Stem Cell Transplantation In Japan Research Articles

Real-World Outcomes of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation in Japan: Retrospective Analysis of the Transplant Registry Unified Management Program Registry

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important therapeutic option for patients with hematologic malignancies. However, the development of graft-versus-host disease (GVHD) after allo-HSCT remains a challenge. Although systemic steroid therapy is the established first-line therapy for acute GVHD (aGVHD) and chronic GVHD (cGVHD), many patients are unresponsive or resistant to corticosteroid therapy, and the response is insufficient. This study aimed to evaluate the clinical characteristics of patients who developed aGVHD and cGVHD after allo-HSCT. This noninterventional, retrospective study used large national registry data from the Transplant Registry Unified Management Program. The study included 29,690 patients with a hematologic disease who underwent their first allo-HSCT between January 2010 and December 2019. The primary study endpoints were the cumulative incidence of aGVHD and cGVHD. The secondary endpoints were overall survival (OS) and nonrelapse mortality (NRM) of patients with aGVHD and cGVHD and OS and NRM of patients who received second-line therapy for aGVHD. Of 29,690 patients who underwent allo-HSCT, the graft source was related bone marrow (RBM) in 2807, related peripheral blood (RPB) in 6167, unrelated bone marrow in 10,556, unrelated peripheral blood (UPB) in 774, and unrelated cord blood in 9339. The cumulative incidence of grade II-IV aGVHD at 100 days was high after the related and unrelated mismatched transplantation. The response rates for first- and second-line therapy for aGVHD were low in the RBM/RPB-mismatched (59.6%/61.6%) and UPB-mismatched subgroups (45.5%), respectively. The 3-year NRM in patients with aGVHD was high in the RPB and UPB mismatched subgroups (37.9% and 31.2%, respectively). Developing a novel treatment for steroid-refractory aGVHD is necessary to improve transplantation outcomes, particularly for patients undergoing HLA-mismatched allo-HSCT.

Ruxolitinib in steroid-refractory acute graft-vs-host disease: Japanese subgroup analysis of the randomized REACH2 trial

Acute graft-versus-host disease (aGvHD) is a major complication after allogeneic hematopoietic stem cell transplantation in Japan and other countries. Nearly one-third of patients do not respond to standard systemic steroid therapy and no standard second-line treatment has been established in Japan. We report efficacy and safety findings of ruxolitinib versus best available therapy (BAT) from a subgroup analysis of the international, phase 3 REACH2 study in Japanese patients with steroid-refractory aGvHD. The primary endpoint was overall response rate (ORR) at day 28. Overall, 9 patients received ruxolitinib and 21 received BAT. The ORR at day 28 (88.9% vs 52.4%) and durable ORR at day 56 (66.7% vs 28.6%) were higher with ruxolitinib versus BAT. The estimated cumulative incidence of loss of response at 6 months was 12.5% with ruxolitinib and 18.2% with BAT. The median failure-free survival was longer with ruxolitinib versus BAT (2.73 vs 1.25 months). The most common adverse events up to day 28 in the ruxolitinib and BAT groups were anemia (55.6% vs 19.0%) and thrombocytopenia (44.4% vs 4.8%, respectively). Ruxolitinib showed better efficacy outcomes and a consistent safety profile compared with BAT in the Japanese subgroup, and the findings were consistent with overall study results.

Effect of the COVID-19 pandemic on allogeneic stem cell transplantation in Japan.

The coronavirus disease 2019 (COVID-19) pandemic affected healthcare quality and access worldwide and may also have negatively affected the frequency and outcomes of allogeneic hematopoietic stem cell transplantation (HSCT). We evaluated the effect of the pandemic on allogeneic HSCT in Japan. Our subjects were patients who received allogeneic HSCT during January 2018-December 2020 in Japan. We assessed differences in yearly number of allogeneic HSCTs and 1-year outcomes in 2020 versus both 2019 and 2018. The total number of patients who received allogeneic HSCT increased from 3621 patients in 2018 and 3708 patients in 2019 to 3865 patients in 2020. Some following changes in allogeneic HSCT methods were observed: patients were older, fewer patients received bone marrow transplantation, fewer patients received transplants from unrelated donors, fewer patients received transplants from matched donors, more patients received reduced-intensity conditioning, and fewer patients received anti-thymocyte globulin in 2020 compared with previous years. HSCT outcomes were not affected, as 1-year overall survival was not significantly different (65.8% in 2020, vs. 66.5% in 2019 and 66.4% in 2018). Our results suggest that we can maintain transplant care during the pandemic by controlling the spread of COVID-19 and modifying HSCT methods.

