Mild Acute Graft-Versus-Host Disease Improves Outcomes After HLA-Haploidentical-Related Donor Transplantation Using Posttransplant Cyclophosphamide and Cord Blood Transplantation

Haploidentical-related donor transplantation using posttransplant cyclophosphamide (PTCy-haplo) and cord blood transplantation (CBT) are valid alternatives for patients with hematological malignancies when HLA-matched donor transplantation (MDT) is unavailable. However, the effects of graft-versus-host disease (GVHD) on outcomes after these transplants have not been fully elucidated. Therefore, we evaluated the effects of acute and chronic GVHD on transplant outcomes after PTCy-haplo transplants and compared them with CBT and MDT. We included a total of 914 adult patients with hematological malignancies in the Kyoto Stem Cell Transplantation Group registry who received PTCy-haplo (N = 120), CBT (N = 402), and MDT (N = 392), and achieved neutrophil engraftment. A multivariate analysis revealed that grade I-II acute GVHD improved of overall survival (OS) after PTCy-haplo [hazard ratio (HR) = 0.39, P = 0.018] and CBT (HR = 0.48, P < 0.001), but not after MDT (HR = 0.80, P = 0.267) compared with patients without acute GVHD. Grade I-II acute GVHD had a trend toward reducing the risk of nonrelapse mortality (NRM) after PTCy-haplo (HR = 0.13, P = 0.060) and this positive effect was significant after CBT (HR = 0.39, P = 0.003). A negative impact of grade III-IV acute GVHD on NRM was observed after CBT and MDT, but not after PTCy-haplo. Limited chronic GVHD had a positive impact on OS after CBT and MDT, but not after PTCy-haplo. In conclusion, mild acute GVHD improved outcomes after PTCy-haplo and CBT, and limited chronic GVHD improved outcomes after CBT and MDT. These data indicated that the effects of GVHD on transplant outcomes depended on transplant platforms

Indication and benefit of upfront hematopoietic stem cell transplantation for T-cell lymphoblastic lymphoma in the era of ALL-type induction therapies

Since the introduction of leukemia-type induction therapies for T-cell lymphoblastic lymphoma (T-LBL), improvements in the long-term outcomes of T-LBL have been reported. However, indications for and the appropriate timing of hematopoietic stem cell transplantation (HSCT) have not yet been established. Therefore, we performed a multicenter retrospective cohort study of patients with T-LBL treated using leukemia-type initial therapies to compare the outcomes after HSCT at different disease stages. We enrolled 21 patients with T-LBL from a total of 11 centers, and all patients received hyper-CVAD as a leukemia-type initial regimen. HSCT was performed during the CR1/PR1 (standard disease) stage in 11 patients, while it was completed at a later or non-remission (advanced disease) stage in 10 patients. Following HSCT, the overall survival rate was significantly greater in standard disease than in advanced-disease patients (79.5% vs. 30.0% at 5 years; hazard ratio (HR) 5.97; p = 0.03), with trend to the lower incidence of relapse in the former group (27.3% vs. 60.0% at 5 years; HR 2.29; p = 0.19). A prognostic difference was not detected between cases treated with allogeneic and autologous HSCTs. Our study suggests that frontline HSCT may be a feasible treatment option for T-LBL, even in the era of leukemia-type initial therapy

癌胎児性糖鎖抗原ラクトテトラオシルセラミド(LcOse[4]Cer)に対する, 2種のヒト型モノクローナル抗体の免疫グロブリン可変領域のシークエンス

本文データは平成22年度国立国会図書館の学位論文(博士)のデジタル化実施により作成された画像ファイルを基にpdf変換したものである京都大学0048新制・課程博士博士(医学)甲第5656号医博第1543号新制||医||581(附属図書館)UT51-94-J88京都大学大学院医学研究科内科系専攻(主査)教授 森 徹, 教授 湊 長博, 教授 大熊 稔学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Risk factors and appropriate therapeutic strategies for thrombotic microangiopathy after allogeneic HSCT

移植後血栓性微小血管障害の発症リスク因子を発見 --KSCTGコホート研究に基づく新たな最適治療戦略--. 京都大学プレスリリース. 2020-07-14.Transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, so far, no large cohort study determined the risk factors and the most effective therapeutic strategies for TA-TMA. Thus, the present study aimed to clarify these clinical aspects based on a large multicenter cohort. This retrospective cohort study was performed by the Kyoto Stem Cell Transplantation Group (KSCTG). A total of 2425 patients were enrolled from 14 institutions. All patients were aged ≥16 years, presented with hematological diseases, and received allo-HSCT after the year 2000. TA-TMA was observed in 121 patients (5.0%) on day 35 (median) and was clearly correlated with inferior overall survival (OS) (hazard ratio [HR], 4.93). Pre- and post-HSCT statistically significant risk factors identified by multivariate analyses included poorer performance status (HR, 1.69), HLA mismatch (HR, 2.17), acute graft-versus-host disease (aGVHD; grades 3-4) (HR, 4.02), Aspergillus infection (HR, 2.29), and veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS; HR, 4.47). The response rate and OS significantly better with the continuation or careful reduction of calcineurin inhibitors (CNI) than the conventional treatment strategy of switching from CNI to corticosteroids (response rate, 64.7% vs 20.0%). In summary, we identified the risk factors and the most appropriate therapeutic strategies for TA-TMA. The described treatment strategy could improve the outcomes of patients with TA-TMA in the future

