Anti-CD19 chimeric antigen receptor T-cell therapy in acute lymphocytic leukaemia: a systematic review and meta-analysis.

BACKGROUND: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable activity in patients with refractory or relapsed acute lymphocytic leukaemia. Various anti-CD19 CAR T-cell constructs have been trialled and responses vary widely among different studies. We aimed to systematically analyse the outcomes of patients with acute lymphocytic leukaemia treated with anti-CD19 CAR T cells and identify factors associated with differences in outcomes. METHODS: We did a systematic review and meta-analysis of published and unpublished clinical trials that reported data on the outcomes of adult or paediatric patients that were treated with anti-CD19 CAR T cells for relapsed or refractory B-cell acute lymphocytic leukaemia, reported between Jan 1, 2012, and April 14, 2020. Studies with two patients or fewer were excluded and summary data were extracted from the reports. The primary outcome was the number of patients who had complete remission at any time after anti-CD19 CAR T-cell infusion. This study is not registered in PROSPERO. FINDINGS: From 1160 studies, we identified 40 potentially appropriate studies, 35 (88%) of which met the eligibility criteria and were included in the final analysis (n=953 patients). The pooled complete remission was 80% (95% CI 75·5-84·8) and heterogeneity between studies was moderate (I2=56·96%). In the prespecified subgroup analyses, 195 (75% [95% CI 66·9-82·9, I2=35·22%]) of 263 patients in adult studies and 242 (81% [72·9-87·2, I2=54·45%]) of 346 patients in paediatric studies achieved complete remission, p=0·24. The pooled complete remission did not significantly differ with anti-CD19 CAR T-cell construct type or single-chain variable fragment clone, but was higher with autologous T-cell origin (727 [83%, 78·5-86·5, I2=44·34%] of 901 patients), compared with allogeneic T-cell origin (29 [55%, 30·6-79·0, I2=62·64%] of 52 patients; p=0·018). 242 (26% [95% CI 18·5-34·1]) of 854 patients developed grade 3 or worse cytokine release syndrome and 97 (12% [6·6-19·2]) of 532 developed grade 3 or worse neurotoxicity. There was no difference in the proportion of patients who achieved complete remission or who had cytokine release syndrome or neurotoxicity between different anti-CD19 CAR T-cell constructs. The risk of bias was assessed as low in 17 studies and moderate in 18 studies. INTERPRETATION: The high response rates after anti-CD19 CAR T-cell therapy can be used to guide the use of therapy in patients with relapsed or refractory acute lymphocytic leukaemia. Comparison studies are required to further determine differences in efficacy between different anti-CD19 CAR T-cell constructs in the setting of relapsed or refractory acute lymphocytic leukaemia. FUNDING: National Cancer Institute, National Comprehensive Cancer Network, Mayo Clinic K2R Research Pipeline, and Mayo Clinic Center for Individualized Medicine.

Management of chemotherapy-induced alopecia (CIA): A comprehensive review and future directions.

OBJECTIVES: To review and summarize the available literature on the management of chemotherapy-induced alopecia (CIA) including complementary and alternative medicine (CAM), and to present CIA's effect on quality of life (QoL). METHODS: Nine databases were searched for CIA-related keywords, including the effect on QoL, and management options. Among 1019 articles found, 54 articles focusing on treatment/prevention or QoL were retrieved. References of selected articles were also checked manually. RESULTS: CIA was found to negatively affect QoL and body image, regardless of head covering status (i.e., for cultural or religious reasons). Most studies related to treatment/prevention of CIA reported on the use of scalp-cooling. The efficacy of CAM treatments was found to be questionable. CONCLUSION: A high incidence rate of CIA exists with certain chemotherapies, and it significantly impairs QoL. Preventive and treatment strategies are incompletely effective. Additional literature is needed to explore potential preventive or therapeutic options for CIA.

Bone Health Management After Hematopoietic Cell Transplantation: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy.

