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Acquired factor V inhibitors after allogeneic hematopoietic stem cell transplantation in a dog.

ABSTRACT: OBJECTIVE:Describe the clinical course and management of a dog that underwent hematopoietic stem cell transplantation (HSCT) for treatment of B-cell lymphoma and developed acquired circulating factor V (FV) inhibitors. CASE SUMMARY:An 8-year-old male castrated Briard dog diagnosed with lymphoma (IVb, B-cell) presented for allogeneic HSCT. Despite multiple platelet, fresh frozen plasma, and red blood cell transfusions prolonged recovery and clinical bleeding occurred. Circulating acquired FV inhibitors were identified and hemorrhage subsequently was managed by immunosuppression. The dog was discharged when clinical resolution of bleeding was achieved. NEW OR UNIQUE INFORMATION PROVIDED:This case report describes a dog undergoing curative intent treatment for lymphoma, and subsequently acquiring factor inhibition, and was successfully managed. Specific coagulation screening to assess for coagulation factor deficiencies or inhibitors is essential in the diagnosis and treatment of patients with refractory bleeding or only transient response to blood transfusion.

SUBMITTER: Masciana J

PROVIDER: S-EPMC7517841 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Acquired factor V inhibitors after allogeneic hematopoietic stem cell transplantation in a dog.

Masciana Joseph J Peterson Nathan N Chretin John J

Journal of veterinary internal medicine 20200720 5

<h4>Objective</h4>Describe the clinical course and management of a dog that underwent hematopoietic stem cell transplantation (HSCT) for treatment of B-cell lymphoma and developed acquired circulating factor V (FV) inhibitors.<h4>Case summary</h4>An 8-year-old male castrated Briard dog diagnosed with lymphoma (IVb, B-cell) presented for allogeneic HSCT. Despite multiple platelet, fresh frozen plasma, and red blood cell transfusions prolonged recovery and clinical bleeding occurred. Circulating a ...[more]

PMID: 32686109

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Project description:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapeutic option for many patients with hematological malignancies and nonmalignant hematopoietic disorders. To achieve stable engraftment of donor hematopoietic stem cells (HSCs), recipient HSC deletion is needed to create space for incoming donor HSCs and donor HSCs must escape immune rejection by the recipient. Conventional allo-HSCT requires high dose of irradiation and/or chemotherapy to produce sufficient host stem cell and immune system ablation to permit donor HSC engraftment. However, these procedures also result in nonspecific tissue injury that can cause short- and long-term adverse effects as well as incite and amplify graft-versus-host-disease (GVHD). The delivery of targeted radiotherapy to hematopoietic tissues with the use of a radioimmunoconjugate (ROIC) as a part of transplant preparative regimen has shown clinical benefits. ROIC clinical data provide evidence for decreased relapse without increased transplant-related mortality by delivering higher targeted radiation to sites of malignancy than when given in a nontargeted fashion. An alternative approach to allo-HSCT has been developed and tested in preclinical mouse models in which nonmyeloablative preconditioning with low dose of the alkylating agent (busulfan) or lower systemic dose of irradiation combined with co-stimulatory pathway blockade (CTLA4-Ig, anti-CD40L monoclonal antibody) and/or immunosuppressive drugs have been used. Under these conditions, mixed chimerism and transplantation tolerance to fully MHC mismatched donor marrow was observed. Recently, several novel proof-of-concept antibody-mediated preconditioning methods have been developed that can selectively target hematopoietic stem and immune cells with minimal overall toxicity. Antibody-drug-conjugate (ADC) combined with reduced intensity conditioning or high dose ADC as single dose monotherapy have shown promise for allo-HSCT in preclinical models. The purpose of the current review is to discuss the literature exploring antibody-based conditioning that includes native antibody, radiolabeled antibody conjugates, and ADC for allo-HSCT.

Project description:BackgroundBased on sequence variation in the UL55 gene that encodes glycoprotein B (gB), human cytomegalovirus (CMV) can be classified into four gB genotypes. Previous studies have suggested an association between CMV gB genotype and clinical outcome in patients who underwent an allogeneic hematopoietic stem cell transplant (HSCT). The goals of this study were identify patients with active infection caused by CMV in recipients of HSCT; determine the prevalence of CMV genotypes in the study group; correlate genotype with CMV disease, acute GVHD and overall survival.MethodsThe diagnosis of active CMV infection after allogeneic HSCT was detected by antigenemia (AGM) and/or nested-PCR (N-PCR). Positive samples from patients with active CMV infection were submitted to genotyping using N-PCR to amplify a region of UL55, followed by restriction analysis based on HinfI and RsaI digestion. Real-time PCR (qPCR) was used to determine the viral load during active CMV infection and antiviral treatment.ResultsSixty-three allogeneic HSCT recipients were prospectively evaluated; 49/63 (78%) patients were infected with CMV genotypes - gB1 19/49 (39%), gB2 17/49 (35%), gB3 3/49 (6%), gB4 7/49 (14%) - and 3 (6%) had mixed CMV genotypes (gB1 + gB3, gB1 + gB4 and gB2 + gB4). Characterized by gastrointestinal disease, CMV disease occurred in 3/49 (6.1%) patients, who had CMV gB3 genotype. These gB3 genotype patients presented an increasing AGM number, mean 125 (± 250) (P = 0.70), and qPCR copies/ml, mean 37938 (SD ± 50542) (P = 0.03), during antiviral treatment, when compared with other CMV genotypes. According to CMV genotypes, stratified overall survival was 55% for gB1, 43% for gB2; 0% for gB3 and 57% for gB4 (P = 0.03).ConclusionsOne of the restrictions of the presented study was the low number of CMV gB sub-cohorts). However, we demonstrated that the frequency of active CMV infection in this HSCT population was high, and the most prevalent genotype in these patients with active CMV infection was gB1 and gB2 genotype (74%). In Brazil, HSCT recipients seem to carry mainly gB1 and gB2 CMV genotype.

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Acquired factor V inhibitors after allogeneic hematopoietic stem cell transplantation in a dog.

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Acquired factor V inhibitors after allogeneic hematopoietic stem cell transplantation in a dog.

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