Success of an International Learning Health Care System in Hematopoietic Cell Transplantation: The American Society of Blood and Marrow Transplantation Clinical Case Forum

The ASBMT Clinical Case Forum (CCF) was launched in 2014 as an online secure tool to enhance interaction and communication among hematopoietic cell transplantation (HCT) professionals worldwide through the discussion of challenging clinical care issues. After 14 months, we reviewed clinical and demographical data on cases posted in the CCF from 1/29/2014 to 3/18/2015. A total of 137 cases were posted during the study period. Ninety-two cases (67%) were allogeneic HCT, 29 (21%) autologous HCT and in 16 (12%) the type of transplant (auto vs. allo) was still under consideration. The diseases most frequently discussed included non-Hodgkin lymphoma (NHL; n = 30, 22%), acute myeloid leukemia (AML; n = 23, 17%) and multiple myeloma (MM; n = 20, 15%). When compared with the US transplant activity reported by the US Department of Health and Human Services, NHL and acute lymphoblastic leukemia cases were overrepresented in the CCF while myeloma was underrepresented (P < 0.001). A total of 259 topics were addressed in the CCF with a median of two topics/case (range 1-6). Particularly common topics included whether transplant was indicated (n = 57, 41%), conditioning regimen choice (n = 44, 32%), and post-HCT complications after day 100 (n = 43, 31%). The ASBMT CCF is a successful tool for collaborative discussion of complex cases in the HCT community worldwide and may allow identification of areas of controversy or unmet need from clinical, educational and research perspectives

Use of busulfan in conditioning for allogeneic hematopoietic stem cell transplantation in adults : a survey by the Transplant Complications Working Party of the EBMT

A survey was carried out among EBMT centers about the use of busulfan for conditioning in allogeneic stem cell transplantation. Of 109 responding centers, 106 used busulfan for conditioning, 102 in conventional myeloablative doses, and 93 in reduced doses (RIC). The route of administration was mostly intravenous, but similar to 10% of the centers gave the drug orally. The number of doses in i.v. administration varied and was in myeloablative conditioning mostly one (50 centers) or four (43 centers) doses a day. Seventeen of the 106 centers used pharmacokinetics for dose adjustment in myeloablative conditioning, nine in RIC. The details of pharmacokinetic monitoring varied markedly. Three quarters of the centers reported adjusting the dose based on obesity in myeloablative conditioning and about 60% in RIC. The most common method for dose calculation was ideal body weight + 0.25 x (actual body weight - ideal body weight). In conclusion, the present survey showed marked heterogeneity in the current practices of busulfan administration for conditioning. The impact of the heterogeneity is not well known. Due to this and the scarcity of support from controlled clinical studies, no clear guidelines can be presented, but some prevailing policies to be recommended were identified.Peer reviewe

Autologous Hematopoietic Stem Cell Transplantation (AHSCT): Standard of Care for Relapsing&#8211;Remitting Multiple Sclerosis Patients

Abstract Autologous hematopoietic stem cell transplantation (AHSCT) has been used in the treatment of highly active multiple sclerosis (MS) for over two decades. It has been demonstrated to be highly efficacious in relapsing–remitting (RR) MS patients failing to respond to disease-modifying drugs (DMDs). AHSCT guarantees higher rates of no evidence of disease activity (NEDA) than those achieved with any other DMDs, but it is also associated with greater short-term risks which have limited its use. In the 2019 updated EBMT and ASBMT guidelines, which review the clinical evidence of AHSCT in MS, AHSCT indication for highly active RRMS has changed from “clinical option” to “standard of care”. On this basis, AHSCT must be proposed on equal footing with second-line DMDs to patients with highly active RRMS, instead of being considered as a last resort after failure of all available treatments. The decision-making process requires a close collaboration between transplant hematologists and neurologists and a full discussion of risk–benefit of AHSCT and alternative treatments. In this context, we propose a standardized protocol for decision-making and informed consent process

Development of a quantitative prediction model for peripheral blood stem cell collection yield in the plerixafor era

