RESUMO
INTRODUCTION: Hepatic veno-occlusive disease (VOD) is a critical medical emergency with a high mortality rate of up to 90% if not promptly treated. Defibrotide is the only approved medication for VOD treatment, exhibiting anti-inflammatory, antithrombotic, and anti-ischemic properties. This report presents a case of severe VOD in a patient undergoing acute lymphoblastic leukemia (ALL) treatment. CASE PRESENTATION: We describe the successful and rapid treatment of severe VOD in an ALL patient using therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and methylprednisolone (MPZ). The patient showed significant clinical and laboratory improvement after this combined therapeutic approach. CONCLUSION: This case highlights the effectiveness of TPE, IVIG, and MPZ in the treatment of severe VOD in ALL patients, providing insights into alternative therapeutic strategies in the absence of Defibrotide.
Assuntos
Hepatopatia Veno-Oclusiva , Imunoglobulinas Intravenosas , Metilprednisolona , Troca Plasmática , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Hepatopatia Veno-Oclusiva/tratamento farmacológico , Hepatopatia Veno-Oclusiva/terapia , Troca Plasmática/métodos , Imunoglobulinas Intravenosas/uso terapêutico , Imunoglobulinas Intravenosas/administração & dosagem , Metilprednisolona/uso terapêutico , Metilprednisolona/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Masculino , Polidesoxirribonucleotídeos/uso terapêutico , Terapia Combinada , FemininoRESUMO
Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a well-recognized complication of allogeneic and autologous hematopoietic cell transplantation (HCT). The diagnosis and treatment of VOD/SOS require the involvement of multiple specialists covering a wide range of expertise. Interprofessional team-based medical care is standard practice for patients undergoing HCT and has been shown to improve patient and provider satisfaction, enhance efficiency, and improve patient outcomes, particularly for patients in complex medical situations like those with VOD/SOS post-HCT. Interdisciplinary team-based models focus on the synthesis and harmonization of knowledge and methods from different disciplines to create an integrative approach to patient care that both maximizes the expertise of each involved specialist and encourages thought beyond each specialist's discipline. Multidisciplinary team members provide additive support and work collaboratively with the core team to provide knowledge from their field. The composition of the interdisciplinary HCT team should center on the needs of the patient and institutional resources and involve the expertise of additional multidisciplinary team members based on clinical needs. This review focuses on interdisciplinary and multidisciplinary team-based care of patients with VOD/SOS post-HCT and provides an example of a collaborative VOD/SOS team that includes transplant physicians, nurses, pharmacists, nutrition/dietary specialists, and intensive care teams.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva , Humanos , Hepatopatia Veno-Oclusiva/etiologia , Hepatopatia Veno-Oclusiva/terapia , Hepatopatia Veno-Oclusiva/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante Autólogo/efeitos adversos , PolidesoxirribonucleotídeosRESUMO
Chemotherapy-induced veno-occlusive disease (VOD) is a rare liver dysfunction seen among pediatric cancer patients which could lead to severe morbidity and mortality. Defibrotide is the commonly used antidote in the management of both stem cell transplant and chemotherapy-associated VOD along with liver supportive measures. Defibrotide is costly and generally not accessible to majority of patients treated at resource poor settings. In this report, we describe the successful management of chemotherapy-induced VOD with timely administration of N-acetyl cysteine.
