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Cytomegalovirus (CMV) infection is a significant complication in hematopoietic cell transplantation (HCT) recipients. Four antiviral drugs are used for preventing or treating CMV: ganciclovir, valganciclovir, foscarnet, and cidofo...
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Cytomegalovirus (CMV) infection is a significant complication in hematopoietic cell transplantation (HCT) recipients. Four antiviral drugs are used for preventing or treating CMV: ganciclovir, valganciclovir, foscarnet, and cidofovir. With prolonged and repeated use of these drugs, CMV can become resistant to standard therapy, resulting in increased morbidity and mortality, especially in HCT recipients. Antiviral drug resistance should be suspected when CMV viremia (DNAemia or antigenemia) fails to improve or continue to increase after 2 weeks of appropriately dosed and delivered antiviral therapy. CMV resistance is diagnosed by detecting specific genetic mutations. UL97 mutations confer resistance to ganciclovir and valganciclovir, and a UL54 mutation confers multidrug resistance. Risk factors for resistance include prolonged or previous anti- CMV drug exposure or inadequate dosing, absorption, or bioavailability. Host risk factors include type of HCT and degree of immunosuppression. Depending on the genotyping results, multiple strategies can be adopted to treat resistant CMV infections, albeit no randomized clinical trials exist so far, after reducing immunosuppression (if possible): ganciclovir dose escalation, ganciclovir and foscarnet combination, and adjunct therapy such as CMV- specific cytotoxic T- lymphocyte infusions. Novel therapies such as maribavir, brincidofovir, and letermovir should be further studied for treatment of resistant CMV.
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Patients with hematologic malignancies and recipients of hematopoietic cell transplantation (HCT) are more likely to experience severe coronavirus disease 2019 (COVID-19) and have a higher risk of morbidity and mortality after inf...
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Patients with hematologic malignancies and recipients of hematopoietic cell transplantation (HCT) are more likely to experience severe coronavirus disease 2019 (COVID-19) and have a higher risk of morbidity and mortality after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Compared with the general population, these patients have suboptimal humoral responses to COVID-19 vaccines and subsequently increased risk for breakthrough infections, underscoring the need for additional therapies, including pre-and postexposure prophylaxis, to attenuate clinical progression to severe COVID-19. Therapies for COVID-19 are mostly available for adults and in the inpatient and outpatient settings. Selection and administration of the best treatment options are based on host factors; virus factors, including circulating SARS-CoV-2 variants; and therapeutic considerations, including the clinical efficacy, availability, and practicality of treatment and its associated side effects, including drug-drug interactions. In this paper, we discuss how we approach managing COVID-19 in patients with hematologic malignancies and recipients of HCT and cell therapy.
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Since Jehovah's Witness (JW) patients diagnosed with leukaemia refuse blood transfusions, they are often denied intensive chemotherapy for fear they could not survive myeloablation without blood transfusion support. Treatment of J...
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Since Jehovah's Witness (JW) patients diagnosed with leukaemia refuse blood transfusions, they are often denied intensive chemotherapy for fear they could not survive myeloablation without blood transfusion support. Treatment of JW patients with acute leukaemia is challenging and carries a higher morbidity and mortality; however, the refusal of blood products should not be an absolute contraindication to offer multiple treatment modalities including haematopoietic stem cell transplantation. In this review we discuss their optimal management and describe alternative modalities to blood transfusions to provide sufficient oxygenation and prevent bleeding.
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Background. CD19-directed chimeric antigen receptor (CAR) T-cell therapy (CAR-T) has emerged as effective for relapsed/refractory large B-cell lymphoma (R/R LBCL). The neurologic toxicity seen with CAR-T, referred to as immune eff...
