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Analyzing the clinical outcomes of switching from cyclosporine to tacrolimus in pediatric hematopoietic stem cell transplantation

Clinical Transplantation (2021)

Koray Yalçın Suna Çelen Suleimen Zhumatayev Hayriye Daloğlu Dayanat Pashayev

Abstract 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.

Nephrotoxicity

Immunosuppression

10.1111/ctr.14328

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Citations (3)

Hematopoietic Stem Cell Transplantation From Unrelated Donor in Children with Beta Thalassemia Major

Biology of Blood and Marrow Transplantation (2018)

Gülsün Karasu Vedat Uygun Hayriye Daloğlu Suar Çakı Kılıç Seda Öztürkmen

Background: Although, regular red cell transfusion and advanced iron chelation therapy alternatives have improved life expectancy, allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option for patients with beta thalassemia major. However, the availability of HLA-matched related donor remains the main obstacle for allogenic HSCT. A few promising studies have been reported but experience with HLA matched unrelated donors is limited. Here, we present the result of 51 children with beta thalassemia major who received allogeneic HSCT from HLA-matched unrelated donors. Patients and methods: We retrospectively assessed 51 unrelated HSCT in children with beta thalassemia major. All patients received busulphan (BU) based myeloablative conditioning regimen. Busulphan was used according to weight adjusted dose and cumulative AUC of 85-90 mg/Lxh. In addition, all patients received fludarabine 150 mg/m2 in five days, cylophosphamide 120 mg/kg in 3 days, thio-tepa 10 mg/kg and ATG 30 mg/kg in 3 days. Cyclosporin-A and MTX were used for graft versus host disease (GVHD) prophylaxis. Donor chimerism was evaluated in either bone marrow or peripheral blood on days +30, +100 and +180. Results: The median age of the patients was 87 months (range 14-184 month). Two of patients were Class I and 49 of them Class II. The median serum ferritin level was 1.277 ng/ml (range, 425-5832). All of the donors were 10/10 matched with HLA high resolution in GVHD direction but 9 of them 9/10 matched in graft failure direction. Thirty-four of them received BM (median TNC: 6.6 × 108, range; 1.62-17.60) and 17 PBSC (median MNC: 7.05 × 108, range; 5.0-13.0) with median CD34+ cell number 7.23 × 106 (range 1.54-15.70). The median neutrophil and platelet engraftment days were 14 and 18 days in PBSC and 17 and 23 days in BM group, respectively. Grade I-IV acute GVHD was observed in 11 patients (22%), six of which experienced Grade II-IV (12%). Chronic GVHD was not observed. Moderate VOD was seen in 15 patients (29%) and treated with defibrotide successfully. We lost one patient because of sepsis on post-transplant day 124. Graft failure was experienced in one and graft rejection in 2 patients. All the other patients are alive with full donor chimerism (between 95.47-100%) with a median 14 months (range 3-46 months) follow up. Probability of thalassemia-free (TFS) and overall survival (OS) were found 92% and 98%, respectively. Discussion and conclusion: These data shown that the results of HSCT from unrelated donors in selected low risk thalassemia patients (Class I & II) may comparable to HSCT from matched sibling donors. We believe that having a fully matched donor is an important role in successful outcomes in patients who underwent unrelated stem cell transplantation. However, it needs further studies with long term follow up and larger study population.

Beta thalassemia

Cumulative incidence

10.1016/j.bbmt.2017.12.512

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Citations (1)

Frequency and Risk Factors of Veno-occlusive Disease After Allogenic Hematopoietic Stem Cell Transplantation in Children

LLM Dergi (2018)

Gülsün Karasu Vedat Uygun Seda Öztürkmen Suar Çakı Kılıç Hayriye Daloğlu

Amaç: Bu çalışmada, merkezimizdeki allojenik hematopoetik kök hücre transplantasyonu (HKHT) sonrası çocuklarda hepatik veno-oklusif hastalık (VOH) insidansını ve klinik özelliklerini değerlendirmek amaçlanmıştır

Occlusive

Hepatic veno-occlusive disease

10.5578/llm.66565

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H1N1 associated encephalitis in a child with acute myeloblastic leukemia and bacteremia due to Klebsiella pneumonia

