DOI： 10.1182/blood-2023-179252

Web of Science

DOI： 10.1182/blood-2023-181258

Web of Science

DOI： 10.1182/blood-2023-174235

Web of Science

Language：Japanese   Publisher：The Japanese Society of Hematology  

<p>A 27-year-old woman with pancytopenia was admitted to our hospital. Bone marrow aspiration revealed 52.2% myeloperoxidase-positive myeloblasts, leading to a diagnosis of acute myeloid leukemia. While a screening test for chimeric genes related to leukemia initially yielded negative results, including for the <i>CBFB::MYH11</i> fusion gene, G-banded karyotyping uncovered the presence of inv (16)(p13.1q22). Further investigation by fluorescence <i>in situ</i> hybridization (FISH) confirmed the split signals for <i>CBFB</i>. A second screening test for leukemia-related chimeric genes with different PCR primers revealed the elusive <i>CBFB::MYH11</i> fusion gene. Subsequently, the type I <i>CBFB::MYH11</i> fusion gene was identified through exhaustive exploration using RNA sequencing for fusion gene discovery. This exceptional case highlights the existence of a distinctive subtype of <i>CBFB::MYH11</i> that may yield false-negative results in conventional chimeric fusion screening, thus emphasizing the indispensable utility of PCR primer modification, FISH, and RNA sequencing in the investigative process.</p>

DOI： 10.11406/rinketsu.64.1503

PubMed

CiNii Research

Language：English   Publisher：International Journal of Hematology  

Relapsed and refractory aggressive lymphoma have a poor prognosis. High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is effective in chemosensitive patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is among the few options for non-chemosensitive patients. 18Fluoro-2-deoxy-d-glucose positron emission tomography–computed tomography (18FDG-PET/CT) is the standard tool for evaluating response to chemotherapy and residual tumor volume. However, accurate assessment of residual tumor volume is not currently being achieved in clinical practice, and its value in prognostic and therapeutic stratification remains unclear. To answer this question, we investigated the efficacy of quantitative indicators, including total metabolic tumor volume (TMTV), in predicting prognosis after auto-HSCT and allo-HSCT. We retrospectively analyzed 39 patients who received auto-HSCT and 28 who received allo-HSCT. In the auto-HSCT group, patients with a higher TMTV had a poor prognosis due to greater risk of relapse. In the allo-HSCT group, patients with a higher TMTV had a lower progression-free survival rate and a significantly higher relapse rate. Neither Deauville score nor other clinical parameters were associated with prognosis in either group. Therefore, pre-transplant TMTV on PET is effective for prognostic prediction and therapeutic decision-making for relapsed or refractory aggressive lymphoma.

DOI： 10.1007/s12185-022-03394-w

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Scopus

PubMed

Language：English   Publisher：(一社)日本血液学会  

造血幹細胞移植(HSCT)施行前の再発・難治性(R/R)悪性リンパ腫患者において、18フルオロ-2-デオキシ-グルコース陽電子放出断層撮影法(18FDG-PET/CT)による総代謝腫瘍体積(TMTV)の評価が予後に与える影響を後方視的に検討した。2007年1月～2015年12月に当院においてHSCT施行前の3ヵ月以内にPET/CT検査を実施したR/R悪性リンパ腫患者67例を対象とした。39例(年齢20～65歳)が自家HSCTを受け、28例(年齢22～69歳)が同種HSCTを受けた。その結果、自家HSCT群のTMTVが大きい患者は、再発リスクが高く、予後が不良であった。同種HSCT群では、TMTVが大きい患者は無増悪生存率が低く、再発率も有意に高かった。Deauvilleスコアやその他の臨床パラメータはいずれも両群の予後と関連しなかった。以上より、HSCT前のPET/CTで評価したTMTVはR/Rアグレッシブリンパ腫の予後予測や治療方針の決定に有効であった。

