Identification of the molecular etiology in rare congenital hemolytic anemias using next-generation sequencing with exome-based copy number variant analysis.

OBJECTIVES: In congenital hemolytic anemias (CHA), it is not always possible to determine the specific diagnosis by evaluating clinical findings and conventional laboratory tests. The aim of this study is to evaluate the utility of next-generation sequencing (NGS) and clinical-exome-based copy number variant (CNV) analysis in patients with CHA. METHODS: One hundred and forty-three CHA cases from 115 unrelated families referred for molecular analysis were enrolled in the study. Molecular analysis was performed using two different clinical exome panels in 130 patients, and whole-exome sequencing in nine patients. Exome-based CNV calling was incorporated into the traditional single-nucleotide variant and small insertion/deletion analysis pipeline for NGS data in 92 cases. In four patients from the same family, the PK Gypsy variant was investigated using long-range polymerase chain reaction. RESULTS: Molecular diagnosis was established in 86% of the study group. The most frequently mutated genes were SPTB (31.7%) and PKLR (28.5%). CNV analysis of 92 cases revealed that three patients had different sizes of large deletions in the SPTB and six patients had a deletion in the PKLR. CONCLUSIONS: In this study, NGS provided a high molecular diagnostic rate in cases with rare CHA. Analysis of the CNVs contributed to the diagnostic success.

Artificial intelligence-driven diagnosis of ß-thalassemia minor & iron deficiency anemia using machine learning models.

Background: Iron deficiency anemia (IDA) and b-thalassemia minor (BTM) are the two most common causes of microcytic anemia, and although these conditions do not share many symptoms, differential diagnosis by blood tests is a time-consuming and expensive process. CBC can be used to diagnose anemia, but without advanced techniques, it cannot differentiate between iron deficiency anemia and BTM. This makes the differential diagnosis of IDA and BTM costly, as it requires advanced techniques to differentiate between the two conditions. This study aims to develop a model to differentiate IDA from BTM using an automated machine-learning method using only CBC data. Methods: This retrospective study included 396 individuals, consisting of 216 IDAs and 180 BTMs. The work was divided into three parts. The first section focused on the individual effects of hematological parameters on the differentiation of IDA and BTM. The second part discusses traditional methods and discriminant indices used in diagnosis. In the third section, models developed using artificial neural networks (ANN) and decision trees are analysed and compared with the methods used in the first two sections.

Difficulties in the diagnosis of HbS/beta thalassemia: Really a mild disease?

Background: HbS/b cases having clinical, hematologic and electrophoretic similarities cannot be sufficiently distinguished from sickle cell anemia cases and are misdiagnosed as sickle cell anemia. This study will investigate the congruence between the HPLC thalassemia scanning tests and the laboratory findings compared to the DNA sequence analysis results of the patients diagnosed with SCA between 2016 and 2020. This study also aims to indicate the current status to accurately diagnose sickle cell anemia and HbS/b in the light of hematologic, electrophoretic and molecular studies. Methods: Fourteen patients who were diagnosed with SCA in hospitals at different cities in Turkey and followed by the Thalassemia Diagnosis, Treatment and Research Center, Mugla Sitki Koçman University were included in this retrospective study. The socio-demographic characteristics, hemogram, hemoglobin variant analysis results and DNA chain analysis results of the patients were taken from the database of the centre and then examined. The informed consents were taken from the patients. The patients were administered a survey containing questions about transfusion history and diagnostic awareness. The Beta-Thalassemia mutations were analysed using a DNA sequencer (Dade Behring, Germany) based on the Sanger method. Results: According to the DNA sequence analysis, the results of these patients diagnosed with SCA in hospitals in different cities of Turkey were the following: of 14 patients, 8 had HbS/b0, and HbS/b+ and one had HbS carrier, and one had Hb-O, and three had SCA. The patient with HbS carrier status also contains three additional mutations, all of which are heterozygous. We discovered that although two of three mutations, which are c.315+16G>C and c.316-185C>T, are previously reported as benign, at least one of the two mentioned mutations, when combined with HbS, causes transfusion-dependent HbS/b. Conclusions: Briefly, HbSS and HbS/b thalassemia genotypes cannot be definitely characterized by electrophoretic and hematologic data, resulting in misdiagnosis. c.315+16G>C and c.316-185C>T are previously reported as benign; at least one of the two mentioned mutations, when combined with HbS, causes transfusion-dependent HbS/b. In undeveloped or some developing countries, molecular diagnosis methods and genetic analyses cannot be used. If mutation analyses could be performed, then such differential diagnosis errors would reduce. However, if mutation analysis cannot be performed, other methods such as HPLC, capillary electrophoresis absolutely be sought to have insight into the parental carriage status.