Turkish Journal of Hematology (2012)

Lale Olcay Seda Öztürkmen Zafer Bıçakcı Arzu Akyay Gülşen İskender

Herein we present a neutropenic 16-year-old female with acute myeloblastic leukemia that developed recurrent generalized seizures while receiving antimicrobial therapy (including oseltamivir) due to pneumonia, bacteremia of Klebsiella pneumoniae, and H1N1 infection.The patient's seizures were controlled using assisted ventilation.Electroencephalography showed that the patient had encephalopathy.Cranial computed tomography (CT), magnetic resonance imaging (MRI), and MRI angiography findings were normal.The patient fully recovered without sequelae.This case indicates that during pandemics of influenza-like diseases H1N1 infection should always be a consideration.

Bacteremia

Klebsiella pneumonia

Klebsiella infections

Klebsiella

10.5505/tjh.2012.80947

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Citations (0)

Mean platelet volume increased in children with asthma

Pediatric Allergy and Immunology (2015)

Mahmut Doğru Alev Aktaş Seda Öztürkmen

10.1111/pai.12381

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Citations (15)

COVID-19 disease in children and adolescents following hematopoietic stem cell transplantation: A report from the Turkish Pediatric Bone Marrow Transplantation Study Group

Authorea (Authorea) (2023)

Ceyhun Bozkurt Volkan Hazar Barış Malbora Alphan Küpesiz Utku Aygüneş

Background: Data on the outcome and risk factors of pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited. Objectives: We aimed to describe risk factors for a severe course and mortality. Method: In this nationwide study, data were collected retrospectively from 28 transplant centers. Results: One hundred ninety-six children [(63.8% male; median age 8.75 (IQR, 4.86-14.30)] who received allogeneic (n: 184, 93.9%) or autologous (n: 12, 6.1%) HSCT were included. The median time from HSCT to SARS-CoV-2 infection was 207.5 days (IQR, 110.2-207.5). The most common clinical manifestation was fever (58.2%), followed by cough (33.7%); 43 cases (21.9%) were asymptomatic. Lower respiratory tract disease (LRTD) and multisystem inflammatory syndrome in children (MIS-C) developed in 58 (29.6%) and 8 (4.1%) patients, respectively. Twenty-six patients (13.3%) required ICU admission. Nine patients died at a median of 17 days (min-max 1-33) after COVID-19 diagnosis, 6 of whom died due to the disease, with a COVID-19 lethality rate of 3.1%. The 6-week overall survival was 95.4% (95% CI 92.5-98.3). Multivariate analysis found that HSCT with a mismatched donor (OR, 8.98, p: 0.039) and LRTD (OR, 61.55, p: 0.001) were independent risk factors for ICU admission; MIS-C (OR, 9.55, p: 0.044) and lymphopenia (OR, 4.01, p: 0.030) at diagnosis were risk factors for mortality. Conclusion: Overall mortality was lower in children than in adult counterparts, and HSCT with a mismatched donor, lymphopenia, LRTD, MIS-C and ICU admission were important risk factors for adverse outcomes.

10.22541/au.168197609.90571507/v1

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Timing of Initiation of Calcineurin Inhibitors in Pediatric Haploidentical Transplantation with Post-Transplantation Cyclophosphamide: Effects on Survival, Relapse, and Cytokine Release Syndrome

Acta Haematologica (2021)

Vedat Uygun Gülsün Karasu Koray Yalçın Seda Öztürkmen Hayriye Daloğlu

The use of unmanipulated haploidentical hematopoietic stem cell transplantations (haplo-HSCT) with post-transplant cyclophosphamide (PTCY) in children has emerged as an acceptable alternative to the patients without a matched donor. However, the timing of calcineurin inhibitors (CNIs) used in combination with PTCY is increasingly becoming a topic of controversy.We evaluated 49 children with acute leukemia who underwent unmanipulated haplo-HSCT with PTCY according to the initiation day of CNIs (pre- or post-cyclophosphamide [CY]).There were no significant differences in the overall survival analysis between the 2 groups. The cumulative incidence of relapse at 2 years was 21.2% in the pre-CY group and 38.9% in the post-CY group (p = 0.33). Cytokine release syndrome (CRS) was observed more frequently in the post-CY group (p = 0.04). The overall survival and event-free survival at 2 years in patients with and without CRS in the pre-CY group were 42.9% versus 87.5% (p = 0.04) and 38.1% versus 87.5% (p = 0.04), respectively.Our study shows that the argument for starting CNI administration after CY is tenuous, and the rationale for not starting CNIs before CY needs to be reconsidered.

