<p>Adult T-cell leukemia/lymphoma (ATL) has a poor prognosis, with mogamulizumab effectively controlling the disease but increasing graft-versus-host disease (GVHD) risk during transplantation if residual levels persist. We herein report a 61-year-old patient with acute-type ATL who underwent mogamulizumab concentration-guided transplantation to avoid severe GVHD despite HLA-mismatched donor transplantation. Post-transplant central nervous system (CNS) relapse was successfully managed with intrathecal chemotherapy alone, achieving long-term remission. Two years post-transplantation, the patient remains in complete remission without relapse or chronic GVHD. This case highlights the importance of assessing mogamulizumab levels for optimal transplantation timing and intrathecal chemotherapy as a strategy for CNS-limited ATL relapse. </p>

DOI： 10.2169/internalmedicine.5598-25

PubMed

CiNii Research

<p>A 54-year-old woman presented with a chief concern of right back pain that had persisted for 3 weeks. Laboratory tests revealed pancytopenia, liver dysfunction, and coagulation abnormalities. She had hepatomegaly and splenomegaly but no lymphadenopathy. No abnormal cells were detected in the bone marrow or on a liver biopsy. Epstein-Barr virus (EBV) DNA levels in the peripheral blood were high at 6.44 log IU/m<i>l</i>, and clonality of EBV-infected cells was confirmed by Southern blot hybridization with a probe targeting the EBV terminal repeat. EBV-infected NK cells were detected using the magnetic bead method. This led to a diagnosis of EBV-associated lymphoproliferative disease (EBV-LPD). As pancytopenia and coagulation abnormalities induced by the development of hemophagocytic syndrome continued to worsen after steroid therapy, we performed intensive chemotherapy followed by umbilical cord blood transplantation. After transplantation, EBV-DNA levels in the peripheral blood were undetectable, with complete donor chimerism. In the present case, the rapid disease progression with an extremely high EBV-DNA level indicated a poor prognosis. Intensive chemotherapy followed by upfront allogeneic hematopoietic cell transplantation may be necessary in patients with rapidly progressing EBV-LPD.</p>

DOI： 10.11406/rinketsu.66.1293

PubMed

CiNii Research

重症急性下部消化管移植片対宿主病(GVHD)に対するメチルプレドニゾロン(mPSL)初期投与量1mg/kg/日と2mg/kg/日の治療成績の差を調べた。2013年7月～2020年6月に同種造血幹細胞移植を行い、重症急性下部消化管GVHDを発症し、初期治療としてmPSL 1mg/kg/日(1mg群)または2mg/kg/日(2mg群)の全身投与が行われた18歳以上の患者57例を後ろ向きに評価した。このうち1mg群は31例(年齢中央値43歳、男性61.3%)、2mg群は26例(年齢中央値51歳、男性61.5%)であった。治療開始14日目の完全寛解率は1mg群が48.4%、2mg群が53.8%で同等であった。治療後100日目の累積ステロイド量(プレドニゾロン換算)は1mg群が59.6mg/kg、2mg群が88.1mg/kgで2mg群が有意に多かった。累積二次治療移行率、菌血症、真菌感染症、サイトメガロウイルス(CMV)抗原血症、CMV感染症発生率、再発率、非再発死亡率、生存率は両群間で同等であったが、非CMVウイルス感染症は1mg群で少なく、その中でもアデノウイルス感染症が有意に少なかった。

症例は56歳女性で、フィラデルフィア染色体陰性のB細胞急性リンパ芽球性白血病(B-ALL)と診断された。8コースのhyper-CVAD/MA療法を施行した結果、最初の完全寛解(CR)を達成した。最後の化学療法から10ヵ月後、骨髄にB-ALLを再発した。ブリナツモマブを2コース投与し、2回目のCRを達成した。初回診断から19ヵ月後に、HLA適合の兄からの同種造血幹細胞移植を行った。その13ヵ月後、骨髄病変を伴わないB-ALLの孤立性髄外再発が発現した。ブリナツモマブ2サイクルにより3回目のCRを達成した。その後、ブリナツモマブとドナーリンパ球輸注をそれぞれ4サイクル追加投与した。移植片対宿主病を発症せず、2回目の同種造血幹細胞移植を受けることなく、2年間の無治療寛解が維持された。

