Tatetsu H, Kato K, Wada A
… +12 more, Hirano T, Ueno S, Miyasato Y, Yamada A, Shichijo T, Higuchi Y, Ueda Y, Nosaka K, Mikami Y, Karube K, Matsuoka M, Yasunaga JI
Int J Hematol
· 2025 Dec · PMID 41117994
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Chimeric antigen receptor (CAR) T cell therapy has significantly improved outcomes for patients with refractory B cell lymphoma. However, rare cases of secondary T cell lymphomas have raised safety concerns. Here, we pre...Chimeric antigen receptor (CAR) T cell therapy has significantly improved outcomes for patients with refractory B cell lymphoma. However, rare cases of secondary T cell lymphomas have raised safety concerns. Here, we present a case of peripheral T cell lymphoma not otherwise specified (PTCL-NOS) that developed eight months following CD19-directed CAR T cell therapy (lisocabtagene maraleucel) in a 66-year-old male patient with recurrent diffuse large B cell lymphoma. The patient initially achieved complete remission but later developed a subcutaneous mass and systemic lymphadenopathy. Histopathology and flow cytometry confirmed a diagnosis of PTCL-NOS with a CD3 + , CD8 + , and CD30 + phenotype, as well as clonal T cell receptor gene rearrangements. No immunoglobulin rearrangements were detected, ruling out a lineage switch. Furthermore, the CAR transgene was undetectable by RNA-in situ hybridization, and flow cytometry showed no CAR protein expression, suggesting that the lymphoma was not caused by CAR gene integration. This case highlights the importance of re-biopsy in cases of suspected relapse following CAR T cell therapy, and emphasizes the need for long-term monitoring. While a direct causal link remains unclear, industry-academia collaboration is crucial for investigating the mechanisms underlying secondary T cell malignancies and improving the safety of CAR T cell therapy.
Int J Hematol
· 2025 Dec · PMID 41107633
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Ph-like ALL is a high-risk subtype with diverse genomic alterations, including CRLF2 rearrangements, JAK2/EPOR mutations, and ABL-class fusions, which are targetable but underdiagnosed in low and middle-income countries...Ph-like ALL is a high-risk subtype with diverse genomic alterations, including CRLF2 rearrangements, JAK2/EPOR mutations, and ABL-class fusions, which are targetable but underdiagnosed in low and middle-income countries (LMICs). This meta-analysis (78 studies, 15,201 patients, 42 countries) highlights disparities in detection and outcomes between high-income countries (HICs) and LMICs. HICs use comprehensive profiling (RNA-seq: 90-95% sensitivity), while LMICs rely on limited FISH/qPCR, detecting only 30-50% of cases due to cost barriers ($1200 vs. $15-42 for LMIC-adapted assays), infrastructure gaps, and delayed turnaround (4-6 weeks vs. < 7 days). CRLF2 rearrangements are found in 50-60% of cases in HMICs vs. 20-30% in LMICs (p < 0.001), while ABL-class fusions are missed in 75% of LMIC patients. Undiagnosed Ph-like ALL correlates with worse survival (5-year OS: 35-45% in LMICs vs. 60-65% in HICs) due to chemotherapy overuse instead of TKIs (e.g., dasatinib improves EFS by 30%). A tiered diagnostic approach, initial CRLF2 flow cytometry ($15, 80% sensitivity), confirmatory PHi-RACE PCR ($42, 95.2% sensitivity), and selective NGS referral could bridge 85% of the detection gap at 90% cost reduction. Cost-effective tools, subsidized NGS networks, workforce training, and WHO-endorsed guidelines could prevent 40-50% of relapses in LMICs.
