記述言語：英語   掲載種別：研究論文（学術雑誌）  

Despite the development of various therapeutic agents, multiple myeloma remains incurable. Recently, T-cell redirected immunotherapy has become a promising strategy for the treatment of refractory myeloma. Clinical trials using chimeric antigen receptor (CAR)-T cells and bispecific antibodies have demonstrated successful anti-myeloma responses in triple-class-refractory patients. However, unique and unwanted immune effects associated with on-target/off-target reactivity of activated immune cells need to be considered and properly managed. This review summarizes recent advances in bispecific antibodies for the treatment of refractory myeloma. It outlines the history of their development, along with a discussion of their mechanisms of action and their current and potential future role in myeloma therapy. As more evidence emerges to inform the timing of CAR-T-cell therapy, the results of clinical trials and off-the-shelf nature of bispecifics also suggest the timing of their treatment. These findings will promote further development and application of bispecifics for refractory myeloma in combination with other appropriate agents.

DOI： 10.1007/s12185-024-03766-4

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)愛媛県臨床検査技師会  

researchmap

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Over the past decade, new therapeutic modalities have markedly improved clinical outcomes for patients with multiple myeloma. Recently, immunotherapy using both bispecific antibodies (BsAb) and chimeric antigen receptor T cells (CAR-T cells) has induced further anti-myeloma responses. Different agents must be combined to overcome the heterogeneity of myeloma cell clones, and new modalities for the treatment of refractory myeloma must also be developed to strengthen therapeutic effects. We have developed a novel BiTE (bispecific T-cell engager)-based modality, referred to as bridging-BiTE (B-BiTE). B-BiTE is able to bind to both an Fc domain of a human immunoglobulin G monoclonal antibody (mAb) and the human CD3 molecule. This enables rapid generation of a mAb/B-BiTE complex and safely induces dual-lymphoid activation of both human T cells and NK cells against myeloma cells. Importantly, sequential immunotherapy using two different mAb/B-BiTE complexes can produce deep and durable anti-myeloma responses. To further advance treatment of multiple myeloma, it is important to determine how to combine and sequence immunotherapy with other agents while considering management of unique adverse events caused by activated immune cells.

DOI： 10.11406/rinketsu.65.428

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)日本輸血・細胞治療学会  

researchmap

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J04824&link_issn=&doc_id=20231229310006&doc_link_id=10.3925%2Fjjtc.69.648&url=https%3A%2F%2Fdoi.org%2F10.3925%2Fjjtc.69.648&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：日本語   出版者・発行元：(一社)日本エイズ学会  

researchmap

記述言語：英語   出版者・発行元：(一社)日本血液学会  

researchmap

記述言語：英語   出版者・発行元：(一社)日本血液学会  

researchmap

記述言語：英語   出版者・発行元：(一社)日本血液学会  

researchmap

記述言語：英語   出版者・発行元：(一社)日本血液学会  

researchmap

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：American Society of Hematology  

Immunotherapy using bispecific antibodies including bispecific T-cell engager (BiTE) has the potential to enhance the efficacy of treatment for relapsed/refractory multiple myeloma. However, myeloma may still recur after treatment due to downregulation of a target antigen and/or myeloma cell heterogeneity. To strengthen immunotherapy for myeloma while overcoming its characteristics, we have newly developed a BiTE-based modality, referred to as Bridging-BiTE (B-BiTE). B-BiTE was able to bind to both a human IgG-Fc domain and the CD3 molecule. Clinically available monoclonal antibodies (mAbs) were bound with B-BiTE prior to administration, and the mAb/B-BiTE complex induced antitumor T-cell responses successfully while preserving and supporting NK-cell reactivity, resulting in enhanced anti-myeloma effects via dual-lymphoid activation. In contrast, any unwanted off-target immune-cell reactivity mediated by mAb/B-BiTE complexes, or B-BiTE itself, appeared not to be observed in vitro and in vivo. Importantly, sequential immunotherapy using two different mAb/B-BiTE complexes appeared to circumvent myeloma cell antigen escape, and further augmented immune responses to myeloma relative to those induced by mAb/B-BiTE monotherapy or sequential therapy with two mAbs in the absence of B-BiTE. Therefore, this modality facilitates easy and prompt generation of a broad panel of bispecific antibodies that can induce deep and durable antitumor responses in the presence of clinically available mAbs, supporting further advancement of reinforced immunotherapy for multiple myeloma and other refractory hematological malignancies.

DOI： 10.1182/blood.2022019082

researchmap

記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本造血・免疫細胞療法学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本造血・免疫細胞療法学会  

症例は混合表現型急性白血病に対する非血縁者間同種骨髄移植の既往歴がある42歳男性で、COVID-19に罹患した。呼吸症状は改善し自覚症状無く退院したが、退院翌日(診断後11日目)の鼻咽頭拭い液でSARS-CoV-2高値を認めた。免疫抑制剤を緩徐に減量し、定期的にCt値および抗原定量値でウイルスの増減を評価した。SARS-CoV-2は126日目に抗原定量値が陰性となった。以上より、COVID-19を発症した重度の免疫不全患者はSARS-CoV-2感染が長期間持続する場合があるため、隔離解除前にウイルス検査を行う必要がある。今までに、SARS-CoV-2の長期間持続感染例に対し、定期的な抗原定量検査により陰性化するまでウイルス量の増減の推移を評価した報告は無い。

researchmap

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J07578&link_issn=&doc_id=20230502380009&doc_link_id=10.7889%2Ftct-22-023&url=https%3A%2F%2Fdoi.org%2F10.7889%2Ftct-22-023&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Abstract

Young adults with myelodysplastic syndrome (MDS) are rare, and the clinical significance of driver mutations has not yet been analysed. We analysed the gene mutations and copy number alterations (CNAs) in younger MDS patients using next-generation sequencing, targeting 68 genes that were recurrently mutated in myeloid malignancies, to investigate the correlation between their genetic alterations and clinical outcomes. We enrolled 55 patients retrospectively (aged < 50 years). At least one mutation was detected in 56% of the patients. The most frequently mutated genes were ASXL1 and RUNX1, 13% each. We defined higher-risk patients as those with ≥ 2 mutations, except for SF3B1 mutation, and/or CNA. The 3-year overall survival (OS) in patients with a higher-risk was lower than that in those with a lower-risk (50.8% vs. 71.8%, P = 0.024). Among the 44 transplant recipients, patients with higher-risk had a significantly lower OS and tended to have a higher cumulative incidence of relapse (CIR) than those with a lower-risk (3-year OS: 38.0% vs. 64.4%, P = 0.039; 3-year CIR: 44.0% vs. 24.1%, P = 0.076). Our results showed that genetic aberrations can predict clinical outcomes in younger MDS patients, despite the low rate of genetic mutations.