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Background. CD19-directed chimeric antigen receptor (CAR) T-cell therapy (CAR-T) has emerged as effective for relapsed/refractory large B-cell lymphoma (R/R LBCL). The neurologic toxicity seen with CAR-T, referred to as immune effector cell-associated neurotoxicity syndrome (ICANS), is poorly understood.To better elucidate the clinical characteristics, treatment outcomes, and correlative biomarkers of (CANS, we review here a single-center analysis of ICANS after CART-cell therapy in R/R LBCL.Methods. Patients (n = 45) with R/R LBCL treated with axicabtagene ciloleucel (axi-cel) were identified. Data regarding treatment course, clinical outcomes, and correlative studies were collected. Patients were monitored and graded for (CANS via CARTOX-10 scoring and Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria, respectively.Results. Twenty-five (56%) patients developed (CANS, 18 (72%) of whom had severe (CTCAE grades 3-4) ICANS. Median time to development of ICANS was 5 days (range, 3-11). Elevated pre-infusion (day 0 [D0]) fibrinogen (517 vs 403 mg/dL, upper limit of normal (ULN) 438 mg/dL, P= 0.01) and D0 lactate dehydrogenase (618 vs 506 units/L, ULN 618 units/L, P= 0.04) were associated with ICANS. A larger drop in fibrinogen was associated with (CANS (393 vs 200, P< 0.01). Development of (CANS of any grade had no effect on complete remission (CR), progression-free survival (PFS), or overall survival (OS). Duration and total dose of steroid treatment administered for ICANS did not influence CR, PFS, or OS.Conclusions. ICANS after CAR-T with axi-cel for R/R LBCL was seen in about half of patients, the majority of which were high grade. Contrary to previous reports, neither development of ICANS nor its treatment were associated with inferior CR, PFS, or OS. The novel finding of high DO fibrinogen level can identify patients at higher risk for ICANS.
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Patients infected with HIV remain at increased risk of mortality and morbidity from diseases that are preventable with vaccines partly due to the persisting immunopathology that results in impaired responses to vaccination despite...
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Patients infected with HIV remain at increased risk of mortality and morbidity from diseases that are preventable with vaccines partly due to the persisting immunopathology that results in impaired responses to vaccination despite virologic suppression. Because data on clinical effectiveness in patients who are immunocompromised remain limited, undervaccination of individuals with HIV poses a major concern. Multiple societies have published recommendations on vaccination in individuals infected with HIV. Many of these recommendations are based on extrapolation of data from clinical trials that usually exclude patients with HIV, although there is a growing body of data from patients infected with HIV as well. In this review, we describe the available literature on vaccine response in the adult patient with HIV as measured by immunogenicity or vaccine efficacy. (C) 2019 Elsevier Inc. All rights reserved.
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Most patients with high CMV-CMI and low-level CMV reactivation did not progress to clinically significant CMV infection. Low CMV-CMI and steroids use were the only predictors for CMV progression from low-level reactivation.Cytomeg...
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Most patients with high CMV-CMI and low-level CMV reactivation did not progress to clinically significant CMV infection. Low CMV-CMI and steroids use were the only predictors for CMV progression from low-level reactivation.Cytomegalovirus (CMV) infections in hematopoietic cell transplant (HCT) recipients cause substantial morbidity and mortality. CMV cell-mediated immunity (CMV-CMI) can be determined by levels of interferon gamma (IFN-) production using an enzyme-linked immunospot (ELISPOT) CMV assay (T-SPOT.CMV assay). In this study, we evaluated the ability of this assay to predict the outcome of low-level CMV reactivation in HCT recipients.
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BACKGROUND: Human metapneumovirus (hMPV) causes upper and lower respiratory tract infections (URIs and LRIs, respectively) in healthy and immunocompromised patients; however, its clinical burden in patients with cancer remains unk...