Mishina T, Manako C, Sugawara T
… +3 more, Tsujimura H, Kumagai K, Takeuchi M
Int J Hematol
· 2026 Feb · PMID 41094327
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Relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) has a poor prognosis, particularly in patients ineligible for autologous stem cell transplantation or cellular immunotherapy. This study evaluated the effe...Relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) has a poor prognosis, particularly in patients ineligible for autologous stem cell transplantation or cellular immunotherapy. This study evaluated the effectiveness of polatuzumab vedotin combined with rituximab and bendamustine (PBR) therapy in comparison to conventional chemotherapy in patients with R/R DLBCL. Of 86 patients with first relapse or primary refractory DLBCL, 32 received PBR in any subsequent line, while 54 received conventional chemotherapy alone. For comparison, 32 baseline-matched patients were selected from these 54 and defined as the conventional chemotherapy group. The median overall survival (OS) for all patients was 17.3 months (range, 1.5-85.7 months), with the PBR-treated group showing significantly improved outcomes (median OS 19.7 vs. 15.8 months, P = 0.025). Univariate and multivariate analyses identified PBR as a favorable prognostic factor for OS. In the second-line setting, 41.2% of patients who received PBR were ≥ 80 years, compared with just 11.1% of those who received salvage regimens. Despite this older age distribution, the PBR group showed a trend toward favorable progression-free survival. These results suggest that PBR therapy is more effective and tolerable than conventional chemotherapy in patients with R/R DLBCL.
Miyawaki K, Nakagaki H, Mori Y
… +12 more, Semba Y, Hirakawa S, Yamaguchi K, Nishihara H, Sasaki K, Sakoda T, Jinnouchi F, Yamauchi T, Shima T, Maeda T, Akashi K, Kato K
Int J Hematol
· 2025 Dec · PMID 41060581
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Post-transplant lymphoproliferative disorders (PTLDs) typically arise months to years after solid-organ transplantation and are frequently driven by Epstein-Barr virus (EBV). However, EBV-negative monomorphic PTLDs are i...Post-transplant lymphoproliferative disorders (PTLDs) typically arise months to years after solid-organ transplantation and are frequently driven by Epstein-Barr virus (EBV). However, EBV-negative monomorphic PTLDs are increasingly recognized as an alternative pathogenesis. We report a case of a 64-year-old man who underwent liver transplantation and was found to have a minute focus of diffuse large B-cell lymphoma (DLBCL) in the resected gallbladder. Given the absence of residual disease and the patient's postoperative frailty, close observation was chosen. Three months later, the patient developed an aggressive clinical relapse characterized by Burkitt-like features, including massive effusions and gastric wall thickening. Retrospective analysis using a 398-gene panel (DISCAVar) revealed that both the initial and recurrent lesions shared an IGH::MYC rearrangement, while the recurrent tumor acquired additional Burkitt lymphoma (BL)-associated mutations (TP53, TCF3, CCND3, DDX3X) absent in the original lesion. These alterations spanned all three molecular subgroups of BL and suggest rapid clonal evolution from a pre-existing MYC-positive clone under post-transplant immunosuppression. Despite treatment with dose-modified EPOCH, the patient's condition deteriorated, and he died 108 days after treatment initiation. This case underscores the value of longitudinal molecular analysis in understanding the pathogenesis of EBV-negative PTLD and identifying high-risk clones before clinical transformation.
Takahata S, Sakatoku K, Shiohara M
… +11 more, Nakaya Y, Horiuchi M, Ido K, Makuuchi Y, Kuno M, Okamura H, Nishimoto M, Nakashima Y, Nakamae M, Hino M, Nakamae H
Int J Hematol
· 2025 Dec · PMID 41045406
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Idiopathic portal hypertension-related refractory ascites (IRA) is a rare but potentially life-threatening complication following allogeneic hematopoietic cell transplantation (allo-HCT). Its pathogenesis remains unclear...Idiopathic portal hypertension-related refractory ascites (IRA) is a rare but potentially life-threatening complication following allogeneic hematopoietic cell transplantation (allo-HCT). Its pathogenesis remains unclear, and optimal diagnostic and therapeutic strategies have yet to be established. Here, we report a case of a 58-year-old man who developed progressive ascites after allo-HCT. Although the clinical findings met diagnostic criteria for hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), liver histology revealed no hallmark features of VOD/SOS, such as sinusoidal dilatation or central venous fibrosis. Instead, portal venopathy with lymphocytic infiltration and fibrosis suggested a subclinical chronic graft-versus-host disease (GVHD)-like pathology, supporting a diagnosis of IRA by exclusion. Treatment with belumosudil, one of the available treatment options for chronic GVHD, was ineffective. Subsequent treatment with ibrutinib, a Bruton's tyrosine kinase inhibitor, led to resolution of ascites within three days. This is the second reported case of successful treatment of IRA with ibrutinib, and highlights the importance of considering ibrutinib-responsive immune-mediated mechanisms in the differential diagnosis of post-transplant ascites. Given the fundamental differences in treatment strategies between IRA and VOD/SOS, our findings underscore the need for accurate diagnosis, including histopathological evaluation, to guide effective therapy and improve patient outcomes in this challenging clinical scenario.
