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  

BACKGROUND: For pediatric recipients, red blood cells (RBCs) are added to bone marrow (BM) collections before low RBC volume BM processing using COBE Spectra (COBE) or Spectra Optia (Optia). However, the processing efficiency of this approach has not been evaluated. This study aimed to evaluate RBC depletion and nucleated cell subpopulation recovery rates in third-party RBC-manipulated BM products processed with the COBE or Optia. STUDY DESIGN AND METHODS: We retrospectively collected data on RBC depletion from low RBC volume BM with third-party RBCs (manipulated group) and on conventional large-volume, BM (unmanipulated group) processing performed between September 2010 and December 2021. All procedures were performed using COBE or Optia. RESULTS: The median residual RBC volume in the manipulated group was 9.5 ml in COBE and 2.5 ml in Optia (p = .01). The median total nucleated cell (TNC) and mononuclear cell (MNC) were comparable between the manipulated groups using each cell separator (TNC, 40.8 vs. 47.1%; MNC, 78.3 vs. 79.4%). The manipulation did not adversely affect TNC and MNC recoveries in either device. In addition, Optia achieved similar CD34+ cell recovery to that in large-BM-volume processing using the same device (147.5 vs. 184.5%, p = .112). During a follow-up period, neutrophil engraftment was achieved in all patients who received third-party RBC-manipulated grafts, and platelet engraftment was achieved in all cases, except one. CONCLUSION: The addition of third-party RBC to low RBC volume BM collections from or for pediatric patients does not have any negative impact on either RBC depletion or hematopoietic cell recovery during processing with the widely used cell separator.

DOI： 10.1111/trf.17039

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/trf.17039

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  

Active infection at the time of allogeneic hematopoietic stem cell transplantation (HSCT) is a risk for non-relapse mortality (NRM) after HSCT. Granulocyte transfusion (GTX) has been used to prevent or treat life-threatening infections in patients with severe neutropenia. However, data are limited on the clinical benefits of GTX during HSCT. We retrospectively analyzed the transplant outcomes of HSCT patients who had undergone GTX between 2012 and 2020. Altogether, 20 patients with documented infection had received 55 GTXs during HSCT. No adverse events were observed during the GTX infusion. The average number of granulocytes was 0.40 (range, 0.10-1.59) × 109/kg. The median neutrophil increment one day after GTX was 515 (range, -6 to 6630)/μl, which was significantly correlated with the infused granulocyte dose (p = 0.0007). A total of 17 of 20 patients achieved neutrophil engraftment. The number of infused granulocytes tended to higher in clinical responders (p = 0.12), and patients receiving ≥ 0.5 × 109/kg showed trend toward to better transplant outcomes (GTX-high vs. GTX-low, 1-year OS; 33% vs. 11%, p = 0.19. 1-year NRM; 44% vs.77%, p = 0.11). The type of red blood sedimenting agents was significantly correlated with the amounts of granulocyte collection. In conclusion, GTX, especially with a high amount of containing granulocytes, could be a safe bridging therapy for neutrophil engraftment after HSCT in patients with active infection.

DOI： 10.1016/j.transci.2022.103453

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/trf.16856

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/trf.16856

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

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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：Elsevier BV  

Peripheral blood progenitor cells (PBPCs) are a predominant graft source in allogeneic hematopoietic cell transplantation. Citrate-induced hypocalcemia remains the most frequent side effect of PBPC apheresis. Although the method for preventing severe adverse events is established, more efficient prophylaxis is required so that volunteer donors can donate PBPCs without pain and anxiety. We studied 80 healthy donors who underwent PBPC harvest between February 2014 and June 2020. Of these, 23 donors who underwent apheresis between February 2014 and December 2015 received only the standard prophylaxis of intravenous calcium gluconate. Oral calcium drinks were provided to 57 donors who underwent apheresis from January 2016 to June 2020 to supplement intravenous calcium gluconate prophylaxis. The ionized calcium (ICa) levels at multiple time intervals and the hypocalcemic symptoms were evaluated. Oral supplementation with a calcium drink maintained significantly higher ICa levels. Analysis using the inverse probability weighted regression adjustment method suggested that calcium drinks reduced the frequency of citrate-related reactions by 39.2 %. Administering a prophylactic oral calcium drink before apheresis with intravenous administration of calcium gluconate is promising to further reduce citrate-induced hypocalcemia in volunteer donors.

DOI： 10.1016/j.transci.2021.103147

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担当区分：筆頭著者   記述言語：日本語   出版者・発行元：The Japan Society of Transfusion Medicine and Cell Therapy  

Spectra Optia^®は，COBE Spectra^®に代わる次世代機であり，自動インターフェイス管理（AIM）システムを採用し全自動的にアフェレーシスを行うことができる．主に臨床使用経験が積まれていた欧州に対し，わが国では2011年7月に認可され今後の使用実績が期待される．<br> 今回，末梢血幹細胞採取におけるSpectra Optia^®（Optia）とCOBE Spectra^®（COBE）の比較を目的として，当院におけるOptia導入前後での末梢血幹細胞採取73件について，機器別採取結果を後方視的に検討した．採取回数はOptia群24回（自家15回，同種9回），COBE群49回（自家36回，同種13回），処理血液量は自家で患者体重（kg）当たり150ml，同種はドナー体重（kg）当たり200mlとした．<br> 単核球回収率は両機種間で有意差はなかったが，採取産物容量，赤血球混入量はOptia群で有意に少なかった．また同種のみで比較した場合，Optia群では採取産物中の血小板混入数が有意に少なかった．副作用面でも重篤なものはなく，血漿成分が過剰に採取されない簡便な全自動型血液成分分離装置としてOptiaは期待できるものと考えられた．<br>