BACKGROUND AIMS: Predicting autologous peripheral blood stem cell (PBSC) collection yield before leukapheresis is important for optimizing PBSC mobilization and autologous stem cell transplantation (ASCT) for treating hematological malignancies. Although guidelines for plerixafor usage based on peripheral blood CD34+ (PB-CD34+) cell count are available, their predictive performance in the real world remains unclear. METHODS: This study retrospectively analyzed 55 mobilization procedures for patients with non-Hodgkin lymphoma or multiple myeloma and developed a novel quantitative prediction model for CD34+ cell collection yield that incorporated four clinical parameters available the day before leukapheresis; namely, PB-CD34+ cell count the day before apheresis (day -1 PB-CD34+), number of prior chemotherapy regimens, disease status at apheresis and mobilization protocol. RESULTS: The effects of PB-CD34+ cell counts on CD34+ cell collection yield varied widely per patient characteristics, and plerixafor usage was recommended in patients with poorly controlled disease or those with a history of heavy pre-treatments even with abundant day -1 PB-CD34+ cell count. This model suggested a more proactive use of plerixafor than that recommended by the guidelines for patients with poor pre-collection condition or those with a higher target number of CD34+ cells. Further, the authors analyzed the clinical outcomes of ASCT and found that plerixafor use for stem cell mobilization did not affect short- or long-term outcomes after ASCT. CONCLUSIONS: Although external validations are necessary, the results can be beneficial for establishing more effective and safer mobilization strategies

Guidelines on the use of extracorporeal photopheresis

Peer reviewe

A Critical Appraisal of Extracorporeal Photopheresis as a Treatment Modality for Acute and Chronic Graft-Versus-Host Disease

Although significant advances have been made in the biologic understanding of graft-versus-host disease (GVHD) and its treatment options, GVHD remains the single most challenging obstacle to the success of allogeneic hematopoietic cell transplantation (HCT) due to high risk of disabling morbidity and mortality. Extracorporeal photopheresis (ECP) has promising effects in controlling steroid-refractory GVHD, both acute and chronic, and it has been studied extensively. Its putative immunomodulatory mechanisms, while not immunosuppressive, position ECP as an attractive treatment strategy for GVHD patients who are already receiving global immunosuppression. However, ECP is relatively underutilized due in part to limited access and time commitment. Here, we review the recent findings on the ECP efficacy in both acute and chronic GVHD, primarily for steroid-refractory status, and we critically appraise its benefits. We also explore salient considerations on the optimal use of ECP in the treatment of refractory GVHD

Autologous Hematopoietic Stem Cell Transplantation in Active Multiple Sclerosis: A Real-world Case Series

Objective To examine outcomes in people with multiple sclerosis (PwMS) treated with autologous hematopoietic stem cell transplantation (AHSCT) in a real-world setting. Methods This was a retrospective cohort study of PwMS treated with AHSCT at 2 centers in London, UK, consecutively between 2012 and 2019 who had ≥6 months of follow-up or died at any time. Primary outcomes were survival free of multiple sclerosis (MS) relapses, MRI new lesions, and worsening of Expanded Disability Status Scale (EDSS) score. Adverse events rates were also examined. Results The cohort includes 120 PwMS; 52% had progressive MS (primary or secondary) and 48% had relapsing-remitting MS. At baseline, the median EDSS score was 6.0; 90% of the evaluable cases showed MRI activity in the 12 months preceding AHSCT. Median follow-up after AHSCT was 21 months (range 6–85 months). MS relapse-free survival was 93% at 2 years and 87% at 4 years after AHSCT. No new MRI lesions were detected in 90% of participants at 2 years and in 85% at 4 years. EDSS score progression–free survival (PFS) was 75% at 2 years and 65% at 4 years. Epstein-Barr virus reactivation and monoclonal paraproteinemia were associated with worse PFS. There were 3 transplantation-related deaths within 100 days (2.5%), all after fluid overload and cardiac or respiratory failure. Conclusions Efficacy outcomes of AHSCT in this real-world cohort are similar to those reported in more stringently selected clinical trial populations, although the risks may be higher. Classification of Evidence This study is rated Class IV because of the uncontrolled, open-label design

An Educational Intervention for Infusion Center Nurses to Improve Their Confidence in Identification and Management of Immunotherapy Adverse Events, Based on Changes in Pre- and Post-test scores: A Quality Improvement Project

