Role of gene therapy in fanconi anemia: A systematic and literature review with future directions

Gene therapy (GT) has been reported to improve bone marrow function in individuals with Fanconi anemia (FA); however, its clinical application is still in the initial stages. We conducted this systematic review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to assess the long-term safety and clinical outcomes of GT in FA patients. Electronic searches from PubMed, Web of Science, Cochrane Library, and Google Scholar were conducted and full texts of articles meeting our inclusion criteria were reviewed. Three clinical trials were included, with a total of nine patients and mean age of 10.7 ± 5.7 years. All patients had lentiviral-mediated GT. A 1-year follow-up showed stabilization in blood lineages, without any serious adverse effects from GT. A metaregression analysis could not be conducted, as very little long-term follow-up data of patients was observed, and the median survival rate could not be calculated. Thus, we can conclude that GT seems to be a safe procedure in FA; however, further research needs to be conducted on the longitudinal clinical effects of GT in FA, for a better insight into its potential to become a standard form of treatment

A multicenter study of romiplostim for chemotherapy-induced thrombocytopenia in solid tumors and hematologic malignancies

Chemotherapy-induced thrombocytopenia (CIT) frequently complicates cancer treatment causing chemotherapy delays, dose reductions, and discontinuation. There is no FDA-approved agent available to manage CIT. This study retrospectively evaluated patients with CIT treated on institutional romiplostim treatment pathways at 4 U.S. centers. The primary outcome was achievement of a romiplostim response [median on-romiplostim platelet count (Plt) ≥75x109/L and ≥30x109/L above baseline]. Secondary outcomes included time to Plt≥100x109/L and rates of the following: Plt<100x109/L, Plt<75x109/L, Plt<50x109/L, thrombocytosis, chemotherapy dose reduction/treatment delay, platelet transfusion, bleeding, and thromboembolism. Multivariable regression was used to identify predictors of romiplostim non-response and compare weekly dosing with intracycle/intermittent dosing. 173 patients (153 solid tumor, 20 lymphoma or myeloma) were treated, with 170 (98%) receiving a median of 4 (range, 1-36) additional chemotherapy cycles on romiplostim. Romiplostim was effective in solid tumor patients: 71% of patients achieved a romiplostim response, 79% avoided chemotherapy dose reductions/treatment delays and 89% avoided platelet transfusions. Median per-patient Plt on romiplostim was significantly higher than baseline (116x109/L vs. 60x109/L, P<0.001). Bone marrow tumor invasion, prior pelvic irradiation, and prior temozolomide predicted romiplostim non-response. Bleeding rates were lower than historical CIT cohorts and thrombosis rates were not elevated. Weekly dosing was superior to intracycle dosing with higher response rates and less chemotherapy dose reductions/treatment delays (IRR 3.00, 95% CI 1.30-6.91, P=0.010) or bleeding (IRR 4.84, 95% CI 1.18-19.89, P=0.029). Blunted response (10% response rate) was seen in non-myeloid hematologic malignancy patients with bone marrow involvement. In conclusion, romiplostim was safe and effective for CIT in most solid tumor patients

The actual and ideal roles of haemophilia treatment centre social workers in the United States and the barriers to ideal roles

INTRODUCTION: Social Workers (SWs) provide valuable services on multidisciplinary teams of Haemophilia Treatment Centres (HTCs). However, their roles have not been defined and standardized. This paper identifies six major SW roles, including counselling, case management, financial/insurance, outreach/programs, administrative, and grants/research. Roles were further classified as \u27actual\u27 roles, those that SWs were actively practicing, and \u27ideal\u27 roles, those that SWs felt were most important for their clients. AIM: The goal of this study was to determine the actual and ideal roles of HTC SWs and the barriers to ideal roles. METHODS: An online survey was tested with a focus group and then e-mailed to 147 SWs who were working in the 141 HTCs across the United States. RESULTS: Fifty-five percent of the SWs completed the survey. Data revealed that SWs\u27 most prominent actual role was case management in their work with three client sub-populations: adult patients, paediatric patients and family members. However, SWs identified counselling as the ideal role that was most important for all client groups. Barriers to practicing ideal roles included lack of SW input, insufficient budgeted time and inadequate training. Salaries were found to be stagnant compared to 2010. Twenty-five percent of SWs reported no supervision. CONCLUSIONS: Survey results gave evidence that although HTC SWs were primarily engaged in case management roles, they wanted to take on larger counselling roles. Efforts should be made to eliminate barriers to ideal SW roles so that SWs can provide additional psychosocial services for HTC patients

Therapy-related myeloid neoplasms - what have we learned so far?

Therapy-related myeloid neoplasms are neoplastic processes arising as a result of chemotherapy, radiation therapy, or a combination of these modalities given for a primary condition. The disease biology varies based on the etiology and treatment modalities patients receive for their primary condition. Topoisomerase II inhibitor therapy results in balanced translocations. Alkylating agents, characteristically, give rise to more complex karyotypes and mutations in p53. Other etiologies include radiation therapy, high-dose chemotherapy with autologous stem cell transplantation and telomere dysfunction. Poor-risk cytogenetic abnormalities are more prevalent than they are in de novo leukemias and the prognosis of these patients is uniformly dismal. Outcome varies according to cytogenetic risk group. Treatment recommendations should be based on performance status and karyotype. An in-depth understanding of risk factors that lead to the development of therapy-related myeloid neoplasms would help developing risk-adapted treatment protocols and monitoring patients after treatment for the primary condition, translating into reduced incidence, early detection and timely treatment

Patient preference for emicizumab versus prior factor therapy in people with haemophilia A: Results from the HAVEN 3 and HAVEN 4 studies

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/170992/1/hae14421.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/170992/2/hae14421_am.pd