DOI： 10.3925/jjtc.59.799

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その他リンク： http://search.jamas.or.jp/link/ui/2014217196

担当区分：筆頭著者   記述言語：英語  

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担当区分：筆頭著者   記述言語：英語  

DOI： 10.1046/j.1365-2141.2003.04216.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Introduction Despite the critical role of bone marrow aspiration and a trephine biopsy (BMAT) in the diagnosis and management of hematological diseases, research on effective teaching methods is limited. Medical students traditionally learn to perform BMAT through observation and replication, which poses a risk to patient safety. Therefore, we developed a novel BMAT simulator for undergraduate medical students using a simulation-based education program. Methods This program, designed for fourth- and fifth-year medical students at Okayama University Medical School, included pre-study materials and one hour of simulation training. Internists practicing hematology served as the controls. Before and after the simulation training, the students completed questionnaires regarding self-confidence, self-evaluation, interest, and knowledge. The procedures were evaluated objectively using a checklist at the end of the program. Results There were significant improvements in self-evaluation, self-confidence, interest, and knowledge acquisition after the simulation program (p≤0.001). The checklist revealed that the mean overall proficiency level of the students was 76.9%, which was significantly higher than that of internists (63.5%) (p≤0.01). Conclusion Our simulation-based education program using the novel BMAT simulator improved medical students' BMAT knowledge and skills.

DOI： 10.2169/internalmedicine.3998-24

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.2556-23

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Abstract

We evaluated the clinical impacts of the concurrent modification of post‐transplant cyclophosphamide (PTCy) dose and tacrolimus (Tac)‐initiation timing in 61 patients with human leukocyte antigen‐haploidentical transplantation. Reduced‐dose PTCy (80 mg/kg) was associated with a higher incidence of moderate‐to‐severe chronic graft‐versus‐host disease (GVHD) than standard‐dose PTCy (100 mg/kg) (35.0% vs. 26.6%, p = 0.053). Notably, early‐initiation Tac (day ‐1) increased moderate‐to‐severe chronic GVHD than standard‐initiation Tac (day 5) in the reduced‐dose PTCy group (p = 0.032), whereas Tac‐initiation timing did not impact chronic GVHD in the standard‐dose PTCy group. These data indicate that the combination of reduced‐dose PTCy and early‐initiation Tac can amplify chronic GVHD.

DOI： 10.1002/jha2.962

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although chimeric antigen receptor T-cell (CAR-T) therapies have dramatically improved the outcomes of relapsed/refractory B-cell malignancies, recipients suffer from severe humoral immunodeficiencies. Furthermore, patients with coronavirus disease 2019 (COVID-19) have a poor prognosis, as noted in several case reports of recipients who had COVID-19 before the infusion. We report the case of a 70-year-old woman who developed COVID-19 immediately before CAR-T therapy for high-grade B-cell lymphoma. She received Tixagevimab-Cilgavimab chemotherapy and radiation therapy but never achieved remission. She was transferred to our hospital for CAR-T therapy, but developed COVID-19. Her symptoms were mild and she was treated with long-term molnupiravir. On day 28 post-infection, lymphodepleting chemotherapy was restarted after a negative polymerase chain reaction (PCR) test was confirmed. The patient did not experience recurrence of COVID-19 symptoms or severe cytokine release syndrome. Based on the analysis and comparison of the previous reports with this case, we believe that CAR-T therapy should be postponed until a negative PCR test is confirmed. In addition, Tixagevimab-Cilgavimab and long term direct-acting antiviral agent treatment can be effective prophylaxis for severe COVID-19 and shortening the duration of infection.

DOI： 10.1007/s12185-024-03711-5

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掲載種別：研究論文（学術雑誌）   出版者・発行元：The Japan Society for Hematopoietic Stem Cell Transplantation  

DOI： 10.7889/tct-23-015

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Thrombocytopenia, anasarca, fever, renal dysfunction, and organomegaly (TAFRO) syndrome is an inflammatory disorder with an unclear pathogenesis. We herein report a case of TAFRO syndrome in remission in a patient who experienced recurrent intracranial bleeding despite a normal platelet count and coagulation system. A further investigation suggested the presence of anti-glycoprotein VI (GPVI) autoantibodies in the plasma, which induced platelet dysfunction and bleeding tendency. No new bleeding or relapse of TAFRO syndrome occurred after immunosuppressive therapy was initiated. These findings may help elucidate the autoimmune pathogenesis of TAFRO syndrome.