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

OBJECTIVES: Impaired B-cell reconstitution after allogeneic hematopoietic cell transplantation (allo-HCT) contributes to the pathogenesis of chronic graft-versus-host disease (cGVHD). Therefore, methods to consistently achieve effective B cell lymphogenesis are required. We assessed the long-term effects of posttransplantation cyclophosphamide (PTCy) use on immune reconstitution in clinical settings, an emerging strategy to suppress allogeneic immunological inflammation early after allo-HCT and prevent subsequent GVHD. METHODS: We comprehensively analyzed peripheral immune cell subsets and measured serum immunoglobulin G (IgG) or cytokine levels in 39 patients who survived for >1 year after allo-HCT. RESULTS: The absolute counts of B1 and IgM memory B cells were significantly lower in patients with severe cGVHD than in those without. The absolute count and percentage (among total CD19+ B cells) of switched memory B cells and serum IgG levels were significantly higher in patients transplanted with PTCy than in those transplanted with conventional GVHD prophylaxis. Interestingly, increased percentages of switched memory B cells and serum IgG levels were observed only in patients transplanted with PTCy and not in those transplanted with umbilical cord blood. CONCLUSIONS: PTCy administration can mediate favorable memory B-cell reconstitution long after allo-HCT and may therefore suppress cGVHD.

DOI： 10.1111/ejh.14280

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

Acute lymphoblastic leukemia (ALL) relapsed after allogeneic hematopoietic cell transplantation (allo-HCT) has a catastrophic prognosis. Blinatumomab, a CD3/CD19-directed bispecific T cell engager, is reportedly effective for advanced B-cell ALL (B-ALL), even after allo-HCT. However, the efficacy of blinatumomab in extramedullary relapse (EMR) is controversial. Donor lymphocyte infusion (DLI) is another immunological treatment worth considering for ALL relapsed after allo-HCT. We report the case of a 56-year-old woman with B-ALL. Allo-HCT was performed during the second complete remission (CR). Thirteen months after allo-HCT, isolated EMR (iEMR) of B-ALL developed without bone marrow lesions. A third CR was achieved with 2 cycles of blinatumomab. An additional four cycles each of blinatumomab and DLI were then administered. The patient did not develop graft-versus-host disease and has confirmed 2-year treatment-free remission without a second allo-HCT. Therefore, blinatumomab was considered an effective salvage therapy for iEMR of B-ALL after allo-HCT, because iEMR could have a lower tumor burden than that seen in systemic relapse, and low tumor burden was a prognostic factor for response to blinatumomab. Furthermore, immunological consolidation therapies could only provoke graft-versus-leukemia effects if the imbalanced effector/target ratio was restored and the tumor burden was lowered through immunosurveillance.

DOI： 10.1007/s12185-024-03839-4

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.trim.2024.102107

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Blastobotrys is a genus of rare yeast that is increasingly recognized as a cause of fungal infections in humans. However, there have been no reports of fungal infections in humans caused by Blastobotrys mokoenaii. We describe a case of invasive fungal infection (IFI) caused by B. mokoenaii in an immunocompromised patient with acute myeloid leukemia (AML). A 46-year-old man with relapsed/refractory AML underwent a second allogeneic peripheral blood hematopoietic stem cell transplantation (allo-PBSCT) during remission. The patient had prolonged neutropenia and received systemic steroid therapy for graft-versus-host disease before the second allo-PBSCT. Uncommon yeast was isolated from the blood cultures obtained on day 4. We initially suspected that the uncommon yeast was Trichosporon spp. based on its morphology. However, unlike Trichosporon spp., in vitro antifungal susceptibility tests showed that this yeast isolate was resistant to micafungin, caspofungin, voriconazole, itraconazole, and fluconazole. We performed DNA sequencing and identified it as B. mokoenaii. B. mokoenaii was persistently isolated from blood cultures taken during combination therapy with liposomal amphotericin B and voriconazole. The patient died of multiorgan failure on day 24. B. mokoenaii can cause severe IFI in immunocompromised patients; however, it may not be correctly identified by routine clinical microbiology testing in a hospital laboratory and DNA sequencing is useful for diagnosis.

