukemia or received intensive chemotherapy. Following VEN approval, VEN + azacitidine (AZA) became the most frequently used initial regimen (56%). Despite higher rates of TP53 mutations and complex karyotypes (35.5%), VEN + AZA achieved comparable response rates (CR + CRi: 64.5%) and overall survival (OS, median 11.7 months) to r7 + 3 (CR + CRi: 64.5%, median OS: 13.1 months), and superior outcomes to cytarabine + aclarubicin + G-CSF (CAG, CR + CRi 37.5%, median OS 6.8 months) or AZA monotherapy (CR + CRi 12.5%, median OS 4.5 months). Early mortality at 60 days from diagnosis was lower with VEN + AZA (3.2%) than with reduced-dose cytarabine plus anthracycline (r7 + 3) (12.9%), CAG (26.7%), or AZA monotherapy (18.8%). Our findings demonstrate a substantial shift in real-world treatment practices following VEN approval and suggest that VEN + AZA is an effective option for older AML patients with adverse genetic features.
Hirao T, Yamamoto H, Kuno M
… +12 more, Watanabe O, Yamaguchi K, Kageyama K, Kaji D, Taya Y, Nishida A, Takagi S, Asano-Mori Y, Yamamoto G, Wake A, Taniguchi S, Uchida N
Int J Hematol
· 2026 Mar · PMID 41854805
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Although HLA-matched related donor transplantation (MRDT) is considered the preferred graft source when available, cord blood transplantation (CBT) is an alternative source, with several studies suggesting a potent graft...Although HLA-matched related donor transplantation (MRDT) is considered the preferred graft source when available, cord blood transplantation (CBT) is an alternative source, with several studies suggesting a potent graft-versus-leukemia effect. We compared outcomes between CBT and MRDT in acute myeloid leukemia (AML) not in remission and examined how pre-engraftment immune reaction (PIR), graft-versus-host disease (GVHD), and HLA mismatch affect CBT outcomes. We retrospectively analyzed 334 patients with AML not in remission who underwent first allo-HSCT using either single-unit CBT (n = 309) or MRDT (n = 25). At 5 years, CBT recipients showed significantly better leukemia-free survival (LFS) (42.0% vs. 17.6%) and lower relapse rates (24.6% vs. 54.0%), with no difference in NRM. Among CBT recipients, patients who developed mild PIR had a lower relapse rate compared with those without PIR (hazard ratio [HR], 0.48). In contrast, severe PIR was associated with higher NRM (HR, 3.13) and worse overall survival (HR, 2.12). Acute GVHD, chronic GVHD, and HLA disparity were not significantly associated with relapse. CBT was associated with superior LFS compared with MRDT in patients with AML not in remission, and PIR occurrence and severity were associated with CBT outcomes.
Kanda J, Wattanakamolkul K, Muromine H
… +1 more, Shiga K
Int J Hematol
· 2026 Jun · PMID 41851584
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This retrospective cohort study using the medical data vision (MDV) database included adult patients who had confirmed diagnosis of cGVHD between 2003 and 2023, were prescribed a steroid prior to diagnosis of cGVHD, and...This retrospective cohort study using the medical data vision (MDV) database included adult patients who had confirmed diagnosis of cGVHD between 2003 and 2023, were prescribed a steroid prior to diagnosis of cGVHD, and received mycophenolate mofetil (MMF), ibrutinib, or ruxolitinib as second- or later-line therapy. Duration of treatment (DoT) and steroid dose reduction during second-line therapy were assessed. Of the 1489 patients whose data were retrieved, 854 were included (median [range] age: 54 [18.0-83.0] years; males: 518 [60.7%]; mean [SD] Charlson Comorbidity Index score: 7.5 [3.5]). Data on second or later lines of treatment were available for 226 patients. The most common second-line therapy used after first-line steroid treatment was MMF (110 [48.67%]), followed by ibrutinib (88 [38.94%]) and ruxolitinib (28 [12.39%]). Median DoT (days) was 95 for MMF, 86 for ibrutinib, and 30 for ruxolitinib. Steroid doses were mostly kept below 0.5 mg/kg/day under all the 3 second-line treatments. These real-world data provide valuable insights into the management of cGVHD with the therapies currently used in Japan.