DOI： 10.2169/internalmedicine.2799-23

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Relapsed and/or refractory (R/R) primary central nervous system lymphoma (PCNSL) has a poor prognosis. A 57-year-old man diagnosed with PCNSL achieved a complete response by high-dose methotrexate-based chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT). The disease was not cured, so he was treated with the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel after the third relapse. However, the disease relapsed again 28 days after CAR T-cell therapy. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was attempted as curative therapy after bridging with second ASCT and tirabrutinib monotherapy. Although a temporary response was achieved, the disease relapsed 98 days after allo-HSCT. While receiving tirabrutinib for relapse after allo-HSCT, the patient developed acute respiratory failure due to transplant-related toxicity and post-transplant thrombotic microangiopathy. He died 175 days after allo-HSCT. Although various treatments for PCNSL have been investigated in recent years, the treatment strategy for R/R PCNSL has not been established. Further studies are warranted to improve the outcomes of patients with R/R PCNSL.

DOI： 10.11406/rinketsu.65.622

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The distribution and clinical impact of cell-of-origin (COO) subtypes of diffuse large B-cell lymphoma (DLBCL) outside Western countries remain unknown. Recent literature also suggests that there is an additional COO subtype associated with the germinal center dark zone, that warrants wider validation to generalize clinical relevance. Here, we assembled a cohort of Japanese patients with untreated DLBCL and determined the refined COO subtypes, that include the dark zone signature (DZsig), using the NanoString DLBCL90 assay. To compare the distribution and clinical characteristics of the molecular subtypes, we used a dataset from the cohort of BC Cancer (BCC) (n = 804). Of the 1050 patients where DLBCL90 assay was successfully performed in our cohort, 35%, 45%, and 6% of patients were identified to be germinal center B-cell-like (GCB)-DLBCL, activated B-cell-like (ABC)-DLBCL, and DZsigpos-DLBCL, respectively, with the highest prevalence of ABC-DLBCL differing significantly from that of BCC (P < 0.001). GCB-DLBCL, ABC-DLBCL, and DZsigpos-DLBCL were associated with two-year overall survival rates of 88%, 75%, and 66%, respectively (P < 0.0001), with patients of the DZsigpos-DLBCL having the poorest prognosis. In contrast, GCB-DLBCL without DZsig showed excellent outcomes following rituximab-containing immunochemotherapy. DZsigpos-DLBCL was associated with the significant enrichment of tumors with CD10 expression, concurrent MYC/BCL2 expression, and depletion of microenvironmental components (all P < 0.05). These results provide evidence of the distinct distribution of clinically relevant molecular subtypes in Japanese DLBCL and that refined COO, as measured by the DLBCL90 assay, is a robust prognostic biomarker that is consistent across geographical areas.

DOI： 10.1182/bloodadvances.2023010402

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The prognostic impact of corticosteroid therapy in patients receiving tisagenlecleucel (tisa-cel) treatment who are more likely to develop cytokine release syndrome (CRS) remains unclear. This study aimed to evaluate the clinical impact and lymphocyte kinetics of corticosteroid administration for CRS in 45 patients with relapsed and/or refractory B-cell lymphoma treated with tisa-cel. This was a retrospective evaluation of all consecutive patients diagnosed with relapsed and/or refractory diffuse large B-cell lymphoma, follicular lymphoma with histologic transformation to large B-cell lymphoma, or follicular lymphoma who received commercial-based tisa-cel treatment. The best overall response rate, complete response rate, median progression-free survival (PFS), and median overall survival (OS) were 72.7%, 45.5%, 6.6 months, and 15.3 months, respectively. CRS (predominantly grade 1/2) occurred in 40 patients (88.9%), and immune effector cell-associated neurotoxicity syndrome (ICANS) of all grades occurred in 3 patients (6.7%). No grade ≥3 ICANS occurred. Patients with high-dose (≥524 mg, methylprednisolone equivalent; n = 12) or long-term (≥8 days; n = 9) corticosteroid use had inferior PFS and OS to patients with low-dose or no corticosteroid use (both P < .05). The prognostic impact remained even in 23 patients with stable disease (SD) or progressive disease (PD) before tisa-cel infusion (P = .015). but not in patients with better disease status (P = .71). The timing of corticosteroid initiation did not have a prognostic impact. Multivariate analysis identified high-dose corticosteroid use and long-term corticosteroid use as independent prognostic factors for PFS and OS, respectively, after adjusting for elevated lactate dehydrogenase level before lymphodepletion chemotherapy and disease status (SD or PD). Lymphocyte kinetics analysis demonstrated that after methylprednisolone administration, the proportions of regulatory T cells (Tregs), CD4+ central memory T (TCM) cells, and natural killer (NK) cells were decreased, whereas the proportion of CD4+ effector memory T (TEM) cells was increased. Patients with a higher proportion of Tregs at day 7 had a lower incidence of CRS, but this did not affect prognosis, indicating that early elevation of Tregs may serve as a biomarker for CRS development. Furthermore, patients with higher numbers of CD4+ TCM cells and NK cells at various time points had significantly better PFS and OS, whereas the number of CD4+ TEM cells did not impact prognostic outcomes. This study suggests that high-dose or long-term corticosteroid use attenuates the efficacy of tisa-cel, especially in patients with SD or PD. Additionally, patients with high levels of CD4+ TCM cells and NK cells after tisa-cel infusion had longer PFS and OS.