Assuntos
Antineoplásicos , Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva , Doenças Vasculares , Criança , Humanos , Polidesoxirribonucleotídeos/farmacologia , Hepatopatia Veno-Oclusiva/terapia , Hepatopatia Veno-Oclusiva/tratamento farmacológico , Análise Custo-Benefício , Acetilcisteína/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/etiologia , Antineoplásicos/efeitos adversosRESUMO
Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) affecting the liver is a rare, possibly life-threatening complication of hematopoietic stem cell transplantation (HSCT). Sinusoidal endothelial cell (SEC) damage triggered by various factors (especially conditioning regimen) results in post sinusoidal portal hypertension due to obstruction of the hepatic vein. Diagnosis is guided by traditional clinical diagnostic criteria; the modified Seattle criteria, the Baltimore and revised European Group for Blood and Marrow Transplantation (EBMT), specifically. While there are promising results of imaging techniques studies in the diagnosis of VOD/SOS, none of those imaging techniques are routinely utilized in diagnosis yet. However, risk stratification is essential; conflicting results have been shown in studies aiming to define risk factors for development of VOD/SOS conducted to date. The only approved drug for the treatment of VOD/SOS yet is defibrotide, with early treatment offering higher chances of survival. In this review, we will focus on pathogenesis, clinical presentation and diagnostic criteria, risk factors, prophylaxis, and treatment of the VOD/SOS occurring post-HSCT.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/diagnóstico , Hepatopatia Veno-Oclusiva/terapia , Condicionamento Pré-Transplante/efeitos adversos , Hepatopatia Veno-Oclusiva/fisiopatologia , Humanos , Incidência , Fatores de RiscoRESUMO
Hepatic veno-occlusive disease (VOD), also termed sinusoidal obstruction syndrome (SOS), is a rare and life threatening complication of hematopoetic stem cell transplantation (HSCT). Many conditions can mimic the clinical signs of VOD/SOS. Differential diagnosis and diagnosis of the disease at an early stage is important, since the severe form of the disease has higher mortality rates and early-initiated specific treatment has better response rates. A sensitive and specific non-invasive imaging technique that can diagnose the disease at an early stage is still an unmet need today. We aimed to determine the role of liver stiffness measurement (LSM) with transient elastograph (TE) for the diagnosis of VOD/SOS after allogeneic HSCT. Between January 2019 and October 2021, a total of 49 patients underwent allogeneic HSCT and were retrospectively analyzed. Thirty-one adult patients who had a two or more LSM value were included in the study. Revised European Society for Blood and Marrow Transplantation (EBMT) was the criteria used for the diagnosis of VOD/SOS. Two of 31 patients developed VOD/SOS (6.4 %). Very high LSM values were detected in all patients who developed VOD/SOS. Early and specific VOD/SOS treatment resulted in improvement of LSM values together with other related features. However, LSM values did not increase significantly in patients with high a bilirubin level (≥2 mg/dl) without VOD/SOS. This study demonstrates that TE might be a promising non-invasive imaging method for diagnosis, follow-up and differential diagnosis of this dismal complication of HSCT. Yet, these results need to be supported by prospective studies.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Hepatopatia Veno-Oclusiva/diagnóstico , Hepatopatia Veno-Oclusiva/terapia , Fígado/diagnóstico por imagem , Adulto , Feminino , Hepatopatia Veno-Oclusiva/patologia , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Hepatic sinusoidal obstruction syndrome (HSOS) is a hepatic vascular disease histologically characterized by edema, necrosis, detachment of endothelial cells in small sinusoidal hepatic and interlobular veins and intrahepatic congestion, which leads to portal hypertension and liver dysfunction. In the Western world, most HSOS cases are associated with myeloablative pretreatment in a hematopoietic stem cell transplantation setting. Here we report a case of a 54 years old female patient, otherwise healthy, with no history of alcoholic ingestion, who presented with jaundice and signs of portal hypertension, including ascites and bilateral pleural effusion. She had no history of liver disease and denied any other risk factor for liver injury, except Senecio brasiliensis ingestion as a tea, prescribed as a therapy for menopause. Acute viral hepatitis and thrombosis of the portal system were excluded in complementary investigation, as well as sepsis, metastatic malignancy and other liver diseases, setting a RUCAM score of 6. Computed tomography demonstrated a diffuse liver parenchymal heterogeneity (in mosaic) and an extensive portosystemic collateral venous circulation, in the absence of any noticeable venous obstruction. HSOS diagnosis was confirmed through a liver biopsy. During the following-up period, patient developed refractory pleural effusion, requiring hemodialysis. Right before starting anticoagulation, she presented with abdominal pain and distention, with findings compatible of mesenteric ischemia by computed tomography. A laparotomy was performed, showing an 80cm segment of small bowel ischemia, and resection was done. She died one day after as a result from a septic shock refractory to treatment. The presented case was related to oral intake of S. brasiliensis, a plant containing pyrrolidine alkaloids, which are one of the main causes of HSOS in the East, highlighting the risk of liver injury with herbs intake.