DOI： 10.1038/s41598-023-29794-4

PubMed

researchmap

その他リンク： https://www.nature.com/articles/s41598-023-29794-4

掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/bjh.19228

Scopus

researchmap

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Informa UK Limited  

BACKGROUND AND OBJECTIVES: Intensity-modulated radiation therapy (IMRT) helps achieve good radiation dose conformity and precise dose evaluation. We conducted a single-centre prospective study to assess the safety and feasibility of total body irradiation with IMRT (IMRT-TBI) using helical tomotherapy in allogeneic haematopoietic stem cell transplantation (allo-HSCT). PATIENTS AND METHODS: Thirty-nine adult patients with haematological malignancy (acute lymphoblastic leukaemia [n = 21], chronic myeloid leukaemia [n = 6], mixed phenotype acute leukaemia [n = 5], acute myeloid leukaemia [n = 4], and malignant lymphoma [n = 3]) who received 12 Gy IMRT-TBI were enrolled with a median follow-up of 934.5 (range, 617-1254) d. At the time of transplantation, 33 patients (85%) achieved complete remission. The conditioning regimen used IMRT-TBI (12 Gy in 6 fractions twice daily, for 3 d) and cyclophosphamide (60 mg/kg/d, for 2 d), seven patients were combined with cytarabine, and five with etoposide. We set dose constraints for the lungs, kidneys and lens as the organs at risk. RESULTS: The mean doses for the lungs and kidneys were 7.50 and 9.11 Gy, respectively. The mean maximum dose for the lens (right/left) was 5.75/5.87 Gy. The 2-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 69, 64, 18 and 18%, respectively. Thirty-six patients developed early adverse events (AEs) (including four patients with Grade 3/4 toxicities), most of which were reversible oral mucositis and may partially have been related to IMRT-TBI. However, the incidence of toxicity was comparable to conventional TBI-based conditioning transplantation. None of the patients developed primary graft failure, or Grade III-IV acute graft-versus-host disease (GVHD). In late complications, chronic kidney disease was observed in six patients, a lower incidence compared to conventional TBI-based conditioning transplantation. No radiation pneumonitis or cataracts were observed in any of the patients. CONCLUSIONS: IMRT-TBI is safe and feasible for haematological malignancies with acceptable clinical outcomes.KEY MESSAGESIMRT-TBI-helical tomotherapy aids in accurate dose calculation and conformity.It could be used without any considerable increase in the rate of TBI-related AEs.Allo-HSCT with IMRT-TBI may be an alternative to conventional TBI for clinical use.

DOI： 10.1080/07853890.2022.2125171

PubMed

researchmap

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

This prospective phase I trial aimed to determine the recommended dose of 3-day total marrow and lymphoid irradiation (TMLI) for a myeloablative conditioning regimen by increasing the dose per fraction. The primary end-point of this single-institution dose escalation study was the recommended TMLI dose based on the frequency of dose-limiting toxicity (DLT) ≤100 days posthematopoietic stem cell transplantation (HSCT); a 3 + 3 design was used to evaluate the safety of TMLI. Three dose levels of TMLI (14/16/18 Gy in six fractions over 3 days) were set. The treatment protocol began at 14 Gy. Dose-limiting toxicities were defined as grade 3 or 4 nonhematological toxicities. Nine patients, with a median age of 42 years (range, 35-48), eight with acute lymphoblastic leukemia and one with chronic myeloblastic leukemia, received TMLI followed by unrelated bone marrow transplant. The median follow-up period after HSCT was 575 days (range, 253-1037). Three patients were enrolled for each dose level. No patient showed DLT within 100 days of HSCT. The recommended dose of 3-day TMLI was 18 Gy in six fractions. All patients achieved neutrophil engraftment at a median of 19 days (range, 14-25). One-year overall and disease-free survival rates were 83.3% and 57.1%, respectively. Three patients experienced relapse, and no nonrelapse mortality was documented during the observation period. One patient died due to disease relapse 306 days post-HSCT. The recommended dose of 3-day TMLI was 18 Gy in six fractions. The efficacy evaluation of this regimen is currently being planned in a phase II study.

DOI： 10.1111/cas.15611

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Informa UK Limited  

Sarcopenia is a prognostic factor for cancer. Because creatinine is formed from creatine phosphate in muscle tissue, urinary creatinine excretion (UCE) serves as an index of muscle volume. However, as of yet, there are no studies assessing the clinical impact of UCE or weight- adjusted urinary creatinine excretion (WA-UCE) on allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. We analyzed the association between pre-transplant WA-UCE and transplant outcomes among 164 adult patients with acute myeloid leukemia in complete remission who underwent their first allo-HSCT at our center. The patients were classified into a high (n = 106) and a low WA-UCE group (n = 58) for predicting overall survival (OS) based on the receiver operating characteristics curve. On multivariate analysis, low WA-UCE was associated with poor OS, progression-free survival and a high incidence of non-relapse mortality. WA-UCE has the potential to be an objective biomarker for predicting transplant outcomes, especially the incidence of infection-related death.