DOI： 10.1016/j.jtct.2023.06.018

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Mechanisms of prolonged cytopenia (PC) after chimeric antigen receptor (CAR) T-cell therapy, an emerging therapy for relapsed or refractory diffuse large B-cell lymphoma, remain elusive. Haematopoiesis is tightly regulated by the bone marrow (BM) microenvironment, called the 'niche'. To investigate whether alterations in the BM niche cells are associated with PC, we analysed CD271+ stromal cells in BM biopsy specimens and the cytokine profiles of the BM and serum obtained before and on day 28 after CAR T-cell infusion. Imaging analyses of the BM biopsy specimens revealed that CD271+ niche cells were severely impaired after CAR T-cell infusion in patients with PC. Cytokine analyses after CAR T-cell infusion showed that CXC chemokine ligand 12 and stem cell factor, niche factors essential for haematopoietic recovery, were significantly decreased in the BM of patients with PC, suggesting reduced niche cell function. The levels of inflammation-related cytokines on day 28 after CAR T-cell infusion were consistently high in the BM of patients with PC. Thus, we demonstrate for the first time that BM niche disruption and sustained elevation of inflammation-related cytokines in the BM following CAR T-cell infusion are associated with subsequent PC.

DOI： 10.1111/bjh.18747

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本造血・免疫細胞療法学会  

DOI： 10.7889/tct-23-014

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.11406/rinketsu.64.331

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1182/bloodadvances.2022008991

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Non-infectious pulmonary complications (NIPCs) after allogeneic hematopoietic stem cell transplantation (HSCT) are associated with poor outcomes. It is important to maximize the effectiveness of primary treatment because secondary treatment has not been established. We analyzed data from 393 patients who underwent allogeneic HSCT during a 10-year period. Thirty-seven were diagnosed with NIPCs, which consisted of idiopathic pneumonia syndrome, bronchiolitis obliterans, and interstitial lung disease including cryptogenic organizing pneumonia. Among these, 18 died (Dead group) while 19 remained alive (Alive group) during the study period. The median time between NIPC diagnosis and first administration of ≥ 1 mg/kg/day corticosteroids (prednisolone dose equivalent) was significantly longer in the Dead group than the Alive group, at 9 days versus 4 days (p = 0.01). We further divided these cases into those who received prednisolone within seven days and after 8 days. We found that the ≤ 7 days group were more likely to survive after their NIPC diagnosis compared to the ≥ 8 days group (p = 0.06). Our analysis showed that early initiation of corticosteroid therapy is associated with long-term survival in NIPCs.

DOI： 10.1007/s12185-022-03517-3

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記述言語：英語  

DOI： 10.1111/tme.12916

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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  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Vaccine-preventable disease (VPD) infections are more severe in immunocompromised hosts. Vaccination against measles, mumps, rubella, and varicella zoster (VZV) (MMRV) is therefore recommended for hematopoietic stem cell transplantation (HCT) recipients. However, studies on adult HCT recipients with VPD infections are limited. At our institution, we have systematically conducted serological MMRV tests as a part of check-up examinations during long-term follow-up (LTFU) after HCT since 2015. This retrospective study aimed to evaluate changes in the serostatus between before and 2 years after allogeneic HCT. Among 161 patients, the pre-transplant seropositivity was 82.7% for measles, 86.8% for mumps, 84.2% for rubella, and 94.3% for VZV. Among 56 patients who underwent LTFU including serological MMRV tests at 2 years after HCT, the percentages maintaining seroprotective antibody levels for measles, mumps, rubella and VZV were 71.5% (40/56), 51.8% (29/56), 48.2% (27/56), and 60.7% (34/56), respectively. Vaccination was recommended for 22 patients, and 12 were vaccinated. Among the 12 vaccinated patients, rates of seroconversion were examined in 2-6 patients for each of the four viruses. They were 100% (3/3) for measles, 33.3% (1/3) for mumps, 50% (3/6) for rubella, and 0% (0/2) for VZV. Further studies are warranted to clarify the effect of vaccination in adult HCT recipients.

DOI： 10.18926/AMO/63718

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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/s12185-022-03306-y

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その他リンク： https://link.springer.com/article/10.1007/s12185-022-03306-y/fulltext.html

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/s12185-022-03290-3

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その他リンク： https://link.springer.com/article/10.1007/s12185-022-03290-3/fulltext.html

記述言語：英語  

Venetoclax (VEN) is an oral B-cell lymphoma-2 (BCL-2) inhibitor that has been widely used to treat various hematological disorders. Recent studies have demonstrated that VEN in combination with fludarabine-enhanced high-dose cytarabine (FLA) is effective for treating relapsed or refractory acute myeloid leukemia (AML). In the combination therapy, salvage chemotherapy and VEN are basically concurrently administrated; however, further optimization may enable the treatment to apply to larger numbers of patients with various clinical backgrounds. Here, we describe a case of refractory AML treated with a sequential combination of the intensive chemotherapy (fludarabine, cytarabine, and mitoxantrone; FLAM) and VEN/AZA to bridge to an unrelated cord blood transplantation (uCBT). By continuously adding VEN/AZA after FLAM, the patient achieved morphologic leukemia free state with only minor toxicities. Blood cell counts did not recover until the time of transplantation because of the deep myelosuppression caused by the treatment sequence, but the infection risk was safely managed during this period. After engraftment, maintenance therapy with VEN/AZA was performed, and the patient has survived without disease recurrence for over 9 months after transplantation. Our case suggests that bridging therapy with VEN and AZA from the time of the last chemotherapy to allogeneic transplantation may provide an effective and tolerable treatment strategy for refractory AML. Further studies of larger numbers of cases are needed to validate the effectiveness of this treatment.