Bone health disturbances commonly occur after hematopoietic cell transplantation (HCT) with loss of bone mineral density (BMD) and avascular necrosis (AVN) foremost among them. BMD loss is related to pretransplantation chemotherapy and radiation exposure and immunosuppressive therapy for graft-versus-host-disease (GVHD) and results from deficiencies in growth or gonadal hormones, disturbances in calcium and vitamin D homeostasis, as well as osteoblast and osteoclast dysfunction. Although the pathophysiology of AVN remains unclear, high-dose glucocorticoid exposure is the most frequent association. Various societal treatment guidelines for osteoporosis exist, but the focus is mainly on menopausal-associated osteoporosis. HCT survivors comprise a distinct population with unique comorbidities, making general approaches to bone health management inappropriate in some cases. To address a core set of 16 frequently asked questions (FAQs) relevant to bone health in HCT, the American Society of Transplant and Cellular Therapy Committee on Practice Guidelines convened a panel of experts in HCT, adult and pediatric endocrinology, orthopedics, and oral medicine. Owing to a lack of relevant prospective controlled clinical trials that specifically address bone health in HCT, the answers to the FAQs rely on evidence derived from retrospective HCT studies, results extrapolated from prospective studies in non-HCT settings, relevant societal guidelines, and expert panel opinion. Given the heterogenous comorbidities and needs of individual HCT recipients, answers to FAQs in this article should be considered general recommendations, with good medical practice and judgment ultimately dictating care of individual patients. Readers are referred to the Supplementary Material for answers to additional FAQs that did not make the core set.

Chronic graft-versus-host disease: Current management paradigm and future perspectives.

INTRODUCTION: The field of allogeneic hematopoietic cell transplantation (allo-HCT) began in the 1950s, and despite a seven decade history of remarkable clinical advances, graft-versus-host-disease (GVHD) remains the greatest obstacle in its success due to considerable morbidity and mortality. Graft-versus-host disease is the second leading cause of transplantation-related mortality (TRM) after relapse of primary disease. There are two main types of GVHD-acute and chronic-differing in the pathogenesis, time of onset, and clinical presentation. OBJECTIVE: This review provides a comprehensive overview of chronic GVHD pathophysiology and current management paradigms, as well as consideration of promising novel therapies. CONCLUSION: Chronic GVHD is a serious disease which may be active for years, or even decades, requiring potentially years of immunosuppressive therapies and placing patients at risk for a number of late complications. While the oral cavity has long been recognized to be a prominent target of GVHD, and in particular, chronic GVHD, it must be recognized and appreciated that it is a complex systemic disease with a wide spectrum of clinical manifestations.

Clinical Utilization of Chimeric Antigen Receptor T Cells in B Cell Acute Lymphoblastic Leukemia: An Expert Opinion from the European Society for Blood and Marrow Transplantation and the American Society for Blood and Marrow Transplantation.

On August 30, 2017 the US Food and Drug Administration approved tisagenlecleucel (Kymriah; Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present, ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring, and disease assessments. To address these issues experts representing the American Society for Blood and Marrow Transplant, the European Society for Blood and Marrow Transplantation, the International Society of Cell and Gene Therapy, and the Foundation for the Accreditation of Cellular Therapy formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.

Symptom burden and integrative medicine in cancer survivorship.

PURPOSE: The purpose of the study was to learn about the level of experience with, interest in, and desire for knowledge about integrative medicine (IM) among cancer survivors. METHODS: Cancer survivors attending the 2014 National Cancer Survivors Day in Rochester, MN, were recruited to participate in a one-page survey about their ongoing health concerns and symptoms, as well as their experience with, interest in, and desire for knowledge about IM. Two-sided t test was used for univariate analyses of impact of sex, time since diagnosis, and age. RESULTS: Among the 260 cancer survivors, 171 persons (female, 74 %; male, 26 %) completed the survey (mean age, 64.6 years). Symptoms most commonly somewhat or more bothersome were fear of recurrence (52 %), stress (43 %), fatigue (43 %), difficulty sleeping (33 %), and weight gain (31 %). The most used IM resources were exercise (75 %), improved nutrition and diet (66 %), stress management (42 %), dietary supplementation (33 %), meditation (25 %), and massage (22 %). Older patients (age, ≥65 years) were less experienced with, interested in, and desiring of knowledge about IM techniques. Sex and time since diagnosis were not strongly predictive of most survey response categories. CONCLUSIONS: Cancer survivors have adverse effects for years into survivorship. They use and express interest in various IM techniques to help manage symptoms. It is critical that oncology providers help survivors address ongoing health concerns. Education about and access to evidence-based IM techniques may have important roles in comprehensive cancer survivorship programs.