Artemis deficiency: A large cohort including a novel variant with increased radiosensitivity.

BACKGROUND: Artemis deficiency is an autosomal recessive disorder characterized by a combined immunodeficiency with increased cellular radiosensitivity. In this review, the clinical and genetic characteristics of 15 patients with DCLRE1C variants are presented. METHODS: The demographic, clinical, immunologic, and genetic characteristics of patients with confirmed DCLRE1C variants diagnosed between 2013 and 2023 were collected retrospectively. Three patients were evaluated for radiosensitivity by the Comet assay, compared with age- and sex-matched healthy control. RESULTS: Seven patients who had severe infections in the first 6 months of life were diagnosed with T-B-NK+ SCID (severe combined immunodeficiency). Among them, four individuals underwent transplantation, and one of those died due to post-transplant complications in early life. Eight patients had hypomorphic variants. Half of them were awaiting a suitable donor, while the other half had already undergone transplantation. The majority of patients were born into a consanguineous family (93.3%). Most patients had recurrent sinopulmonary infections (73.3%), and one patient had no other infection than an acute respiratory infection before diagnosis. Two patients (13.3%) had autoimmunity in the form of autoimmune hemolytic anemia. Growth retardation was observed in only one patient (6.6%), and no malignancy was detected in the surviving 11 patients during the median (IQR) of 21.5 (12-45) months of follow-up. Three patients who had novel variants exhibited increased radiosensitivity and compromised DNA repair, providing a potential vulnerability to malignant transformation. CONCLUSION: Early diagnosis, radiation avoidance, and careful preparation for transplantation contribute to minimizing complications, enhancing life expectancy, and improving the patient's quality of life.

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.

Rapamycin Controls Lymphoproliferation and Reverses T-Cell Responses in a Patient with a Novel STIM1 Loss-of-Function Deletion.

PURPOSE: Deficiency of stromal interaction molecule 1 (STIM1) results in combined immunodeficiency accompanied by extra-immunological findings like enamel defects and myopathy. We here studied a patient with a STIM1 loss-of-function mutation who presented with severe lymphoproliferation. We sought to explore the efficacy of the mTOR inhibitor rapamycin in controlling disease manifestations and reversing aberrant T-cell subsets and functions, which has never been used previously in this disorder. METHODS: Clinical findings of the patient were collected over time. We performed immunological evaluations before and after initiation of rapamycin treatment, including detailed lymphocyte subset analyses, alterations in frequencies of circulating T follicular helper (cTFH) and regulatory T (Treg) cells and their subtypes as well as T cell activation and proliferation capacities. RESULTS: A novel homozygous exon 2 deletion in STIM1 was detected in a 3-year-old girl with severe lymphoproliferation, recurrent infections, myopathy, iris hypoplasia, and enamel hypoplasia. Lymphoproliferation was associated with severe T-cell infiltrates. The deletion resulted in a complete loss of protein expression, associated with a lack of store-operated calcium entry response, defective T-cell activation, proliferation, and cytokine production. Interestingly, patient blood contained fewer cTFH and increased circulating follicular regulatory (cTFR) cells. Abnormal skewing towards TH2-like responses in certain T-cell subpopulations like cTFH, non-cTFH memory T-helper, and Treg cells was associated with increased eosinophil numbers and serum IgE levels. Treatment with rapamycin controlled lymphoproliferation, improved T-cell activation and proliferation capacities, reversed T-cell responses, and repressed high IgE levels and eosinophilia. CONCLUSIONS: This study enhances our understanding of STIM1 deficiency by uncovering additional abnormal T-cell responses, and reveals for the first time the potential therapeutic utility of rapamycin for this disorder.

Evaluation of childhood malignancies presenting with musculoskeletal manifestations from two different divisions: a multicenter study.