Hematopoietic stem cell transplantation in Japan, a report from a Nationwide Survey in 2021

Hematopoietic stem cell transplantation in Japan, a report from a Nationwide Survey in 2021

Hematopoietic stem cell transplantation in Japan, a report from a Nationwide Survey in 2020

Hematopoietic stem cell transplantation in Japan, a report from a Nationwide Survey in 2020

Outcome and Risk Factors for Therapy-Related Myeloid Neoplasms Treated with Allogeneic Stem Cell Transplantation in Japan.

This study aimed to investigate allogeneic hematopoietic cell transplantation (HCT) outcomes and risk factors in adult patients with therapy-related myeloid neoplasm (t-MN) using Japanese registry data. Between 2002 and 2012, a total 12,169 adult patients underwent HCT for acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML). Of these, 565 with t-MN were identified. The median patient age was 54 years (range, 16 to 80 years). Three hundred and ninety-eight patients had AML, 154 had MDS, and 13 had CMML. Lymphoma and breast cancer were the major previous malignancies. Favorable karyotypes were detected in 84 patients, and poor karyotypes were identified in 235. Two-thirds (66%) of the patients were in nonremission at HCT. Overall survival at 3 years in patients with t-MN was 31% (95% confidence interval [CI], 27% to 35%), equivalent to that in those with secondary MN (32%; 95% CI, 30% to 34%), and 44% in the de novo cohort (95% CI, 43% to 45%). The cumulative incidence of relapse and nonrelapse mortality at 3 years was 40% and 33%, respectively. The outcomes of HCT for t-MN in Japan were comparable to those in large-scale studies in Europe and the United States.

Hematopoietic stem cell transplantation in Japan, a report from a Nationwide Survey in 2019

Hematopoietic stem cell transplantation in Japan, a report from a Nationwide Survey in 2019

The clinical and economic burden of cytomegalovirus management post allogeneic hematopoietic stem cell transplantation in Japan – a retrospective database study

Introduction: Reactivation of cytomegalovirus (CMV) infection is a major threat and it causes significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). There remains, however, a paucity of evidence regarding the economic burden of current CMV management in Japan. The aim of this study is to characterize the healthcare resource utilization (HCRU) and cost incurred for CMV management post allo-HSCT, using a Japanese hospital claims database.Methods: Patients who underwent allo-HSCT between April 2010 and March 2018 were identified and followed up for 180 days.Results: In total, 916 patients were included for analysis and categorized into CMV (−) group and CMV (+) group based on the presence of a CMV episode within 100 days post allo-HSCT. A CMV episode was defined as evidence of receiving at least one dose of the following anti-CMV drugs, ganciclovir, foscarnet, or valganciclovir. The mean (± standard deviation [SD]) total length of stay was 93.6 (± 43.7) days in the CMV (+) group, which was significantly longer than 55.9 (±40.6) days in the CMV (−) group, and this trend was more pronounced in patients with multiple CMV episodes. The mean (±SD) total medical cost within 180 days post allo-HSCT was US$122,328 (±56,977) in the CMV (+) group, while the mean total medical cost was US$75,344 (±43,821) in the CMV (−) group. Moreover, transfusion and antimicrobial use was observed as the major medication cost component, which is suggestive of the indirect effect of CMV episodes.Conclusion: This study demonstrated that CMV episodes post allo-HSCT were associated with increased HCRU and cost.

The effectiveness of busulfan-based conditioning regimens for stem cell transplantation against lymphomas in children, adolescents, and young adults in Japan.

Conditioning regimens for stem cell transplantation (SCT) involving total body irradiation (TBI) are generally preferred over busulfan (BU)-based ones for lymphoid malignancies. However, reports of favorable results using BU against lymphomas have recently emerged. This study sought to compare the effectiveness of BU and TBI regimens for SCT against lymphomas. We retrospectively analyzed 893 lymphoma patients who underwent primary SCT in Japan between 1980 and 2015. The median age of all patients was 18 years (range, 0-30 years) with 589 males, 303 females, and 1 patient whose sex was unknown. Overall survival (OS) was not different between those receiving BU and TBI (P=0.672). OS in patients receiving autologous SCT was significantly better with BU over TBI regimens (P=0.038), particularly in children (0-15years) (P=0.024). Conversely, OS in adolescents and young adults (AYAs; 16-30years) receiving allogeneic SCT was significantly worse with BU over TBI regimens (P=0.035). Overall, BU regiments had comparable effectiveness to TBI conditioning regimens, and, although less effective for AYAs with allogeneic SCT, were particularly more effective than TBI regimens for children who received autologous SCT.

