COVID-19 disease in children and adolescents following allogeneic hematopoietic stem cell transplantation: A report from the Turkish pediatric bone marrow transplantation study group.

BACKGROUND: Data on the risk factors and outcomes for pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited. OBJECTIVES: The study aimed to analyze the clinical signs, risk factors, and outcomes for ICU admission and mortality in a large pediatric cohort who underwent allogeneic HSCT prior to COVID-19 infection. METHOD: In this nationwide study, we retrospectively reviewed the data of 184 pediatric HSCT recipients who had COVID-19 between March 2020 and August 2022. RESULTS: The median time from HSCT to COVID-19 infection was 209.0 days (IQR, 111.7-340.8; range, 0-3845 days). The most common clinical manifestation was fever (58.7%). While most patients (78.8%) had asymptomatic/mild disease, the disease severity was moderate in 9.2% and severe and critical in 4.4% and 7.6%, respectively. The overall mortality was 10.9% (n: 20). Deaths were attributable to COVID-19 in nine (4.9%) patients. Multivariate analysis revealed that lower respiratory tract disease (LRTD) (OR, 23.20, p: .001) and lymphopenia at diagnosis (OR, 5.21, p: .006) were risk factors for ICU admission and that HSCT from a mismatched donor (OR, 54.04, p: .028), multisystem inflammatory syndrome in children (MIS-C) (OR, 31.07, p: .003), and LRTD (OR, 10.11, p: .035) were associated with a higher risk for COVID-19-related mortality. CONCLUSION: While COVID-19 is mostly asymptomatic or mild in pediatric transplant recipients, it can cause ICU admission in those with LRTD or lymphopenia at diagnosis and may be more fatal in those who are transplanted from a mismatched donor and those who develop MIS-C or LRTD.

The impact of Treosulfan-based conditioning for inborn errors of immunity: Is dose monitoring crucial?

INTRODUCTION: In children with inborn errors of immunity (IEI) who will receive a hematopoietic stem cell transplant (HSCT) treosulfan-based conditioning is currently preferred. The aim of this study was to investigate early and late outcomes in pediatric IEI patients receiving pre-HSCT treosulfan and to examine the effect of treosulfan dose monitoring on outcomes. METHODS: Seventy-three pediatric patients receiving this management between 2015 and 2022 were included. RESULTS: Overall survival rate was 80%, and event-free survival was 67.8%. A larger treosulfan dose AUC after first application increased the rate of early toxicity (p = .034) and slowed lymphocyte engraftment (r = .290; p = .030). Underlying disease, treosulfan AUC, donor type, stem cell type, number of immunosuppressive agents, the dose of anti-thymocyte globulin, and post-transplantation cyclophosphamide did not to increase risk of acute graft-versus-host disease. The risk of mixed chimerism (MC) in patients with autoimmune lymphoproliferative syndrome and leukocyte adhesion deficiency were higher than those with severe combined immunodeficiency (p = .021 and p = .014, respectively). The risk of MC was lower in those receiving peripheral blood stem cells (SC) compared with bone marrow derived SC (OR = .204, p = .022). CONCLUSION: The AUC of the treosulfan dose was not associated with poorer late outcomes. Treosulfan is an agent that can be used safely in the IEI patient group,  level measurement appears essential to identify early toxicities. Prospective studies with more extended follow-up periods are needed.

Evaluation of the risk factors for BK virus-associated hemorrhagic cystitis in pediatric bone marrow transplantation patients: Does post-transplantation cyclophosphamide increase the frequency?

BACKGROUND: BKV-HC is one of the most significant complications of HSCT. This retrospective study aimed to determine the frequency of BKV-HC in pediatric patients undergoing HSCT, detect the associated risk factors for the development of BKV-HC, and explore the effects of post-transplantation Cy use. METHODS: Three hundred twenty-seven patients (girls: 121, boys: 206) were analyzed according to sex, conditioning regimen, transplantation type, donor relatedness, stem cell source, the presence and grade of aGVHD, CMV co-existence, and Cy use. RESULTS: Multivariate analysis confirmed the prognostic importance of age (OR: 4.865), TBI use, the presence of aGVHD (OR: 2.794), CMV coinfection (OR: 2.261), and Cy use (OR: 27.353). A statistically significant difference was found between the mean BKV-HC follow-up times compared with post-transplantation Cy intake (p < .001). The BKV-HC rate increased as the number of risk factors of the patient increased. CONCLUSION: BKV-HC is an essential complication of HSCT primarily associated with Cy use, the presence of aGVHD, and donor relatedness. The present study shows that the use of Cy in the post-transplantation period further increases BKV-HC risk in pediatric patients, regardless of dose.