DOI： 10.1159/000526697

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 72-year-old man presented with chorea while undergoing treatment for recurrence of nodal peripheral T-cell lymphoma with T follicular helper (TFH) phenotype. An examination by brain N-isopropyl-p-iodoamphetamine (123I-IMP)-single photon emission computed tomography (SPECT) revealed no abnormalities other than a decreased cerebral blood flow (CBF) in the left striatum. After four courses of salvage chemotherapy, his clinical symptoms and asymmetric cerebral perfusion improved, suggesting that the decreased CBF had caused chorea. The significance of brain SPECT has not been fully clarified in patients with chorea-associated malignant lymphoma, warranting further investigations. Brain SPECT is an alternative approach to identify abnormalities in such patients.

DOI： 10.2169/internalmedicine.7180-21

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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  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A bloodstream infection (BSI) is the most common serious infectious complication of hematopoietic stem cell transplantation (HSCT). BSI promotes an inflammatory state, which exacerbates acute graft-versus-host disease (GVHD). We investigated whether a Gram-negative rod bloodstream infection (GNR-BSI), which develops early after allo-HSCT, affected the onset or exacerbated acute GVHD in 465 patients who underwent allo-HSCT from 1995 through 2015 at a single institution. Eighty-eight patients (19%) developed BSI during the study period. Among the cultures, 50 (57%) were Gram-positive cocci (GPC) and 31 (35%) were GNR. Of the 465 patients, 187 (40%) developed acute GVHD of grade II or higher within the first 100 days post-allogeneic HSCT: 124 (27%) had acute GVHD grade II, 47 (10%) had grade III, and 16 (3%) had grade IV. Multivariate analysis revealed that GNR-BSI was a significant risk factor for grade II-IV acute GVHD (grade II-IV: hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.03-2.97; grade III-IV: HR 2.37, 95% CI 1.03-5.43). These results suggest that GNR-BSI may predict the onset and exacerbation of acute GVHD.

DOI： 10.18926/AMO/62219

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記述言語：英語  

Acute promyelocytic leukemia (APL) is a hematological emergency that requires urgent intervention because of the high incidence of early hemorrhagic death. When patients with APL experience a synchronous solid organ tumor, the tumor's treatment must also be done properly. Differentiation-inducing therapy using arsenic trioxide (ATO) has less hematological toxicity compared to cytotoxic chemotherapy and might be preferable for untreated APL patients with a synchronous solid organ tumor. Here we describe the first successful case of untreated APL and synchronous endometrial cancer (in an adult Japanese woman) treated with ATO consolidation therapy and the subsequent surgery and chemotherapy for endometrial cancer.

DOI： 10.18926/AMO/61904

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記述言語：英語  

DOI： 10.1038/s41598-021-86066-9

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記述言語：英語  

DOI： 10.1038/s41375-021-01167-8

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記述言語：英語  

Owing to the poor prognosis of relapsed or refractory acute lymphoblastic leukemia (ALL), hematopoietic stem cell transplantation (HSCT) followed by effective salvage therapy is required. Inotuzumab ozogamicin (INO) was developed for ALL refractory to standard chemotherapy. However, previous reports suggest that sinusoidal obstruction syndrome (SOS) risk increases in patients with HSCT receiving INO, especially with dual alkylating agents. We report a case of relapsed Philadelphia chromosome-negative B-ALL where the patient underwent haploidentical HSCT using fludarabine/total body irradiation conditioning and posttransplant cyclophosphamide. Successful engraftment was achieved without SOS development.

DOI： 10.1016/j.lrr.2021.100241

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hematological diseases after solid organ transplant (SOT) are an emerging issue as the number of long-term SOT survivors increases. Expertise in managing patients requiring allogeneic hematopoietic stem cell transplantation (HSCT) after SOT from independent donors is needed; however, clinical reports of HSCT after SOT are limited, and the feasibility and risk are not well understood. In particular, HSCT in prior lung transplant recipients is thought to be complicated as the lung is immunologically distinct and is constantly exposed to the surrounding environment. Herein, we describe a case of successful HSCT in a patient with myelodysplastic syndromes who had previously received a lung transplant from a deceased donor for bronchiolitis obliterans syndrome. Reports about cases of HSCT after lung transplant are quite rare; thus, we discuss the mechanisms of immune tolerance through the clinical course of our case. This case suggests that HSCT after SOT can be considered a therapeutic option in cases where the transplanted organ is functionally retained and the hematological disease is in remission.