Cumulative incidence

Cytokine Release Syndrome

10.1159/000521211

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Citations (2)

Granulocyte transfusion therapy in paediatric patients with severe neutropenic infection

Transfusion and Apheresis Science (2013)

Seda Öztürkmen Fevzi Altuntaş Lale Olcay

Oliguria

Leukopenia

Platelet Transfusion

10.1016/j.transci.2013.04.022

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Citations (16)

Timing of Initiation of Calcineurin Inhibitors in Pediatric Haploidentical Transplantation with Post-Transplantation Cyclophosphamide: Effects on Survival, Relapse, and Cytokine Release Syndrome

Research Square (Research Square) (2021)

Vedat Uygun Gülsün Karasu Koray Yalçın Seda Öztürkmen Hayriye Daloğlu

Abstract The use of unmanipulated haploidentical stem cell transplantations (haplo-HSCT) with post-transplant cyclophosphamide (PTCY) in children has emerged as an acceptable alternative to the patients without a matched donor. However, the timing of calcineurin inhibitors (CNI) used in combination with PTCY is increasingly becoming a topic of controversy. We evaluated 49 children with acute leukemia who underwent unmanipulated haplo-HSCT with PTCY according to the initiation day of CNIs (pre- or post-CY). There were no significant differences in the overall survival analysis between the two groups. The cumulative incidence of relapse at 2 years was 21.2% in the pre-CY group and 38.9% in the post-CY group (p = 0.33). Cytokine release syndrome (CRS) was observed more frequently in the post-CY group. Our study shows that the argument for starting CNI administration after CY is tenuous, and the rationale for not starting CNI before CY needs to be reconsidered.

Cumulative incidence

Cytokine Release Syndrome

10.21203/rs.3.rs-428093/v1

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Citations (0)

Clinical Effects of Vitamin D in Children with Asthma

International Archives of Allergy and Immunology (2014)

Mahmut Doğru Heves Kırmızıbekmez Gül Yeşiltepe Mutlu Alev Aktaş Seda Öztürkmen

Both asthma and vitamin D deficiency are common among children. The results from studies examining the relationship between them are contradictory. The aim of this study is to determine the relationship between the clinical parameters of asthma and vitamin D status in children.One hundred and twenty children diagnosed with asthma and followed-up in our hospital were included in the study. The control group included 74 children with no evidence of allergic disease. The eosinophil counts, IgE levels and serum 25 OH cholecalciferol [25(OH)D] levels were measured.The patient group consisted of 73 (60.8%) males and 47 (39.2%) females with a mean age of 4.4 ± 1.2 years. There was no significant difference between the patient and control groups with respect to gender and age. The mean 25(OH)D level was 21.49 ± 7.74 ng/ml in the study group and 23.94 ± 8.97 ng/ml in the control group, and this difference was not significant (p = 0.094). The patients with asthma were grouped according to their vitamin D status as 'deficient' (group 1), 'insufficient' (group 2) and 'normal' (group 3). The sociodemographic features, duration of illness, number of hospitalizations, number of sensitivities to allergens, eosinophil count and serum IgE levels were not found to be different between the groups. However, the total number of exacerbations, asthma severity and systemic glucocorticoid need in the previous year were significantly higher in the deficiency group (p < 0.05).Vitamin D levels were not significantly different in patients with asthma. Vitamin D deficiency was common in the study group as well as in the control group. The clinical severity of disease, the number of exacerbations and the systemic glucocorticoid need were related to vitamin D level.

Group B

Group A

10.1159/000366279

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Citations (48)