DOI： 10.1016/j.jiac.2023.12.002

PubMed

症例は再発性で治療抵抗性の急性骨髄性白血病(AML)の46歳男性で、寛解期に2回目の同種末梢血造血幹細胞移植(allo-PBSCT)を受けた。allo-PBSCT前に好中球減少が遷延し、移植片対宿主病に対する全身ステロイド療法が施行された。day4の血液培養から形態学的にトリコスポロン属に似た酵母が分離された。しかし、in vitro感受性試験で、分離菌はトリコスポロン属とは異なり、ミカファンギン、カスポファンギン、ボリコナゾール、イトラコナゾールおよびフルコナゾールに耐性であった。DNAシーケンシングにより菌はBlastobotrys mokoenaiiと判明した。アムホテリシンBリポソーム製剤とボリコナゾールの併用療法中の血液培養でB.mokoenaiiが継続して分離された。患者は多臓器不全によりday24に死亡した。

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Myelodysplastic syndrome (MDS) is well known to be complicated by systemic inflammatory autoimmune disease (SIADs). However, it remains unclear how the prognosis after allogenic hematopoietic stem cell transplantation (allo-HSCT) in patients with MDS is impacted by SIADs that occur before allo-HSCT. Therefore, we hypothesized that SIADs before allo-HSCT may be a risk factor for negative outcomes after allo-HSCT in patients with MDS. We conducted a single-center, retrospective, observational study of sixty-nine patients with MDS or chronic myelomonocytic leukemia who underwent their first allo-HCT. Fourteen of the patients had SIADs before allo-HSCT. In multivariate analysis, the presence of SIADs before allo-HSCT was an independent risk factor for overall survival (HR, 3.36, 95% confidence interval: 1.34-8.42, p = 0.009). Endothelial dysfunction syndrome was identified in five of 14 patients with SIADs who required immunosuppressive therapy or intensive chemotherapy, and notably, all patients with uncontrollable SIADs at allo-HSCT developed serious endothelial dysfunction syndrome and died in the early phase after allo-HSCT. The development of SIADs in the context of MDS is thought to reflect the degree of dysfunction of hematopoietic cells in MDS and suggests a higher risk of disease progression. In addition, MDS patients with SIADs before allo-HSCT are considered to be at higher risk of endothelial dysfunction syndrome because of preexisting vascular endothelial dysfunction due to SIADs. In conclusion, SIADs before allo-HSCT constitute an independent risk factor for death in MDS patients undergoing allo-HSCT.

DOI： 10.1007/s00277-024-05772-2

PubMed

International / domestic magazine：International journal  

DOI： 10.1038/s41408-024-01064-0

PubMed

末梢血幹細胞採取後の有害事象フォローアップのために電話を用いてドナーの健康調査を行う場合がある。頻繁な連絡を要する際に電話は不向きであり,新たな調査手法として,ドナーが医療者に電子的患者報告型アウトカム(ePRO)を報告するためのWebアプリケーションを開発した。血縁あるいは非血縁の健常ドナーを対象として,電話と比べたアプリの有用性を評価する前向き観察研究を行った。アプリ群ではドナーが1日1回症状をePROとして入力し,電話群では定められた日に医療者が架電して症状を聞き取った。観察期間は,入院中を除く,GCSF製剤の初回投与時点から採取後のフォローアップ外来初回受診時点までの期間とした。各群8人ずつ評価し,年齢中央値は32歳(19～58歳),女性が9例(56.3%)であった。血縁者ドナーは電話群の8例全員,アプリ群の4例であった。医療者が健康情報を得た日数はアプリ群で有意に多く(観察期間に占める割合の平均値;27.0% vs 53.5%,p<0.05),医療者が健康調査に要した総時間や1回の健康調査に要した時間の平均値はアプリ群で有意に小さかった。ドナーの負担感や幹細胞提供の満足感に差はなかった。アプリは電話と比べて,ドナーの負担を増やさず医療者の負担を軽減し,より多くの健康情報を得ることができると示唆された。(著者抄録)