National survey on total-body irradiation prior to reduced-intensity stem cell transplantation in Japan: The Japanese Radiation Oncology Study Group.

Reduced-intensity stem cell transplantation (RIST) minimizes the adverse effects of traditional hematopoietic stem cell transplantation, and low-dose total-body irradiation (TBI) is administered over a short period prior to RIST (TBI–RIST). Different institutes adopt different approaches for the administration of TBI–RIST, and since no study had previously investigated this issue, a survey of the TBI schedules in Japan was conducted. In October 2015, the Japanese Radiation Oncology Study Group initiated a national survey of TBI–RIST procedures conducted between 2010 and 2014. Of 186 institutions performing TBI, 90 (48%) responded to the survey, 78 of which performed TBI–RIST. Of 2488 patients who underwent TBI for malignant disease at these institutions, 1412 (56.8%) patients were treated for leukemia, 477 (19.2%) for malignant lymphoma, 453 (18.2) for myelodysplastic syndrome, 44 (1.8%) for multiple myeloma, and 102 (4.1%) for other malignant diseases. Further, 206 (52.0%) of 396 patients (a high proportion of patients) who underwent TBI for benign disease had aplastic anemia. The TBI–RIST equipment and treatment methods were similar to those used for myeloablative regimens. Routinely shielded organs included the lungs (43.6%), eyes (50.0%) and kidneys (10.2%). The ovaries (14.1%), thyroid (6.4%) and testicles (16.7%) were also frequently shielded, possibly reflecting an emphasis on shielding reproductive organs in children. TBI–RIST was performed more frequently than myeloablative conditioning in patients with benign disease. Genital and thyroid shielding were applied more frequently in patients treated with TBI–RIST than in patients treated with myeloablative conditioning. In conclusion, this study indicates the status of TBI–RIST in Japan and can assist future efforts to standardize TBI–RIST treatment methods and to design a future multicenter collaborative research study.

Predictors of parental distress during acute phase of pediatric hematopoietic stem cell transplantation in Japan: A multicenter prospective study.

The purposes of this study were (1) to describe the levels of anxiety and depressive symptoms in parents of children undergoing hematopoietic stem cell transplantation (HSCT) before (Time 1 [T1]) and one month after transplantation (Time 2 [T2]), and (2) to identify the pre-HSCT factors that predict anxiety and depressive symptoms in fathers and mothers one month after transplantation. A prospective quantitative study was conducted at four children's hospitals between June 2015 and September 2016 using self-administered questionnaires and medical records. Parents from 23 families, including 19 fathers and 23 mothers, completed the Hospital Anxiety and Depression Scale (cutoff score: 8) and provided information regarding their stress appraisal, coping strategies, family functioning, demographic characteristics, and children's health-related quality of life. Hierarchical multiple regression analysis was performed to identify the variables that predicted T2 paternal and maternal anxiety and depressive symptoms. Among the parents, 15 fathers (79%) and 11 mothers (48%) reported anxiety symptoms, and 13 fathers (68%) and 9 mothers (39%) reported depressive symptoms above the cutoff level for clinical relevance at T1. Similarly, 11 fathers (58%) and 6 mothers (26%) reported anxiety symptoms, and 10 fathers (53%) and 9 mothers (39%) reported depressive symptoms above the cutoff level at T2. Overall, parents' anxiety and depressive symptoms did not differ significantly between T1 and T2. For fathers, both T1 depressive symptoms and the understanding of their children's medical situation through communication with other parents and consultation with medical staff predicted T2 paternal depressive symptoms. For mothers, T1 maternal anxiety symptoms and marital satisfaction predicted T2 anxiety symptoms. The medical staff should understand that parents of children undergoing HSCT experience considerable psychological distress throughout the treatment process, and therefore, they should adopt unique approaches to reduce such distress.

Hematopoietic stem cell transplantation in Japan, a report from a Nationwide Survey in 2018

Hematopoietic stem cell transplantation in Japan, a report from a Nationwide Survey in 2018

National survey of myeloablative total body irradiation prior to hematopoietic stem cell transplantation in Japan: survey of the Japanese Radiation Oncology Study Group (JROSG).