Central Nervous System Fungal Infections in Children With Leukemia and Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Study.

BACKGROUND: Central nervous system fungal infections (CNSFI) are seen in patients with hematologic malignancies and have high morbidity and mortality. Because of their rarity, there is limited data on CNSFI in children with no established treatment protocols or guidelines. MATERIALS AND METHODS: In this multicenter retrospective study, 51 pediatric patients with leukemia, 6 of whom had undergone bone marrow transplantation, with proven or probable CNSFI were evaluated. Fungal infections were defined as proven or probable based on European Organisation for Research and Treatment of Cancer criteria. Proven CNSFI was diagnosed by appropriate central nervous system (CNS) imaging or tissue sample findings in combination with positive microbiological results of cerebrospinal fluid. A positive culture, microscopic evidence of hyphae, a positive result of the galactomannan assays are defined as positive microbiological evidence. Probable CNSFI was defined as appropriate CNS imaging findings together with proven or probable invasive fungal infections at another focus without CNS when there is no other explanatory condition. Data was collected by using the questionnaire form (Supplemental Digital Content 1, http://links.lww.com/JPHO/A541 ). RESULTS: Seventeen patients had proven, 34 patients had probable CNSFI. Headaches and seizures were the most common clinical findings. The median time between the onset of fever and diagnosis was 5 days. The most common fungal agent identified was Aspergillus . Sixteen patients received single-agent, 35 received combination antifungal therapy. Surgery was performed in 23 patients. Twenty-two patients (43%) died, 29 of the CNSFI episodes recovered with a 20% neurological sequelae. CONCLUSION: CNSFIs should be considered in the differential diagnosis in patients with leukemia and refractory/recurrent fever, headache, neurologicalocular symptoms, and a radiologic-serological evaluation should be performed immediately. Early diagnosis and prompt management, both medical and surgical, are essential for improving clinical outcomes.

Primary immunodeficiencies: HSCT experiences of a single center in Turkey.

BACKGROUND: Primary immunodeficiency diseases (PID) are characterized by the occurrence of frequent infections and are caused by many genetic defects. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment option for the majority of PID. As a Pediatric Hematology-Oncology-Immunology Transplantation Unit, we wanted to present our HSCT experience regarding treatment of primary immunodeficiency diseases. METHODS: 58 patients were included in the study between January 2014 and June 2019. We searched 9/10 or 10/10 matched-related donor (MRD) firstly, in the absence of fully matched-related donor. We screened matched unrelated donor (MUD) from donor banks. MRD was used in 24 (41.3%) patients, MUD in 20 (34.4%) patients, and haploidentical donors in 14 (24.1%) patients. Demographic data, HSCT characteristics, and outcome were evaluated. While 16 patients had severe combined immunodeficiency (SCID), the remaining was non-SCID. RESULTS: Of the 58 patients, 38 were male and 20 were female. Median age at transplantation was 12 months (range: 2.5-172 months). Combined immunodeficiencies consisted 67.2% of patients. Mean follow-up time was 27 months (6 months-5 years). Median neutrophil, lymphocyte, and thrombocyte engraftment days were similar in comparison of both donor type and stem cell source. The most common complication was acute GvHD in 15 (25.8%) patients. In total, five patients (31%) belonging to the SCID group and 10 patients (23.8%) belonging to the non-SCID group died. Our total mortality rate was 15 (25.8%) in all patients. CONCLUSIONS: We would like to present our HSCT experiences as a pediatric immunology transplantation center. Existing severe infections before transplantation period, BCGitis, and CMV are important issues of transplantation in Turkey. However, the follow-up time is shorter than some studies, our results regarding complications and survival are similar to previous reports.

Neuroimaging findings of posterior reversible encephalopathy syndrome (PRES) following haematopoietic stem cell transplantation in paediatric recipients.