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT), and stratification of the high-risk group before transplantation is significant. Serum autotaxin (ATX) levels have been reported to increase in patients with liver fibrosis caused by metabolic inhibition from liver sinusoidal endothelial cells. Considering that the pathophysiology of VOD/SOS begins with liver sinusoidal endothelial cell injury, an increase in serum ATX levels may precede the onset of VOD/SOS. A retrospective study with 252 patients, including 12 patients with VOD/SOS, who had received allo-HCT was performed. The cumulative incidence of VOD/SOS was higher in the group with serum ATX levels before conditioning (baseline ATX) above the upper reference limit (high ATX group, p < 0.001), and 1-year cumulative incidences were 22.7% (95% confidence interval [95%CI], 3.1-42.4%) and 3.5% (95%CI, 1.1-5.8%), respectively. In the multivariate analysis, elevated baseline ATX was identified as an independent risk factor for VOD/SOS development and showed an additive effect on the predictive ability of known risk factors. Furthermore, the incidence of VOD/SOS-related mortality was greater in the high ATX group (16.7% vs. 1.3%; p = 0.005). Serum ATX is a potential predictive marker for the development of VOD/SOS.

DOI： 10.1007/s00277-024-05685-0

PubMed

International / domestic magazine：International journal  

DOI： 10.1038/s41409-024-02231-4

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

Hepatomegaly is an extramedullary disease (EMD) manifestation of hematological malignancy. Although EMD before allogeneic hematopoietic stem cell transplantation (allo-HCT) is a risk factor for relapse in patients not in complete remission (NonCR) patients, the significance of hepatomegaly to allo-HCT is unclear. We conducted a single-center retrospective observational study of 140 patients with acute leukemia and myelodysplastic syndrome who underwent allo-HCT at our institution from 2014 to 2019. Hepatomegaly was assessed by ultrasonography using the liver index (LI). In the univariable analysis, the LI/height ratio was significantly associated with relapse (hazard ratio [HR] per standard deviation [sd]: 1.51, 95% confidence interval [CI] 1.18-1.93, p = 0.001, sd = 13.8) in NonCR patients (n = 62), but showed no significant association in CR patients (n = 78) (HR per sd: 0.95, 95% CI 0.64-1.39, p = 0.780, sd = 8.7). In multivariable analysis, the LI/height ratio was significantly associated with relapse (HR per sd: 1.34, 95% CI 1.02-1.78, p = 0.037) after adjusting for the refined disease risk index and conditioning intensity. Interaction analysis showed a noteworthy but not statistically significant association between the LI/height ratio and CR status (p = 0.110). In conclusion, our findings suggest that the LI may be a risk factor for relapse in NonCR patients after allo-HCT.

DOI： 10.1007/s12185-023-03707-7

PubMed

急性白血病や骨髄異形成症候群で非完全寛解期にある患者において同種造血幹細胞移植(allo-HCT)を受ける前の肝脾腫が移植後の転帰、特に再発に及ぼす影響を検討した。2014年から2019年までに当施設でallo-HCTを受けた急性白血病と骨髄異形成症候群の患者140例(年齢16～68歳)を対象に単施設の後ろ向き観察研究を行った。肝腫大は肝指数(LI)を用いた超音波検査により評価した。単変量解析において、非完全寛解患者(n=62)ではLI/身長比は再発と有意に関連していたが、完全寛解患者(n=78)では有意な関連を示さなかった。多変量解析では、疾患リスク指数と移植前処置の強度で調整した後、LI/身長比は再発と有意に関連していた。交互作用解析では、LI/身長比と寛解状態との間に関連が認められたが、有意ではなかった。

Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: No comparative data have shown significant survival differences between HLA-mismatched unrelated donor (MMUD) transplantation and cord blood (CB) transplantation, each with reduced-intensity/reduced-toxicity conditioning (RIC/RTC). However, advances in graft-versus-host disease (GVHD) prophylaxis might help update current strategies. METHODS: We retrospectively compared the outcomes of first allogeneic hematopoietic cell transplantation from MMUDs (n = 15) or single unrelated CB (n = 35) after RIC/RTC. RESULTS: The median age was 60 years. The MMUD group had a numerically lower 100-day incidence of grade III-IV acute GVHD (7% vs. 29%, P = 0.079) and non-relapse mortality (0% vs. 40%, P = 0.12). Eight MMUD recipients received anti-thymocyte globulin, bortezomib, or posttransplant cyclophosphamide for GVHD prophylaxis. They did not develop grade III-IV acute GVHD. The MMUD group had significantly better 5-year overall survival than the CB group (62% vs. 31%, P = 0.021), although relapse rates were similar. A multivariable analysis and sensitivity analysis also showed trends toward higher overall survival in the MMUD group. CONCLUSION: MMUD with better GVHD prophylaxis might be preferred over CB in patients with older age and comorbidities.

DOI： 10.1016/j.trim.2024.101988

PubMed

Publishing type：Research paper (scientific journal)  

<p>Health surveys to assess adverse events after peripheral blood stem cell harvest (PBSCH) have conventionally been conducted by phone, but phone calls are suboptimal for conducting frequent surveys. We developed a web-based application (donor app) that enables donors to inform healthcare professionals (HCPs) of their health status as an electronic patient-reported outcome (ePRO). In this prospective observational study, we compared the usefulness of this donor app to phone calls for conducting health surveys. App users reported ePRO daily, and patients called by HCPs reported their health status at least once a week when called. The observation period was from the first administration of granulocyte colony-stimulating factor to the first follow-up visit after PBSCH, excluding the hospitalization period. Each group consisted of eight donors with a median age of 32 years (range: 19-58). Nine (56.3%) were female. There were eight related donors in the phone call group and four in the donor app group. During the observation period, HCPs obtained health status reports more frequently from app users than from phone call recipients (mean proportion of days with reports made during the observation period, 27.0% vs 53.5%; <i>p</i><0.05). Average time spent by the HCPs for one follow-up and total follow-ups were both significantly shorter when the donor app was used. There were no differences in donor burden or satisfaction with donation. Our study suggests that use of a donor app could provide more detailed health survey data without increasing the burden on donors and HCPs.</p>

DOI： 10.11406/rinketsu.65.321

PubMed

CiNii Research

Other URL： https://ndlsearch.ndl.go.jp/books/R000000004-I033556716

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

INTRODUCTION: The graft-versus-leukemia effect of HLA-B leader dimorphism, i.e., methionine (M) or threonine (T) at position -21 of the leader sequence, has been observed in HLA-haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide (PTCy-haplo). However, the biological mechanism has been unclear, and the contributions of HLA-B leader genotype to risk reduction of relapse might be dependent on posttransplant cyclophosphamide (PTCy) doses. METHODS: To investigate whether the effect of HLA-B leader dimorphism was modified by the PTCy dose, we retrospectively analyzed 99 patients who received PTCy-haplo. RESULTS: In the low-dose PTCy group, the patient M+ HLA-B leader genotype did not significantly affect the cumulative incidence of relapse (CIR) but negatively impacted the overall survival (OS) compared to the M- genotype. In contrast, in the high-dose PTCy group, patients with the M+ genotype had a decreased CIR, but no significant difference in the OS was observed between patients with the M+ and M- genotypes. Regardless of PTCy doses, the patient M+ genotype had detrimental effects on nonrelapse mortality. CONCLUSION: Our findings suggest that the effect of the patient HLA-B leader genotype is modified by the PTCy dose, providing immunological insight into the PTCy dosage and supporting further studies to investigate the underlying mechanisms.

DOI： 10.1159/000538078

PubMed

Presentation type：Oral presentation (general)  

Presentation type：Poster presentation  

Presentation type：Symposium, workshop panel (nominated)  

Presentation type：Oral presentation (general)  

Presentation type：Oral presentation (general)  

Presentation type：Oral presentation (general)