DOI： 10.1080/10428194.2022.2109334

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Invasive mucormycosis is a refractory fungal infection. Central nervous system (CNS) mucormycosis is a rare complication caused by infiltration from the paranasal sinuses or hematogenous dissemination. Here, we present a case of a brain abscess, due to mucormycosis, diagnosed using burr craniotomy. A 25-year-old Japanese woman with relapsed-refractory acute lymphoblastic leukemia underwent cord blood transplantation (CBT). The patient experienced prolonged and profound neutropenia, and oral voriconazole was administered as primary antifungal prophylaxis. The patient received a conditioning regimen on day -11 and complained of aphasia and right hemiparesis on day -6. Magnetic resonance imaging (MRI) revealed a T2-weighted high-intensity area in the left frontal cortex. A brain abscess was suspected, and liposomal amphotericin B (L-AMB) administration was started. The patient underwent CBT as scheduled and underwent neutrophil engraftment on day 14. Although the patient achieved complete remission on day 28, her consciousness level gradually deteriorated. MRI revealed an enlarged brain lesion with a midline shift sign, suggesting brain herniation. Craniotomy was performed to relieve intracranial pressure and drain the abscess on day 38, and a diagnosis of cerebral mucormycosis was confirmed. The L-AMB dose was increased to 10 mg/kg on day 43. Although the patient's consciousness level improved, she died of hemorrhagic cystitis and aspiration pneumonia. Cerebral mucormycosis should be suspected if neurological symptoms are observed in stem cell transplant recipients. Prompt commencement of antifungal therapy and debridement are crucial because mucormycosis has a poor prognosis.

DOI： 10.1016/j.jiac.2022.08.003

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Immune checkpoint inhibitor (ICI) therapy increases the risk of immune-related adverse events (irAEs). In particular, combination checkpoint blockade (CCB) targeting inhibitory CTLA-4 and PD-1 receptors could lead to irAEs at a higher rate than ICI monotherapy. Management of irAEs is important while using ICIs. However, there are no reliable biomarkers for predicting irAEs. The aim of this study was to elucidate early B cell changes after CCB therapy in patients with renal cell carcinoma (RCC) and verify whether B cells can be a predictor of irAEs. This prospective cohort study was conducted with 23 Japanese patients with metastatic RCC. An increase in the proportion of CD21lo B cells and CD21lo memory B cells was confirmed following CCB therapy. Although there were no differences in clinical outcomes between irAE and no-irAE groups, the proportion of CD21lo B cells at baseline was lower in the irAE group, with a significant increase after the first cycle of CCB therapy. Further analysis revealed a moderate correlation between irAEs and CD21lo B cell levels at baseline (area under the curve: 0.83, cut-off: 3.13%, sensitivity: 92.3, specificity: 70.0). This finding indicates that patients with low baseline CD21lo B cell levels warrant closer monitoring for irAEs. The clinical registration number by the Certified Review Board of Ehime University is No. 1902011.

DOI： 10.3390/jpm12060888

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Cyclophosphamide (CY)-induced cardiotoxicity involves rare lethal complications. We previously reported the cardiac events of 811 allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients; 12 out of 811 recipients (1.5%) developed fatal heart failure. The mortality rate was also very high (91.6%, 11/12). CY dose (200 mg/kg or more) was reported as the independent risk factor. The main disease in patients treated with 200 mg/kg or more of CY was severe aplastic anemia (AA). Therefore, we reduced the dose of CY during conditioning for AA (from 200 to 100 mg/kg), and then we analyzed the clinical features of 294 patients who received a total dose of at least 100 mg/kg of CY. We also compared the clinical features between the current study and our previous study. The proportion of patients treated with at least 200 mg/kg of CY was reduced from 4.2% to 0%. However, CY-induced heart failure occurred in four of the 294 patients (1.4%), which was similar to the finding reported in our previous study (1.5%). Two of these four patients received a post-transplant CY (PTCy) regimen (CY 100 mg/kg). All four patients were treated in the cardiac intensive care unit (C-ICU), and two patients survived. In summary, even the CY dose of 120 mg/kg or less would cause cardiotoxicity. We should also carefully monitor patients treated with PTCy, considering the possibility of CY-induced cardiotoxicity. Early diagnosis and ICU management have contributed to improved outcomes.

DOI： 10.1111/ajco.13674

PubMed

researchmap

その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/ajco.13674

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s12185-021-03234-3

PubMed

researchmap

その他リンク： https://link.springer.com/article/10.1007/s12185-021-03234-3/fulltext.html

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Variants of the t (8;21) (q22;q22) involving chromosome 8, 21, and other chromosomes account for about 3% of all t (8;21) (q22;q22) in patients with acute myeloid leukemia (AML). However, the prognosis of AML with variant t (8;21) remains unknown due to the scarcity of reported cases. Herein we report a case of AML with t (6;21;8) (p23;q22;q22). Fluorescence in situ hybridization confirmed a RUNX1-RUNX1T1 fusion signal on the derivative chromosome 8. This is the first report on a variant of t (8;21) involving the breakpoint 6p23. After induction chemotherapy, our patient achieved complete remission and has been stable for four years.

DOI： 10.11406/rinketsu.63.104

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Fludarabine with intravenous busulfan (6.4 mg/kg; FB2) and fludarabine with intermediate-dose melphalan (140 mg/m2; FM140) are the most widely used reduced-intensity conditioning (RIC) regimens for allogeneic hematopoietic stem cell transplantation. FM140 generally has a lower relapse rate and higher non-relapse mortality (NRM), resulting in overall survival (OS) comparable to that seen with FB2. To evaluate the effect of reducing the melphalan dose, we retrospectively compared transplant outcomes in 156 patients who received FB2 (n = 103) or FM80 (n = 53) at our center (median age: 63 years; range 27-72 years). All patients received 4-Gy total body irradiation. Three-year OS, the cumulative incidence of relapse, and NRM were comparable between groups (FB2 vs. FM80, 58% vs. 47%, p = 0.24; 30% vs. 36%, p = 0.57; 17% vs. 21%, p = 0.44, respectively). There was no significant difference in the cumulative incidence of graft-versus-host disease (GVHD) at day 100, chronic GVHD at 3 years, or the 3-year GVHD-free/relapse-free survival rate. In the high-risk disease group, patients receiving FM80 tended to have lower 3-year OS (FB2 vs. FM80, 48% vs. 17%, p = 0.06). In summary, transplant outcomes following FB2 or FM80 were comparable except in patients with high-risk disease.