BACKGROUND: Haematopoietic stem cell transplantation (HSCT) is used worldwide in various malignant and nonmalignant childhood diseases, including haematologic, genetic, autoimmune and metabolic disorders, and is the only curative treatment for many of these illnesses. The survival rates of many childhood diseases have been increased due to HSCT treatment. However, associated complications are still important for management. Central nervous system (CNS) complications in paediatric HSCT recipients can be associated with high morbidity and significantly contribute to mortality. Posterior reversible encephalopathy syndrome (PRES) is one of the most common CNS complications in patients with neurological symptoms following HSCT. Magnetic resonance imaging (MRI) is the modality of choice and shows typical bilateral vasogenic oedema at the posterior parts of the cerebral hemispheres; however, various atypical imaging manifestations can also occur. In this study, we retrospectively examined CNS complications in our paediatric HSCT recipients with a focus on the typical and atypical neuroimaging manifestations of PRES following HSCT. METHODS: We retrospectively reviewed the medical records of 300 consecutive paediatric HSCT recipients from January 2014 to November 2018. A total of 130 paediatric HSCT recipients who experienced neurological signs and symptoms and were evaluated with neuroimaging studies following HSCT were enrolled in the study. The timing of CNS complications was defined according to immune status, including the pre-engraftment period (< 30 days after HSCT), the early postengraftment period (30-100 days after HSCT), and the late postengraftment period (> 100 days after HSCT), which were defined as phases 1, 2 and 3, respectively. RESULTS: Overall, 130 paediatric HSCT recipients experienced neurological signs and symptoms and therefore underwent neuroimaging examinations. Among these 130 patients, CNS complications were present in 23 patients (17.6%, 23/130), including 13 (56.5%) females and 10 (43.5%) males with a median age of 8.0 years (range, 8 months to 18.0 years). Among these 23 patients, 14 cases of PRES (60.9%), 5 (21.7%) cases of leukoencephalopathy, 3 cases of acute subdural haemorrhage (ASDH) (13%) and 1 (4.3%) case of fungal CNS infection were identified by neuroimaging. On MRI, typical parietooccipital vasogenic oedema was present in 78.5% of the PRES cases (11/14). The following atypical neuroimaging manifestations were observed: isolated involvement of the bilateral frontal lobes in 1 case, isolated cerebellar vermis involvement in 1 case, and isolated basal ganglia involvement in 1 case. Restricted diffusion associated with cytotoxic damage was demonstrated in 2 of 14 cases, one of which also showed subacute cytotoxic injury with ADC pseudonormalization. CONCLUSION: Paediatric HSCT recipients presenting with CNS signs and symptoms should be evaluated by neuroimaging studies for timely diagnosis and early management. PRES is the most common CNS complication and may present with atypical MRI manifestations, which should not dissuade a PRES diagnosis in appropriate clinical settings.

Comparison of Hematopoietic Stem Cell Transplantation Results in Patients with ß-Thalassemia Major from Three Different Graft Types.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the curative therapy for ß-thalassemias that induces severe life-threatening complications. The human leukocyte antigen (HLA) registries and umbilical cord blood banks have carried out diligent searches to find matched unrelated donors (MUDs) for about 70.0% of patients from 2000 onwards. The chance of finding a non-sibling fully matched family donors is higher in some ethnic groups in which consanguineous marriages are common. We have studied and compared transplant complications and outcomes in different graft types (sibling, non-sibling family and unrelated). The non-sibling matched family donor (MFD) group consisted of four mothers, three fathers, five cousins, one paternal uncle and one paternal aunt. There was no significant difference in the mean transfused CD34+ cells, engraftment, median days of neutrophil and platelet recovery were achieved (p > 0.05). The distribution of postttransplant complication did not show any significant difference between groups (p > 0.05). In univariate analysis and multivarite analyses, age, gender, Pesaro risk group (I-II vs. III) and ABO incompatibilty demonstrated a significant difference in disease free survival (p < 0.05). Furthermore, in the second step of investigating overall survival (OS), age, gender and Pesaro risk group (I-II vs. III) showed a significant difference (p < 0.05). There was no significant difference in transplant-related mortality (TRM) between groups. Non-sibling related donor transplants are important for populations where consanguineous marriages are common. Transplant groups according to graft type had similar thalassemia-free survival (TFS) and OS when using a treosulfan-based regimen in our study.

Invasive Saprochaete capitata Infection in a Patient with Autosomal Recessive CARD9 Deficiency and a Review of the Literature.