IVS-II-16 (G>C) (HBB: c.315+16G>C) or IVS-II-666 (C>T) (HBB: c.316-185C>T) Mutations Trigger an Hb S (HBB: c.20A>T)/ß+-Thalassemia Phenotype in an Hb S Trait Patient.

Sickle cell trait is a medical condition caused by the presence of both mutant Hb S (HBB: c.20A>T) and normal Hb A alleles. Although sickle cell trait is typically considered to be asymptomatic and benign, genetic modifiers and mutations can lead to severe clinical complications. In this study, the possible pathogenicity of the IVS-II-16 (G>C) (HBB: c.315+16G>C) and IVS-II-666 (C>T) (HBB: c.316-185C>T) mutations, which are considered to be neutral polymorphisms, and the association between the Hb S mutation are presented. To the best of our knowledge, these polymorphisms have not been previously reported in any sickle cell trait patient, and no relevant studies have been conducted. We recently studied a 40-year-old woman (proband), diagnosed to be an Hb S/ß-thalassemia (ß-thal) carrier. ß-Globin mutations were analyzed using a DNA sequencer based on the Sanger method. The HbVar and ClinVar databases show IVS-II-16 and IVS-II-666 to be intronic mutations. However, statements in these data banks contradict our findings. In the present study, a transfusion-dependent Hb S patient, behaving as an Hb S/ß-thal case due to these mutations, was reported. These mutations have not been previously reported in an Hb S patient. Although the IVS-II-16 and IVS-II-666 mutations were previously reported as benign, they converted the Hb S phenotype to transfusion-dependent Hb S/ß-thal when combined with Hb S. In this regard, IVS-II-16 and IVS-II-666 mutations may not be innocent, as previously thought.

The effect of measurement area size on the reliability of myocardial iron load measurement in cardiac magnetic resonance imaging examinations of thalassemia patients

Background/aim: The aim of this study was to evaluate the intraobserver and interobserver reliability of cardiac T2* MRI measurements in different region of interest (ROI) sizes. Materials and methods: Cardiac T2* MRIs of 24 thalassemia major patients were evaluated. Two different ROI sizes were used for measurement. In the first measurement, an ROI approximately 5 mm in diameter was used in the interventricular septal myocardium. In the other method, the whole ventricular septal myocardium was used as the measurement. The intraobserver and interobserver variabilities were assessed with the intraclass correlation coefficient (ICC). Results: The measurement of the first observer, the ICC of the small-sized ROI (ssROI), was 0.869, and the measurement for the second observer, the ICC of the ssROI, was 0.659. The ICC of the whole-septal ROI (wsROI) was 0.991 for the first observer and 0.980 for the second observer. Interobserver variability, for the mean measurement, was 0.442 for the ICC of ssROI and 0.883 for the ICC of wsROI. Conclusion: For the evaluation of myocardial iron load with T2* MRI we suggest making measurements with ROI, including all of the interventricular septum, as a consequence of high intraobserver and interobserver consistency.

ß2-Microglobulin, Neutrophil Gelatinase-Associated Lipocalin, and Endocan Values in Evaluating Renal Functions in Patients with ß-Thalassemia Major.

Chronic anemia, transfusion-associated iron deposition, and chelating agents lead to renal impairment in ß-thalassemia (ß-thal) patients. The present study aimed to determine the most reliable and practical method in assessing and predicting renal injury in ß-thal major (ß-TM) patients. Therefore, we assessed the predictive values of urine ß2-microglobulin (ß2-MG) and neutrophil gelatinase-associated lipocalin (NGAL) levels, their ratios to urine creatinine, and serum endocan level. Sixty ß-TM patients and 30 healthy controls were included. Renal functions of the patients and controls were evaluated by means of urine protein/creatinine ratio, urine ß2-MG, urine NGAL, and serum endocan level. The ß-TM and control groups were comparable in terms of the demographic characteristics. Of the ß-TM patients, 26.7% had glomerular hyperfiltration and 41.7% had proteinuria. Compared with the control group, the ß-TM group had significantly higher levels of urine protein/creatinine, urine ß2-MG, urine ß2-MG/creatinine, urine NGAL, urine NGAL/creatinine, and serum endocan. These parameters did not differ between the chelating agent subgroups in the patient group. Urine ß2-MG/creatinine and NGAL/creatinine ratios were the parameters with high specificity in predicting proteinuria. There were significant correlations of urine ß2-MG, urine NGAL, and serum endocan levels with serum ferritin concentration. Urine ß2-MG/creatinine, NGAL/creatinine, and protein/creatinine ratios were correlated with each other in the patient group. Positive correlations of urine ß2-MG, urine NGAL, and serum endocan levels with serum ferritin concentration indicated that iron deposition was associated with endothelial damage and renal injury.

