The activities and regulatory landscape of cellular therapies including hematopoietic cell transplantation in the world.

A variety of cellular therapies including hematopoietic cell transplantation (HCT) hold the promise to treat medical conditions and diseases that currently have limited or no effective therapeutic options. A number of cellular therapies other than HCT, such as CAR T-cell therapy, are currently in preclinical and clinical development and the field is rapidly growing. The current activity of cellular therapies, including HCT, in the clinical setting are summarized in this article. Collaborative efforts from all relevant professionals and organizations will be of great importance to overcome substantial challenges in clinical development and post-launch evidence collection of cellular therapies. Harmonization among decision-makers also plays a critical role in reinforcing consistency and improving efficiencies of the regulatory and health technology assessment process. For the long-term safety follow-up of patients undergoing cellular therapies, registries for HCT are able to manage the complexity of data and in the best position to introduce and monitor future innovative cellular therapies for a variety of hematological disorders.

Worldwide Network for Blood and Marrow Transplantation Recommendations for Establishing a Hematopoietic Stem Cell Transplantation Program in Countries with Limited Resources, Part II: Clinical, Technical, and Socioeconomic Considerations.

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. Although this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state-of-the-art treatments, including transplantation, by providing financial, technological, legal, ethical, and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population and potentially provide long-term cost savings by circumventing the need for their citizens to seek care abroad. The costs of establishing an HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. In addition, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT, and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation for establishing HSCT programs, with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in resource-constrained settings.

The Japan Marrow Donor Program, 25 years of experience in achieving 20,000 bone marrow transplantations: organization structure, activity, and financial basis.

The Japan Marrow Donor Program (JMDP), established in 1991, has continued to grow in its capacity to facilitate unrelated bone marrow (BMT) and peripheral blood stem cell transplantation (PBSCT) for the past 25 years in Japan. The current donor pool is 463,465 (as of 31 December 2016) and 20,237 transplants were performed with the help of the Japanese Red Cross, government, and supporters. As JMDP introduced PBSCT in 2010, the vast majority of transplants are BMT. All donors are fully typed for HLA-A, B, C, and DR. The peak age of registered donors is around 40 years. The 8/8 HLA-matched donors are found in our registry for 96% of the patients and 54% of the patients receive a transplant. The median time between the initiation of donor search and the transplantation is approximately 122 days. The median interval between the initiation of donor search and identification of the first potential donor is 40 days. The most common diseases for which unrelated BMT/PBSCT is indicated are acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS), and malignant lymphoma. In recent years we have seen a marked increase in elderly patients who received BMT.

[Clinical features and quality of life assessment in Japanese PNH patients enrolled in the International PNH Registry].

The aim of the present study was to clarify the clinical characteristics and quality of life (QOL) of Japanese patients (N=116) enrolled in the International PNH Registry, compared to the whole registry cohort (N=3,457), censored as of March 2015. The proportion of patients treated with eculizumab was comparable between the two cohorts; the Japanese cohort showed higher levels of lactate dehydrogenase and lower hemoglobin values at baseline. Compared to the whole cohort, the Japanese cohort had a greater incidence of bone marrow failure (67.4% vs 56.8%), but fewer episodes of thrombotic events in their medical history (6.4% vs 13.3%), and lower reported rates of abdominal pain (11.9% vs 33.9%), dysphagia (1.7% vs 16.4%), and erectile dysfunction (5.6% vs 25.3%). Additionally, assessment of QOL using FACIT-Fatigue and EORTC QLQ-C30 confirmed that the Japanese cohort had better QOL scores in most of the QOL subscales at baseline. These data are the first report of QOL outcomes for the Japanese cohort in the International PNH Registry; further assessments are ongoing.

Cost of Illness of Japanese Patients with Chronic Lymphocytic Leukemia (CLL), and Budget Impact of the Market Introduction of Ibrutinib.

BACKGROUND: Ibrutinib was introduced in Japan in 2016 as a new oral treatment option for patients with relapsed/refractory (RR) chronic lymphocytic leukemia (CLL). There is increasing interest from the Japanese government to assess economic aspects of new medical interventions, especially in the area of oncology. OBJECTIVE: We describe the treatment patterns of Japanese patients with CLL, estimate the cost of the disease from a health insurance perspective, and predict the budget impact of the introduction of ibrutinib. METHODS: A budget impact model was set up and populated with data that were collected from a survey of Japanese hematologists (n = 202) and official statistics. Uncertainty was addressed by one-way sensitivity analysis of several model parameters. RESULTS: Among the 2000 Japanese CLL patients, 42.2% have not yet commenced medical treatment, 29.1% were on a treatment break, and 26.8% received medical treatment, mainly rituximab in combination with either fludarabine or bendamustine. Among the patients under medical treatment, 65.7% were receiving first-line treatment and 34.3% were receiving second-line or later treatment. In Japan, the estimated burden of illness for 2015 was ¥1563 million for RR CLL and ¥5471 million for overall CLL. The expected average budget impact of introducing ibrutinib is ¥3077 million per year for the next 5 years. CONCLUSION: Due to low disease prevalence, the burden of illness in Japan is low compared with Western countries.

Questionnaire survey on current status of home care and support for patients with hematological diseases.

In order to survey the current status of home care and support for patients with hematological diseases, questionnaires were sent to 3,591 hospitals and home care facilities in Tokyo and surrounding prefectures. The first survey showed that 81.7% of medical staff members at hospitals reported that they had experience with home care and support, but only 24.9% of home care facility staff members had such experience. The second questionnaire, surveying 1,202 personnel, identified four factors hampering successful establishment of home care and support networks for hematological diseases. These included insufficient familial support for patients, difficulty making end of life decisions by family members and patients, limited access to transfusion support, and financial problems.

Quantitative assessment of protein-bound tyrosine nitration in airway secretions from patients with inflammatory airway disease.

Because reactive nitrogen species (RNS) have potent inflammatory activity, they may be involved in the inflammatory process in pulmonary diseases. We recently reported increased numbers of 3-nitrotyrosine immunopositive cells, which are evidences of RNS production, in the sputum of patients with chronic obstructive pulmonary disease (COPD) and patients with asthma compared with healthy subjects. In the present study, we attempted to quantify this protein nitration in the airways by means of high-performance liquid chromatography (HPLC) used together with an electrochemical detection system that we developed. Sputum samples were obtained from 15 stable COPD patients, 9 asthmatic patients and 7 healthy subjects by using hypertonic saline inhalation. The values for the molar ratio of protein-bound 3-nitrotyrosine/tyrosine in patients with asthma (4.31 +/- 1.13 x 10(-6), p < 0.05) and patients with COPD (3.04 +/- 0.36 x 10(-6), p < 0.01) were significantly higher than those in healthy subjects (1.37 +/- 0.19 x 10(-6)). The levels of protein-bound 3-nitrotyrosine in the airways were not significantly different in asthmatic patients and COPD patients. A significant negative correlation was found between values for protein-bound 3-nitrotyrosine/tyrosine and % FEV1 values in patients with COPD (r = -0.53, p < 0.05) but not in patients with asthma. These results suggest that our HPLC-electrochemical method is useful for quantifying RNS production in human airways. More importantly, they show that increased RNS production in the airways seems to contribute in a critical way to the pathogenesis of COPD, and that the effects of RNS in airways may differ in asthma and COPD.