PURPOSE: Autosomal recessive (AR) CARD9 deficiency is an inherited immune disorder which results in impaired innate immunity against various fungi. Superficial and invasive fungal infections, mainly caused by Candida or Trichophyton species, are the hallmark of CARD9 deficiency. Together with the increasing number of CARD9-deficient patients reported, different pathogenic fungal species have been described such as Phialophora, Exophiala, Corynespora, Aureobasidium, and Ochroconis. Saprochaete capitata is an opportunistic infectious agent in immunocompromised patients and is a common cause of invasive fungal disease in patients with hematological malignancies. In this study, we investigated the causative genetic defect in a patient with S. capitata fungal infection which disseminated to lymph nodes and common bile duct. METHODS: The identification of the isolated yeast strain was made by direct microscopic examination and confirmed by internal transcribed spacer (ITS) sequencing. We applied whole exome sequencing to search for the disease-causing mutation. Sanger sequencing was used to validate the mutation in the patient and his parents. RESULTS: S. capitata was isolated from the biopsy specimen as the causative microorganism responsible for the invasive fungal disease in the patient. Whole exome sequencing revealed a homozygous c.883C > T, (p.Q295*) mutation in CARD9, confirmed by Sanger sequencing. CONCLUSIONS: This is the first report of invasive Saprochaete infection associated with autosomal recessive (AR) CARD9 deficiency in the literature and thereby further extends the spectrum of fungal diseases seen in these patients.

Magnetic resonance imaging during management of patients with transfusion-dependent thalassemia: a single-center experience.

BACKGROUND: Cardiac and hepatic magnetic resonance imaging evaluation during treatment can tailor physicians' chelation therapy titrations. AIM: The aim of the study was to assess the relationship of cardiac and hepatic T2* values with chelation therapy in patients with transfusion-dependent thalassemia (TDT). METHODS: A total of 106 patients with TDT who were followed up in Istanbul Medical Faculty Thalassemia Center were evaluated for the study. Forty-eight (45%) patients with TDT had more than one consecutive MRI examination. The patients were divided into three subgroups according to the cardiac T2* values as the high-risk group (T2* MRI < 10 ms), medium-risk group (T2* MRI 10-20 ms), and the low-risk group (T2* MRI > 20 ms). RESULTS: The majority of patients used DFX (deferasirox) (79%) and deferiprone (DFP) (17%). Approximately 80% of patients according to cardiac T2* value and 40% of patients according to hepatic T2* value were initially in the low-risk group. Patients with follow-up MRI examinations exhibited significant improvement in liver iron concentration, which correlated with an increase in hepatic T2* values. The decrease of liver iron concentration was prominent in the DFX group (p < 0.01). The serum ferritin level was significantly correlated with liver iron concentrations (rs = 0.65, p < 0.001), hepatic T2* value (rs = - 0.62, p < 0.001), but not with cardiac T2* value (rs = - 0.20, p = 0.07). CONCLUSION: Cardiovascular and hepatic MRI is a useful follow-up tool during the assessment of risk groups and chelation therapy of patients with TDT. Consecutive MRI tests showed good monitoring of cardiac and liver iron overload.

Olfactory dysfunction and quality of life in patients with transfusion-dependent thalassemia.

Transfusion-dependent thalassemia (TDT) is a group of thalassemia syndromes that require regular blood transfusions for survival. It is unknown whether the sense of smell of patients with TDT is affected, and if so, whether smell loss has an adverse effect on quality of life (QOL). Olfactory thresholds were measured using Snap & Sniff® wands. QOL was assessed via the Short Form-36 (SF-36) questionnaire. Forty-two TDT patients from the Thalassemia Center in Istanbul Medical Faculty were tested (mean age 26.6 years), along with 42 healthy controls (mean age 28.0 years). Mean olfactory sensitivity was lower in the TDT patients than the controls (p < 0.0001). TDT was associated with lower mean QOL scores on the domains of physical function (p < 0.0001), physical role limitation (p = 0.011), and general health (p < 0.0001). Within the TDT group, significant correlations were present between the threshold scores and physical function, physical role limitation, emotional role limitation, and general health. Patients with TDT are less sensitive to odors than healthy controls and the lower olfactory test scores are related to lower quality of life, suggesting that decreased smell function is an additional complication of this disease.

Epidemiologic and microbiologic evaluation of catheter-line bloodstream infection in a pediatric hematopoietic stem cell transplant center.