Retrospective evaluation of children with immune thrombocytopenic purpura and factors contributing to chronicity.

OBJECTIVE: Immune thrombocytopenic purpura (ITP) is the most common cause of acquired thrombocytopenia children. The aim of this retrospective study is to describe presenting features and clinical characteristics of ITP and evaluate clinical course, treatment modalities, and complications and determine the effects of preceding infection history, age, gender, treatment modality, and admission platelet count on chronicity. METHOD: Two hundred and eleven patients who were diagnosed ITP and followed-up in Department of Pediatric Hematology, Ankara Children Hematology Oncology Education and Research Hospital between January 2008 and September 2012 were included. Age of the patients, gender, date of admission, date of diagnosis, complaint in the application, previous infection and laboratory tests were recorded. RESULTS: Mean age of the patients on diagnosis was 5.4 ± 4.1 years. The female/male ratio was 1.03. The clinical courses were determined as acute or chronic in 72% and 28% of patients respectively. Mean age at diagnosis was significantly higher in chronic ITP (p < 0.01). Chronic course was significantly higher in female patients (p < 0.05). The most frequent complaint was bruises on the skin (68%). The most common physical examination findings were petechiae, purpura and ecchymosis (89%). Patients with a history of past infection (53.6%) and who had serologically positive infection (15.6%) frequently had acute course (p < 0.01). The most common serologically positive infection was Rubella. The mean platelet count was significantly higher in chronic ITP (p < 0.01). In the initial treatment of patients admitted in the acute phase, megadose methylprednisolone (MDMP) was used in 31% of patients, intravenous immune globulin (IVIG) in 55% of patients and anti-D in 2% of patients while 12% did not receive any treatment. There were no significant differences between the recurrence rate and treatment modality (p > 0.05). CONCLUSION: In our study, in females and in patients without any history of past infection, platelet count >20 × 109/L and initial diagnosis age > 10 years were found to increase the probability of chronic disease, which is compatible with the literature.

Evaluation of endocrine and metabolic dysfunctions after hematopoietic stem cell transplantation in children: a study from Turkey.

BACKGROUND: Endocrine organs are highly susceptible to effects of high-dose chemotherapy. The objective of the study was to evaluate endocrine and metabolic complications after hematopoietic stem cell transplantation (HSCT) in children. METHODS: The patients who underwent HSCT in our center from April 2010 to October 2014 with at least 1 year follow-up were analyzed retrospectively. RESULTS: One-hundred children (M/F:59/41; mean age 8.9±4.8 years, mean follow-up time 3.4±1.2 years) were included in the study. Female hypogonadism was the most common endocrine dysfunction (35.7%), followed by growth impairment (29.4%), malnutrition (27.4%), dyslipidemia (26%), low bone mineral density (BMD) (25%), hypothyroidism (13%) and insulin resistance (12%). Patients who underwent HSCT >10 years of age were significantly at risk for hypogonadism, metabolic syndrome, growth impairment and malnutrition (p<0.05). CONCLUSIONS: Endocrine or metabolic dysfunctions are more prevalent in children who are older than 10 years of age at HSCT. Children who underwent HSCT should be followed-up by a multidisciplinary team during puberty and adolescence.

Effects of stem cell transplantation on bone mineral density and vitamin D status in children with thalassemia major.

