RESUMEN
OBJECTIVES: Graft-versus-host disease (GvHD) is one of the leading causes of morbidity and mortality in patients undergoing allogeneic HSCT, and effective prevention of GvHD is critical for the success of the HSCT procedure. Calcineurin inhibitors (CNI) have been used for decades as the backbone of GvHD prophylaxis. In this study, the efficacy and safety of Cyclosporine A (CsA) and tacrolimus (TCR) were compared in pediatric HSCT for thalassemia. MATERIALS AND METHODS: This is a retrospective analysis of 129 pediatric patients who underwent HSCT with the diagnosis of thalassemia at Medicalpark Göztepe and Antalya Hospitals between January 2017 and December 2020. RESULTS: Despite the GvHD prophylaxis, grade II-IV acute GvHD developed in 29 patients. Of these patients, 12 had only gut, 10 had only skin, 6 had combined gut and skin, and one had only liver GvHD. Fifteen of these 29 patients were in the CsA group, and 14 of them were in the TCR group. There was no significant difference between the groups in terms of acute GvHD occurrence, GvHD stage, or involvement sites. In terms of CNI-related toxicity, neurotoxicity in 15 (CsA n = 9, TCR n = 6) and nephrotoxicity in 18 (CsA n = 4, TCR n = 14) patients were observed. While there was no difference between the two groups in terms of neurotoxicity, more nephrotoxicity developed in patients using TCR (p = .013). There was no significant difference between the groups in terms of engraftment syndrome, veno-occlusive disease, CMV reactivation, PRES, or graft rejection. CONCLUSION: Regarding GvHD, there was no difference in efficacy between TCR and CsA usage. Patients taking TCR experienced noticeably higher nephrotoxicity in terms of adverse effects. This difference should be considered according to the patient's clinical situation while choosing a CNI.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Talasemia , Humanos , Niño , Ciclosporina/uso terapéutico , Tacrolimus/uso terapéutico , Inmunosupresores/uso terapéutico , Estudios Retrospectivos , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Injerto contra Huésped/epidemiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Inhibidores de la Calcineurina/uso terapéutico , Receptores de Antígenos de Linfocitos TRESUMEN
OBJECTIVE: The selection of graft-vs. -host disease (GvHD) prophylaxis is vital for the success of hematopoetic stem cell transplantation (HSCT), and calcineurin inhibitors (CNI) have been used for decades as the backbone of GvHD prophylaxis. The aim of this study is to analyze the results of switching cyclosporine (CSA) to tacrolimus because of acute GvHD, engraftment syndrome (ES), persistent low level of CSA, or various CSA-associated adverse events in the first 100 days of pediatric HSCT. MATERIALS AND METHODS: This is a retrospective analysis of 192 patients who underwent allogeneic hematopoietic stem cell transplantation at Medicalpark Göztepe and Antalya Hospitals between April 2014 and May 2019 had therapy switched from CSA to tacrolimus-based immunosuppression within 100 days of transplant. RESULTS: The reasons for conversion to tacrolimus were low level of CSA (n = 70), aGvHD (n = 63), CSA-associated neurotoxicity (n = 15), CSA-associated nephrotoxicity (n = 10), hypertension (n = 10), allergic reactions (n = 9), ES (n = 7), CSA-associated hepatotoxicity (n = 5), and vomiting (n = 3). The median day after transplant for conversion to tacrolimus for all patients was day 20 (range 0-100 days). Response rates to conversion were 38% for GvHD, 86% for neurotoxicity, 50% for nephrotoxicity, 60% for hepatotoxicity, 80% for hypertension, 66% for vomiting, and 57% for ES. Twenty-nine patients (15%) experienced tacrolimus-associated toxicities after therapy conversion to tacrolimus. Neurotoxicity emerged as posterior reversible encephalopathy syndrome (PRES), which was the most common toxicity observed after conversion (18/29 patients). CONCLUSION: Our data support the quick conversion to tacrolimus in the condition of persistent low CSA levels with acceptable efficacy and safety. Although both drugs are CNI and share a very similar mechanism of action, the conversion could be preferred especially in specific organ toxicities with special attention for neurotoxicity after conversion.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Síndrome de Leucoencefalopatía Posterior , Niño , Ciclosporina/uso terapéutico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Inmunosupresores/uso terapéutico , Estudios Retrospectivos , TacrolimusRESUMEN
BACKGROUND: ALD is a rare X-linked peroxisomal metabolic disorder with many distinct phenotypes of disease that emerge on a wide scale from adrenal insufficiency to fatal cALD which progresses to a vegetative state within a few years. Currently, HSCT is the only treatment method known to stabilize disease progression in patients with cALD. In this study, we aim to report our HSCT experience in patients with cALD and the factors that determine the success of HSCT, as a single-center experience. METHODS: The study cohort involves 23 boys with cALD and three patients with ALD trait and new-onset abnormal behavior who underwent allogeneic HSCT between January 2012 and September 2019 in our transplantation center. Loes scoring, NFS, scale and MFD were performed for evaluating the severity of the cerebral disease. The study cohort was divided into two groups according to baseline NFS and Loes score: early-stage (NFS ≤ 1 and Loes score <9) and advanced stage (NFS > 1 or Loes score ≥9). RESULTS: The pretransplant stage of disease impacted both OS and MFD-free survival. The estimated OS and MFD-free survival at 3 years in patients with advanced disease were 46.1% (95% CI 19.0-73.2) and 23.1% (95% CI 0.2-46.0), respectively, and all patients with the early disease were alive (p: .004) and MFD-free (p < .001) at 3 years. CONCLUSION: This study demonstrated that early HSCT is vital in patients with cALD. The early-stage disease had a significant survival advantage and free from disease progression after HSCT.
Asunto(s)
Adrenoleucodistrofia/terapia , Trasplante de Células Madre Hematopoyéticas , Adrenoleucodistrofia/mortalidad , Factores de Edad , Niño , Preescolar , Estudios de Seguimiento , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Trasplante HomólogoRESUMEN
Severe aplastic anemia (SAA) is a life-threatening hematological disease characterized by the suppression of the bone marrow. Patients with SAA are predisposed to recurrent bacterial infections and invasive fungal infections (IFI) due to profound and persistent neutropenia. Mucorales are the second most common cause of IFI encountered in SAA. Here we present a pediatric case of SAA with active mucormycosis infection of the paranasal sinuses. In the first step, surgical debridement was performed and combined antifungal therapy (liposomal amphotericin B, posaconazole, caspofungin) was started. Due to severe neutropenia, daily granulocyte transfusion was added to therapy. Hyperbaric oxygen therapy was applied for wound healing. After all this the patient went under flap surgery. One week after the successful flap procedure, HSCT was performed and he had no complications related to HSCT. The patient was followed in the outpatient clinic for 6 months with posaconazole. Now, he is out of drugs and followed without problems for 15 months after HSCT. Our case confirms that urgent HSCT with multiple therapies (surgical debridement, granulocyte support, combined antifungal therapy, hyperbaric O2) is crucial for saving life in SAA patients with active mucormycosis.