DOI： 10.1007/s12185-021-03233-4

PubMed

researchmap

その他リンク： https://link.springer.com/article/10.1007/s12185-021-03233-4/fulltext.html

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

Although the indications for allogeneic hematopoietic stem cell transplantation (allo-HSCT) as a treatment for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) and Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (B-ALL) are similar, few studies have compared its outcomes for T-ALL/LBL and Ph-negative B-ALL. The clinical data of 28 patients with T-ALL, 16 with T-LBL, and 99 with Ph-negative B-ALL who underwent the first allo-HSCT from 2000 to 2019 were retrospectively analyzed. Complete remission (CR) rates at allo-HSCT were 79 %, 63 %, and 75 % for T-ALL, T-LBL, and B-ALL, respectively; the 3-year overall survival (OS) rates were 55.7 %, 56.2 %, and 58.6 %, respectively (p = 0.92). Univariate analysis revealed that disease subtypes were not significantly associated with OS (B-ALL vs. T-ALL: hazard ratio [HR]=0.89, p = 0.70; T-LBL vs. T-ALL: HR=0.87, p = 0.75), and CR at allo-HSCT was the only prognostic factor for OS (HR=0.25, p < 0.001). Multivariate analysis demonstrated that CR at allo-HSCT was the only predictor of OS (HR=0.24, p < 0.001). In all three disease subtypes, patients in CR at allo-HSCT tended to have a lower cumulative incidence of relapse than did those in non-CR (T-ALL: 13.6 % vs. 50.0 %, p = 0.10; T-LBL: 20.0 % vs. 50.0 %, p = 0.21; B-ALL: 10.0 % vs. 56.0 %, p < 0.01). Thus, the outcomes of allo-HSCT for T-ALL/LBL were comparable to those of Ph-negative B-ALL. Irrespective of the disease subtypes, achieving CR before allo-HSCT was associated with a favorable OS. Further advances in chemotherapy before allo-HSCT and defining the optimal timing of allo-HSCT would improve the prognosis of patients with T-ALL/LBL.

DOI： 10.1016/j.leukres.2021.106627

PubMed

researchmap

記述言語：英語   出版者・発行元：(一社)日本血液学会  

researchmap

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients are at high risk of developing invasive pneumococcal disease (IPD) with substantial morbidity and mortality. Pneumococcal polysaccharide vaccine (PPSV23) and pneumococcal conjugate vaccine (PCV13) are the primary prevention strategy. The difference between the Japanese and international guidelines is limited except when to start PCV13. However, Japanese data regarding the incidence of IPD after allo-HSCT that include vaccination status are limited. Therefore, we aimed to study the clinical characteristics of patients with IPD following allo-HSCT, focusing on unvaccinated patients. We retrospectively reviewed allo-HSCT recipients between April 2005 and December 2018 at Komagome Hospital. Among 1,091 recipients, 11 (1008/100,000 recipients) developed 13 episodes of IPD. The median period from the first allo-HSCT to the first IPD episode was 686 days (10-3040 days). Ten patients developed IPD before vaccination, and seven of these unvaccinated patients with late-onset IPD were ineligible for vaccination based on domestic guidelines. Although appropriate treatments resulted in a good short-term prognosis, most episodes of IPD developed in unvaccinated allo-HSCT recipients. Our data support the promotion of better adherence to the current guidelines and the importance of pneumococcal vaccination even years after allo-HSCT to protect against late-onset IPD.

DOI： 10.1007/s12185-021-03146-2

PubMed

researchmap

その他リンク： https://link.springer.com/article/10.1007/s12185-021-03146-2/fulltext.html

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1038/s41409-021-01249-2

researchmap

その他リンク： http://www.nature.com/articles/s41409-021-01249-2

記述言語：日本語   出版者・発行元：(一社)日本内科学会  

症例は53歳男性で、白血球61000/μl(blast 17%)、Hb 8.0g/dl、血小板51000/μlで急性白血病が疑われた。当科入院時、DICスコアは9点(旧厚生省基準)であり、既に造血器腫瘍に伴う播種性血管内凝固症候群(DIC)の合併を認めた。速やかに骨髄検査を施行し急性白血病は否定され、WHO分類改訂第4版に記載の項目全てに該当したことから非定型慢性骨髄性白血病(aCML)と診断した。第1病日より、ヒドロキシウレアの内服を行ったが、白血球減少効果に乏しく、凝固異常の改善も得られなかったため、第7病日よりCA(cytarabine、aclarubicin)療法を開始した。第13病日に喀血があり、酸素化の急激な増悪を認め、CT所見より、DICに伴う肺胞出血と診断した。大量に喀血したことから、挿管のうえ人工呼吸器管理とし、気道圧開放換気(APRV)による人工換気を開始したところ、P/F比は68から440まで改善した。第28病日に一度抜管を試みたが、その時点でDICの改善が不十分であったことから、抜管後に大量喀血を来たし、再挿管となった。DICの治療として、原病のaCMLの治療を徹底することが重要であると判断し、翌日より、ヒドロキシウレアの内服を併用したCA療法2コース目を施行した。その結果、十分な血球減少が得られ、それに伴い凝固異常の改善を認めた。その後、白血球減少の影響で人工呼吸器関連肺炎を合併し、急性呼吸窮迫症候群を発症したが、APRVによる呼吸管理および抗菌薬投与により、全身状態は徐々に改善し、第105病日に人工呼吸器を離脱することができた。

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

<title>Abstract</title>Cytomegalovirus (CMV) infection is a major complication during allogeneic stem cell transplantation (allo-SCT). However, mechanisms of adaptive immunity that drive this remain unclear. To define early immunological responses to CMV after transplantation, we using next-generation sequencing to examine the repertoire of T-cell receptors in CD8⁺/CMV pp65 tetramer⁺ cells (CMV-CTLs) in peripheral blood samples obtained from 16 allo-SCT recipients with HLA-A*24:02 at the time of CMV reactivation. In most patients, TCR beta repertoire of CMV-CTLs was highly skewed (median Inverse Simpson’s index: 1.595) and, 15 of 16 patients shared at least one TCR-beta clonotype with ≥ 2 patients. The shared TCRs were dominant in 12 patients and, two clonotypes were shared by about half of the patients. Similarity analysis showed that CDR3 sequences of shared TCRs were more similar than unshared TCRs. TCR beta repertoires of CMV-CTLs in 12 patients were also analyzed after 2–4 weeks to characterize the short-term dynamics of TCR repertoires. In ten patients, we observed persistence of prevailing clones. In the other two patients, TCR repertoires became more diverse, major clones declined, and new private clones subsequently emerged. These results provided the substantive clue to understand the immunological behavior against CMV reactivation after allo-SCT.