Establishment of a Predictive Model for GvHD-free, Relapse-free Survival after Allogeneic HSCT using Ensemble Learning

アンサンブル学習を用いた造血幹細胞移植予後予測モデルの開発 --機械学習を用いた新規生存時間解析手法の実装--. 京都大学プレスリリース. 2021-12-28.Graft-versus-host-disease-free, relapse-free survival (GRFS) is a useful composite endpoint that measures survival without relapse or significant morbidity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to develop a novel analytical method that appropriately handles right-censored data and competing risks to understand the risk for GRFS and each component of GRFS. This study was a retrospective data-mining study on a cohort of 2207 adult patients who underwent their first allo-HSCT at the Kyoto Stem Cell Transplantation Group (KSCTG), a multi-institutional joint research group of 17 transplantation centers in Japan. The primary endpoint was GRFS. A stacked ensemble of Cox proportional hazard regression and seven machine learning algorithms was applied to develop a prediction model. The median age of patients was 48 years. For GRFS, the stacked ensemble model achieved better predictive accuracy evaluated by C-index than other top-of-the-art competing risk models (ensemble model: 0.670, Cox-PH: 0.668, Random Survival Forest: 0.660, Dynamic DeepHit: 0.646). The probability of GRFS after 2 years was 30.54% for the high-risk and 40.69% for the low-risk group, respectively (hazard ratio [HR] compared to the low-risk group: 2.127; 95% CI: 1.19-3.80). We developed a novel predictive model for survival analysis that showed superior risk stratification to existing methods using a stacked ensemble of multiple machine learning algorithms

Single Cord Blood Transplantation Versus HLA-Haploidentical-related Donor Transplantation Using Posttransplant Cyclophosphamide in Patients With Hematological Malignancies

[Background.] Unrelated cord blood (UCB) and haploidentical related donor transplantation using posttransplant cyclophosphamide (PTCy-haplo) have become alternative options to treat patients with hematological malignancies without a HLA-matched donor. [Methods.] We conducted a retrospective study using registry data from the Kyoto Stem Cell Transplantation Group for patients with hematological malignancies who received their first allogeneic hematopoietic cell transplantation using a single UCB unit (n = 460) or PTCy-haplo (N = 57) between 2013 and 2019. [Results.] We found that overall survival in the UCB group was comparable to that in the PTCy-haplo group (hazard ratio, 1.00; 95% confidence interval, 0.66-1.52), although neutrophil and platelet engraftment were significantly delayed. Nonrelapse mortality risk and the incidence of graft-versus-host disease in the UCB group were also comparable to those in the PTCy-haplo group. Although the relapse risk was similar between the UCB group and the PTCy-haplo group regardless of the disease risk, acute myeloid leukemia patients benefit from UCB transplant with a significantly lower relapse rate (hazard ratio, 0.38; 95% confidence interval, 0.18-0.76). [Conclusions.] UCB transplant gives outcomes comparable to PTCy-haplo transplant, and both UCB and PTCy-haplo units are suitable as alternative donor sources for patients without an HLA-matched sibling or unrelated donor

Mild Acute Graft-Versus-Host Disease Improves Outcomes After HLA-Haploidentical-Related Donor Transplantation Using Posttransplant Cyclophosphamide and Cord Blood Transplantation

Haploidentical-related donor transplantation using posttransplant cyclophosphamide (PTCy-haplo) and cord blood transplantation (CBT) are valid alternatives for patients with hematological malignancies when HLA-matched donor transplantation (MDT) is unavailable. However, the effects of graft-versus-host disease (GVHD) on outcomes after these transplants have not been fully elucidated. Therefore, we evaluated the effects of acute and chronic GVHD on transplant outcomes after PTCy-haplo transplants and compared them with CBT and MDT. We included a total of 914 adult patients with hematological malignancies in the Kyoto Stem Cell Transplantation Group registry who received PTCy-haplo (N = 120), CBT (N = 402), and MDT (N = 392), and achieved neutrophil engraftment. A multivariate analysis revealed that grade I-II acute GVHD improved of overall survival (OS) after PTCy-haplo [hazard ratio (HR) = 0.39, P = 0.018] and CBT (HR = 0.48, P < 0.001), but not after MDT (HR = 0.80, P = 0.267) compared with patients without acute GVHD. Grade I-II acute GVHD had a trend toward reducing the risk of nonrelapse mortality (NRM) after PTCy-haplo (HR = 0.13, P = 0.060) and this positive effect was significant after CBT (HR = 0.39, P = 0.003). A negative impact of grade III-IV acute GVHD on NRM was observed after CBT and MDT, but not after PTCy-haplo. Limited chronic GVHD had a positive impact on OS after CBT and MDT, but not after PTCy-haplo. In conclusion, mild acute GVHD improved outcomes after PTCy-haplo and CBT, and limited chronic GVHD improved outcomes after CBT and MDT. These data indicated that the effects of GVHD on transplant outcomes depended on transplant platforms