Ichikawa H, Yakushijin K, Inui Y
… +17 more, Takemoto N, Tsuji T, Iida K, Kamido S, Harima I, Okazoe-Hirakawa Y, Matsumoto S, Sakai R, Kurata K, Kitao A, Saito Y, Kawamoto S, Yamamoto K, Ito M, Murayama T, Matsuoka H, Minami H
Int J Hematol
· 2026 Jul · PMID 41840330
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Prediction and early diagnosis are critical for the effective treatment of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) after hematopoietic stem cell transplantation (HSCT). This study aimed to invest...Prediction and early diagnosis are critical for the effective treatment of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) after hematopoietic stem cell transplantation (HSCT). This study aimed to investigate the utility of clinical hepatic indices easily calculated in routine practice, namely the Endothelial Activation and Stress Index (EASIX), aspartate aminotransferase-to-platelet ratio index (APRI), Fibrosis-4 (FIB-4), reversed Albumin-Bilirubin grade (rALBI), Model for End-Stage Liver Disease (MELD), and MELD score and the serum sodium concentration (MELDNa). We retrospectively analyzed longitudinal clinical data from 175 allogeneic HSCTs at our institution. The 22 patients who eventually developed clinical SOS/VOD were used as the reference standard. At baseline, EASIX, APRI, FIB-4, rALBI, MELD, and MELDNa were analyzed using the receiver operating characteristic method, with resulting area under the curve (95% confidence interval) of 0.739 (0.607-0.871), 0.770 (0.641-0.898), 0.760 (0.645-0.875), 0.672 (0.530-0.815), 0.577 (0.440-0.713), and 0.642 (0.449-0.784), respectively. After HSCT, these indices were also associated with SOS/VOD, even 7 days before diagnosis (all p-values < 0.001). In conclusion, clinical hepatic indices are useful for prediction and early diagnosis of SOS/VOD in allogeneic HSCT recipients. Further studies are required to determine their optimal clinical application.
Int J Hematol
· 2026 Mar · PMID 41832377
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With the advent of complement inhibition therapy, the severe thrombotic complications of paroxysmal nocturnal hemoglobinuria (PNH)-once described as the most vicious acquired thrombophilic state-no longer pose the same i...With the advent of complement inhibition therapy, the severe thrombotic complications of paroxysmal nocturnal hemoglobinuria (PNH)-once described as the most vicious acquired thrombophilic state-no longer pose the same imminent clinical threat. Nevertheless, thrombotic events still occur, albeit at much lower frequency, raising both clinical and mechanistic questions. Among the most pressing are: Under what circumstances does anti-complement therapy fail to prevent thrombosis, and which patient- or therapy-specific factors contribute to this risk? When and where should anticoagulation, anti-platelet therapy, or even prophylaxis be considered? At a mechanistic level, what are the drivers of complement-mediated thrombosis in PNH, and how do they differ from those in other thrombotic conditions involving complement activation? This review addresses these questions by summarizing current evidence on complement-induced thrombosis, integrating clinical and experimental findings. It highlights unresolved issues, including when complement blockade is insufficient and explores the distinction between complement-driven thrombotic states, such as PNH, and intrinsic complement-related diseases without thrombotic complications, such as C3 glomerulopathy. Finally, it proposes a pragmatic framework for anticoagulation and prophylaxis and provides an outlook on critical directions for basic and clinical research, with the goal of further elucidating the complex interplay between complement activation and thrombosis.
This study evaluated the efficacy and safety of high-dose romiplostim (ROMI) combined with horse anti-thymocyte globulin (hATG) and cyclosporine A (CyA) as first-line immunosuppressive therapy for aplastic anemia (AA). W...This study evaluated the efficacy and safety of high-dose romiplostim (ROMI) combined with horse anti-thymocyte globulin (hATG) and cyclosporine A (CyA) as first-line immunosuppressive therapy for aplastic anemia (AA). We retrospectively analyzed eight patients who received hATG + CyA + ROMI at a single institution between October 2023 and January 2025. ROMI was initiated at 10 μg/kg/week and escalated to 20 μg/kg. Hematologic responses were evaluated at weeks 14 and 27. At week 27, the overall response rate was 100% and the complete response rate was 85.7%. Only one episode of grade ≥ 3 anaphylaxis attributed to hATG was observed. High-dose ROMI combined with hATG and CyA demonstrated favorable efficacy and tolerability as a first-line treatment for transfusion-dependent AA. However, larger prospective studies are required to confirm these findings.
Inano T, Sugimoto Y, Ohishi K
… +12 more, Gotoh A, Ito T, Ichii M, Shimoda K, Lin S, Zagrijtschuk O, Qin A, Sato M, Kawase H, Sato T, Komatsu N, Kirito K
Int J Hematol
· 2026 Jun · PMID 41801560
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Ropeginterferon alfa-2b, a monopegylated interferon α-2b, is a cytoreductive treatment for polycythemia vera (PV). In Japan, the current regimen involves titration in 50-µg increments every 2 weeks until reaching the max...Ropeginterferon alfa-2b, a monopegylated interferon α-2b, is a cytoreductive treatment for polycythemia vera (PV). In Japan, the current regimen involves titration in 50-µg increments every 2 weeks until reaching the maximum dose (500 µg), which requires considerable time. This phase 3b, open-label, single-arm, multicenter study (October 2023-July 2024) assessed the efficacy and safety of a three-step dose escalation regimen (day 1: 250 µg, week 2: 350 µg, week 4: 500 µg) of ropeginterferon alfa-2b in Japanese patients with PV (NCT06002490). Twenty-one patients were included (mean age: 57 years); most (95.2%) received ropeginterferon alfa-2b for at least 24 weeks. The complete hematologic response rate (primary endpoint; hematocrit < 45%, no phlebotomy in the previous 12 weeks, platelet count ≤ 400 × 10/L, and white blood cell count ≤ 10 × 10/L) was 23.8% (95% confidence interval 8.2, 47.2) at week 12 and 57.1% (34.0, 78.2) at week 24. Most patients (90.5%) reached the maximum dose of 500 µg by week 4. All patients had treatment-emergent adverse events, but none led to death, treatment discontinuation, or study withdrawal. This three-step dose escalation regimen of ropeginterferon alfa-2b has the potential to provide faster therapeutic effects in patients with PV without additional safety concerns.