Language：English   Publisher：American Journal of Ophthalmology Case Reports  

Purpose: This article presents a case of panuveitis that occurred after unrelated allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a patient with lymphoma-type human T-cell leukemia virus type-1 (HTLV-1)-associated adult T-cell leukemia (ATL). Observations: A 45-year-old man developed unilateral panuveitis 18 months after undergoing allo-HSCT. He underwent vitrectomy, and depositions of grey-white granules localized on the retinal artery were observed in the eye. Cytological examination of the vitreous aspirates showed that the atypical lymphoid cells stained positive for CD3 and CD8, but negative for CD4, B-cell markers, and cytomegalovirus antigen. Interphase fluorescence in situ hybridization using X‐ and Y‐chromosome probes revealed complete donor chimerism in CD8+ T cells in the vitreous aspirates. Conclusions and importance: Donor-derived CD8+ T lymphocytes can induce panuveitis like HTLV-1-assiciated uveitis after allo-HSCT in patients with ATL. Pathological diagnosis of vitreous infiltration by vitrectomy is helpful in patients with ATL. Donor-derived CD8+ T lymphocytes-induced panuveitis is recurrent but susceptible to regional corticosteroid treatment.

DOI： 10.1016/j.ajoc.2022.101673

Scopus

PubMed

Language：English   Publisher：International Journal of Hematology  

Prophylactic use of letermovir (LMV) markedly reduces the incidence of early clinically significant cytomegalovirus (csCMV) infection within the first 100 days after allogeneic hematopoietic cell transplantation (allo-HCT), which improves transplant outcomes. However, some patients eventually develop late-csCMV infection (beyond day 100) after completing LMV prophylaxis. To assess the incidence of late-csCMV infection as well as its risk factors and impacts on transplant outcome, a total of 81 allo-HCT recipients who had not developed early csCMV infection during LMV prophylaxis were retrospectively analyzed. Among them, 23 (28.4%) patients developed late-csCMV infection (until day 180) at a median time of 131 days after transplantation and 30 days after LMV discontinuation, respectively. Late-csCMV infection was correlated with apparent delayed immune reconstitution: patients transplanted from HLA-mismatched donors (hazard ratio [HR] = 13.0, p = 0.011) or CMV-IgG-negative donors (HR = 2.39, p = 0.043) had a significantly higher risk. In this study, transplant outcomes did not differ between patients with and without late-csCMV infection. This suggests a need to clarify the efficacy of extended administration of LMV for preventing late-csCMV infection in a larger number of allo-HCT recipients, especially those with “high-risk” donors.

DOI： 10.1007/s12185-022-03348-2

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Scopus

PubMed

Language：English   Publisher：(一社)日本血液学会  

早期に臨床的に意義のあるサイトメガロウイルス(csCMV)感染がなく、レテルモビル(LMV)予防投与を完了した同種造血細胞移植(allo-HCT)レシピエントにおいて、晩期csCMV感染に関連する危険因子を後方視的に検討した。2018年6月から2021年2月までに当院でallo-HCTを受け、csCMV感染予防のための予防的LMVを受けた患者81例(年齢18～70歳)を対象とした。そのうち23例(28.4%)はCMV再活性化を起こし、抗CMV薬による初回介入までの期間の中央値はallo-HCT後で131日(範囲103～166日)、LMV中止後で30日(範囲5～67日)であった。晩期csCMV初回感染の治療期間中央値は21日(範囲12～43日)であった。晩期csCMVは免疫再構成の遅れと明らかに相関していた。HLA不一致ドナー(HR 13.0、p=0.011)またはCMVに対するIgG陰性ドナー(HR 2.39、p=0.043)からのallo-HCTはリスクが有意に高かった。また、晩期CMV感染の有無による移植成績に差は認められなかった。以上より、より多くのallo-HCTレシピエント、特に「高リスク」ドナーから移植を受けるレシピエントにおいて、LMV長期投与の晩期csCMV感染予防に対する効果を明らかにする必要性が示唆された。