DOI： 10.1038/s41598-020-79363-2

researchmap

その他リンク： http://www.nature.com/articles/s41598-020-79363-2

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.ijid.2020.10.010

PubMed

researchmap

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

<title>Abstract</title>
Total body irradiation using intensity-modulated radiation therapy total body irradiation (IMRT-TBI) by helical tomotherapy in allogeneic hematopoietic stem cell transplantation (allo-HSCT) allows for precise evaluation and adjustment of radiation dosage. We conducted a single-center pilot study to evaluate the safety of IMRT-TBI for allo-HSCT recipients. Patients with hematological malignancies in remission who were scheduled for allo-HSCT with TBI-based myeloablative conditioning were eligible. The primary endpoint was the incidence of adverse events (AEs). Secondary endpoints were engraftment rate, overall survival, relapse rate, non-relapse mortality, and the incidence of acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively). Between July 2018 and November 2018, ten patients were recruited with a median observation duration of 571 days after allo-HSCT (range, 496–614). D80% for planning target volume (PTV) in all patients was 12.01 Gy. Average D80% values for lungs, kidneys and lenses (right/left) were 7.50, 9.03 and 4.41/4.03 Gy, respectively. Any early AEs (within 100 days of allo-HSCT) were reported in all patients. Eight patients experienced oral mucositis and gastrointestinal symptoms. One patient experienced Bearman criteria grade 3 regimen-related toxicity (kidney and liver). All cases achieved neutrophil engraftment. There was no grade III–IV aGVHD or late AE. One patient died of sinusoidal obstruction syndrome 67 days after allo-HSCT. The remaining nine patients were alive and disease-free at final follow-up. Thus, IMRT-TBI was well tolerated in terms of early AEs in adult patients who underwent allo-HSCT; this warrants further study with longer observation times to monitor late AEs and efficacy.

DOI： 10.1093/jrr/rraa078

PubMed

researchmap

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Bone turnover markers (BTMs) are useful parameters for assessing fracture risk and unlike bone mineral density (BMD), can be measured at any institution. However, BTM values have not been established in patients post-allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the practicality of BTMs in patients who underwent allo-HSCT by measuring levels of the serum bone resorption marker, tartrate-resistant acid phosphatase-5b (TRACP-5b), and the bone formation marker, bone-specific alkaline phosphatase (BAP), together with BMD, 1 month before and 6 months after allo-HSCT. Patients were classified into either the alendronate group (n = 14) if alendronate treatment (35 mg orally per week) was administered before allo-HSCT or within 1 month after allo-HSCT, or the control group (n = 16), in which patients did not receive alendronate treatment. Despite the high frequency of corticosteroids users in the alendronate group (71.4 vs. 18.9%; p < 0.01), the mean percentage changes in BMD at the lumbar spine (- 2.9 vs. - 3.1%; p = 0.44) and femoral neck (- 3.2 vs. - 4.1%; p = 1.00), TRACP-5b levels (- 4.8 vs. 9.9%; p = 0.45), and BAP levels (6.9 vs. 1.0%; p = 0.85) during 6 months did not differ significantly between the alendronate and control groups. Additionally, the percentage changes in BMD at the lumbar spine were negatively associated with the TRACP-5b levels 6 months after allo-HSCT (p = 0.03, r = 0.40). Our results indicate the possible effectiveness of alendronate treatment in allo-HSCT patients. BTM levels could be useful to monitor the BMD changes.

DOI： 10.1007/s00277-020-04090-7

PubMed

researchmap

その他リンク： http://link.springer.com/article/10.1007/s00277-020-04090-7/fulltext.html

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Second allogeneic hematopoietic stem cell transplantation (allo-HSCT) has a low survival outcome and a high non-relapse mortality (NRM) rate which is a major obstacle to this treatment. We hypothesized that the status of malnourishment after first allo-HSCT as represented by the geriatric nutritional risk index (GNRI) could be used as a prognostic factor to determine the outcomes of second allo-HSCT. A total of 108 patients with a median age of 42 (range, 17-69) years, who received second allo-HSCT for disease recurrence after first allo-HSCT from our institution, were included in this study. Low GNRI had a significant impact on NRM at 2 years after second allo-HSCT: 56.9% in patients with GNRI ≤ 92 compared with 27.5% in patients with GNRI > 92 (P = 0.002). In multivariate analysis, GNRI of ≤ 92 was the only significant factor for NRM (hazard ratio [HR] 2.29, 95% confidence interval [CI] 1.15-4.56, P = 0.018). High-risk disease status at second allo-HSCT (HR 2.74, 95% CI 1.46-5.14, P = 0.002) and GNRI of ≤ 92 (HR 1.70, 95% CI 1.02-2.82, P = 0.042) were identified as significant factors for overall survival (OS). A score of 1 was assigned to each factor, and the OS rate at 2 years after second allo-HSCT decreased according to the score: 53.0% in patients with score 0, 32.3% with score 1, and 2.5% with score 2 (P < 0.001). In conclusion, GNRI could be a useful predictor for the outcomes of second allo-HSCT. A prospective study in other cohorts is warranted to validate the findings of our study.

DOI： 10.1007/s00277-020-04089-0

PubMed

researchmap

その他リンク： http://link.springer.com/article/10.1007/s00277-020-04089-0/fulltext.html

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Informa UK Limited  

DOI： 10.1080/10428194.2020.1731499

PubMed

researchmap

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1038/s41409-019-0541-1

PubMed

researchmap

その他リンク： http://www.nature.com/articles/s41409-019-0541-1

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s12185-020-02821-0

PubMed

researchmap

その他リンク： http://link.springer.com/article/10.1007/s12185-020-02821-0/fulltext.html