BACKGROUND: Children who underwent hematopoietic stem cell transplant (HSCT) transplants are at high risk of developing central-line-associated bloodstream infections (CLABSIs). The present study aimed to identify possible risk factors for mortality by analyzing the clinical and laboratory characteristics of patients diagnosed with CLABSI in our pediatric hematopoietic stem cell transplant unit. METHODS: The initial CLABSI episodes of 102 children were analyzed. Medical records of the patients were evaluated by preformed standardized surveys. Univariate analysis and multivariate logistic regression analysis were performed to identify risk factors for mortality. RESULTS: Thirty-five patients (34.3%) were female. The median age was 48 months (3-204). The median time to onset of CLABSI was 19 days (4-150). The gram-negative and gram-positive bacteria ratio among the causative agents was 57.8% to 34.3%. The mortality rate was 12.6%. The presence of severe neutropenia, initiation of inappropriate empirical antibiotic therapy, the presence of hypotension, persistent bacteremia, pediatric intensive care unit admission, growth of carbapenemase-positive gram-negative microorganism and multidrug-resistant bacteria were significantly high in the mortality group when compared to survivors. The presence of hypotension, inappropriate empirical antibiotic therapy, and persistent bacteremia were found to be independent risk factors for mortality. CONCLUSIONS: Rational use of antibiotics, active surveillance and screening of patients together with improved infection control practices may reduce the incidence and the consequences of CLABSIs.

The Effects of Having a Child with Cancer on Parental Psychology: A Cross-Sectional Study.

Objective: In childhood cancers, parents are affected psychologically as well as children. We aimed to evaluate the effect of childhood cancer type and stage, as well as elapsed time from diagnosis, on the anxiety and stress indicators among parents. Materials and Methods: Patients aged between 0-18 years and diagnosed with cancer who were receiving chemotherapy (0-1 month, 1-6 month, 6-12 month) and completed treatment were included. Parents of those children (mother or father) who agreed to participate this study were also included. The personal information form and three psychological assessment scales (Beck Hopelessness Scale (PSS), Psychological Resilience Scale (PRS), Uncertainty Intolerance Scale (IUS)) were used for assessment of mental health of the parents. Scores of the scales and clinical features of the children with cancer were compared statistically. Results: The study included 84 parents (57 mothers, 27 fathers) and 84 children. The rate of children with solid tumors was 60% (n:50) and 40% of them were metastatic, which means advanced stage. The rate of the children with leukemia was 40% (n:34) and 23% of them were in high-risk group. According to the type (leukemia vs. solid tumors) and stage (high risk/advanced stage vs. others) of the cancer, there was no statistical difference among parents in the psychological scales (p > 0.05). Additionally, results of the psychological scales showed no significant difference between mothers and fathers (p > 0.05). The hopelessness scores are significantly higher among parents whose child's treatment is terminated compared with those whose active therapy is ongoing, and resilience scores are higher among parents who have less than 1 month since diagnosis of childhood cancer than later periods. Conclusions: The regular assessment of mental health among parents of children with cancer across all the survivorship trajectory: at the time of diagnosis, during active therapy, and after treatment.

The effect of a multispecies synbiotic mixture on the duration of diarrhea and length of hospital stay in children with acute diarrhea in Turkey: single blinded randomized study.

Probiotics have been successfully used for the treatment of acute diarrhea in children and this effect depends on the strains and dose. The aim of this study was to assess the effect of a synbiotic mixture on the duration of diarrhea and the length of hospital stay in children with acute watery diarrhea. This is a prospective randomized, multicenter single blinded clinical trial in hospitalized children with acute watery diarrhea. All children were treated with conventional hydration therapy with or without a daily dose of a synbiotic (2.5 × 10(9) CFU live bacteria including Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum, Bifidobacterium longum, Enterococcus faecium, and 625 mg fructooligosaccharide) for 5 days. The primary endpoint was duration of diarrhea and duration of hospitalization was the secondary endpoint. Among 209 eligible children, 113 received the synbiotic mixture and 96 served as a control. The duration of diarrhea was significantly shorter (∼36 h) in children receiving the synbiotic group than the controls (77.9 ± 30.5 vs. 114.6 ± 37.4 h, p < 0.0001). The duration of hospitalization was shorter in children receiving the synbiotic group (4.94 ± 1.7 vs. 5.77 ± 1.97 days, p = 0.002). The effect of synbiotic mixture on diarrhea started after 24th hours and stool frequency significantly decreased after 24th and 48th hours. The percentage of diarrhea-free children is significantly higher in synbiotic group at 48th and 72nd hours of synbiotic group. In conclusion, this study showed a reduction in diarrhea duration by approximately 36 h and a reduction in the duration of hospitalization with approximately 1 day in children with acute diarrhea with this synbiotic mixture.

Any Concern About Delays in the Diagnosis of Childhood Cancers During the COVID-19 Pandemic?