A myeloablative regimen that includes total-body irradiation (TBI) before hematopoietic stem cell transplantation results in higher patient survival rates than achieved with regimens without TBI. The TBI protocol, however, varies between institutions. In October 2015, the Japanese Radiation Oncology Study Group initiated a national survey of myeloablative TBI (covering 2010–2014). Among the 186 Japanese institutions performing TBI, 90 (48%) responded. The 82 institutions that had performed myeloablative TBI during this period treated 2698 patients with malignant disease [leukemia (2082 patients, 77.2%), malignant lymphoma (378, 14%)] and 37 with non-malignant disease [severe aplastic anemia (20, 54%), inborn errors of metabolism (5, 14%)]. A linear accelerator was used at all institutions. The institutions were divided into 41 large and 41 small institutions based on the median number of patients. The long source–surface distance technique was the method of choice in the 34 institutions (82.9%) and the moving-couch technique in the 7 (17.1%) in the large institutions. The schedules most routinely used by the participating institutions consisted of 12 Gy/6 fractions/3 days (26 institutions, 63.5%) in the large institutions. The dose rate varied from 5 to 26 cGy/min. The lungs and lenses were routinely shielded in 23 large institutions (56.1%), and only the lungs in 9 large institutions (21.9%). At lung-shielding institutions, the most frequent maximum acceptable total dose for the lungs was 8 Gy (19 institutions, 27.5%). Our results reveal considerable differences in the TBI methods used by Japanese institutions and thus the challenges in designing multicenter randomized trials based on TBI.

Hematopoietic stem cell transplantation in Japan, a report from Nationwide Survey 2017

Hematopoietic stem cell transplantation in Japan, a report from Nationwide Survey 2017

Feasibility of High-dose Iodine-131-metaiodobenzylguanidine Therapy for High-risk Neuroblastoma Preceding Myeloablative Chemotherapy and Hematopoietic Stem Cell Transplantation: a Study Protocol.

Objective(s):High-risk neuroblastoma is a childhood cancer with poor prognosis despite modern multimodality therapy. Internal radiotherapy using 131I-metaiodobenzylguanidine (MIBG) is effective for treating the disease even if it is resistant to chemotherapy. The aim of this study is to evaluate the safety and efficacy of 131I-MIBG radiotherapy combined with myeloablative high-dose chemotherapy and hematopoietic stem cell transplantation.Methods:Patients with high-risk neuroblastoma will be enrolled in this study. A total of 8 patients will be registered. Patients will receive 666 MBq/kg of 131I-MIBG and after safety evaluation will undergo high-dose chemotherapy and hematopoietic stem cell transplantation. Autologous and allogeneic stem cell sources will be accepted. After engraftment or 28 days after hematopoietic stem cell transplantation, the safety and response will be evaluated.Conclusion: This is the first prospective study of 131I-MIBG with high-dose chemotherapy and hematopoietic stem cell transplantation in Japan. The results will be the basis of a future nationwide clinical trial.

National Survey on Total Body Irradiation Before Reduced-Intensity Stem Cell Transplantation in Japan

National Survey on Total Body Irradiation Before Reduced-Intensity Stem Cell Transplantation in Japan

Hematopoietic stem cell transplantation in Japan, a report from Nationwide Survey, 2016

Hematopoietic stem cell transplantation in Japan, a report from Nationwide Survey, 2016

A Revised International Staging System of Multiple Myeloma in the Era of Novel Agents and Autologous Stem Cell Transplantation in Japan: A Multicenter Retrospective Collaborative Study of the Japanese Society of Myeloma