DOI： 10.1007/s12185-020-02967-x

PubMed

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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/s41409-020-01100-0

PubMed

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その他リンク： http://www.nature.com/articles/s41409-020-01100-0

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  

Post-transplant lymphoproliferative disorder (PTLD) is one of the most serious complications of allogeneic hematopoietic stem cell transplantation (HSCT). Rituximab is effective for PTLD; however, rituximab can produce adverse effects, including hypogammaglobulinemia. Here, we present the case of an 18-year-old female with refractory cytopenia of childhood who developed persistent selective hypogammaglobulinemia with low immunoglobulin G (IgG) 2 and IgG4 levels and monoclonal protein after rituximab therapy against probable PTLD. Despite B-cell recovery, the serum IgG levels gradually declined, reaching < 300 mg/dL at 33 months after rituximab treatment. In addition, class-switched memory (CD27 + IgD -) B cells were limited in phenotypic analysis. These findings suggest that peri-HSCT rituximab may contribute to an abnormal B-cell repertoire induced by impaired immunoglobulin class switch.

DOI： 10.1007/s12185-020-02886-x

PubMed

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その他リンク： http://link.springer.com/article/10.1007/s12185-020-02886-x/fulltext.html

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pulmonary alveolar proteinosis (PAP) is an uncommon lung disorder characterized by the excessive accumulation of surfactant-derived lipoproteins in the pulmonary alveoli and terminal bronchiole. Secondary PAP associated with primary myelofibrosis (PMF) is extremely rare, and to our knowledge, no autopsy case has been reported. We herein report an autopsy case of secondary PAP occurring in a patient with PMF who was treated with the Janus kinase 1/2 inhibitor ruxolitinib. We confirmed a diagnosis of PAP with complications based on the pathological findings at the autopsy. Notably, this case might suggest an association between ruxolitinib treatment and PAP occurrence.

DOI： 10.2169/internalmedicine.4082-19

PubMed

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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  

BACKGROUND Cross-matched platelet (cross-matched PLT) transfusion is effective for immune-mediated platelet transfusion refractoriness (PTR), but is more costly and time-consuming for physical cross-match than using standard PLT units. Recent studies have reported the utility of human leucocyte antigens (HLA) virtual cross-matched PLT (HLA-matched PLT) that is defined as HLA-A/B matched or no antibody against donor-specific antigen. Here, we evaluated the effect of HLA-matched PLTs for PTR in post hematopoietic stem cell transplant (HSCT) recipients. STUDY DESIGN AND METHODS Our study included a total of 241 PLTs in 16 patients who underwent HSCT at Okayama University Hospital between 2010 and 2017, receiving either HLA-matched or cross-matched PLTs. We calculated the 24-hour corrected count increments (CCI-24) to evaluate the effect of PLTs. A CCI-24 >= 4500 was considered to be a successful transfusion. RESULTS We analyzed 139 cross-matched PLTs and 102 HLA-matched PLTs. In the immune-mediated PTR, the rate of successful transfusion was 60.5% for cross-matched PLT and 63.4% for HLA-matched PLT (p = 0.825). On the other hand, the median CCI-24 for cross-matched PLT transfusions and HLA-matched PLT transfusions were 1856 and 5824 (p < 0.001), with a success rate of 28.1 and 54.1% in cases with non-immune-mediated PTR, respectively (p = 0.001). CONCLUSION The effectiveness of HLA-matched PLT is not inferior to cross-matched PLT. This result indicates that physical cross-match can be omitted in post HSCT PTR.

DOI： 10.1111/trf.15664

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41598-020-74174-x.

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記述言語：英語  

DOI： 10.1007/s12185-019-02659-1

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.transci.2019.05.011

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.18926/AMO/56652

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The number of patients who are successfully discharged from the intensive care unit (ICU) after hematopoietic stem cell transplantation (HSCT) remains limited. Most previous studies have evaluated short-term outcomes using ICU mortality; there have been comparatively fewer reports of long-term outcomes. We retrospectively analyzed 39 HSCT patients admitted to the ICU for the first time between April 2008 and July 2014. Performance status was evaluated in four long-term survivors in July 2016. Median age at ICU admission was 54 years (range 30-68). In total, 33 patients (70.2%) required mechanical ventilation and 31 patients (66%) required dialysis. The median OS from first ICU admission was 41 days (95% confidence interval [CI]: 22-64) and the 1-year survival rate was 12.8% (95% CI 4.7-25.2). No statistically significant factors were associated with short-term outcomes. Among long-term outcomes, a second or subsequent HSCT and neutropenia at ICU admission were significant risk factors. Four of 10 ICU survivors have survived with good performance status for a median of 1994 (1203-2633) days. Our results suggest that the number of prior transplants and neutropenia at ICU admission may influence OS.