Language：English   Publisher：International Journal of Hematology  

Post-transplant cytomegalovirus (CMV) disease can be almost completely avoided by current infection control procedures. However, CMV reactivation occurs in more than half of patients, and some patients can develop clinically resistant CMV infections. Whether resistance is due to the host’s immune status or a viral resistance mutation is challenging to confirm. Therefore, a prospective observational analysis of refractory CMV infection was conducted in 199 consecutive patients who received allogeneic hematopoietic stem cell transplantation at a single institution. Among them, 143 (72%) patients received anti-CMV drugs due to CMV reactivation, and only 17 (8.5%) exhibited refractory CMV infection. These patients had clinically refractory infection. However, viral genome analysis revealed that only one patient exhibited a mutation associated with the anti-CMV drug resistance. Clinical resistance was mainly correlated with host immune factors, and the incidence of resistance caused by gene mutations was low at the early stage after a transplantation.

DOI： 10.1007/s12185-021-03218-3

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Scopus

PubMed

Language：English   Publisher：(一社)日本血液学会  

同種造血幹細胞移植を受けた患者199例を対象に、サイトメガロウイルス(CMV)pp65抗原陽性細胞数や抗CMV薬への反応性を前向きに検討した。早期死亡(好中球生着前の死亡と定義)は8例に認められた。患者36例は、臨床経過中および移植後1年までCMV抗原血症(pp65抗原陽性細胞を染色して検査)を発症しなかった。患者155例は、移植後の中央値34日(範囲9～97)で少なくとも1回、CMV抗原血症の検査結果が陽性であった。追跡期間中の白血球5万個あたりのCMV pp65抗原陽性細胞の最大数の中央値は5個(範囲1～332)であった。患者143例(72%)はCMV再活性化により抗CMV薬を投与され、17例(8.5%)は臨床的に難治性CMV感染症であった。ウイルスゲノム解析の結果、抗CMV薬耐性に関連する変異を有する患者は1例のみであった。以上より、CMV感染症の臨床抵抗性は主に宿主の免疫因子と相関しており、遺伝子変異による抗CMV薬抵抗性の発生は移植後早期には少ないことが示された。

Language：English   Publisher：BBA Advances  

The fusion protein RUNX1-ETO is an oncogenic transcription factor generated by t(8;21) chromosome translocation, which is found in FAB-M2-type acute myeloid leukemia (AML). RUNX1-ETO is known to dysregulate the normal RUNX1 transcriptional network, which should involve essential factors for the onset of AML with t(8;21). In this study, we screened for possible transcriptional targets of RUNX1 by reanalysis of public data in silico, and identified C11orf21 as a novel RUNX1 target gene because its expression was down-regulated in the presence of RUNX1-ETO. The expression level of C11orf21 was low in AML patient samples with t(8;21) and in Kasumi-1 cells, which carry RUNX1-ETO. Knockdown of RUNX1-ETO in Kasumi-1 cells restored C11orf21 expression, whereas overexpression of RUNX1 up-regulated C11orf21 expression. In addition, knockdown of RUNX1 in other human leukemia cells without RUNX-ETO, such as K562, led to a decrease in C11orf21 expression. Of note, the C11orf21 promoter sequence contains a consensus sequence for RUNX1 binding and it was activated by exogenously expressed RUNX1 based on our luciferase reporter assay. This luciferase signal was trans-dominantly suppressed by RUNX1-ETO and site-directed mutagenesis of the consensus site abrogated the reporter activity. This study demonstrated that C11orf21 is a novel transcriptional target of RUNX1 and RUNX1-ETO suppressed C11orf21 transcription in t(8;21) AML. Thus, through this in silico approach, we identified a novel transcriptional target of RUNX1, and the depletion of C11orf21, the target gene, may be associated with the onset of t(8;21) AML.

DOI： 10.1016/j.bbadva.2022.100047

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PubMed

Language：English  

Language：English  

Language：Japanese  

Language：Japanese  

Language：English