OBJECTIVE: The lockdown precautions during the COVID-19 pandemic led to concerns about the delayed diagnosis of malignancies. This study aimed to compare the duration of complaints at home and the presence of metastasis at diagnosis during the pre-pandemic and pandemic period in children with cancer. MATERIALS AND METHODS: All children diagnosed with cancer and followed up in our clinic between 2017 and 2022 were included. Patients with a diagnosis of acute/chronic leukemia were excluded. Age, gender, cancer type, duration of complaints, and presence of metastasis at diagnosis of the children were recorded. The duration of complaints and presence of metastasis at diagnosis were compared statistically before and after March 11, 2020, the start point of the COVID-19 pandemic in our country. RESULTS: A total of 161 patients diagnosed with cancer were analyzed retrospectively; 61% of patients were males and 39% were females. These patients were diagnosed with brain tumors (23.6%), lymphomas (23%), neuroblastoma (13.7%), rhabdomyosarcomas (10.6%), Ewing's sarcoma (4.3%), osteosarcoma (3.7%), Wilm's tumor (3.7%), and germ cell tumors (3.1%). The duration of complaint was longer during the pandemic than before the pandemic (median: 45 days vs. 30 days) (P < .05). The presence of metastases at diagnosis was 45.3% in the prepandemic period, while it was 40% during the pandemic with no statistical difference (P > .5). CONCLUSION: We concluded that the duration of complaint before diagnosis was longer during the pandemic, while this delay did not affect the metastasis rate at diagnosis in children with cancer. The high rates of distant metastases in newly diagnosed patients both before and during the pandemic suggest that more studies are needed to diagnose these patients earlier.

Acute complications observed during intensive chemotherapy in pediatric patients with acute lymphoblastic leukemia: Single-center experience.

OBJECTIVE: In childhood acute lymphoblastic leukemia (ALL), very promising results were obtained thanks to the developments in treatment strategies in recent years. However, acute complications during treatment continue to be the important causes of mortality and morbidity. In this study, acute complications that develop during the treatment of ALL in childhood were evaluated. METHODS: Medical records of 47 patients treated according to (ALL Intercontinental Berlin-Frankfurt-Münster) 2009 protocol between 2016 and 2021 were evaluated retrospectively. RESULTS: Of 47 patients, 28 (59.6%) were male and 19 (40.4%) were female. The mean age at diagnosis was 5.9±4.2 years. Forty-four patients (93.6%) were pre-B cell ALL, 3 patients (6.4%) were pre-T cell ALL. Of 47 patients, 9 (19.1%) were high risk, 32 (68.1%) were intermediate risk, and 6 (12.8%) were standard risk. Acute complications developed in 38 patients (80.8%). Among these complications, infectious complications are the most common and these were followed by gastrointestinal complications, drug-related reactions, thrombotic, neurological, and endocrine/metabolic complications, respectively. CONCLUSION: In terms of complications that may develop, the threshold of suspicion should be kept low, and patients should be treated with the same medical team in fully equipped centers with a multidisciplinary approach. Inpatient treatment strategies should be applied especially in the early stages of treatment. The importance of inpatient treatment strategy, especially in the early stages of treatment, is emphasized.

The Use of Allogeneic Mesenchymal Stem Cells in Childhood Steroid-Resistant Acute Graft-Versus-Host Disease: A Retrospective Study of a Single-Center Experience

Objective: Steroid-resistant acute graft-versus-host disease (srAGVHD) is the most important cause of morbidity and mortality after allogeneic stem cell transplantation. There are several treatment methods available, including mesenchymal stem cell (MSC) application. The aim of this study was to evaluate the results of MSC therapy performed in children with srAGVHD. Materials and Methods: MSC therapy was used in our center between November 2014 and December 2017 for 22 patients who developed srAGVHD. The patients were retrospectively evaluated in terms of treatment response and survival. Results: After application of MSCs, complete response was obtained in 45.5% of the subjects, partial response was obtained in 13.6%, and no response was obtained in 40.9%. We found that 45.5% of the patients were alive and 54.5% had died and our treatment results were similar to those in the literature. Response to MSC treatment was found to be the only prognostic marker affecting mortality. Conclusion: MSC application is a treatment method that can be used safely together with other treatment methods in srAGVHD, a condition that has a high mortality rate. There are almost no acute side effects. There are also no serious long-term side effects in the literature. Prospective randomized studies are required to obtain high-quality data.