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ABSTRACT: In the setting of a learning collaborative, we conducted an international multicenter phase 2 clinical trial testing the hypothesis that nonmyeloablative-related haploidentical bone marrow transplant (BMT) with thiotepa and posttransplant cyclophosphamide (PTCy) will result in 2-year event-free survival (no graft failure or death) of at least 80%. A total of 70 participants were evaluable based on the conditioning protocol. Graft failure occurred in 8 of 70 (11.4%) and only in participants aged <18 years; all had autologous reconstitution. After a median follow-up of 2.4 years, the 2-year Kaplan-Meier-based probability of event-free survival was 82.6%. The 2-year overall survival was 94.1%, with no difference between children and adult participants. After excluding participants with graft failure (n = 8), participants with engraftment had median whole blood donor chimerism values at days +180 and +365 after transplant of 100% (n = 58), respectively, and 96.6% (57/59) were off immunosuppression 1 year after transplant. The 1-year grade 3 to 4 acute graft-versus-host disease (GVHD) rate was 10%, and the 2-year moderate-severe chronic GVHD rate was 10%. Five participants (7.1%) died from infectious complications. We demonstrate that nonmyeloablative haploidentical BMT with thiotepa and PTCy is a readily available curative therapy for most adults, even those with organ damage, compared to the more expensive myeloablative gene therapy and gene editing. Additional strategies are required for children to decrease graft failure rates. The trial was registered at www.clinicaltrials.gov as #NCT01850108.
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Anemia de Células Falciformes , Trasplante de Médula Ósea , Enfermedad Injerto contra Huésped , Trasplante Haploidéntico , Humanos , Trasplante de Médula Ósea/métodos , Trasplante de Médula Ósea/efectos adversos , Masculino , Femenino , Niño , Adolescente , Adulto , Anemia de Células Falciformes/terapia , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante Haploidéntico/métodos , Preescolar , Adulto Joven , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Acondicionamiento Pretrasplante/métodos , Persona de Mediana Edad , Tiotepa/administración & dosificación , Tiotepa/uso terapéuticoRESUMEN
INTRODUCTION: Increased use of oral anticancer agents (OAAs) has empowered adults with chronic lymphocytic leukemia (CLL) and chronic myelogenous leukemia (CML) to manage their therapy, but this shift may complicate medication use, particularly among adults with multiple chronic conditions (MCC). METHODS: This retrospective cohort study used 2013-2018 commercial and Medicare claims data to assess medication use in adults with CML or CLL. To be included, patients must have been at least 18 years old, diagnosed with and had 2+ claims for an OAA indicated for either CML or CLL, continuously enrolled 12 months before and after OAA initiation, and treated for (2+ fills) at least two select chronic conditions. Proportion of days covered (PDC) determined medication adherence and was compared for 12 months before and after OAA initiation by Wilcoxon signed-rank tests, McNemar's tests, and difference-in-differences models. RESULTS: Among CLL patients, mean OAA adherence in the first year of therapy was 79.8% (SD: 21.1) and 74.7% (SD: 24.9) for commercial and Medicare patients, respectively; mean adherence for CML patients was 84.5% (SD: 15.8) and 80.1% (SD: 20.1) for commercial and Medicare patients, respectively. Adherence and the proportion adherent (PDC ≥ 80%) to comorbid therapies was generally unchanged following OAA initiation. Consistently unremarkable changes in MCC adherence were observed in 12-month difference-in-differences models, but significant decline was observed in MCC adherence after 6 months of OAA use. CONCLUSIONS: OAA initiation among adults with CML or CLL was not associated with significant, initial changes to adherence to medications for chronic diseases.
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Antineoplásicos , Leucemia Linfocítica Crónica de Células B , Leucemia Mielógena Crónica BCR-ABL Positiva , Afecciones Crónicas Múltiples , Anciano , Adulto , Humanos , Estados Unidos , Adolescente , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Estudios Retrospectivos , Medicare , Antineoplásicos/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Cumplimiento de la MedicaciónRESUMEN
INTRODUCTION: Venetoclax is utilized with low-dose cytarabine or a hypomethylating agent for the treatment of acute myeloid leukemia. Clinical trials report a risk of tumor lysis syndrome and the package insert recommends a venetoclax dose ramp-up at the initiation. The purpose of this study was to evaluate the risk of tumor lysis syndrome in a large population of patients with acute myeloid leukemia outside of a clinical trial and evaluate the incidence of hospital-acquired complications during inpatient ramp-up. METHODS: We performed a retrospective study of adult patients with acute myeloid leukemia receiving venetoclax with a hypomethylating agent or low-dose cytarabine. The primary outcome was the incidence of tumor lysis syndrome. Secondary outcomes included risk factors for tumor lysis syndrome, length of admission, and incidence of hospital-acquired complications. RESULTS: One hundred thirteen patients were included. Although all patients were given some form of prophylaxis, the incidence of tumor lysis syndrome was 8.8%. All were laboratory tumor lysis syndrome; one with hyperuricemia, nine with hypocalcemia, and ten with hyperphosphatemia. Six patients received sevelamer. Tumor lysis syndrome was resolved in all cases. No clinical tumor lysis syndrome occurred. Hepatic dysfunction, tumor lysis syndrome high-risk stratification, higher baseline white blood cell count, and lactate dehydrogenase levels were more common in the tumor lysis syndrome group. Hospital-acquired complications reached 13% in those directly admitted for dose ramp-up. CONCLUSIONS: Tumor lysis syndrome was uncommon and manifested as minor lab abnormalities. White blood cell count continues to be an indicator of risk for tumor lysis syndrome. Those who present with an elevated white blood cell or are otherwise at high risk for tumor lysis syndrome should be admitted for ramp-up. Otherwise, initiation and monitoring of venetoclax are feasible in the outpatient setting.
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Leucemia Mieloide Aguda , Síndrome de Lisis Tumoral , Adulto , Humanos , Síndrome de Lisis Tumoral/etiología , Síndrome de Lisis Tumoral/tratamiento farmacológico , Estudios Retrospectivos , Leucemia Mieloide Aguda/complicaciones , Citarabina , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
For patients with high risk myeloid disease, allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy. Unfortunately, many of these patients relapse after HCT and have a limited survival. The recent approval of venetoclax, an orally bioavailable BCL-2 inhibitor, resulted in significant responses in treatment naïve acute myeloid leukemia (AML), and off-label use in the relapsed/refractory setting is increasing. We report the outcomes of 21 patients who underwent allogeneic HCT for myeloid disease, relapsed with AML, and were treated with venetoclax. Several patients had poor risk features including antecedent hematologic malignancy (6/21), complex karyotype (6/21), and TP53 mutations (5/21). The median age was 64.5 years and time from HCT to relapse was 5.7 months (range: 0.9 to 44.9 months). Of the 19 patients who were assessed for response, there were meaningful treatment responses seen in eight patients: five CR, three CRi, zero PR, for an ORR of 42.1%. Treatment effect was seen in six additional patients, including four in the morphologic leukemia-free state. Nine patients maintained their response for ≥3 months and eight were receiving therapy at data cut. Post-HCT AML relapse has an exceedingly poor outcome, and venetoclax-based therapy is a potent therapy option that should be studied prospectively in this setting.
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Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Terapia Recuperativa , Sulfonamidas/administración & dosificación , Adulto , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
BACKGROUND: Haploidentical bone marrow transplant (haplo-BMT) offers near universal donor availability as a curative modality for individuals with severe sickle cell disease (SCD). However, the required intense immunodepletion is associated with increased infectious complications. A paucity of data exists on immune reconstitution following haplo-BMT for SCD. METHODS: A multi-institution learning collaborative was developed in the context of a phase II clinical trial of a non-myeloablative, related haplo-BMT with post-transplant cyclophosphamide for SCD. We report results from a cohort of 23 patients for whom immune reconstitution data up to one year were available. RESULTS: Median age was 14.8 years. Out of 23, 18 participants received pre-conditioning with azathioprine, hydroxyurea, and hypertransfusions. 70% (16/23) of participants had multiple indications for haplo-BMT. We observed excellent immune reconstitution of CD4, CD8, CD19, and CD56 cellular subsets by 6 months post transplant. Engraftment rate and event-free survival in this cohort were 100% and 96%, respectively. 70% (16/23) of patients had at least one viral reactivation or infection, including CMV 35% (8/23), HHV-6 22% (5/23), and polyoma virus 17% (4/23), with no cases of post-transplant lymphoproliferative disease. CONCLUSION: Further prospective studies are needed to better characterize immune reconstitution and the immunologic basis for increased viral reactivation following haplo-BMT with post-transplant cyclophosphamide for SCD.
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Anemia de Células Falciformes/complicaciones , Trasplante de Médula Ósea/efectos adversos , Ciclofosfamida/administración & dosificación , Reconstitución Inmune , Inmunosupresores/administración & dosificación , Activación Viral , Adolescente , Adulto , Niño , Ensayos Clínicos Fase II como Asunto , Supervivencia sin Enfermedad , Enfermedad Injerto contra Huésped , Humanos , Estudios Prospectivos , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Haploidéntico/efectos adversos , Adulto JovenRESUMEN
PURPOSE: Oral oncolytics have improved survival in hematological cancers like chronic myeloid leukemia, chronic lymphocytic leukemia/small lymphocytic lymphoma, and multiple myeloma; however, it is unclear of the extent to which initiating these treatments might impact adherence to oral therapies for pre-existing comorbid chronic conditions. METHODS: Adults diagnosed with and prescribed oral oncolytics for chronic myeloid leukemia, chronic lymphocytic leukemia/small lymphocytic lymphoma, or multiple myeloma between 2013 and 2016 and with continuous eligibility six months before and after oral oncolytic initiation were identified from the Truven Health MarketScan databases. Among those identified, patients with pre-existing diabetes, hypertension, and/or hyperlipidemia with ≥1 fill for oral comorbid therapies were selected. Adherence to oral oncolytics and comorbid therapies was measured using the proportion of days covered metric. Wilcoxon signed-rank tests assessed changes in adherence for comorbid therapies after initiation of an oral oncolytic. Unadjusted difference-in-difference models assessed the impact of adherence to oral oncolytics on changes in adherence to comorbid therapies. RESULTS: Significant reductions in adherence after oncolytic initiation were observed across the comorbid therapies and were highest for patients taking lipid-lower agents (10.7-15.6%). Unadjusted difference-in-difference models revealed consistent and significantly lower reductions in adherence for those taking antihypertensives (chronic myeloid leukemia: p = 0.03; chronic lymphocytic leukemia/small lymphocytic lymphoma: p = 0.007; multiple myeloma: p = 0.09) and adherent to oral oncolytics. CONCLUSION: Initiation of oral oncolytics may negatively impact adherence to oral therapies for chronic comorbid conditions, necessitating the need for medication management strategies to help patients adhere to their entire medication regimen.
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Antineoplásicos/administración & dosificación , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Cumplimiento de la Medicación , Adolescente , Adulto , Anciano , Antihipertensivos/uso terapéutico , Comorbilidad , Bases de Datos Factuales , Diabetes Mellitus/tratamiento farmacológico , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Estudios Retrospectivos , Adulto JovenRESUMEN
Administration of immune effector cell (IEC) therapy is a complex endeavor requiring extensive coordination and communication of various healthcare and administrative teams. Chimeric antigen receptor (CAR) T cells are the most established IEC therapy available. As of July 2018 two commercial gene therapy products, tisagenlecleucel and axicabtagene ciloleucel, have been approved by the US Food and Drug Administration. To gain insight into the infrastructure and practices across the country, the American Society for Blood and Marrow Transplantation Pharmacy Special Interest Group conducted an electronic survey on the current administrative, logistic, and toxicity management practices of CAR T cell therapy across the United States. This survey consists of 52 responses from institutions of varying sizes, most of which (â¼80%) had previous investigational experience with CAR T cell therapy. Absorbing the energy of this exciting new treatment has challenged hematopoietic cell transplant programs across the country to strengthen department infrastructure, develop new committees and policies, and implement significant education to ensure safe administration. With the variety of experience with CAR T cell therapy, we hope this survey can contribute to the existing published literature and provide support and consensus to established and developing IEC programs and practice guidelines.
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Antígenos CD19/uso terapéutico , Terapia Genética , Receptores de Antígenos de Linfocitos T/administración & dosificación , Receptores Quiméricos de Antígenos/administración & dosificación , Antígenos CD19/administración & dosificación , Productos Biológicos , Humanos , Inmunoterapia Adoptiva , Guías de Práctica Clínica como Asunto , Estados UnidosRESUMEN
Allogeneic hematopoietic cell transplantation (HCT) patients are at an increased risk of developing central line-associated bloodstream infections (CLABSIs) due to prolonged periods of myelosuppression, immunosuppression, and indwelling catheter days. CLABSIs are among the most serious complications in HCT recipients and can lead to prolonged hospitalizations, intensive care unit admissions, lengthy antimicrobial therapies, and increased mortality. There is a lack of data regarding the incidence and risk factors associated with the development of CLABSIs in the HCT population undergoing outpatient transplantation. This was a single-center, retrospective analysis of adult patients who underwent allogeneic HCT between July 2012 and July 2016 in an outpatient transplant unit at a tertiary academic medical center. The primary outcome was the cumulative incidence of CLABSIs from the date of central line placement through the first 100 days post-transplantation. Secondary outcomes included risk factors for CLABSI, number of hospitalizations due to CLABSI, mortality rate at 6 months post-transplantation, and the cumulative incidence, speciation, and presence of multidrug resistance in identified microorganisms. Three hundred fifty-nine patients underwent allogeneic HCT at Vanderbilt University Medical Center and 352 were included for analysis. The cumulative incidence of CLABSIs was 9%, with the majority occurring within the first 30 days post HCT (67%). The use of a matched unrelated donor (MUD) and/or haploidentical donor (odds ratio, 3.993; 95% confidence interval [CI], 1.329 to 12.001; P = .0136) and use of an ablative conditioning regimen (odds ratio, 2.394; 95% CI, 1.052 to 5.446; P = .0374) were independently associated with development of a CLABSI on multivariate analysis. The most common organism implicated in CLABSI was Staphylococcus epidermidis (34%). Patients who developed a CLABSI had an almost 5 times higher risk of mortality at 6 months post-transplantation compared with patients who did not develop a CLABSI (hazard ratio, 4.932; 95% CI, 2.463 to 9.878; P < .001). There is a low incidence of CLABSIs in patients undergoing HCT in the outpatient setting. Patients who underwent HCT using a MUD or haploidentical donor and received ablative conditioning were at higher risk for developing CLABSIs. Overall mortality at 6 months post-transplantation was higher in patients who developed a CLABSI. Additional prospective studies are needed to confirm these observations.
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Cateterismo Venoso Central/efectos adversos , Trasplante de Células Madre Hematopoyéticas , Unidades de Cuidados Intensivos , Pacientes Ambulatorios , Acondicionamiento Pretrasplante , Adulto , Anciano , Infecciones Relacionadas con Catéteres/etiología , Supervivencia sin Enfermedad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Secondary acute myeloid leukemia (sAML) has been associated with inferior outcomes compared with de novo AML. Little is known about patient risk factors and outcomes in sAML after allogeneic hematopoietic stem cell transplantation (HCT); thus, this large systemic analysis of the European Society for Blood and Bone Marrow Transplantation registry was performed. This study included 4997 patients with sAML who received HCT from 2000 to 2016. In univariate analysis the 2-year cumulative incidence of chronic graft-versus-host disease (GVHD), relapse, and nonrelapse mortality (NRM) were 33.5% (95% confidence interval [CI], 32% to 34.9%), 33.7% (95% CI, 32.3% to 35.1%), and 27.5% (95% CI, 26.1% to 28.7%), respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free survival (GRFS) at 2 years were 44.5% (95% CI, 43% to 46%), 38.8% (95% CI, 37.4% to 40.3%), and 27.2% (95% CI, 25.9% to 28.6%), respectively. In multivariate analysis, patients receiving myeloablative regimens had decreased relapse (hazard ratio, .859; 95% CI, .761 to .97; P = .01), higher NRM (hazard ratio, 1.175; 95% CI, 1.03 to 1.341; P = .02), and no differences in OS, LFS, and GRFS compared with patients receiving reduced-intensity conditioning regimens. Active disease, adverse cytogenetics, older age, Karnofsky performance status (≤80%), ex vivo T cell depletion, other malignant hematologic diseases, and patient cytomegalovirus seropositivity were associated with inferior OS and LFS. These variables should be considered in patients with sAML in need of HCT, and further study regarding the impact of conditioning regimens on relapse is needed.
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Trasplante de Médula Ósea/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Europa (Continente) , Femenino , Humanos , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenAsunto(s)
Antineoplásicos Alquilantes/efectos adversos , Ciclofosfamida/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante Haploidéntico/efectos adversos , Activación Viral , Virosis/etiología , Antineoplásicos Alquilantes/uso terapéutico , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/etiología , Humanos , Huésped Inmunocomprometido , Factores de Riesgo , Activación Viral/inmunología , Virosis/diagnósticoRESUMEN
Hematopoietic stem cell transplantation (HSCT) remains the only curative option for several hematological malignancies. Its use has continued to grow, with an estimated 23,500 transplants performed annually in the United States alone. The acute toxicities that occur from conditioning chemotherapy can impact the peri-transplant period and have substantial implications on patients' tolerability and outcomes, irrespective of the treatment of their disease. Chemotherapy-induced nausea vomiting (CINV), mucositis, transplant-associated thrombotic microangiopathy (TA-TMA), and sinusoidal obstruction syndrome, also known as a veno-occlusive disease (SOS/VOD) can all have significant implications for patients. These acute complications begin with the start of conditioning chemotherapy and add to potential toxicity for patients throughout the early post-transplant period, from Day +30 for CINV, mucositis, and SOS, and which can continue through at least Day +100 with the onset of TA-TMA. These toxicities must be prevented and managed appropriately. This review will summarize the literature surrounding them and guide their management.
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Chimeric antigen receptor T-cell therapy (CAR-T) has altered the treatment landscape of several hematologic malignancies. Until recently, most CAR-T infusions have been administered in the inpatient setting, due to their toxicity profile. However, the advent of new product constructs, as well as improved detection and management of adverse effects, have greatly increased the safety in administering these therapies. CAR-T indications continue to expand, and inpatient administration is associated with increased healthcare resource utilization and overall cost. Therefore, transitioning CAR-T administration to the outpatient setting has been of great interest in an effort to improve access, reduce financial burden, and improve patient satisfaction. Establishment of a successful outpatient CAR-T requires several components, including a multidisciplinary cellular therapy team and an outpatient center with appropriate clinical space and personnel. Additionally, clear criteria for outpatient administration eligibility and for inpatient admission with pathways for prompt toxicity evaluation and admission, and toxicity management guidelines should be implemented. Education about CAR-T therapy and its associated toxicities is imperative for all clinical staff, as well as patients and their caregivers. Finally, rigorous financial planning and close collaboration with payers to ensure equitable access, while effectively managing cost, are essential to program success and sustainability. This review provides a summary of currently published experiences, as well as expert opinion regarding implementation of an outpatient CAR-T program.
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The first series of chimeric antigen receptor T (CAR-T) cell therapy products were approved in 2017 to 2019 and have shown remarkable efficacy in both clinical trials and the real-world setting, but at the cost of prolonged patient hospitalization. As the toxicity management protocols were refined, the concept of cellular therapy administered in the outpatient setting gained steam, and single institutions began to perform certain aspects of CAR-T monitoring in the outpatient setting for select patients. However, there are many considerations for a successful outpatient program. In anticipation of increasing use of CAR-T-cell therapy in the outpatient setting as a mechanism to overcome frequent hospital bed shortages and high cost of inpatient care, the American Society for Transplantation and Cellular Therapy convened a group of experts in hematology, oncology, and cellular therapy to provide a comprehensive review of the existing publications on outpatient CAR-T cell therapy, discuss selected ongoing clinical trials of outpatient CAR-T, and describe strategies to optimize safety without compromising efficacy for patients treated and monitored in the outpatient setting.
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Receptores Quiméricos de Antígenos , Humanos , Estados Unidos , Receptores Quiméricos de Antígenos/uso terapéutico , Pacientes Ambulatorios , Inmunoterapia Adoptiva/efectos adversos , Sociedades , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
Febrile neutropenia (FN) is a complication in approximately 90% of autologous stem cell transplant (SCT) patients. Guidelines support early broad-spectrum antibiotics (BSA) to prevent morbidity and mortality. However, in patients who are clinically stable and deemed to have a fever of unknown origin, the optimal duration of BSA is unknown. Accumulating evidence suggests that de-escalation of BSA in select patients may decrease duration of BSA exposure without compromising clinical outcomes such as infection, recurrent fever, and readmission. With this, a de-escalation protocol was implemented at Vanderbilt University Medical Center (VUMC) to identify autologous SCT patients who may benefit from early de-escalation of BSA. The objectives of this study were to analyze the impact of early empiric antibiotic de-escalation on the duration of BSA as well as its impact on the incidence of recurrent fever and documented infection in autologous SCT patients. This was a single-center, retrospective study evaluating patients older than 18 years of age who underwent autologous SCT and experienced an episode of FN from January 2018 to December 2022 at VUMC (Nâ¯=â¯195). The protocol was initiated on January 1, 2020, to de-escalate BSA back to prophylaxis in stable neutropenic patients determined to have a fever of unknown origin. The primary outcome was the number of BSA days within 30 days. Secondary clinical outcomes included recurrent fever, documented infection, readmission, 30-day mortality, and 90-day non-relapsed mortality (NRM). Outcomes were compared across pre- and postprotocol groups with a Wilcoxon rank sum test, Pearson chi-square test, or regression analysis as appropriate. The median BSA duration was 4.7 and 2.7 days in the pre- and postprotocol groups, respectively (P < .001). Recurrent fever (14.2% versus 16.0%, Pâ¯=â¯.726), documented infection (1.7% versus 6.7%, Pâ¯=â¯.068), and readmission (13.3% versus 22.7%, Pâ¯=â¯.091) within 30 days were not significantly different between the two groups. Neither 30-day mortality (0.8% versus 1.3%, Pâ¯=â¯.736) nor 90-day NRM (0.8% versus 1.3%, Pâ¯=â¯.736) differed. The implementation of an early de-escalation protocol for autologous SCT patients who develop FN was associated with a reduction in duration of BSA compared to the preprotocol group without a significant difference in readmission, recurrent fevers, and documented infections. This study adds to existing evidence that early de-escalation of BSA in FN patients with a fever of unknown origin who are afebrile and clinically stable is safe and reduces unnecessary antibiotic use.
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The age effect in severe aplastic anemia (SAA) following allogeneic hematopoietic cell transplantation (HCT) favors the use of reduced intensity conditioning (RIC) regimens in older adults. We implemented a non-myeloablative regimen consisting of fludarabine, cyclophosphamide, and rituximab (FCR) to improve HCT outcomes in SAA. Patients who underwent first HCT for SAA utilizing an FCR regimen between January 2016 and May 2022 were included. Outcomes analyzed included time to engraftment, incidence of graft failure, GVHD, viral reactivation, disease recurrence, and GVHD-free, relapse-free survival (GRFS). Among 24 patients included, median age was 43.5 years (22-62) and a variety of donor types and stem cell sources were represented. At median follow-up of 26.9 months (2.4-72.7), no cases of grade III-IV acute (aGVHD) or severe chronic GVHD (cGVHD) were recorded. Viral reactivation was minimal, and there were no cases of graft failure or PTLD, with 100% disease-free and overall survival at last follow up. The estimate of 1-year GRFS was 86.3% (95% CI: 72.8-100%), with moderate cGVHD accounting for all events. The FCR regimen in SAA was well tolerated, even in older adults, with 100% disease-free survival with low GVHD and infection rates. These encouraging findings should be validated in larger prospective trials.
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Hematopoietic stem cell transplantation (HSCT) is an integral part of the treatment strategy in patients with a hematological disorder. Chemotherapy-induced nausea and vomiting (CINV) is still an issue in patients who undergo HSCT. While several guidelines for the antiemetic therapy against CINV have been published, there is no detailed information about appropriate antiemetic drugs for each conditioning regimen in HSCT. Various studies reported that the triplet of 5-HT3RA, NK1RA, and dexamethasone appears useful in HSCT. However, each antiemetic has unique adverse effects or interactions with specific drugs. Here, we review the literature relating to clinical trials on the prevention of CINV, and summarize the information to clarify the benefit of antiemetic regimens.
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Improvements in chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), and multiple myeloma (MM) treatment options have increased the 5-year survival rates for patients with these hematologic malignancies. In addition to cancer management, these patients may need help to manage multiple chronic conditions (MCC). The overall objective of this study is to examine the impact and implementation of a model that coordinates care between oncology and primary care pharmacists for people taking an oral anti-cancer agent (OAAs) and medications for comorbid chronic conditions. This is a multi-center, prospective, single-arm pilot study that will recruit up to 40 patients from Michigan Medicine and Vanderbilt University Medical Center (VUMC). Eligible participants will be 18 years of age or older, prescribed an OAA, have a diagnosis of either CML, CLL or MM, and be diagnosed with and taking medication for at least two specified chronic conditions. The Pharmacists Coordinated Care Oncology Model (PCOM) is a two-month intervention that builds upon current pharmacist clinical responsibilities. Generally, participants will complete a patient-reported outcome measure at 2 and 6 weeks post-OAA initiation that is sent to their oncology pharmacist, and they will also receive a comprehensive medication review at week 4 from a primary care pharmacist for their chronic medications. The pharmacists will communicate about the results via electronic medical record (EMR) and intervene if necessary. The primary endpoints are (1) dose-adjusted OAA proportion of days covered (PDC), and (2) PDC for chronic condition medications. PDCs will be determined via prescription records. The association of OAA and chronic medication PDCs will be quantified via correlation and chi-squared tests. The association between symptom experience and OAA adherence will be examined via correlation analyses. For implementation, characteristics of patient participants, feasibility, acceptability, adoption, fidelity, and trialability will be described. Data will be collected via EMR and pharmacist and patient interviews. Median/IQR for acceptability, adoption and fidelity will be reported, and patient interviews will be analyzed using a grounded theory approach and pharmacist interviews will be analyzed using thematic analyses.
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Adoptive cellular therapy has made a landmark change within the treatment paradigm of several hematologic malignancies, and novel cellular therapy products, such as chimeric antigen receptor T-cell therapy (CART), have demonstrated impressive efficacy and produced durable responses. However, the CART treatment process is associated with significant toxicities, healthcare resource utilization, and financial burden. Most of these therapies have been administered in the inpatient setting due to their toxicity profile. Improved toxicity management strategies and a better understanding of cellular therapy processes are now established. Therefore, efforts to transition CART to the outpatient setting are warranted with the potential to translate into enhanced patient quality of life and cost savings. A successful launch of outpatient CART requires several components including a multidisciplinary cellular therapy team and an outpatient center with appropriate clinical space and personnel. Telemedicine should be incorporated for closer monitoring. Additionally, clear criteria for admission upon clinical decompensation, a pathway for prompt inpatient transition, and clear toxicity management guidelines should be implemented. Effective education about cellular therapy and toxicity management is imperative, especially for the Emergency Department and Intensive Care Unit teams. Here, we have outlined the various logistical and clinical considerations required for the care of CART patients, which will aid centers to establish an outpatient CART program.
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Objective: To evaluate whether rates of healthcare-associated infections (HAIs) changed during the coronavirus disease 2019 (COVID-19) pandemic in malignant hematology and stem cell transplant patients. Design: A retrospective, cohort study. Patients: The study included malignant hematology and stem cell transplant patients admitted between March 1, 2019, through July 31, 2019, and March 1, 2020, through July 31, 2020. Methods: Rates of catheter-associated urinary tract infections (CAUTIs), central-line-associated bloodstream infections (CLABSIs), central-line-associated mucosal barrier injury infections (CLAMBIs), and Clostridioides difficile infections (CDIs) during the pandemic were compared to those in a control cohort. Secondary outcomes included the rate of non-COVID-19 respiratory viruses. Results: The rate of CAUTIs per 1,000 hospital days was 0.435 before the pandemic and 0.532 during the pandemic (incidence rate ratio [IRR], 1.224; 95% confidence interval [CI], 0.0314-47.72; P = .899). The rate of CLABSIs was 0.435 before the pandemic and 1.064 during the pandemic (IRR, 2.447; 95% CI, 0.186-72.18; P = .516). The rate of CLAMBIs was 2.61 before the pandemic and 1.064 during the pandemic (IRR 0.408, 95% CI 0.057-1.927; P = .284). The rate of CDIs was 2.61 before the pandemic and 1.579 during the pandemic (IRR, 0.612; 95% CI, 0.125-2.457; P = .512). Non-COVID-19 respiratory virus cases decreased significantly from 12 (30.8%) to 2 cases (8.3%) (P = 0.014). Conclusions: There was no significant difference in HAIs among inpatient malignant hematology and stem cell transplant patients during the COVID-19 pandemic compared to those of a control cohort. Rates of infection were low among both cohorts. Rates of community-acquired respiratory viruses decreased significantly during the pandemic among this population.
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PURPOSE: Increased use of oral anticancer agents (OAAs) has empowered adults with multiple myeloma (MM) to manage their oncolytic therapy, but such a shift may result in issues with medication use, particularly among patients being concurrently treated for pre-existing, multiple chronic conditions. METHODS: This retrospective cohort study used 2013-2018 commercial and Medicare claims data to assess medication use in adults with MM. To be included, adults (18 years and older) must have been diagnosed with and had 2+ claims for an OAA, had continuous enrollment for 12 months before and after OAA initiation, and have been previously diagnosed with and had prescription fills for 2+ select chronic conditions. The proportion of days covered metric assessed medication adherence and was compared for 12 months before and after the OAA initiation by Wilcoxon signed-rank tests, McNemar's tests, and difference-in-differences models. RESULTS: The mean OAA adherence in the first year of therapy was 58.3% (standard deviation: 24.5) and 65.1% (standard deviation: 27.01) for commercial and Medicare patients, respectively. Adherence and the proportion adherent (proportion of days covered ≥ 80%) to comorbid therapies generally declined in the first year after OAA initiation. Changes in medication use were particularly noticeable among those on antihypertensive therapy: adjusted analyses uncovered a 2.5% (Medicare) and 5.2% (commercial) difference in adherence to these medications between those initially adherent and nonadherent to OAA therapy (both P < .05). CONCLUSION: Initiating OAA therapy in adults with MM may complicate an already complex treatment regimen, resulting in poor overall medication adherence in patients with multiple comorbid conditions.