DOI： 10.1007/s12185-018-2536-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Studies examining risk factors associated with vasovagal reactions (VVRs) during autologous blood donations, especially in younger subjects, have been limited. The aim of the present study was to define risk factors for VVRs during preoperative autologous blood donation in patients, including those younger than 18 years old. We retrospectively analyzed 4192 autologous, preoperative blood donations between 2007 and 2015 at Okayama University Hospital. Eighty-seven (2.08%) of the patients experienced VVRs. VVRs occurred approximately three times as often in patients 0-17 years old (16/320, 5.0%) than in patients 18 years and older (71/3872, 1.8%). In particular, VVRs occurred more frequently in those 10-13 years old, and decreased with older age (P = 0.006). In a univariate analysis, younger age, lower body mass index, lower systolic blood pressure, lower body weight, lower total blood volume, female gender, first-time collection, and higher heart rate were associated with a higher incidence of VVRs. In a multivariate analysis, lower systolic blood pressure (P < 0.001), higher heart rate (P = 0.007), and first-time collection (P = 0.015), remained independent predictors of VVRs. These results emphasize the need for careful attention during blood collection.

DOI： 10.1007/s12185-017-2204-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Azacitidine (Aza) and donor lymphocyte infusion (DLI) therapy has recently been reported as an effective salvage therapy for relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Despite the high response rate and relatively long period of remission, most patients relapse again. The immunologic mechanism of the response and limited efficacy remain unknown. CASE REPORT: Aza + DLI therapy was performed for a patient with therapy-related MDS (t-MDS), who had relapsed after allogeneic peripheral blood stem cell transplantation. We observed a powerful graft-versus-leukemia (GVL) effect accompanied by an evident Wilms tumor antigen 1 (WT1)-specific CD8 T-cell response. Remission continued for 15 months, but finally the patient relapsed. The kinetics of the WT1-specific CD8 T cells were inversely associated with WT1 messenger RNA (mRNA), suggesting a WT1-driven GVL effect. DISCUSSION: A difference of T-cell phenotype between the whole T cells and the WT1-specific CD8 T cells was observed. It is of note that the memory phenotype of the WT1-specific T cell was limited and decreased early. The immunoescape mechanism was partly supported by loss of the memory phenotype due to failure of expansion and differentiation. CONCLUSION: Our data suggested that a WT1-specific T-cell response at least partly contributes to the GVL effect induced by Aza + DLI. A strategy for maximizing and maintaining the memory phenotype of the CTL may be required for durable remission.

DOI： 10.1016/j.jcyt.2016.12.007

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pulmonary complications in patients with hematological malignancies are often caused by infection but are sometimes associated with an underlying disease such as organizing pneumonia (OP). Here, we report a case of life-threatening steroid-resistant OP associated with myelodysplastic syndrome (MDS) and successfully performed allogeneic hematopoietic cell transplantation (HSCT). A 33-year-old female with refractory anemia with excess blasts-1 that had progressed from refractory anemia with ringed sideroblasts and concomitant Sweet's syndrome was admitted. Multiple pulmonary infiltrates were revealed on a chest computed tomography scan, which progressively worsened even after chemotherapy and corticosteroid therapy. No evidence of infection was observed in bronchoalveolar lavage fluid. A histological examination of a transbronchial lung biopsy specimen showed lymphocyte invasion with fibrosis, indicating that the pulmonary infiltrates were OP associated with MDS. Before transplantation, she suffered from respiratory failure and required oxygen supplementation. She developed idiopathic pneumonitis syndrome on day 61 that responded well to corticosteroid therapy, and the OP pulmonary infiltrates improved gradually after HSCT, She was discharged on day 104 and is well without recurrence of OP or MDS 2 years after HSCT.

DOI： 10.1186/2193-1801-3-3

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記述言語：日本語   出版者・発行元：The Japan Society of Transfusion Medicine and Cell Therapy  

岡山大学病院では，1998年に本邦初の生体肺移植が行われて以降2009年3月までに52例の生体肺移植と15例の脳死肺移植の計67例の肺移植が行われた．特に脳死肺移植では，限られた時間内に血液製剤を準備する必要があり，これまでの肺移植における血液製剤使用量から術前準備量について検討を行った．<br> 赤血球製剤の平均準備量は57.4U，平均使用量は33.5U，C/T比（交差試験単位数/輸血血液単位数）1.73であった．FFPの平均準備量は43.3U，平均使用量は19.4Uで，PCの平均準備量は27.7U，平均使用量は19.8Uであった．両肺移植の平均血液使用量が，赤血球製剤37.9U，FFP 21.8U，PC 22.8Uであったのに対し，片肺移植の平均血液使用量は，赤血球製剤11.5U，FFP 7.0U，PC 4.5Uで有意差が認められた．また，赤血球製剤を100U以上準備した症例が5例あり，全て両肺移植で，うち3例が脳死移植であった．<br> 肺移植では，症例毎の癒着の程度の相違等で一律の血液準備量の決定は難しいと考えられるが，今回の肺移植における血液製剤使用量の検討から血液の必要量については，両肺移植か片肺移植であるか，恐らく，人工心肺の使用の有無が大きな因子であることが示唆された．また，緊急の脳死肺移植や大量の血液製剤準備に対応できるよう，日常的に異型適合血の選択を含めた緊急時の対応と診療科等との連携を深めることが必要であると考えられた．<br>

DOI： 10.3925/jjtc.56.606

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その他リンク： http://search.jamas.or.jp/link/ui/2011048595