HSCT is a curative treatment in TM, but conditioning and immunosuppressive treatment may affect bone metabolism. In this retrospective study, we aimed to compare BMD, vitamin D status, and growth in children with TM who underwent HSCT to those in children with TD TM. Twenty-three children with TM who underwent HSCT (mean age 7.1 years [1.03-14.7]) and 24 children with TD thalassemia (mean age 9.8 years [1.6-14]) were recruited. Lumbar spine BMD of TD thalassemia patients was higher than those in patients who had HSCT at both baseline and second-year assessments (P=.009, P<.001, respectively). However, BMD Z scores or serum 25-OH vitamin D levels were not different in two groups. Being >10 years of age was a significant risk factor for low BMD, height, and weight Z score for both groups. Patients who underwent HSCT with Pesaro risk class II or III had higher risk for low BMD compared to those risk class I patients (P=.044). In conclusion, children with TM who were >10 years at HSCT are at risk for low BMD and growth retardation. HSCT had no effect on BMD deficit in children with TM.

The Incidence of Ototoxicity in Patients Using Iron Chelators.

OBJECTIVE: In this study, we aimed to detect the incidences of ototoxicity in patients with hemoglobinopathies taking deferoxamine (DFO), deferiprone, and deferasirox using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) scale to obtain more objective data. MATERIALS AND METHODS: Fifty-five transfusion-dependent patients were evaluated in this study. The NCI CTCAE scale was used to assess ototoxicity levels. The average ferritin and hemoglobin levels, the type of iron chelator, and the duration of therapy of all the patients were recorded. RESULTS: Ototoxicity was observed in 15 patients (31.9 %), all of whom were taking DFO. The median age was 19.5 (6-43) in patients without ototoxicity and 29 (16-50) in those with ototoxicity; this difference was statistically significant (p<0.05). The median ferritin and pre-tx Hb levels were 1391 ng/mL and 9.06 mg/dL, respectively, in patients with ototoxicity and 986.7 ng/mL and 9.24 mg/dL, respectively, in those without ototoxicity; these differences were not significant (p>0.05). Ototoxicity was not observed in the eight patients who used only deferasirox and deferiprone. CONCLUSION: The ototoxicity incidence with DFO at doses below 50 mg/kg/day was 27.3%. Deferiprone and deferasirox were not associated with ototoxic effects in patients taking these drugs.

Factors associated with bone marrow stem cell yield for pediatric allogeneic stem cell transplantation: The impact of donor characteristics.

The aim of this study was to investigate the effects of donor characteristics on CD34+ cell yield in BM harvest. Between April 2010 and November 2013, consecutive donors who underwent BM harvesting in our BM transplantation unit were retrospectively investigated. Donors were classified into two groups: those who donated BM without mobilization (steady-state BM donors) and those who received G-CSF for stem cell mobilization (G-CSF-primed BM donors). Donor characteristics (age, gender, race, body weight, BMI, and laboratory factors including donor's leukocyte, platelet, and monocyte) and their relationship with total nuclear cell and CD34+ cell numbers has been evaluated. A total of 64 healthy related donors (29 males/35 females, median age 11.2 years; 49 [76.6%] younger than 18 and 36 [56.3%] younger than 12 years) were included in the study. The median CD34+ cell yield in the harvest was 0.12×106 /L (0.02-0.21) in SS-BM donors and 0.18×106 /L (0.09-0.67) in GP-BM donors (P=.03). Median of CD34+ cell count given to recipients was 2.6×106 /recipient body weight (1.3-19.3) in SS-BM yields and 3.8×106 /recipient body weight (1.1-10.2) in GP-BM yields, respectively. Multiple regression analysis showed that donor height and pre-G-CSF platelet were the most important parameters to obtain a sufficient BM harvest. Our data suggest that the shorter donors and the donors with higher thrombocyte counts may offer more hematopoietic stem cell. The height and thrombocyte count of the donors should be taken into consideration before planning the targeted CD34+ cell count especially for pediatric donors.

Comparison of prophylactic use of intravenous immunoglobulin versus Pentaglobin® in pediatric patients after hematopoietic stem cell transplantation.

There are few studies evaluating the use of IgM-enriched IVIG (Pentaglobin(®) ) in HSCT recipients. This study aimed to compare the efficacy of prophylactic use of IVIG versus prophylactic use of Pentaglobin(®) within the first 100 days after allogeneic HSCT. We performed a prospective, randomized study of the use of prophylactic IVIG versus prophylactic use of Pentaglobin(®) in patients after allogeneic HSCT. The first dose of IVIG or Pentaglobin(®) was given before conditioning regimen and after transplant was given on day +1, +8, +15, and +22. And then, it was given if IgG level was below 400 mg/dL. Twenty-seven patients in IVIG group and 32 patients in Pentaglobin(®) group were included in the study. There were no significant differences in the duration of neutropenia, hospitalization, fever, and in the number of pyrexial episode, septicemia, bacteremia, local infection, CMV infection, acute GVHD, VOD, and adverse events between the IVIG group and Pentaglobin(®) group. Randomized placebo-controlled trials are needed to conclude that utilization of IVIG or Pentaglobin(®) has no beneficial effect in HSCT.