Uno S, Nakakoji M, Midorikawa S
… +5 more, Kitano T, Tajiri R, Hayakawa J, Minehata K, Suzuki T
Int J Hematol
· 2026 Feb · PMID 41037197
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Real-world treatment patterns and clinical outcomes for patients with lower-risk myelodysplastic syndromes (LR-MDS) in Japan are insufficiently characterized. This study assessed treatment patterns, clinical outcomes, co...Real-world treatment patterns and clinical outcomes for patients with lower-risk myelodysplastic syndromes (LR-MDS) in Japan are insufficiently characterized. This study assessed treatment patterns, clinical outcomes, costs, and healthcare resource utilization of patients with LR-MDS in Japan using the AsMedix electronic health record database. The study included 177 patients aged ≥ 18 years with LR-MDS, identified between April 1, 2017, and March 31, 2022. Of these, 79 were transfusion dependent (TD) and 98 were non-transfusion dependent (NTD). Treatment patterns were diverse, and 57 (32.2%) patients received hypomethylating agents (combination or monotherapy) as first-line treatment. Median (95% confidence interval) overall survival was 32.6 months (17.6-not evaluable) among TD patients who achieved red blood cell transfusion independence (RBC-TI) ≥ 8 weeks during weeks 1-24, compared with 22.3 months (10.1-not evaluable) among those who did not (P = 0.17). Among NTD patients, maintaining NTD status was also associated with longer median overall survival. Furthermore, patients who achieved or maintained RBC-TI incurred roughly half the monthly medical costs per individual compared with those who did not, highlighting the clinical and economic importance of reducing RBC transfusion requirements. Further research is needed to understand the impacts of treatment on patients with LR-MDS-related anemia in Japan.
Tokuhira M, Nakayama H, Toyama K
… +24 more, Takano M, Iriyama N, Takahata A, Sato E, Senpuku Y, Kawakami M, Okada K, Tanaka K, Abe T, Osada Y, Yamamoto K, Watanabe J, Hayashi T, Sekiguchi Y, Kimura Y, Oshikawa G, Nakagawa M, Suzuki K, Kumagai T, Toyota S, Miura K, Ikezoe T, Nakazato T, Mori T
Int J Hematol
· 2026 Feb · PMID 41037196
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Although novel therapeutic agents, including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies, have markedly improved outcomes in multiple myeloma (MM), the disease remains incurable and...Although novel therapeutic agents, including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies, have markedly improved outcomes in multiple myeloma (MM), the disease remains incurable and is associated with various causes of death. However, comprehensive analyses of mortality patterns, particularly early mortality, are still limited. In this study, we focused on patients who died within one year of treatment initiation (1-year group), based on data from the J-CHARGE-MM database showing that 146 out of 461 total deaths (31.7%) occurred within the first year. The most common cause of death was disease progression (43.2%), followed by infection (primarily pneumonia and sepsis), which frequently occurred within the first few months of induction therapy. Cardiac-associated events, such as heart failure and cardiac amyloidosis (including suspected cases), accounted for 14.4% of deaths, and sudden death for 7.5%. Multivariate analysis revealed that early mortality was significantly associated with age ≥ 65 years, elevated serum lactate dehydrogenase (LDH), elevated serum C-reactive protein (CRP), and poor performance status (PS ≥ 3), compared with later deaths. These findings support that early mortality in MM may be reduced through comprehensive cardiac evaluation and proactive infection prevention strategies, particularly in elderly patients with elevated CRP, elevated LDH, or poor PS.