記述言語：英語   掲載種別：研究論文（学術雑誌）  

In this report, we examined plasma stromal cell-derived factor-1 levels in normal healthy donors for allogeneic peripheral blood stem cell transplantation (PBSCT) and in patients for autologous PBSCT using an enzyme-linked immunosorbent assay. The average level of plasma stromal cell-derived factor-1 was 2197pg/ml before granulocyte colony-stimulating factor administration and 1899 pg/ml on day 4, demonstrating a significant decrease in the peripheral blood of healthy donors (P = 0.0003). In patients for autologous PBSCT, a significant decrease of plasma stromal cell-derived factor-1 in the peripheral blood was also observed (P = 0.0464). However, the physiologic gradient of stromal cell-derived factor-1 between peripheral blood and bone marrow was never inverted in normal healthy donors or in autologous PBSCT patients. Our results suggest that stromal cell-derived factor-1 may not be involved in the granulocyte colony-stimulating factor-induced release of CD34+ cells to the peripheral blood. Further studies of a possible additive effect of granulocyte colony-stimulating factor and stromal cell-derived factor-1 are warranted.

DOI： 10.1038/sj.bmt.1703901

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担当区分：筆頭著者   記述言語：英語  

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記述言語：英語   出版者・発行元：(一社)日本血液学会  

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記述言語：英語   出版者・発行元：(一社)日本血液学会  

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記述言語：英語   出版者・発行元：(一社)日本血液学会  

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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  

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記述言語：日本語   出版者・発行元：(一社)日本リンパ網内系学会  

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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  

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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  

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記述言語：日本語   出版者・発行元：(一社)日本血液学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床検査医学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床検査医学会  

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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  

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記述言語：英語   出版者・発行元：WILEY  

DOI： 10.1111/trf.15872

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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  

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記述言語：日本語   出版者・発行元：(一社)日本臨床検査医学会  

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記述言語：日本語   出版者・発行元：(一社)日本リンパ網内系学会  

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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  

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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  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC HEMATOLOGY  

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DOI： 10.1182/blood-2018-99-112365

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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  

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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  

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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  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER SCIENCE INC  

DOI： 10.1016/j.bbmt.2017.12.382

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC HEMATOLOGY  

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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  

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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  

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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  

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記述言語：日本語  

DOI： 10.3925/jjtc.63.3

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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  

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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  

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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  

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記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

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記述言語：日本語   出版者・発行元：一般社団法人 日本輸血・細胞治療学会  

Jr&lt;sup&gt;a&lt;/sup&gt;抗原は，国際輸血学会（ISBT）No.901.005に属する高頻度抗原であり，Jr&lt;sup&gt;a&lt;/sup&gt;陰性の頻度は日本人で約0.065％と推定されている．今回我々は，非血縁者間同種骨髄移植実施後15日目に，ドナー由来と考えられる抗Jr&lt;sup&gt;a&lt;/sup&gt;を検出した慢性骨髄性白血病・急性転化の症例を経験したので報告する．患者は50歳代男性，A型，RhD（＋），Jr（a＋），不規則抗体陰性であった．ドナーは40歳代女性，A型，RhD（＋），Jr（a－）で抗Jr&lt;sup&gt;a&lt;/sup&gt;を保有していた．骨髄移植後12日目に直接抗グロブリン試験が，15日目に不規則抗体検査が陽転化し，抗Jr&lt;sup&gt;a&lt;/sup&gt;が検出された．不規則抗体陰性であった移植後9・11・14日目は，クロスマッチ適合のランダム赤血球濃厚液をそれぞれ2単位輸血し，抗Jr&lt;sup&gt;a&lt;/sup&gt;が検出された移植後15日目から36日目まで，Jr（a－）のRCCを計16単位輸血したが，その間，臨床的に溶血性輸血副作用を疑う所見は認めなかった．21日目に好中球の生着が確認され，39日目の輸血検査にて直接抗グロブリン試験が陰性化，さらに53日目には不規則抗体陰性となった．抗Jr&lt;sup&gt;a&lt;/sup&gt;の臨床的意義には議論があるが，症例を蓄積し，ドナーが不規則抗体を保有する場合において，選択すべき移植後の血液製剤に関するガイドラインが作成されることが望ましいと考えられた．

DOI： 10.3925/jjtc.60.483

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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  

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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  

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記述言語：日本語   出版者・発行元：(一社)日本リンパ網内系学会  

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開催年月日： 2022年5月12日 - 2022年5月14日

記述言語：日本語   会議種別：口頭発表（一般）  

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開催年月日： 2021年6月4日 - 2021年6月6日

記述言語：日本語   会議種別：口頭発表（一般）  

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開催年月日： 2021年3月5日 - 2021年3月7日

記述言語：日本語   会議種別：口頭発表（一般）  

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開催年月日： 2020年3月

記述言語：日本語   会議種別：口頭発表（一般）  

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開催年月日： 2019年11月21日 - 2019年11月24日

記述言語：日本語   会議種別：口頭発表（一般）  

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開催年月日： 2019年5月23日 - 2019年5月25日

記述言語：日本語   会議種別：口頭発表（一般）  

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記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

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記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

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