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Allogeneic hematopoietic stem cell transplantation (HSCT) could be the only curative therapy for patients with relapsed/refractory acute leukemia (RRAL). Many reports have described unmanipulated haploidentical HSCT (HID-HSCT) using high-dose antithymocyte globulin (ATG). However, the transplant outcomes of HID-HSCT using very low-dose ATG (thymoglobulin, 2-2.5 mg/kg) and methylprednisolone (mPSL, 1 mg/kg) for patients with RRAL have not been reported. We compared the outcomes of 46 patients with RRAL who underwent HID-HSCT using very low-dose ATG (thymoglobulin) and mPSL with the outcomes of 72 patients who underwent non-HID-HSCT. Patient characteristics differed regarding conditioning intensity (myeloablative; 19.6% in HID-HSCT vs. 61.1% in non-HID-HSCT, P < 0.001) and having undergone multiple HSCT (26.1% vs. 11.1%, P = 0.045). However, we found no significant differences in the 1-year overall survival (OS, 31.7% vs. 29.1%; P = 0.25), disease-free survival (DFS, 20.5% vs. 23.7%; P = 0.23), cumulative incidence of relapse (CIR, 40.0% vs. 42.8%; P = 0.92), non-relapse mortality (NRM, 39.5% vs. 33.5%; P = 0.22), or 100-day grade II-IV acute graft-versus-host disease (32.6% vs. 34.7%; P = 0.64) following HID-HSCT vs. non-HID-HSCT, respectively. Subgroup analysis stratified by disease and intensity of conditioning regimen demonstrated the same results between HID-HSCT and non-HID-HSCT. Furthermore, multivariate analysis showed that HID-HSCT was not an independent prognostic factor for OS (hazard ratio (HR) = 0.95 [95% confidence interval (CI), 0.58-1.58]), DFS (HR = 1.05 [95%CI, 0.67-1.68]), CIR (HR = 0.84 [95%CI, 0.48-1.47]), or NRM (HR = 1.28 [95%CI, 0.66-2.46]). In summary, transplant outcomes for RRAL were comparable in the HID-HSCT and non-HID-HSCT groups. HID-HSCT using very low-dose ATG and mPSL for RRAL may be a viable alternative to non-HID-HSCT.

DOI： 10.1007/s00277-019-03865-x

PubMed

researchmap

その他リンク： http://link.springer.com/article/10.1007/s00277-019-03865-x/fulltext.html

担当区分：責任著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

There have been many reports regarding tyrosine kinase inhibitor (TKI) administration to prevent relapse following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). However, there are no commonly accepted standards for the choice of TKIs. We retrospectively analyzed the clinical features of Ph+ALL patients who received TKIs after allo-HSCT at our institution. The prophylactic administration of TKIs (pro) occurred in eight patients, and six patients received preemptive TKI administration (pre). The median follow-up period after allo-HSCT was 1,427 (range, 161-2,428) days in the pro group and 773.5 (range, 156-2,243) days in the pre group. Only one patient with non-hematological complete remission before allo-HSCT relapsed among the patients in the pro group. In the pre group, four patients treated with only TKIs achieved negativity of minimal residual disease. The 2-year overall survival rate after allo-HSCT was 85.7% in the pro group and 100% in the pre group. We used lower doses of TKIs compared with previous reports and this analysis shows that the dose is safe and effective as the treatment.

DOI： 10.11406/rinketsu.61.11

PubMed

researchmap

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Vacuolar myelopathy (VM) is known to be a neurological complication in patients with acquired immunodeficiency syndrome (AIDS). In autopsy-based studies, VM was reported in approximately 20-50% of patients with AIDS. It manifests in various says, mainly presenting as a painless spastic paraparesis with a sensory ataxia. We present a rare case of VM after bone marrow transplantation (BMT) in a patient without AIDS. A 50-year-old man developed weakness in the lower legs, leg muscle atrophy, and difficulty in walking 86 days after BMT. The patient died from septic shock on day 309. The autopsy revealed intralamellar vacuolation in the spinal white matter, which was compatible with VM.

DOI： 10.11406/rinketsu.61.1625

PubMed

researchmap

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

OBJECTIVE: The purpose of this study was to describe the clinical features of nocardiosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT), focusing on new Nocardia species. METHODS: We retrospectively reviewed data from patients with nocardiosis after allo-HSCT treated at our hospital and documented cases in the medical literature. RESULTS: Fifty-seven cases were identified from our institution and the literature review. Although 51 patients (89.5%) responded to initial treatment, 28 (49.1%) patients were switched over to other treatment regimens due to the recurrence of nocardiosis or adverse events of antimicrobials. Nocardiosis-attributed mortality occurred in ten patients (17.5%). Antimicrobial susceptibilities varied among intra- and inter-species except linezolid (LZD). In the present study, five species were newly discovered after 2000, including N. cyriacigeorgica, N. veterana, N. abscessus, N. aobensis, and N. mexicana. All isolates of N. cyriacigeorgica, N. veterana, N. abscessus, and N. aobensis were sensitive to trimethoprim/sulfamethoxazole, amikacin (AMK), imipenem (IPM), and LZD; however, N. mexicana was resistant to AMK and IPM. CONCLUSION: Newly identified Nocardia species have various antimicrobial susceptibility patterns. Long-term maintenance therapy could be challenging due to the adverse events of antimicrobials, especially in the allo-HSCT setting. Prudent evaluation is crucial for selecting a second-line or further treatment options.

DOI： 10.1016/j.ijid.2019.10.003

PubMed

researchmap

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1002/hon.2614

PubMed

researchmap

その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/hon.2614

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s12185-019-02677-z

PubMed

researchmap

その他リンク： http://link.springer.com/article/10.1007/s12185-019-02677-z/fulltext.html

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s00277-019-03668-0

PubMed

researchmap

その他リンク： http://link.springer.com/article/10.1007/s00277-019-03668-0/fulltext.html

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Autologous stem-cell transplantation is an effective procedure for the treatment of multiple myeloma, and involves the collection of hematopoietic stem cells (HSCs). However, in some patients, HSCs in the bone marrow fail to mobilize. Pomalidomide upregulates CXCR4 in hematopoietic stem cells, in a manner similar to that of lenalidomide, and is, thus, likely to have a negative impact on hematopoietic stem-cell mobilization in multiple myeloma patients. Here, we report the two cases in which hematopoietic stem cells were mobilized using plerixafor plus granulocyte-colony stimulating factor after exposure to lenalidomide and pomalidomide. Use of plerixafor with a sufficient washout period may lead to successful mobilization following pomalidomide use, although further study of this potential use is needed.