Abstract Survival outcomes of patients with multiple myeloma (MM) vary considerably depending on the presence or absence of disease-related risk factors [i.e., advanced ISS (International Staging System) stage, CAs (cytogenetic abnormalities), etc.], patient-related risk factors, and/or treatment-related risk factors. ISS, developed in 2006 by the IMWG (International Myeloma Working Group), has been considered an important disease-related baseline prognostication model and has been used in routine clinical practice worldwide. However, it is solely determined by the serum biochemistry data without taking account of CAs which are currently identified as the most powerful prognostic indicator for MM. Recently, a Revised ISS (R-ISS) scoring system which is accounting the presence or absence of serum LDH abnormality as well as CAs such as t(4;14), t(14;16), or del(17p) in addition to the ISS stage has been proposed (Oliva S, et al. EHA 2014, #S1289). In the present study, we applied the R-ISS to the Japanese MM patients diagnosed between 2001 and 2012 and compared the clinical relevance of the R-ISS with that of the original ISS in the era of novel agents and autologous stem cell transplantation (ASCT). Clinical data of 3,270 patients were collected from 38 centers; however, ISS and R-ISS were only applicable to 2,998 and 788 patients, respectively. Patient characteristics including age, gender, type of M protein, Durie and Salmon stage, ISS stage, and chromosomal abnormalities were not significantly different between the patients to which ISS and R-ISS were applied. In the 788 patients evaluable for the R-ISS analysis, distribution of the patients according to the ISS stages I, II, and III were 31.4%, 35.8%, and 32.8%, respectively, whereas that of the R-ISS stages were 22.2%, 67.6%, and 10.2%, respectively. Median overall survival (OS) for the ISS stages I, II, and III were 100.7, 65.2, and 50.9 months, respectively, and that of R-ISS stages I, II, and III were 152.8, 62.4, and 40.5 months, respectively. Accordingly, the difference of survival time between the stages seemed more distinct in R-ISS compared with the performance of the original ISS. According to the analysis by the ISS, there were no significant difference in the median OS between the patients whether initially treated with novel agents or with conventional chemotherapy (stage I, 91.2 vs 84.6 months, p=0.054; stage II, 64.1 vs 62.5 months, p=0.18; and stage III, 41.2 vs 37.2 months, p=0.24). In contrast, the analysis by the R-ISS disclosed a beneficial effect of novel therapy than with conventional chemotherapy, particularly in patients with stage I disease (stage I, not reached vs 87.6 months, p=0.018; stage II, 78.8 vs 61.7 months, p=0.075; and stage III, 37.5 vs 45.3 months, p=0.87). As for ASCT, both ISS and R-ISS stages showed a significant difference in the median OS between the patients treated with ASCT and those without ASCT (ISS stages: stage I, 101.3 vs 78.8 months, p=0.40; stage II, 83.8 vs 52.4 months, p=0.0002; stage III, 67.5 vs 31.7 months, p=0.0004; and R-ISS stages: stage I, not reached vs 90.7 months, p=0.21; stage II, 74.2 vs 56.5 months, p<0.00001; stage III, 73.8 vs 37.5 months, p=0.11). Thus, our results have demonstrated that R-ISS is a useful model for the risk assessment of Japanese patients with MM. Notably, the outcome of MM patients with R-ISS stage I showed a dramatic improvement by the initial treatment with novel agents and ASCT. However, the survival benefit remained unmet in patients with advanced stages of R-ISS even in the era of novel agents and ASCT, and further development of therapeutic strategies is needed in high-risk patients with MM. Disclosures Sunami: Takeda pharmaceutical Compani Limited: Research Funding; ONO PHAMACEUTICAL CO.,LTD: Research Funding.

Judgmental criteria by physical therapists for the patients receiving allogeneic hematopoietic stem cell transplantation in Japan

torque on the gleno-humeral joint in any shoulder at any degree of elevation on the scapular plane. Conclusion(s): The maximum (2.94 Nm) adduction torque on the glenohumeral joint set in this study is a value equivalent to the abduction torque which supports the whole upper limbs at a 30◦ angle with no applied load. During elevation in the scapular plane of −10 to 30◦, the tensile force on the supraspinatus tendon which balances the adduction torque applied to the joint increased. A large moment arm of the supraspinatus tendon on the humeral head at −10 to 0◦ elevation reduces tensile force of the supraspinatus tendon, on the other hand, decreased moment arm of the supraspinatus tendon during elevation of 10 to 30◦ increased the tensile force. Moreover, adaptation of the supraspinatus tendon by upward force of the humeral head during −0 to 0◦ elevation might increase the strain of the superficial fibers. Implications: The surface layer of the supraspinatus tendon is more elongated during elevation from−10 to 0◦, but at 10◦ or more of scapular plane elevation there was no elongation. It is appears that care must be taken isometric elevation at −10 or 0◦ as the possibility of tear in the surface layer of rotator cuff due to increased strain on the tendon.

PSY11 - The actual clinical use of Antifungal Drugs in Patients who received Hematopoietic Stem Cell Transplantation in Japan: a retrospective database study

PSY11 - The actual clinical use of Antifungal Drugs in Patients who received Hematopoietic Stem Cell Transplantation in Japan: a retrospective database study