Assuntos
Hepatopatia Veno-Oclusiva/diagnóstico , Hepatopatia Veno-Oclusiva/etiologia , Senécio/efeitos adversos , Brasil , Evolução Fatal , Feminino , Hepatopatia Veno-Oclusiva/terapia , Humanos , Pessoa de Meia-IdadeRESUMO
Hepatic veno-occlusive disease (HVOD), alias sinusoidal obstruction syndrome, may develop as a complication of chemotherapy in the setting of hematopoietic stem cell transplantation. HVOD is less frequently described after exposure to chemotherapy in the nontransplant setting and can also be a complication after ingestion of toxins, such as pyrrolizidine alkaloids. Veno-occlusive disease may also affect the lungs, and it is therefore termed pulmonary veno-occlusive disease (PVOD). Similarly, PVOD can develop after exposure to chemotherapeutic agents in the treatment of solid and hematological malignancies. In addition, PVOD has also been linked to autoimmune disorders and occupational solvent exposure. Finally, the heritable form of PVOD is due to biallelic mutations of the EIF2AK4 gene. Both HVOD and PVOD share common histopathological features and pathophysiologic mechanisms. Both clinical disorders are rare complications that can appear after exposure to the common inciting trigger of chemotherapeutic agents. The present review aims to summarize the current knowledge of HVOD and PVOD and to describe both similarities as well as differences regarding both conditions.
Assuntos
Hepatopatia Veno-Oclusiva/patologia , Pneumopatia Veno-Oclusiva/patologia , Animais , Diagnóstico Diferencial , Modelos Animais de Doenças , Predisposição Genética para Doença , Hepatopatia Veno-Oclusiva/diagnóstico , Hepatopatia Veno-Oclusiva/etiologia , Hepatopatia Veno-Oclusiva/terapia , Humanos , Prognóstico , Pneumopatia Veno-Oclusiva/diagnóstico , Pneumopatia Veno-Oclusiva/etiologia , Pneumopatia Veno-Oclusiva/terapia , Ratos , Fatores de RiscoRESUMO
Hepatic veno-occlusive disease (HVOD) characterized by endothelial cell dysfunction is one of the serious complications after hematopoietic stem-cell transplantation or chemotherapeutic drug application. The mortality of HVOD patients with multiorgan dysfunction is as high as 80%. The primary aim of this study was to evaluate whether the infusion of human umbilical cord-derived endothelial colony forming cells (hUC-ECFCs) could mitigate HVOD injury and investigate the underlying mechanism. We found that the expression of chemokine C-X-C chemokine ligand 12 (CXCL12) was markedly increased in the livers of HVOD mice. Meanwhile, hUC-ECFCs infusion could significantly ameliorate liver injury in HVOD mice, which was accompanied by hUC-ECFCs recruitment in the liver, reduced liver pathological alterations, and decreased serum alanine aminotransferase and aspartate aminotransferase activity. Besides, CXCL12-induced migration in hUC-ECFCs was partly impeded by chemokine receptor type 7 (CXCR7) silence or CXCR4 blockage. In conclusion, our results demonstrated that hUC-ECFCs could mitigate HVOD through homing to the injured liver via the CXCL12-CXCR4/CXCR7 signaling pathway.