The Effect of Granulocyte Colony-Stimulating Factor on Immune-Modulatory Cytokines in the Bone Marrow Microenvironment and Mesenchymal Stem Cells of Healthy Donors.

Granulocyte colony stimulating factor (G-CSF) is sometimes administered to donors before bone marrow (BM) harvest. G-CSF-primed (G-BM) and unprimed BM (U-BM)-derived mesenchymal stem cells (MSC) were obtained from 16 healthy donors and were expanded in vitro. Their proliferative characteristics, morphology, and differentiation capacity were examined. Supernatants of the second passage of MSCs were evaluated for transforming growth factor ß1, hepatocyte growth factor, and prostaglandin E2 (PGE2) levels and compared with controls. The analyses of cytokines in the G-BM- and U-BM-derived MSCs supernatants revealed that PGE2 levels were significantly lower in the G-CSF-primed samples. These cytokines were also measured in BM plasma. The level of hepatocyte growth factor in G-BM plasma was significantly increased. The current study is the first to show the effects of G-CSF on the BM microenvironment of healthy human donors. The preliminary data suggest that G-BM- and U-BM-derived MSCs have similar morphologic/phenotypic properties and differentiation capacity but differ in their secretory capacity. Significant changes in cytokine levels of BM plasma in G-CSF-primed donors were also demonstrated. These findings suggest that BM MSCs and changes in the BM microenvironment may contribute to the effects of G-CSF on inflammation and immunomodulation.

The Prevalence of Hemoglobinopathies in Young Adolescents in the Province of Mugla in Turkey: Results of a Screening Program.

Thalassemia is an autosomal recessive inherited blood disorder. It is prevalent in Mediterranean countries such as Sardinia, Greece, Cyprus, Turkey, Lebanon and also Southeast Asia. Our aim was to investigate the carrier prevalence of thalassemia and other hemoglobinopathies in adolescents who live in Mugla Province, Turkey. We analyzed retrospectively the surveys conducted at primary schools between 1997 and 2013. Complete blood count (CBC) and high performance liquid chromatography (HPLC) were used to screen for thalassemia and hemoglobinopathies. Patients were diagnosed as having thalassemia trait if the mean corpuscular volume (MCV) was ≤ 80.0 fL, mean corpuscular hemoglobin (Hb) was ≤ 27.0 pg and Hb A2 levels were ≥ 3.5%. A total of 164,814 students were analyzed. The median age of the students was 13.5 years (minimum 13.0, maximum 14.0). The total number of students with abnormal HPLC results was 5861 (3.8%). There was a significant decrease in the newborn of new thalassemia patients found with screening programs for hemoglobinopathies in Mugla Province from 1997 to 2013. The number of students with abnormal HPLC results for thalassemia, sickle cell disease and other Hb traits were 3.2, 0.15 and 0.4%, respectively. It is important to recognize that including Hb, MCV, red blood cell (RBC) count and HPLC tests for carrier screening are necessary to find hemoglobinopathies. Our study supported that the number of new patients significantly decreased using these screening programs from 1997 to 2013.

Venous Thromboembolism after Allogeneic Pediatric Hematopoietic Stem Cell Transplantation: A Single-Center Study.

INTRODUCTION: Venous thromboembolism (VTE) in children who undergo hematopoietic stem cell transplantation (HSCT) has high morbidity. The aim of this study is to assess the incidence of VTE in allogeneic pediatric HSCT recipients and the contribution of pretransplant prothrombotic risk factors to thrombosis. METHODS: We retrospectively evaluated 92 patients between April 2010 and November 2012 undergoing allogeneic HSCT who had completed 100 days post-HSCT. Before HSCT, coagulation profiles; acquired and inherited prothrombotic risk factors including factor V Leiden, prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T, and MTHFR A1298C mutations; and serum homocysteine and lipoprotein(a), plasma antithrombin III, protein C, and protein S levels were obtained from all patients. RESULTS: In the screening of thrombophilia, 8 patients (9%) were heterozygous for factor V Leiden, 5 (6%) were homozygous for MTHFR 677TT, 12 (14%) were homozygous for MTHFR 1298CC, and 2 (2%) were heterozygous for prothrombin G20210A mutation. We observed VTE in 5 patients (5.4%); a prothrombotic risk factor was found in 3 out of these 5 patients, while 4 out of 5 patients had central venous catheters. It was determined there was no significant relationship between VTE and inherited prothrombotic risk factors. DISCUSSION AND CONCLUSION: VTE after HSCT seems to be a low-frequency event that may be due to low-dose, low-molecular-weight heparin prophylaxis, and the role of inherited prothrombotic risk factors cannot be entirely excluded without a prospective study.