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BACKGROUND: Human metapneumovirus (hMPV) causes upper and lower respiratory tract infections (URIs and LRIs, respectively) in healthy and immunocompromised patients; however, its clinical burden in patients with cancer remains unknown. METHODS: In a retrospective study of all laboratory-confirmed hMPV infections treated at the authors' institution between April 2012 and May 2015, clinical characteristics, risk factors for progression to an LRI, treatment, and outcomes in patients with cancer were determined. RESULTS: In total, 181 hMPV infections were identified in 90 patients (50%) with hematologic malignancies (HMs), in 57 (31%) hematopoietic cell transplantation (HCT) recipients, and in 34 patients (19%) with solid tumors. Most patients (92%) had a community-acquired infection and presented with URIs (67%), and 43% developed LRIs (59 presented with LRIs and 19 progressed from a URI to an LRI). On multivariable analysis, an underlying HM (adjusted odds ratio [aOR], 3.11; 95% confidence interval [CI], 1.12-8.64; P=.029), nosocomial infection (aOR, 26.9; 95% CI, 2.79-259.75; P=.004), and hypoxia (oxygen saturation [SpO(2)], 收起
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Over the past decade, reported incidence of human metapneumovirus (hMPV) has increased owing to the use of molecular assays for diagnosis of respiratory viral infections in cancer patients. The seasonality of these infections, dif...
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Over the past decade, reported incidence of human metapneumovirus (hMPV) has increased owing to the use of molecular assays for diagnosis of respiratory viral infections in cancer patients. The seasonality of these infections, differences in sampling strategies across institutions, and small sample size of published studies make it difficult to appreciate the true incidence and impact of hMPV infections. In this systematic review, we summarized the published data on hMPV infections in hematopoietic cell transplant recipients and patients with hematologic malignancy, focusing on incidence, hMPV-associated lower respiratory tract infection (LRTI), mortality, prevention, and management with ribavirin and/or intravenous immunoglobulins. Although the incidence of hMPV infections and hMPV-associated LRTI in this patient population is similar to respiratory syncytial virus or parainfluenza virus and despite lack of directed antiviral therapy, the mortality rate remains low unless patients develop LRTI. In the absence of vaccine to prevent hMPV, infection control measures are recommended to reduce its burden in cancer patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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Hematopoietic cell transplant (HCT) recipients have lower immune response to influenza vaccination and are susceptible to lower respiratory tract infection (LRI) and death. We determined clinical characteristics and outcomes of la...
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Hematopoietic cell transplant (HCT) recipients have lower immune response to influenza vaccination and are susceptible to lower respiratory tract infection (LRI) and death. We determined clinical characteristics and outcomes of laboratory-confirmed influenza, including 2014/H3N2 infection, in 146 HCT recipients. An immunodeficiency scoring index (ISI) was applied to identify patients at high risk for LRI and death. Thirty-three patients (23%) developed LRI and 7 (5%) died within 30 days of diagnosis. Most patients received antiviral therapy (83%); however, only 18% received it within 48 hours of symptom onset. The incidence of LRI was significantly higher in the ISI high-risk group than it was in the low-risk group (P < .001). Receiving early antiviral therapy was associated with a substantial reduction in LRI for all ISI risk groups with the greatest risk reduction observed in the high-risk group. When compared with previous seasons, no significant differences in patient outcomes were observed during the 2014/H3N2 season; however, antiviral therapy was more promptly initiated in the latter season. The ISI that was originally developed for respiratory syncytial virus may help identify HCT recipients at risk for progression to LRI and mortality after influenza infection. These patients should be monitored more closely. Early initiation of antiviral therapy for influenza in HCT recipients, regardless of the ISI risk group, may improve morbidity as well as mortality. (C) 2016 American Society for Blood and Marrow Transplantation.
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Cytomegalovirus (CMV) reactivation is a clinically significant complication in hematopoietic stem cell transplant (HCT) recipients. Alternative therapy for multidrug-resistant CMV is limited and often fails. Leflunomide has been u...
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Cytomegalovirus (CMV) reactivation is a clinically significant complication in hematopoietic stem cell transplant (HCT) recipients. Alternative therapy for multidrug-resistant CMV is limited and often fails. Leflunomide has been used to treat resistant CMV infections, however, data on efficacy, safety, and guidance for therapeutic drug level monitoring are lacking. In this report, we describe 3 HCT recipients with multi-drug resistant CMV infections who received leflunomide as adjuvant and salvage therapy. The therapeutic effect of leflunomide as an anti-CMV agent based on virologic responses and therapeutic drug monitoring were evaluated. (C) 2016 Elsevier B.V. All rights reserved.
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