Assuntos
Hepatopatia Veno-Oclusiva/terapia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Animais , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Quimiocina CXCL12/metabolismo , China , Células Endoteliais/metabolismo , Hepatopatia Veno-Oclusiva/metabolismo , Hepatopatia Veno-Oclusiva/patologia , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Receptores CXCR/metabolismo , Receptores CXCR4/metabolismo , Cordão Umbilical/citologiaRESUMO
BACKGROUND: Sinusoidal obstruction syndrome (SOS) is a life-threatening complication after hematopoietic stem cell transplantation (HSCT). Most adult patients with SOS present with jaundice, whereas hyperbilirubinemia does not always occur in children. Additionally, while late-onset SOS is rare in adults, 15-20% of SOS cases develop beyond day 30 after HSCT in children. PROCEDURE: We investigated the incidence and prognosis of children with anicteric and late-onset SOS. We retrospectively analyzed the data of patients who developed SOS after HSCT conducted at our center between 2000 and 2016. RESULTS: A total of 22 patients with a median age of 6.5 years (range: 0-16), including 14 males and eight females, developed SOS. Eight of the twenty-two patients were diagnosed as having anicteric SOS, and nine as having late-onset SOS. Patients with anicteric SOS had significantly lower incidence of SOS-related death at 100 days after HSCT (12.5% vs 64.3%, P = 0.03) and higher 2-year overall survival (OS) rate (60.0% vs 14.3%, P = .04) than patients with icteric SOS. One patient with anicteric SOS died from progression of SOS. There were no significant differences observed in these endpoints between patients who developed SOS before and after 21 days from HSCT. CONCLUSIONS: Careful monitoring is needed for the development of SOS even in the absence of jaundice, and even at 3 weeksafter HSCT in children.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva/mortalidade , Adolescente , Idade de Início , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Hepatopatia Veno-Oclusiva/etiologia , Hepatopatia Veno-Oclusiva/terapia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
PURPOSE: Sinusoidal obstruction syndrome (SOS) is one of the most serious complications post haematopoietic stem cell transplantation (HSCT). The diagnosis of SOS is clinical, but nurses should be involved in the pre-transplant risk assessment period and play a crucial role in the early detection of signs and symptoms during and after hospitalization. The aim of this work is to achieve a consensus on nurses' behaviour in caring for SOS. METHODS: On behalf of the Italian Group for Bone and Marrow Transplantation (GITMO), a promoter committee was established to put in place a consensus conference approach. A multidisciplinary group of GITMO together with four nurses, three haematology physicians and one patient representative acted as jury, who reviewed the reports and wrote recommendations and suggestions. Recommendations gaining 100% of consensus were considered 'Golden Points of Care'; if a consensus was achieved by ≥ 75% of the jury's members, those recommendations were defined as 'Good Practices'. RESULTS: Eighteen papers written by nurses as first authors have been identified. Golden Points of Care and Good Practices were worked out for the following topics: nurses' role in general, nurses' role in pre-transplant assessment, pre-transplant risk assessment and risk stratification, baseline monitoring, suspected mild or moderate SOS, suspected severe or very severe SOS and late-onset cases. CONCLUSION: SOS is relatively rare; therefore, a holistic approach to the patients' needs considering nursing role as essential may result in better care outcomes.
Assuntos
Hepatopatia Veno-Oclusiva/enfermagem , Adulto , Transplante de Medula Óssea/efeitos adversos , Criança , Consenso , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/diagnóstico , Hepatopatia Veno-Oclusiva/terapia , Humanos , Itália , Masculino , Papel do Profissional de Enfermagem , Medição de RiscoRESUMO
Hepatic sinusoidal obstruction syndrome (HSOS) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively evaluated the incidence, risk factors, treatment and survival for HSOS after allo-HSCT in Turkey. We also reported our experience of defibrotide (DF) for HSOS prophylaxis in high-risk (HR) patients. Across Turkey, 1153 patients from 10 centers were enrolled in the study. We evaluated the medical records of patients who were treated with allo-SCT between January 2012 and December 2015. The study included 1153 patients (687 males/466 females) with median age of 38 (15-71) years. The incidence of HSOS was 7.5 % (n = 86). The incidences of HSOS in the HR/DF+, HR/DF- and standard risk (SR) group were 8%, 66.7 % and 6.2 %, respectively. The rate of HSOS development was not statistically different between HR/DF + and SR group (p = 0.237). HSOS prophylaxis (defibrotide) was significantly decreased HSOS-related mortality (p = 0.004). The incidence of HSOS was found similar to literature in this large Turkish cohort. Defibrotide prophylaxis appears to be associated with low incidence of HSOS development and reduced HSOS-related mortality. Although these results are promising, future studies are needed to support the efficacy of defibrotide prophylaxis in patients with risk of HSOS.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Hepatopatia Veno-Oclusiva/terapia , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Turquia , Adulto JovemRESUMO
Hepatic sinusoidal obstruction syndrome (HSOS) is a hepatic vascular disease presenting with abdominal distension, pain in the hepatic region, ascites, jaundice, and hepatomegaly. In China, this disease is often associated with the oral intake of plants that contain pyrrolidine alkaloids. The existing guidelines are limited to HSOS associated with hematopoietic stem cell transplantation in Western countries. The Hepatobiliary Diseases Committee of the Chinese Society of Gastroenterology convened an expert consensus conference on the diagnosis and treatment of PA-HSOS to evaluate current research in China and abroad. The "Nanjing criteria" developed by the committee to diagnose PA-HSOS include a confirmed history of PA-containing plant use and (i) abdominal distention and/or pain in the hepatic region, hepatomegaly, and ascites; (ii) elevation of serum total bilirubin or abnormal laboratory liver tests; (iii) evidence on enhanced computed tomography or magnetic resonance imaging; or (iv) pathological evidence that rules out other known causes of liver injury. Supportive symptomatic treatment, anticoagulant therapy, and placement of a transjugular intrahepatic portosystemic shunt for patients who do not respond to medical treatment are effective for the treatment of PA-HSOS. The benefits of glucocorticoids and prostaglandin E1 in PA-HSOS are not clear.
Assuntos
Consenso , Hepatopatia Veno-Oclusiva/induzido quimicamente , Hepatopatia Veno-Oclusiva/terapia , Plantas/química , Alcaloides de Pirrolizidina/efeitos adversos , Anticoagulantes/uso terapêutico , Bilirrubina/sangue , Biomarcadores , China , Hepatopatia Veno-Oclusiva/diagnóstico , Hepatopatia Veno-Oclusiva/fisiopatologia , Humanos , Testes de Função Hepática , Imageamento por Ressonância Magnética , Derivação Portossistêmica Cirúrgica/métodos , Alcaloides de Pirrolizidina/isolamento & purificação , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND AND AIMS: Hematopoietic stem cell transplantation related hepatic vein occlusive disease (HSCT-HVOD) has been researched extensively; however, little is known about the clinical features and treatment of pyrrolizidine alkaloid-induced HVOD (PA-HVOD). This retrospective single centre study examined the clinical and laboratory characteristics of 108 patients with acute PA-HVOD and explored the efficacy of anticoagulation and TIPS therapy. METHODS: The study included 108 consecutive patients with PA-HVOD between July 2008 and June 2016. The clinical manifestations and the results of laboratory and imaging tests were evaluated. The survival rates of patients treated with different approaches were recorded. RESULTS: Serum total bilirubin was <34.2 µmol/L (2 mg/dL) in approximately 40% of patients. More than 90% of patients were presented with hepatomegaly, uneven liver perfusion in the balance phase, compressive stenosis of the hepatic segmental inferior vena cava and decreased peak velocity of portal vein blood flow. Severe portal hypertension was observed in all patients undergoing HVPG examination or TIPS operation. Anticoagulation therapy with low molecular weight heparin combined with warfarin was significantly more effective than liver protection and supportive therapy, and TIPS further improved the prognosis of patients who did not respond to anticoagulation therapy. The total effective rate of the anticoagulation-TIPS ladder therapeutic strategy was 91%. CONCLUSIONS: Patients with PA-HVOD had different characteristics than those with HSCT-HVOD. Anticoagulation and TIPS treatment may be effective for patients with PA-HVOD.
Assuntos
Hepatopatia Veno-Oclusiva/induzido quimicamente , Fígado/patologia , Alcaloides de Pirrolizidina/efeitos adversos , Idoso , Anticoagulantes/uso terapêutico , Bilirrubina/sangue , Feminino , Hepatopatia Veno-Oclusiva/terapia , Humanos , Hipertensão/etiologia , Masculino , Pessoa de Meia-Idade , Derivação Portossistêmica Transjugular Intra-Hepática , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Hepatic veno-occlusive disease (HVOD) caused by Gynura segetum has been increasingly reported in China in recent years. The aim of this retrospective study was to identify independent prognostic markers for survival in patients with Gynura segetum-induced HVOD and to evaluate the effect of anticoagulants and transjugular intrahepatic portosystemic shunt (TIPS) on survival rate. METHODS: Clinical data including symptoms, signs, imaging characteristics, laboratory test results, results of liver tissue biopsies, type of treatment during follow-up and clinical outcomes were collected. Univariate, multivariate and time-dependent Cox regression analyses were performed. RESULTS: Survival rates were 91% (95% confidence interval [CI], 82-95%), 64% (95% CI, 53-69%) and 57% (95% CI, 51-65%) at 1, 3 and 60 months, respectively. Total bilirubin, albumin and hepatic encephalopathy were independent prognostic markers of survival. Anticoagulants were administered to 76% of the patients. Among 75 patients treated with anticoagulants, 49 patients (65.3%) were cured, whereas 26 patients (34.7%) died; the cure rate in anticoagulant-treated patients was higher than that of those not treated with anticoagulants (χ2 = 9.129, P = 0.004). Cure rate of the anticoagulation + TIPS treatment group was 64.3%, which was also higher than that of the non-anticoagulation group; however, this was not significantly different (χ2 = 3.938, P = 0.096). CONCLUSIONS: The presence of hepatic encephalopathy, serum bilirubin and albumin levels were major prognostic factors for Gynura segetum-induced HVOD. Anticoagulation therapy significantly increased the cure rate; however, TIPS treatment did not have a beneficial effect on the cure rate.
Assuntos
Medicamentos de Ervas Chinesas/efeitos adversos , Hepatopatia Veno-Oclusiva/induzido quimicamente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Bilirrubina/sangue , Feminino , Encefalopatia Hepática/etiologia , Hepatopatia Veno-Oclusiva/sangue , Hepatopatia Veno-Oclusiva/complicações , Hepatopatia Veno-Oclusiva/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Derivação Portossistêmica Cirúrgica , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/metabolismo , Taxa de Sobrevida , Adulto JovemRESUMO
Maintaining fluid balance, pre- and post-MA-HCT is essential and usually requires frequent administration of diuretics. Hepatic sinusoidal obstructive syndrome is potentially life-threatening, especially when associated with AKI and MOF. This study describes six patients who developed AKI-associated SOS and diuretic-resistant FO who subsequently underwent CRRT using standardized management guidelines for fluid balance post-HCT. Retrospective chart review was done for HCT patients between September 2011 and October 2013 at a tertiary care children's hospital. Thirty-four patients underwent MA-HCT in the study period. Six patients had SOS complicated by diuretic-resistant FO and underwent CRRT. Defibrotide was used in three patients. Median time on CRRT was 10.5 days. Sixty-six percent (N = 4 of 6) of patients had full resolution of SOS symptoms with a mortality rate of 34% (N = 2 of 6). Among patients who had full recovery of SOS symptoms, one patient developed AKI, end-stage renal diseases and underwent kidney transplantation 34-months post-HCT. Thus, of six included patients, two died and one developed ESRD with only 50% (N = 3 of 6) good outcome. Use of a standardized, evidence-based fluid balance protocol and early initiation of CRRT for HCT-related AKI/SOS was associated with good outcomes.
Assuntos
Injúria Renal Aguda/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/terapia , Terapia de Substituição Renal/métodos , Injúria Renal Aguda/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Oligonucleotides (oligos) have been under clinical development for approximately the past 30 years, beginning with antisense oligonucleotides (ASOs) and apatmers and followed about 15 years ago by siRNAs. During that lengthy period of time, numerous clinical trials have been performed and thousands of trial participants accrued onto studies. Of all the molecules evaluated as of January 2017, the regulatory authorities assessed that six provided clear clinical benefit in rigorously controlled trials. The story of these six is given in this review.
Assuntos
Aptâmeros de Nucleotídeos/uso terapêutico , Morfolinos/uso terapêutico , Oligonucleotídeos Antissenso/uso terapêutico , Oligonucleotídeos/uso terapêutico , Polidesoxirribonucleotídeos/uso terapêutico , Tionucleotídeos/uso terapêutico , Ensaios Clínicos como Assunto , Retinite por Citomegalovirus/genética , Retinite por Citomegalovirus/terapia , Retinite por Citomegalovirus/virologia , Aprovação de Drogas , Hepatopatia Veno-Oclusiva/genética , Hepatopatia Veno-Oclusiva/patologia , Hepatopatia Veno-Oclusiva/terapia , Humanos , Hipercolesterolemia/genética , Hipercolesterolemia/patologia , Hipercolesterolemia/terapia , Degeneração Macular/genética , Degeneração Macular/patologia , Degeneração Macular/terapia , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/patologia , Atrofia Muscular Espinal/terapia , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/patologia , Distrofia Muscular de Duchenne/terapiaRESUMO
Veno-occlusive disease (VOD) is a common and potentially fatal complication in children undergoing hematopoietic cell transplantation (HCT). It occurs in about one-third of all patients undergoing transplantation and is fatal in 50% of patients with severe disease. Early intervention and specific treatment with defibrotide are associated with improved outcomes. However, there is a lack of supportive care guidelines for management of the multiorgan dysfunction seen in most cases. There is high variability in the management of VOD, which may contribute to the increased morbidity and mortality. Although there is ample research in the specific treatment of VOD, there is paucity of literature regarding the management of ascites, transfusions requirements, fluids and electrolyte dysfunction, delirium, and investigations in children with VOD. The joint working committees of the Pediatric Acute Lung Injury and Sepsis Investigators and the Pediatric Blood and Marrow Transplantation Consortium collaborated to develop a series of evidence-based supportive care guidelines for management of VOD. The quality of evidence was rated and recommendations were made using Grading of Recommendations, Assessment, Development and Evaluation criteria. This manuscript is part 1 of the series and focuses on the need to develop these guidelines; methodology used to establish the guidelines; and investigations needed for diagnosis, prophylaxis, and treatment of VOD in children.
Assuntos
Lesão Pulmonar Aguda , Hepatopatia Veno-Oclusiva/terapia , Sepse , HumanosRESUMO
Hepatic veno-occlusive disease, or sinusoidal obstruction syndrome (VOD/SOS), is a serious and potentially fatal complication of conditioning for hematopoietic stem cell transplantation (HSCT) or of chemotherapy regimens alone. Defibrotide is a complex mixture of single-stranded polydeoxyribonucleotides that is approved in the United States for treating hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT and in the European Union, Israel, and South Korea for treating severe hepatic VOD/SOS post-HSCT. Defibrotide was previously available in the United States as an investigational drug through a treatment protocol (treatment IND) study. Interim results of that large, treatment IND study of patients with VOD/SOS and with or without multiorgan dysfunction (MOD; also known as multiorgan failure) are presented here. Defibrotide was administered i.v. at 6.25 mg/kg every 6 hours (25 mg/kg/day), with a recommended treatment duration of at least 21 days. Enrolled patients (n = 681) were diagnosed with VOD/SOS based on Baltimore or modified Seattle criteria or liver biopsy analysis. Among the 573 HSCT recipients, 288 (50.3%; 95% confidence interval [CI], 46.2% to 54.4%) were alive at day +100 post-HSCT. Day +100 survival for the pediatric (≤16 years) and adult (>16 years) subgroups was 54.5% (95% CI, 49.1% to 60.0%; n = 174 of 319) and 44.9% (95% CI, 38.8% to 51.0%; n = 114 of 254), respectively. In the MOD subgroup, 159 of 351 patients (45.3%; 95% CI, 40.1% to 50.5%) of patients were alive at day +100 post-HSCT. Treatment with defibrotide was generally well tolerated, and drug-related toxicities were consistent with previous studies. Adverse events were reported in 69.6% of safety-evaluable patients (399 of 573). Other than VOD/SOS and associated MOD symptoms, the most commonly reported treatment-emergent adverse event was hypotension (13.8%). Day +100 survival results observed in this trial were consistent with results seen in previous trials of defibrotide for VOD/SOS in adult and pediatric patients. These data support the potential benefit of defibrotide in treating a VOD/SOS patient population that includes those with and without MOD.