Nakamura M, Noda S, Nishikawa A
… +1 more, Matsumoto J
Int J Hematol
· 2026 May · PMID 41801559
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The development of chimeric antigen receptor (CAR)-T cell products is accelerating worldwide. CAR-T cell therapy represents one of the most significant therapeutic advances, as it elicits remarkably effective and durable...The development of chimeric antigen receptor (CAR)-T cell products is accelerating worldwide. CAR-T cell therapy represents one of the most significant therapeutic advances, as it elicits remarkably effective and durable clinical responses. Approved CAR-T cell products target one of two antigens on B cells: CD19 or B cell maturation antigen (BCMA). In Japan, all CAR-T cell products are approved for the treatment of relapsed or refractory hematologic malignancies, including acute lymphoblastic leukemia, B cell lymphomas, and multiple myeloma. Although CAR-T cell therapy is indisputably one of the most recommended therapies, it has faced scrutiny for its high cost and several unresolved issues. This article outlines issues with and important considerations for CAR-T cell products reviewed by the Pharmaceuticals and Medical Devices Agency. We describe the approval process for CAR-T cell products; differences in indications for their use, including optimal clinical use guidelines; and manufacture of CAR-T cells, especially out-of-specification products. We also describe key considerations in the regulatory review of CAR-T cell products, with a focus on clinical evaluation.
Takenaka R, Tomiyama M, Watanabe H
… +4 more, Yamada S, Morishita E, Suga Y, Asakura H
Int J Hematol
· 2026 Jul · PMID 41801558
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Currently, no established treatments for disseminated intravascular coagulation (DIC) specifically target fibrinolysis. We previously demonstrated that prophylactic administration of tissue plasminogen activator (tPA) to...Currently, no established treatments for disseminated intravascular coagulation (DIC) specifically target fibrinolysis. We previously demonstrated that prophylactic administration of tissue plasminogen activator (tPA) to a lipopolysaccharide (LPS)-induced rat DIC model improved DIC pathophysiology. However, the optimal duration of tPA administration and its effectiveness when administered therapeutically remain unclear. In the present study, we investigated whether tPA remains effective when administered at the same dosage over different durations, and whether therapeutic administration is also effective. We found that both prophylactic and therapeutic administration of tPA increased D-dimer levels, reduced serum creatinine and the renal glomerular fibrin deposition rate, suppressed the formation of thrombin-antithrombin complex and interleukin-6, and attenuated decreases in platelet count. Furthermore, with both prophylactic and therapeutic administration of tPA, most markers of DIC pathophysiology demonstrated greater improvements with longer administration of tPA, from 15 min to 8 h. No bleeding tendency was observed based on urinary hemoglobin levels. These results suggest that a lower tPA dose rate and longer duration of administration may enhance efficacy and safety in the LPS-induced rat DIC model. A reduced dosage and extended duration of tPA administration could represent a new treatment option for clinical DIC and warrants further investigation.
Shimoda K, Takenaka K, Kitamura H
… +3 more, Dohi K, Yoshimoto R, Kirito K
Int J Hematol
· 2026 May · PMID 41779123
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Polycythemia vera (PV) is a myeloproliferative neoplasm that is treated according to the patient's thrombosis risk, including cytoreductive therapies for those at high-risk for thrombosis. Ropeginterferon alfa-2b, a mono...Polycythemia vera (PV) is a myeloproliferative neoplasm that is treated according to the patient's thrombosis risk, including cytoreductive therapies for those at high-risk for thrombosis. Ropeginterferon alfa-2b, a mono-pegylated interferon α-2b, is a new cytoreductive therapy for PV. This expert consensus study, conducted before ropeginterferon alfa-2b recommendations were added to the Japanese guidelines, used a four-phase Delphi method to survey 18 Japanese hematology experts and develop suggestions for ropeginterferon alfa-2b use in Japan. Several scenarios where ropeginterferon alfa-2b treatment is considered appropriate for patients with PV were identified, including: 1) low-risk patients requiring cytoreductive therapy (excluding low-risk patients requiring cytoreductive therapy due to splenomegaly); 2) patients intolerant or resistant to hydroxyurea treatment; 3) high-risk patients aged ≤ 70 years, even if hematocrit < 45% is achieved and maintained under hydroxyurea treatment; and 4) patients who wish to conceive or who are pregnant and require cytoreductive therapy. This is the first expert consensus study using the Delphi method to examine cytoreductive therapy for Japanese patients with PV and contributes to the appropriate selection of patients for ropeginterferon alfa-2b in clinical practice.