BACKGROUND: Immunotherapy is a treatment that uses the body’s immune system to fight diseases. It is used for the management of many conditions but is mainly utilized in cancer treatment. Immunotherapy has been shown to improve quality of life and increase survival rates in metastatic disease. A major limitation of immunotherapy are the adverse events (AE), or adverse effects, that may cause a delay in treatment, lead to hospitalization, or in extreme cases, mortality. In this study the terms adverse events and adverse effects will be used interchangeably. DESIGN: Pre- and post-test survey design. METHODS: Data was collected from a sample of 23 Infusion Center nurses following an education intervention on identification and management of immunotherapy adverse events, using the Oncology Nurse Immunotherapy Confidence Survey (ONICS) instrument modified for this QI project. RESULTS: The pre- and post-test scores revealed a 39% increase in Infusion Centers nurses’ confidence regarding identification and management of immunotherapy adverse events shown. These findings were established as statically significant (p \u3e 0.0001). CONCLUSIONS: Novice nurses and experienced nurses new to the Oncology specialty would most benefit from this intervention. Department orientation policies can be reviewed and modified based on the data from this project to improve the quality of patient care

American Society for Transplantation and Cellular Therapy Pharmacy Special Interest Group Position Statement on Pharmacy Practice Management and Clinical Management for COVID-19 in Hematopoietic Cell Transplantation and Cellular Therapy Patients in the United States

The coronavirus-19 (COVID-19) pandemic poses a significant risk to patients undergoing hematopoietic stem cell transplantation (HCT) or cellular therapy. The American Society for Transplantation and Cellular Therapy Pharmacy Special Interest Group Steering Committee aims to provide pharmacy practice management recommendations for how to transition clinical HCT or cellular therapy pharmacy services using telemedicine capabilities in the inpatient and outpatient settings to maintain an equivalent level of clinical practice while minimizing viral spread in a high-risk, immunocompromised population. In addition, the Steering Committee offers clinical management recommendations for COVID-19 in HCT and cellular therapy recipients based on the rapidly developing literature. As the therapeutic and supportive care interventions for COVID-19 expand, collaboration with clinical pharmacy providers is critical to ensure safe administration in HCT recipients. Attention to drug-drug interactions (DDIs) and toxicity, particularly QTc prolongation, warrants close cardiac monitoring and potential cessation of concomitant QTc-prolonging agents. Expanded indications for hydroxychloroquine and tocilizumab have already caused stress on the usual supply chain. Detailed prescribing algorithms, decision pathways, and specific patient population stock may be necessary. The COVID-19 pandemic has challenged all members of the healthcare team, and we must continue to remain vigilant in providing pharmacy clinical services to one of the most high-risk patient populations while also remaining committed to providing compassionate and safe care for patients undergoing HCT and cellular therapies

ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells

Chimeric antigen receptor (CAR) T cell therapy is rapidly emerging as one of the most promising therapies for hematologic malignancies. Two CAR T products were recently approved in the United States and Europe for the treatment ofpatients up to age 25years with relapsed or refractory B cell acute lymphoblastic leukemia and/or adults with large B cell lymphoma. Many more CAR T products, as well as other immunotherapies, including various immune cell- and bi-specific antibody-based approaches that function by activation of immune effector cells, are in clinical development for both hematologic and solid tumor malignancies. These therapies are associated with unique toxicities of cytokine release syndrome (CRS) and neurologic toxicity. The assessment and grading of these toxicities vary considerably across clinical trials and across institutions, making it difficult to compare the safety of different products and hindering the ability to develop optimal strategies for management of these toxicities. Moreover, some aspects of these grading systems can be challenging to implement across centers. Therefore, in an effort to harmonize the definitions and grading systems for CRS and neurotoxicity, experts from all aspects of the field met on June 20 and 21, 2018, at a meeting supported by the American Society for Transplantation and Cellular Therapy (ASTCT; formerly American Society for Blood and Marrow Transplantation, ASBMT) in Arlington, VA. Here we report the consensus recommendations of that group and propose new definitions and grading for CRS and neurotoxicity that are objective, easy to apply, and ultimately more accurately categorize the severity of these toxicities. The goal is to provide a uniform consensus grading system for CRS and neurotoxicity associated with immune effector cell therapies, for use across clinical trials and in the postapproval clinical setting