DOI： 10.1007/s12185-019-02622-0

PubMed

researchmap

その他リンク： http://link.springer.com/article/10.1007/s12185-019-02622-0/fulltext.html

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

BACKGROUND: Disseminated adenovirus (ADV) infection is a fatal complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), however, it is rare following autologous peripheral blood stem cell transplantation (auto-PBSCT) or chemotherapy alone. CASE: A 66-year-old Japanese female with relapsed and refractory multiple myeloma (RRMM) received auto-PBSCT, achieving partial response. To obtain a greater response, pomalidomide/dexamethasone was started on day 28 after auto-PBSCT, but was stopped on day 41 due to thrombocytopenia, fever, and gross hematuria. Additionally, she complained of abdominal pain on day 46. Blood tests revealed elevation of transaminases and alkaline phosphatase. There was no evidence of bacterial or fungal infections or progression of MM. ADV titer in urine and serum were 3.41 × 105 copies/mL and 6.76 × 103 copies/mL, respectively. CT scans revealed cystitis, urethritis, and peritonitis. Since more than two organs were infected with ADV, she was diagnosed with disseminated ADV disease. After 5 weeks of supportive care, all symptoms resolved. ADV titer decreased to 5.90 × 102 copies/mL in urine and became negative in serum on day 80. However, she succumbed to the MM a little more than a month later. CONCLUSION: Disseminated ADV infection can occur even in non-allogeneic transplant settings, such as in severely immunocompromised patients with MM who receive auto-PBSCT and repeated salvage therapies. Although it is a rare event, the mortality rate of this disease is very high, and hence, early diagnosis and interventions are needed in suspected cases.

DOI： 10.1016/j.jiac.2018.11.011

PubMed

researchmap

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Dealing with the recent series of allogeneic hematopoietic stem cell transplantation (allo-SCT) performed this decade, we reassessed the clinical impact of pretransplant surgical procedures (SP) for pulmonary lesions of invasive fungal disease (IFD) on subsequent transplant outcome. We focused on the clinical outcomes of seven patients with pulmonary IFD who underwent segmentectomy (n = 4), lobectomy (n = 2) or abscess incision with drainage only (n = 1), and compared results to those of 21 patients carrying pulmonary IFD who never underwent invasive SP before allo-SCT. The rate of exacerbation of pulmonary lesions by 180 days after allo-SCT did not differ significantly between groups (32.2% vs 42.9%, P = 0.69). Moreover, no significant differences in non-relapse mortality (46.4% vs 42.3%, P = 0.93) or overall survival (53.6% vs 30.9%, P = 0.45) at 1 year were evident between groups. These results indicate that pretransplant SP for pulmonary lesions might have no survival benefit under the current antifungal prophylaxis or treatment modality.

DOI： 10.1111/tid.13023

PubMed

researchmap

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s12185-018-2554-8

PubMed

researchmap

その他リンク： http://link.springer.com/content/pdf/10.1007/s12185-018-2554-8.pdf

掲載種別：研究論文（学術雑誌）  

DOI： 10.1182/BLOOD-2019-129711

Web of Science

researchmap

掲載種別：研究論文（学術雑誌）  

DOI： 10.1182/BLOOD-2019-128031

Web of Science

researchmap

掲載種別：研究論文（学術雑誌）  

DOI： 10.1182/BLOOD-2019-122401

Web of Science

researchmap

掲載種別：研究論文（学術雑誌）  

DOI： 10.1182/BLOOD-2019-122894

Web of Science

researchmap

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Informa UK Limited  

DOI： 10.1080/10428194.2018.1441410

PubMed

researchmap

記述言語：英語   出版者・発行元：AMER SOC HEMATOLOGY  

0

Web of Science

researchmap

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BioMed Central Ltd.  

Background: Stenotrophomonas maltophilia (S. maltophilia) bacteremia causes significant morbidity and mortality in immunocompromised hosts. However, incidence and risk factors for mortality in S. maltophilia bacteremia following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain controversial. The primary aim of this study is to clarify factors associated with poor prognosis of allo-HSCT recipients with S. maltophilia bacteremia. Methods: From January 2005 to December 2014, patients with hematological diseases and S. maltophilia bacteremia at a single transplantation center in Japan were examined for incidence and 90-day mortality. Prognostic factors associated with 90-day mortality among allo-HSCT recipients were analyzed by log-rank test, and significant variables in the univariate analysis were included in the multivariate Cox proportional-hazards regression model. Results: A total of 65 patients, including 47 patients undergoing allo-HSCT, developed S. maltophilia bacteremia. The incidence of S. maltophilia bacteremia was significantly higher in allo-HSCT recipients compared to patients not receiving allo-HSCT (6.53 vs. 0.36 per 100 admissions, respectively
p &lt
0.01). The overall 90-day mortality in allo-HSCT recipients was 43%. Independent risk factors for 90-day mortality were low serum albumin (&lt
3.0 g/dl) (HR = 10.86
95% CI, 3.27-36.12) and high serum C-reactive protein (CRP) (≥10.0 mg/dl) (HR = 3.28
95% CI, 1.00-10.72). Among 9 patients with both high CRP and low albumin, 5 had pneumonia at the onset of bacteremia and the remaining 4 patients developed pneumonia in a median of 3 days (range, 1 to 8 days) even under effective treatment. All 9 patients eventually died in a median of 2 days (range, 2 to 32 days). The probabilities of developing pneumonia in patients with or without high CRP and low albumin levels were 100% (9/9) and 10.5% (4/38), respectively (p &lt
0.01). Conclusions: Allo-HSCT recipients had higher rates of S. maltophilia bacteremia than did patients not receiving allo-HSCT. High serum CRP and low serum albumin at the onset of bacteremia are predictive of disease progression to pneumonia and poor prognosis.

DOI： 10.1186/s12879-017-2745-6

Scopus

PubMed

researchmap

担当区分：責任著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We report three cases of fusariosis that occurred during the treatment of acute leukemia, during the past 5 years at our institution. Case 1: A 70-year-old male with relapsed and refractory acute lymphoblastic leukemia (ALL) developed fever and multiple nodular lesions in both the lungs. Blood culture that was subsequently obtained revealed Fusarium species. Treatment with liposomal-amphotericin B (L-AMB) was ineffective, and the condition of the patient deteriorated rapidly leading to death. Case 2: A 28-year-old male with T-ALL developed echthyma gangrenosum (EG) ulcers on the scrotum during conditioning for transplantation. Antifungal therapy with L-AMB was ineffective, and later, itraconazole and micafungin (MCFG) were introduced. However, the engraftment was not achieved, and the patient died on day 27. Microbiological examination of EG samples collected on day 13 revealed infection by Fusarium species post mortem. Case 3: A 50-year-old male with blast crisis of chronic myeloid leukemia developed EG primarily on the trunk during chemotherapy. The patient died without any response to L-AMB and MCFG. A culture obtained from EG on day 19 yielded Fusarium species, post mortem. The prognosis of fusariosis is extremely poor. However, skin lesions such as EG may assist in the early diagnosis of the disseminated disease.