Pandharipande AS, Jain S, Singh A
… +7 more, Verma S, Baby EP, Gaire H, Bhattacharya S, Tulsiyan A, Singh S, Radhakrishnan N
Int J Hematol
· 2026 Feb · PMID 41037195
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INTRODUCTION: The real-world data on treatment and outcome of hemophilia patients using extended half-life products in developing countries remain scarce. This is largely due to delayed diagnosis, poor joint outcomes, in...INTRODUCTION: The real-world data on treatment and outcome of hemophilia patients using extended half-life products in developing countries remain scarce. This is largely due to delayed diagnosis, poor joint outcomes, increased morbidity, and limited access to prophylaxis and newer products for treatment and prevention. AIM: To analyze the response to extended half-life factor (EHL) prophylaxis in patients with severe hemophilia A and B with advanced arthropathy. METHODS: Patients with severe hemophilia A and B who received EHL factor concentrates for prophylaxis at our center were included in this analysis. Data collected included bleed frequency, joint involvement, annualized bleed rate (ABR), number of hospital visits, and Hemophilia Joint Health Score (HJHS) prior to prophylaxis. Breakthrough bleeds while on prophylaxis were also recorded. RESULTS: A total of 31 patients were started on EHL prophylaxis and followed up for a period ranging from 4 to 91 weeks. A reduction in the bleeding rate was noticed in all with significant reversal of target joints. Additionally, patients remained bleed-free during rehabilitation following joint surgery as well as psoas bleed-related compression neuropathy. CONCLUSION: EHL prophylaxis appears to be an effective strategy even for patients with baseline target joints with significant arthropathy, thus reducing the extent of disability in these patients.
Kojima K, Tsuge N, Yoshida S
… +4 more, Umebara D, Nishida Y, Miyazaki S, Asagiri T
Int J Hematol
· 2026 Feb · PMID 41004032
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Unbalanced whole-arm translocation der(5;19)(p10;q10) is a rare but recurrent cytogenetic aberration noted in patients with myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). Eight cases of MDS/AML with de...Unbalanced whole-arm translocation der(5;19)(p10;q10) is a rare but recurrent cytogenetic aberration noted in patients with myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). Eight cases of MDS/AML with der(5;19)(p10;q10) have been previously reported. Here, we describe three additional cases of MDS with der(5;19)(p10;q10) at our institution, in which we identified myeloid malignancy-associated mutations using next-generation sequencing. All patients had two TP53 mutations, each with >10% variant allele frequency, suggesting double-hit TP53 mutations. Double-hit TP53 mutations are only found in approximately 2% of patients with MDS, and may be involved in the development of the cytogenetic abnormalities der(5;19)(p10;q10), +19, and complex karyotype, often associated with exposure to alkylating agents. We propose der(5;19)(p10;q10) as a potential cytogenetic indicator of biallelic TP53 inactivation through double-hit mutations. These data suggest that MDS with der(5;19)(p10;q10) is clinically characterized by aberrant CD7 expression in blasts, a tendency for leukemic transformation, resistance to anti-leukemia therapies, and poor survival outcomes. We also noted that cases of der(5;19)(p10;q10) MDS/AML have been reported exclusively by Japanese institutions. Geographical and ethnic factors may contribute to oncogenesis, which can be triggered by exposure to alkylating agents.
Yahya D, Ayran M, Özden F
… +6 more, Abedi AH, Kaya SY, Beköz HS, Çakır A, Maral S, Kaynar L
Int J Hematol
· 2025 Dec · PMID 41004031
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INTRODUCTION: Graft-versus-host disease (GVHD) is a serious immune reaction that usually occurs after allogenic stem cell transplants and can affect organs, such as skin, gastrointestinal (GI) system, and liver. The deve...INTRODUCTION: Graft-versus-host disease (GVHD) is a serious immune reaction that usually occurs after allogenic stem cell transplants and can affect organs, such as skin, gastrointestinal (GI) system, and liver. The development of GVHD after autologous stem cell transplantation (auto-SCT) is rarely observed and only a few cases have been reported in the literature. CASE PRESENTATION: A 21-year-old patient who underwent auto-SCT for neurofibromatosis type 1 developed severe GI-GVHD confirmed by histopathology. She responded inadequately to systemic corticosteroids, indicating steroid-refractory disease. Subsequent addition of the JAK1/2 inhibitor ruxolitinib resulted in rapid clinical improvement. CONCLUSION: This clinical case scenario suggests that ruxolitinib could be a treatment option in rare cases of GVHD following auto-SCT.
Yasuda I, Nagaya S, Yui R
… +3 more, Imai Y, Kuwajima Y, Morishita E
Int J Hematol
· 2026 Feb · PMID 40991172
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Hereditary protein C (PC) deficiency is a thrombotic disorder caused by variants in the PC gene (PROC). In this study, we identified a novel variant, p.Leu173Pro (L173P), and a previously reported variant, p.Val241Leu (V...Hereditary protein C (PC) deficiency is a thrombotic disorder caused by variants in the PC gene (PROC). In this study, we identified a novel variant, p.Leu173Pro (L173P), and a previously reported variant, p.Val241Leu (V241L), in two unrelated Japanese families with venous thrombosis. We investigated the mechanisms by which these variants lead to type I PC deficiency. PC expression vectors were constructed and transiently expressed in human embryonic kidney 293 cells. Cell lysates and culture supernatants were subsequently analyzed by Western blotting, and intracellular trafficking was evaluated. Both PC-L173P and PC-V241L variants exhibited significantly reduced extracellular secretion compared to the wild-type PC. Furthermore, PC-L173P underwent proteasome-mediated intracellular degradation, whereas PC-V241L appeared to accumulate within the endoplasmic reticulum. This study elucidates the mechanism by which type I PC deficiency arises from distinct secretion defects: intracellular degradation and retention. Although both PROC variants result in type I PC deficiency, their differing intracellular fates are likely attributable to the mutation site and the physicochemical properties of the substituted amino acids. These findings underscore the heterogeneity of secretion defects in type I PC deficiency and provide novel insights into its molecular pathophysiology.
Int J Hematol
· 2025 Dec · PMID 40976809
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Langerhans cell histiocytosis (LCH) is a rare type of histiocytosis with various clinical manifestations. The differential diagnosis for an infiltrative process in the mesentery includes histiocytosis, such as Erdheim-Ch...Langerhans cell histiocytosis (LCH) is a rare type of histiocytosis with various clinical manifestations. The differential diagnosis for an infiltrative process in the mesentery includes histiocytosis, such as Erdheim-Chester disease (ECD) and Rosai-Dorfman disease (RDD), but mesenteric involvement has never been reported. Here we present the first documented case of LCH. A 24-year-old man presented with diabetes insipidus and was diagnosed with LCH via mesenteric biopsy, which demonstrated mesenteric involvement and the BRAF mutation. He was treated with trametinib 2 mg once daily, and FDG-PET/CT at 6 months after treatment initiation showed complete remission. Our report suggests that trametinib is a promising treatment option for non-BRAF mutant LCH with mesenteric involvement.
Int J Hematol
· 2026 Feb · PMID 40971052
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This study investigated late renal, liver, endocrine, and cardiac outcomes in 52 Kurdish children aged 7-18 years who underwent bone marrow transplantation (BMT) for β-thalassemia major (β-TM). Boys had higher levels of...This study investigated late renal, liver, endocrine, and cardiac outcomes in 52 Kurdish children aged 7-18 years who underwent bone marrow transplantation (BMT) for β-thalassemia major (β-TM). Boys had higher levels of hemoglobin and alkaline phosphatase than girls. Conversely, girls exhibited higher levels of SGPT, ferritin, T4, and eGFR. In all patients, BUN (71.15%), ALP (100%), PT (96.15%), TSB (34.62%), and serum ferritin (48.08%) were elevated, while Hb (57.69%) and serum creatinine (42.31%) were lower than normal. At ages 1-5, 6-10, and 11-15 years, patients had significantly lower serum ferritin (1053.0, 212.0, and 105.05; p = 0.0004) and SGOT (30.0, 22.0, and 26.50; p = 0.0231) levels. Echocardiography showed normal heart function in 47 patients (90.39%), with minor abnormalities observed in only 9.61%. The mean eGFR was 89.70 (SD: 22.93), with girls showing a significantly higher average (98.83) than boys (72.70; p < 0.0001). Kidney function was most often mildly decreased (55.77%), followed by normal/increased (40.39%), and mild-to-moderately decreased (3.85%). Girls were more likely to have normal/ increased kidney function (61.54%), while boys predominantly had mildly decreased kidney function (76.92%) with no significant difference between ages in all patients. Most of the children with β-TM had mildly decreased kidney function and higher liver function test values.
Tominaga R, Fujiwara SI, Honda S
… +17 more, Yokoyama D, Noguchi A, Furuki S, Koyama S, Murahashi R, Nakashima H, Hyodo K, Kawaguchi SI, Toda Y, Umino K, Minakata D, Ashizawa M, Yamamoto C, Hatano K, Sato K, Ohmine K, Kanda Y
Int J Hematol
· 2026 Feb · PMID 40965710
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This study explored the relationship between body temperature (BT) and heart rate (HR) data during acute myeloid leukemia (AML) treatment, using relative bradycardia (RB) as an index. RB trends were also assessed in conf...This study explored the relationship between body temperature (BT) and heart rate (HR) data during acute myeloid leukemia (AML) treatment, using relative bradycardia (RB) as an index. RB trends were also assessed in confirmed infections and during intensive chemotherapy. Data from AML patients who received induction therapy (anthracycline and cytarabine) at Jichi Medical University Hospital between May 2015 and December 2023 were analyzed. A total of 1000 febrile events (axillary temperature ≥ 37.8 °C) in 97 patients were included. Multivariate analysis showed an HR increase of 6.57 bpm (95% CI 4.44-8.70) per 1 °C rise in BT. RB, defined as BT ≥ 37.8 °C with HR < 90 bpm, was observed in 630 events (63.0%). RB was more likely with age ≥ 44 years, hemoglobin ≥ 6.5 g/dL, and reduced-intensity regimens. In contrast, BT ≥ 38.6 °C, diastolic BP ≥ 70 mmHg, oxygen therapy, CRP ≥ 7.13 mg/dL, and incomplete hematologic recovery decreased the likelihood of RB. In addition, RB was significantly associated with documented infection (OR = 2.32, 95% CI 1.17-4.61, p = 0.016). RB frequently occurred during AML induction therapy, and may serve as an indicator of infection.
Tanoue S, Saito T, Yokoyama H
… +9 more, Ishii H, Ouchi-Nakano A, Hosoba R, Hattori D, Sato K, Motohashi S, Nishiwaki K, Dobashi N, Yano S
Int J Hematol
· 2026 Jan · PMID 40940607
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Previous studies have shown that the blood concentration of calcineurin inhibitors is related to the incidence of acute graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT)....Previous studies have shown that the blood concentration of calcineurin inhibitors is related to the incidence of acute graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, its utility as an indicator for GVHD relapse prevention and graft-versus-tumor effect assessment has mostly been investigated in umbilical cord blood transplantation. We hypothesized that the simple area under the tacrolimus (TAC) concentration (AUTC) early after transplantation reflects TAC pharmacokinetics more accurately than the mean TAC concentration (MTC), and analyzed the relationship of AUTC with outcomes after unrelated allo-HSCT for myeloid malignancies. We set cut-off values of MTCs and AUTCs using receiver-operating-characteristic curves for each outcome. Patients with high MTC in week 3 (MTC 3) had a lower cumulative incidence of acute GVHD. High MTC 3 was associated with a higher relapse rate in univariate analysis, but was not significant in multivariate analysis. Meanwhile, high AUTC in week 3 (AUTC 3) was a predictor of relapse, worse relapse-free survival, and overall survival in both univariate and multivariate analysis. Development of acute GVHD was not associated with relapse. Therefore, AUTC 3 after unrelated allo-HSCT for myeloid malignancies may better reflect the relapse prevention effect of immunosuppression intensity than MTC or development of acute GVHD.
Kanemasa Y, Sadato D, Isogai M
… +8 more, Ogawa M, Hirama C, Kawaji H, Yamaguchi T, Harada Y, Hishima T, Oboki K, Shimoyama T
Int J Hematol
· 2025 Nov · PMID 40938575
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Diffuse large B cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma, has variable treatment responses and distinct molecular subtypes. Despite therapeutic advances, a significant number of patients exp...Diffuse large B cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma, has variable treatment responses and distinct molecular subtypes. Despite therapeutic advances, a significant number of patients experience treatment failure or relapse. Recent genetic subtyping methods, such as the LymphGen algorithm, classify DLBCL into molecular subtypes. However, a subset of cases remains categorized as "LymphGen-unclassifiable" ("Other" group in the LymphGen classification). These cases lack distinctive genetic features and present challenges for risk assessment. In this study, we aimed to identify prognostic genetic markers specific to LymphGen-unclassifiable DLBCL. Using a discovery cohort from the National Cancer Institute, we identified genetic alterations in CDKN2A and PIM1 that were significantly associated with overall survival in this patient group. We then validated the model in a separate cohort from Komagome Hospital in Tokyo. Our model, combined with the International Prognostic Index (IPI), identified high-risk LymphGen-unclassifiable DLBCL patients within the high-risk IPI group, showing a 2-year overall survival rate of 38% versus 72%. This approach could support the development of more targeted therapies by improving prognostic accuracy and advancing understanding of LymphGen-unclassifiable DLBCL.
Dohtan S, Nagata Y, Yamashita M
… +9 more, Ikeda R, Koyauchi K, Takagi F, Uchiyama S, Oka S, Adachi M, Mitsui K, Takemura T, Ono T
Int J Hematol
· 2026 Jan · PMID 40938574
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Outbreaks of measles and rubella occasionally occur, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients face an increased risk of mortality from measles. This retrospective observational study...Outbreaks of measles and rubella occasionally occur, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients face an increased risk of mortality from measles. This retrospective observational study assessed immunological responses to MR vaccination and long-term changes in antibody titers in adult allo-HSCT recipients. The measles and rubella cohorts included 36 and 33 patients, respectively, who received MR vaccination between March 2010 and December 2023. MR vaccination significantly increased IgG titers against measles from 5.48 (± 3.61) at T0 (pre-vaccination) to 14.15 (± 10.31) at T1 (1 year post-vaccination) and against rubella from 3.90 (± 2.82) at T0 to 58.93 (± 44.46) at T1 (both p < 0.001). Multivariate analyses in the measles cohort showed that lower IgG antibody titers at T0 were significantly associated with high responder status (OR 0.57, 95% CI 0.35-0.96, p = 0.029). High responders had significant mean changes in IgG antibody titers from T0 to each time point from T1 to T5 (5 years post-vaccination) for both measles and rubella. The annual decline in IgG titers was predicted to be 2.14 (p = 0.002) for measles and 3.15 (p = 0.51) for rubella in high responders. Despite high antibody titers, these levels decline over time, emphasizing the importance of regular monitoring and potential revaccination.