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The role of eculizumab in treating Shiga-toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) patients with neurological involvement remains unclear. We describe two distinctly different STEC-HUS patients with neurologic involvement successfully managed with eculizumab, and perform a literature review of all published cases. Both patients had complete resolution of neurological symptoms after initiation of eculizumab. Eighty patients with STEC-HUS treated with eculizumab were identified in the literature, 68.7% had complete resolution of neurological symptoms. Based on our experience and literature review, three prevailing themes were noted: 1) Early eculizumab administration optimized neurological outcomes, 2) Symptom resolution may not be immediate, neurological symptoms may initially worsen before improvement, and 3) Plasma exchange yielded no benefit. Early administration of eculizumab may reverse neurotoxicity in patients with STEC-HUS.
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PURPOSE: To describe the impact of an inpatient clinical oncology pharmacy technician program. METHODS: A retrospective study was conducted to observe outcomes in patients discharged from the hematology/oncology or bone marrow transplant (BMT) units at Indiana University Health in the year before (April 1, 2016-March 31, 2017) compared with the year after (April 1, 2018-March 31, 2019) the implementation of expanded technician services. The technician performed admission medication histories and ensured access to discharge medications. RESULTS: There were 1,169 and 1,112 encounters included in the pre- and post-technician cohorts. The median age was lower (54 v 61 years; P < .001), and there was a higher percentage of male patients (62% v 52.3%; P < .001) in the pre- compared with post-technician cohort. There were a higher percentage of oncology (36.4% v 31%; P = .007) and no difference in hematology (37.4% v 40.2%; P = .17) nor BMT encounters (26.3% v 28.8%; P = .18) in the pre- compared with post-technician cohort. The discharge prescription capture rate increased (42.7% v 78.5%; P < .001) from the pre- to post-technician cohort, resulting in a 34.2% increase ($314,639.46 in US dollars [USD]-$422,129.20 USD) in retail pharmacy revenue. More admission medication histories were completed by pharmacy staff (64.4% v 91.9%; P < .001), and there was an increase in the Hospital Consumer Assessment of Healthcare Providers and Systems-derived patient satisfaction results for both hematology/oncology (79% v 88%; P < .001) and BMT units (77% v 84%; P = .02) in the pre- compared with post-technician cohort. There was no difference in rates of unplanned readmissions (16.4% v 18.2%; P = .69) in the pre- compared with post-technician cohort. CONCLUSION: The overall capture rate of discharge prescriptions, revenue for the retail pharmacy, and patient satisfaction scores significantly increased after the implementation of expanded, inpatient clinical pharmacy technician services.
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Patients undergoing allogenic hematopoietic stem cell transplantation (HSCT) are at an increased risk of mortality due to transplantation-related complications in the first year post-transplantation, owing in part to the profound immune dysregulation with T cell and B cell lymphopenia and functional impairment. Although several large studies have reported higher mortality rates from Coronavirus disease 2019 (COVID-19) in HSCT recipients, to date no study has focused on the impact of early COVID-19 infection on immune reconstitution post-transplantation and the correlation with transplantation outcomes. We retrospectively analyzed 61 consecutive adult patients who underwent their first allogeneic HSCT at our institution. Thirteen patients (21.3%) experienced early COVID-19 infection, with a median time to diagnosis of 100 days post-transplantation. In multivariable analysis, patients with early COVID-19 infection had significantly worse overall survival (adjusted hazard ratio [aHR], 4.06; 95% confidence interval [CI], 1.26 to 13.05; P = .019) and progression-free survival (aHR, 6.68; 95% CI, 2.11 to 21.11; P = .001). This was attributed mainly to higher nonrelapse mortality (NRM) among early COVID-19 patients (P = .042). Allogeneic HSCT recipients with early COVID-19 infection had significant delays in absolute lymphocyte count (95% CI, -703.69 to -56.79; P = .021), CD3+CD4+ cell (95% CI, -105.35 to -11.59; P = .042), CD3+CD8+ cell (95% CI, -324.55 to -57.13; P = .038), and CD3-CD56+ cell (95% CI, -193.51 to -47.31; P = .014) recovery compared to those without early COVID-19 infection. Our findings suggest that patients with early COVID-19 infection after allogeneic HSCT have higher NRM and worse survival, at least in part due to impaired immune reconstitution post-transplantation.
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COVID-19 , Transplante de Células-Tronco Hematopoéticas , Reconstituição Imune , SARS-CoV-2 , Transplante Homólogo , Humanos , COVID-19/mortalidade , COVID-19/imunologia , COVID-19/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , SARS-CoV-2/imunologia , Transplante Homólogo/efeitos adversos , IdosoRESUMO
OBJECTIVE: There are significant disparities in outcomes among Hispanic patients with acute lymphoblastic leukemia (ALL). Recent studies have demonstrated favorable outcomes of pegaspargase-containing ALL regimens (PEG-CAR) in young adults however, outcomes in Hispanic ethnicity continue to be underreported. METHODS: We evaluated outcomes of newly diagnosed, adult B-cell ALL Hispanic and non-Hispanic patients consecutively treated with a PEG-CAR or HyperCVAD between January 2011 and November 2022. The primary endpoint was event-free survival (EFS) while secondary endpoints included cumulative incidence of relapse and overall survival (OS). RESULTS: Among 105 included patients, 48 (45.7%) were treated with a PEG-CAR and 57 (54.3%) with HyperCVAD. Median age was 38 years (range, 18-75 years), 61% were Hispanic, and 35.2% had poor-genetic risk. Hispanic patients demonstrated significantly worse 5-year EFS with a PEG-CAR compared to that seen with HyperCVAD (HR, 2.58; 95% CI, 1.32-5.04; p = .006) whereas non-Hispanic patients had better outcomes with PIR (52.4% vs. 42.0%). Hispanic ethnicity (p = .015) and male sex (p = .019) were independent predictors for poor OS. CONCLUSIONS: Hispanic patients with B-cell ALL had worse EFS with a PEG-CAR as compared with HyperCVAD. Future studies will aim to confirm these findings and establish a tailored treatment approach for this high-risk population.
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Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto Jovem , Humanos , Masculino , Adulto , Asparaginase/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Polietilenoglicóis/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Estudos RetrospectivosRESUMO
INTRODUCTION: Nirmatrelvir/ritonavir (NIM/r) inhibits tacrolimus metabolism resulting in a profound drug-drug interaction that is further complicated by the use of azole antifungals. CASE PRESENTATIONS: We describe three strategies, in 4 patient cases, for the initiation of NIM/r in allogeneic hematopoietic stem cell transplant (alloHSCT) recipients on tacrolimus at the time of diagnosis. Patients 1 and 2 (strategy 1) experienced prolonged, elevated tacrolimus concentrations after an empiric 33% reduction in tacrolimus dose and adjustment of azole antifungal at NIM/r initiation (strategy 1) and with complete discontinuation of tacrolimus and azole antifungal at NIM/r initiation (strategy 2). Patients 3 and 4 (strategy 3) did not experience elevated tacrolimus concentrations on NIM/r treatment with complete discontinuation of tacrolimus and azole antifungal and a 12-24-h delay in NIM/r initiation. Reinitiation of tacrolimus after NIM/r completion resulted in variable tacrolimus concentrations. CONCLUSION: NIM/r-tacrolimus is a serious drug-drug interaction which can be mitigated by early discontinuation of tacrolimus and azole antifungals, close monitoring, and reinitiation of tacrolimus and antifungal 48-72 h after completion of therapy.
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Treatment of acute lymphoblastic leukemia (ALL) requires both systemically and locally directed therapies to prevent central nervous system (CNS) recurrence. In response to restrictions brought on by the COVID-19 pandemic, our institution adopted triple intrathecal (IT) chemotherapy for CNS prophylaxis during HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine). We retrospectively reviewed records of newly diagnosed adult all patients who were consecutively treated with HyperCVAD between January 2011 and July 2022. Outcomes of patients who received triple IT chemotherapy and standard of care (SOC) CNS prophylaxis were compared. The primary endpoint was CNS relapse-free survival (RFS) while secondary endpoints included cumulative incidence of relapse, overall survival, number of outpatient, and total ITs per patient, and CNS treatment-related toxicities. A total of 37 patients including 21 in the triple IT and 16 in the SOC cohorts were evaluated. There were no differences between the triple IT and SOC cohorts with respect to CNS-RFS (89.6% vs. 80.4%; HR, 1.55; 95% CI, 0.45-5.39; p = .49), cumulative incidence of relapse (8.9% vs. 19.6%; HR, 1.14; 95% CI, 0.3-5.3; p = .87), and overall survival (89.6% vs. 85.7%; HR, 0.91; 95% CI, 0.20-4.21; p = .90) at 2-years. Significantly fewer IT doses were administered in the triple IT cohort (p = .011) and the number of additional outpatient appointments to administer IT chemotherapy were markedly reduced as 98.6% of IT doses were administered during scheduled admissions compared to 76.8% (p < .001). The adoption of triple IT chemotherapy did not increase CNS treatment-related toxicities but rather, the inverse was observed. Triple IT chemotherapy during HyperCVAD represents a feasible alternative to SOC CNS prophylaxis, especially during times of resource restriction and when minimization of patient exposures is desired.
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COVID-19 , Neoplasias do Sistema Nervoso Central , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Adulto , Estudos Retrospectivos , Pandemias , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Metotrexato/uso terapêutico , Recidiva , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/prevenção & controle , Vincristina/efeitos adversosRESUMO
Human herpesvirus 6 (HHV-6) reactivation is common after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with higher mortality and increased transplantation-related complications. We hypothesized that preemptive treatment with a short course of foscarnet at a lower cutpoint of plasma HHV-6 viral load would be effective in treating early HHV-6 reactivation, preventing complications and precluding hospitalization of these patients. We reviewed outcomes of adult patients (age ≥18 years) who received preemptive treatment with once-daily foscarnet 60 to 90 mg/kg for 7 days for HHV-6 reactivation after allo-HSCT at our institution between May 2020 and November 2022. Plasma HHV-6 viral load was monitored by quantitative PCR twice monthly in the first 100 days post-transplantation and twice weekly after reactivation until resolution. Eleven patients with a median age of 46 years (range, 23 to 73 years) were included in the analysis. HSCT was performed with a haploidentical donor in 10 patients and with an HLA-matched related donor in 1 patient. The most common diagnosis was acute leukemia (9 patients). Myeloablative and reduced-intensity conditioning regimens were used in 4 and 7 patients, respectively. Ten of the 11 patients received post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis. The median follow-up was 440 days (range, 174 to 831 days), and the median time to HHV-6 reactivation was 22 days post-transplantation (range, 15 to 89 days). The median viral load at first reactivation was 3,100 copies/mL (range, 210 to 118,000 copies/mL), and the median peak viral load was 11,300 copies/mL (range, 600 to 983,000 copies/mL). All patients received a short course of foscarnet at either 90 mg/kg/day (n = 7) or 60 mg/kg/day (n = 4). In all patients, plasma HHV-6 DNA was undetectable at completion of 1 week of treatment. No HHV-6 encephalitis or pneumonitis occurred. All patients achieved neutrophil and platelet engraftment after a median of 16 days (range, 8 to 22 days) and 26 days (range, 14 to 168 days), respectively, with no secondary graft failure. No complications related to foscarnet administration were noted. One patient with very high HHV-6 viremia had recurrent reactivation and received a second course of foscarnet as an outpatient. A short course of once-daily foscarnet is effective in treating early HHV-6 reactivation post-transplantation and may reduce the incidence of HHV-6-related and treatment-related complications and preclude hospitalization in these patients.
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Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 6 , Adulto , Humanos , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Adolescente , Foscarnet/uso terapêutico , Herpesvirus Humano 6/fisiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante Homólogo , DNA ViralAssuntos
Anticorpos Biespecíficos , Antineoplásicos , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Antineoplásicos/efeitos adversos , Anticorpos Biespecíficos/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológicoRESUMO
BACKGROUND: Guidelines recommend using discharge checklists to discharge patients receiving parenteral nutrition (PN). Transition-of-care (TOC) tools have not been extensively studied in the PN population. The purpose of this study is to evaluate the impact of a standardized PN discharge checklist on TOC for PN patients. METHODS: This is an Institutional Review Board-approved, retrospective quasi-experimental study of patients discharged receiving PN between January 1, 2014, and May 31, 2018. The primary end point was the completion of a PN discharge bundle (identification of a responsible provider to monitor PN after discharge, meeting daily caloric requirement of 20-35 kcal/kg/d, cycling PN prior to discharge). Secondary end points included documentation of PN discharge checklist components, hospital length of stay, frequency of 30-day hospital encounters, cause of hospital encounters, and time to readmission. RESULTS: Fifty encounters were included in the pregroup and postgroup each (n = 100). There was a significant increase in completion of the TOC bundle in the postgroup (54% vs 76%, P = .035), driven by identification of a responsible provider for outpatient PN management (54% vs 82%, P = .005). Other PN discharge checklist components impacted included the following: case manager had the PN prescription for home infusion (50% vs 80%, P = .003), assessment for home glucometer (40% vs 90%, P < .001), and PN plan-of-care note documentation at discharge (18% vs 82%, P < .001). CONCLUSIONS: A standardized PN discharge checklist improved completion of discharge bundle.