DOI： 10.11406/rinketsu.58.2375

PubMed

researchmap

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Society of Internal Medicine  

Extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is relatively rare. The most commonly reported sites in acute lymphoblastic leukemia (ALL) patients after allo-HSCT are soft tissue and the central nervous system, and the gastrointestinal system is an uncommon site. We herein report a unique case with massive hematemesis resulting from gastrointestinal relapse of ALL after allo-HSCT. Upper gastrointestinal endoscopy showed bleeding from a 1.5-cm submucosal tumorous lesion with central ulceration on the anterior wall of the stomach. At the same time, computed tomography revealed extramedullary relapse at the breast and bilateral adrenal glands.

DOI： 10.2169/internalmedicine.8646-16

Scopus

PubMed

researchmap

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Tokyo  

From January 2012 to September 2015, 49 patients received biosimilar filgrastim (BF) after allogeneic bone marrow transplantation (BMT, n = 31) or peripheral stem cell transplantation (PBSCT, n = 18) in our institution. To evaluate the clinical impact of BF on transplant outcomes of these patients, we compared hematological recovery, overall survival (OS), disease-free survival (DFS), transplantation-related mortality (TRM), cumulative incidence of relapse (CIR), and acute and chronic graft-versus-host disease (GVHD) with those of control patients who received originator filgrastim (OF) after BMT (n = 31) or PBSCT (n = 18). All cases were randomly selected from a clinical database in our institution. In both the BMT and PBSCT settings, neutrophil recovery (17 vs. 19 days in BMT
13 vs. 15 days in PBSCT) and platelet recovery (27 vs. 31 days in BMT
17 vs. 28 days in PBSCT) were essentially the same between BF and OF. They were also comparable in terms of OS, DFS, TRM, CIR, and the incidence of acute GVHD and chronic GVHD. On multivariate analysis, the use of BF in both BMT and PBSCT was not a significant factor for adverse transplant outcomes. Although BF significantly reduced filgrastim costs in both BMT and PBSCT, total hospitalization costs were not significantly different between BF and OF.

DOI： 10.1007/s12185-016-2085-0

Scopus

PubMed

researchmap

その他リンク： http://link.springer.com/article/10.1007/s12185-016-2085-0/fulltext.html

記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

Ph陽性急性リンパ性白血病の予後を改善するため,同種造血幹細胞移植後にチロシンキナーゼ阻害薬(TKI)を投与する報告が近年なされているが,投与が望ましい患者や投与方法など一定の見解は得られていない。今回,単一施設での移植後TKI投与について後方視的に解析を行った。予防的投与(pro)は8例,先制的投与(pre)は6例であった。観察期間中央値はpro 1,427(161〜2,428)日,pre 773.5(156〜2,243)日であった。Proでは非寛解期で移植が行われた1例が再発した。Preの4例はTKI投与のみで微小残存病変(MRD)陰性となった。2年全生存率はpro 85.7%,pre 100%であった。本解析では既報よりも低用量のTKI投与を行ったが,安全で有効である可能性が示唆された。(著者抄録)

researchmap

その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01540&link_issn=&doc_id=20200204190003&doc_link_id=1390002184872228352&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390002184872228352&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

researchmap

記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

researchmap

記述言語：英語   出版者・発行元：(一社)日本血液学会-東京事務局  

researchmap

記述言語：英語   出版者・発行元：(一社)日本血液学会-東京事務局  

researchmap

記述言語：英語   出版者・発行元：(一社)日本血液学会-東京事務局  

researchmap

記述言語：英語   出版者・発行元：(一社)日本血液学会-東京事務局  

researchmap

記述言語：英語   出版者・発行元：(一社)日本血液学会-東京事務局  

researchmap

記述言語：英語   出版者・発行元：(一社)日本血液学会-東京事務局  

researchmap

記述言語：英語   出版者・発行元：(一社)日本血液学会-東京事務局  

researchmap

記述言語：英語   出版者・発行元：(一社)日本血液学会-東京事務局  

researchmap

記述言語：英語   出版者・発行元：(一社)日本血液学会-東京事務局  

researchmap

記述言語：英語   出版者・発行元：(一社)日本血液学会-東京事務局  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本輸血・細胞治療学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

過去5年間当院で急性白血病治療中にフザリウム症を発症した3例を報告する。症例1:70歳男性。再発難治性急性リンパ性白血病(ALL)で発熱と両肺多発結節影がみられ、血液培養でFusarium属を検出、liposomal-amphotericin B(L-AMB)奏効せず死亡。症例2:28歳男性。ALLに対する移植前処置中に陰嚢にecthyma gangrenosum(EG)様の皮疹が出現L-AMBは無効であり、itraconazoleとmicafungin(MCFG)を追加したが、好中球生着せずday 27に死亡。生前提出したEGの培養からFusarium属が検出。症例3:50歳男性。慢性骨髄性白血病急性転化の化学療法中、体幹にEG様皮疹が出現、L-AMB、MCFG奏効せず、死後EGからFusarium属が検出。フザリウム症は極めて予後不良であるがEGに着目することで早期診断につながる可能性がある。(著者抄録)

researchmap

記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

researchmap

記述言語：日本語   出版者・発行元：老年者造血器疾患研究会  

症例は2015年時76歳の女性。68歳時急性骨髄性白血病(AML:acute myeloid leukemia)と診断され、71歳7ヵ月時に第3寛解期でミニ移植を施行した。前処置関連毒性は軽度で、day 17に好中球は生着した。day 30からskin stage 2の急性移植片対宿主病(aGVHD:acute graft-versus-host disease)を発症した他は有害事象なく、day 58に退院した。移植後5年経過したが、再発やGVHDを認めず、良好な状態を維持している。高齢者における造血幹細胞移植の位置付けはいまだ確立されていないが、年齢だけでなく他のリスク因子を一つ一つ的確に吟味した上で実施すれば有効な治療手段となり得る。(著者抄録)

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：老年者造血器疾患研究会  

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap