دورية أكاديمية
Use of Eculizumab in Pediatric Patients with High-Risk Transplantation-Associated Thrombotic Microangiopathy: Outcomes and Risk Factors Associated with Response and Survival. A Retrospective Study on Behalf of the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC).
| العنوان: | Use of Eculizumab in Pediatric Patients with High-Risk Transplantation-Associated Thrombotic Microangiopathy: Outcomes and Risk Factors Associated with Response and Survival. A Retrospective Study on Behalf of the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC). |
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| المؤلفون: | Benítez Carabante MI; Division of Pediatric Hematology and Oncology, Hospital Universitari Vall d´Hebron, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain., Bueno D; Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario La Paz, idiPAZ Research Institute, Madrid, Spain., Alonso García L; Division of Pediatric Hematology and Oncology, Hospital Universitari Vall d´Hebron, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain., López Torija I; Department of Pediatric Hematology and Oncology, Hospital Santa Creu i Sant Pau, Barcelona, Spain., Marsal J; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, Barcelona, Spain., Fernandez Navarro JM; Department of Pediatric Hematology and Oncology, Hospital Universitari i Politècnic la Fe, Valencia, Spain., Uria Oficialdegui ML; Division of Pediatric Hematology and Oncology, Hospital Universitari Vall d´Hebron, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain., Panesso M; Division of Pediatric Hematology and Oncology, Hospital Universitari Vall d´Hebron, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain., Molina B; Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain., Beléndez Bieler C; Department of Pediatric Hematology and Oncology, Hospital General Universitario Gregorio Marañón, Madrid, Spain., Palomo P; Department of Pediatric Hematology and Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain., Pérez Martínez A; Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario La Paz, idiPAZ Research Institute, Madrid, Spain., Diaz-de-Heredia C; Division of Pediatric Hematology and Oncology, Hospital Universitari Vall d´Hebron, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Electronic address: cristina.diazdeheredia@vallhebron.cat. |
| المصدر: | Transplantation and cellular therapy [Transplant Cell Ther] 2024 Jun; Vol. 30 (6), pp. 601.e1-601.e13. Date of Electronic Publication: 2024 Mar 21. |
| نوع المنشور: | Journal Article; Multicenter Study |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc Country of Publication: United States NLM ID: 101774629 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-6367 (Electronic) Linking ISSN: 26666367 NLM ISO Abbreviation: Transplant Cell Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [New York] : Elsevier Inc., [2021]- |
| مواضيع طبية MeSH: | Antibodies, Monoclonal, Humanized*/therapeutic use , Thrombotic Microangiopathies*/drug therapy , Thrombotic Microangiopathies*/etiology , Hematopoietic Stem Cell Transplantation*/adverse effects, Humans ; Retrospective Studies ; Male ; Female ; Child ; Risk Factors ; Child, Preschool ; Adolescent ; Treatment Outcome ; Infant ; Spain/epidemiology ; Complement Inactivating Agents/therapeutic use |
| مستخلص: | Transplantation-associated thrombotic microangiopathy (TA-TMA) is associated with high morbidity and mortality. Although survival has improved significantly with the introduction of eculizumab, the need for improvement remains, especially in high-risk patients. This study aimed to describe the results obtained with eculizumab in a pediatric cohort with the attempt to define which risk factors could determine the response to treatment. We designed a national multicenter retrospective study of children treated with eculizumab for high-risk TA-TMA. The study cohort comprised 29 patients who had undergone a first (n = 28) or second (n = 1) allogeneic hematopoietic stem cell transplantation (HSCT) for malignant (n = 17) or nonmalignant (n = 12) disease. The median time from HSCT to TA-TMA diagnosis was 154 days (interquartile range [IQR], 103 to 263 days). Eleven patients (38%) who were initially diagnosed with low- to intermediate-risk TA-TMA progressed to high-risk TA-TMA (hrTA-TMA), within a median time of 4 days (IQR, 1 to 33 days). SC5b-9 was increased in 90% of 20 patients in whom it was measured. Renal (n = 12), pulmonary (n = 1), and intestinal (n = 1) biopsy confirmed the diagnosis in 12 of 14 patients (85%). Seventeen patients (58%) had extrarenal involvement with serositis (n = 13; 44,8%), pulmonary (n = 12; 41,4%), gastrointestinal (n = 8; 27.6%), cardiovascular (n = 7; 24.1%), or central nervous system (CNS) (n = 2; 6.9%) involvement. The median time from hrTA-TMA diagnosis to the initiation of eculizumab was 7 days (IQR, 1 to 8 days). Overall, 19 patients (65.5%) responded to eculizumab, of whom 17 (58.6%) achieved a complete response and 2 (6.9%) achieved a partial response. The remaining 10 patients (34.5%) did not show any of response. The overall response rate to eculizumab for TA-TMA was 27.59% (95% confidence interval [CI], 14.87% to 47.66%) at 1 month, 55.17% (95% CI, 38.43% to 73.48%) at 3 months, and 62.07% (95% CI, 45.10% to 79.13%) at 6 months after eculizumab initiation. In multivariate analysis, the pulmonary involvement decreased the probability of response (hazard ratio [HR], .18; P = .0298). The 1-year overall survival (OS) was 55.2% (95% CI, 35.6% to 71.0%) for the whole cohort and 83.3% (95% CI, 56.7% to 94.3%) for patients who responded to eculizumab. Pulmonary involvement (HR, 14.93; P = .0043) and CNS involvement (HR, 8.63; P = .0497) were associated with a statistically significant decrease in survival. We found that patients diagnosed with hrTA-TMA with pulmonary involvement had a poor response to eculizumab, and that patients with pulmonary and CNS involvement had significantly decreased survival. Given these results, we hypothesize that providing eculizumab therapy at an early stage of the disease before organ damage is established might significantly improve the response and, consequently, survival. (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Children; Eculizumab; Hematopoietic stem cell transplantation (HSCT); Transplantation-associated thrombotic microangiopathy (TA-TMA) |
| المشرفين على المادة: | A3ULP0F556 (eculizumab) 0 (Antibodies, Monoclonal, Humanized) 0 (Complement Inactivating Agents) |
| تواريخ الأحداث: | Date Created: 20240323 Date Completed: 20240530 Latest Revision: 20240814 |
| رمز التحديث: | 20240815 |
| DOI: | 10.1016/j.jtct.2024.03.019 |
| PMID: | 38521410 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 2666-6367 |
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| DOI: | 10.1016/j.jtct.2024.03.019 |