Clinical outcomes and graft characteristics in pediatric hematopoietic stem cell transplantation: Effect of granulocyte-colony stimulating factor priming.

In this study, we aimed to determine the effect(s) of G-CSF priming on graft and transplantation parameters and compare these findings with those obtained without priming. A total of 64 pediatric patients transplanted from HLA-matched family donors were enrolled in the study. Twenty-nine patients received G-CSF primed marrow (G-BM group) and 35 patients received steady state bone marrow (S-BM group). Number of total nucleated cells (TNC) and CD34(+) cells, CFU-GM colony number, neutrophil and platelet engraftment times, total length of stay in hospital, overall and disease free survival, and occasions of acute and chronic GvHD has been compared between these two groups. Granulocyte colony stimulating factor primed bone marrow (G-BM) yielded higher numbers of CD34(+) cells, TNCs, and CFU-GM colony numbers compared to those obtained in S-BM. The neutrophil engraftment time, platelet engraftment time, length of stay in hospital, overall survival and disease free survival were not different between G-BM and S-BM groups. Also the cumulative incidence of grades II-IV acute and chronic GvHD were similar. It was observed that the use of G-CSF did not increase the risk of acute or chronic GvHD. We concluded that use of G-CSF for stem cell mobilization is an effective and safe method in children.

DOCK8 deficiency: clinical and immunological phenotype and treatment options - a review of 136 patients.

Mutations in DOCK8 result in autosomal recessive Hyper-IgE syndrome with combined immunodeficiency (CID). However, the natural course of disease, long-term prognosis, and optimal therapeutic management have not yet been clearly defined. In an international retrospective survey of patients with DOCK8 mutations, focused on clinical presentation and therapeutic measures, a total of 136 patients with a median follow-up of 11.3 years (1.3-47.7) spanning 1693 patient years, were enrolled. Eczema, recurrent respiratory tract infections, allergies, abscesses, viral infections and mucocutaneous candidiasis were the most frequent clinical manifestations. Overall survival probability in this cohort [censored for hematopoietic stem cell transplantation (HSCT)] was 87 % at 10, 47 % at 20, and 33 % at 30 years of age, respectively. Event free survival was 44, 18 and 4 % at the same time points if events were defined as death, life-threatening infections, malignancy or cerebral complications such as CNS vasculitis or stroke. Malignancy was diagnosed in 23/136 (17 %) patients (11 hematological and 9 epithelial cancers, 5 other malignancies) at a median age of 12 years. Eight of these patients died from cancer. Severe, life-threatening infections were observed in 79/136 (58 %); severe non-infectious cerebral events occurred in 14/136 (10 %). Therapeutic measures included antiviral and antibacterial prophylaxis, immunoglobulin replacement and HSCT. This study provides a comprehensive evaluation of the clinical phenotype of DOCK8 deficiency in the largest cohort reported so far and demonstrates the severity of the disease with relatively poor prognosis. Early HSCT should be strongly considered as a potential curative measure.

Secondary antifungal prophylaxis in pediatric hematopoietic stem cell transplants.

Invasive fungal infections (IFIs) constitute a leading cause of morbidity and infection-related mortality among hematopoietic stem cell transplant (HSCT) recipients. With the use of secondary prophylaxis, a history of IFI is not an absolute contraindication to allo-HSCT. However, still, IFI recurrence remains a risk factor for transplant-related mortality. In this study, of the 105 children undergoing HSCT between April 2010 and February 2013, 10 patients who had IFI history before transplantation and had undergone allo-HSCT were evaluated retrospectively to investigate results of secondary prophylaxis. In conclusion, our study shows that amphotericin B and caspofungin was successful as secondary antifungal prophylaxis agents with no relapse of IFI. In addition, after engraftment, secondary prophylaxis was continued with voriconazole orally in 4 patients that yielded good results.