BACKGROUND: The aim of the study was to evaluate the approaches of pediatric rheumatologists and pediatric hematologists to patients with similar musculoskeletal (MSK) complaints and to highlight the differences that general pediatricians should consider when referring patients to these specialties. METHODS: This is a cross-sectional study involving the patients who applied to pediatric rheumatology centers with MSK complaints and were diagnosed with malignancy, as well as patients who were followed up in pediatric hematology centers with a malignancy diagnosis, and had MSK complaints at the time of admission. RESULTS: A total of 142 patients were enrolled in the study. Of these patients, 83 (58.4%) applied to pediatric rheumatology centers, and 59 (41.6%) applied to pediatric hematology centers. Acute lymphoblastic leukemia (ALL) was the most common diagnosis among the patients who applied to both centers, with 80 cases (56.3%). The median age of diagnosis was 87 (interquartile range, IQR: 48-140) months. The most common preliminary diagnosis in pediatric rheumatology centers was juvenile idiopathic arthritis (JIA), with 37 cases (44.5%). MSK involvement was mainly seen as arthralgia, and bone pain. While arthralgia (92.7%) was the most common complaint in rheumatology centers, bone pain (88.1%) was more common in hematology centers. The most frequently involved joints were the knee (62.9%), ankle (25.9%), hip (25%), and wrist (14%). The most common laboratory abnormalities were high lactate dehydrogenase (LDH), high C-reactive protein (CRP), anemia, and high erythrocyte sedimentation rate (ESR). Thrombocytopenia, neutropenia, and high LDH were statistically significantly more frequent in patients admitted to hematology centers than in patients admitted to rheumatology centers (p < 0.001, p=0.014, p=0.028, respectively). Patients who applied to rheumatology clinics were found to have statistically significantly higher CRP levels (p=0.032). CONCLUSIONS: Malignancies may present with only MSK system complaints in childhood. Therefore, malignancies should be included in the differential diagnosis of patients presenting with MSK complaints.

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.

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.

Hematopoietic stem cell transplantation activities and HRQOL of refugee or asylum seeker children in Turkey: A multicenter study.

BACKGROUND: Refugee or asylum seekers (RAS) children are at increased risk of physical, developmental, and behavioral health issues. The aim of this study was to evaluate clinical and psychosocial outcomes of hematopoietic stem cell transplantation (HSCT) in RAS children and compare health-related quality of life (HRQOL) to those of Turkish peers. METHODS: This retrospective study included patients who underwent HSCT aged 0-18 years and completed 100-day post-transplant. The PedsQL 4.0 Generic Core Scale was used in children over 5 years old to compare HRQOL. RESULTS: A total of 166 RAS patients (M/F: 106 /60) underwent 174 HSCTs (six patients had two, and one had three HSCT) compared to 66 Turkish patients. The mean age of the patients in the RAS group was 7.8 ± 4.9 years and similar to controls. A total of 124 patients (75%) were from Syria, and 49 (25%) were from other countries in the Middle East and Africa. The cause of migration was war in 121 (74%) RAS patients. Complications of HSCT were no different between the groups. However, the rate of neutropenic sepsis was significantly higher in the RAS group (p = 0.004). The total scores of HRQOL were not different between RAS and controls. In the RAS group, ratings of social functioning were lower in patients with consanguinity or non-malignant disease or who had match-related donors. DISCUSSION: Identifying areas of difficulty in subscales of HRQOL may help physicians to classify patients who need additional supportive care. Regular monitoring and supporting physical needs may result in better functional outcomes after HSCT.

Clinical and Laboratory Factors Affecting the Prognosis of Severe Combined Immunodeficiency.

PURPOSE: Severe combined immunodeficiency (SCID) is one of the most severe forms of inborn errors of immunity characterized by absence or loss of function in T cells. The long-term outcomes of all forms of SCID have been evaluated in a limited number of studies. We aimed to evaluate the pre- and post-transplant manifestations of SCID patients and determine the factors affecting the survival of patients. METHODS: We included 54 SCID patients (classical SCID, Omenn syndrome, atypical SCID (AS)) in this study. We evaluated the clinical presentation, infections, and outcome of hematopoietic stem cell transplantation (HSCT). Lymphocyte subsets and T-cell receptor (TCR) repertoire were analyzed by flow cytometry. RESULTS: The median age at diagnosis was 5 (range: 3-24) months and follow-up time was 25 (range: 5-61) months. Symptom onset and diagnostic ages were significantly higher in AS compared to others (p = 0.001; p < 0.001). The most common SCID phenotype was T-B-NK + , and mutations in recombination-activating genes (RAG1/2) were the prominent genetic defect among patients. The overall survival (OS) rate was 83.3% after HSCT, higher than in non-transplanted patients (p = 0.001). Peripheral blood stem cell sources and genotypes other than RAG had a significant favorable impact on CD4+ T cells immune reconstitution after transplantation (p = 0.044, p = 0.035; respectively). Gender matching transplantations from human leukocyte antigen (HLA)-identical and non-identical donors and using peripheral blood stem cell source yielded higher B-cell reconstitution (p = 0.002, p = 0.028; respectively). Furthermore, receiving a conditioning regimen provided better B-cell reconstitution and chimerism (p = 0.003, p = 0.001). Post-transplant TCR diversity was sufficient in the patients and showed an equal distribution pattern as healthy controls. The OS rate was lower in patients who underwent transplant with active infection or received stem cells from mismatched donors (p = 0.030, p = 0.015; respectively). CONCLUSION: This study identifies diagnostic and therapeutic approaches predictive of favorable outcomes for patients with SCID.

Bladder granulocytic sarcoma in a child: case report and literature review.

BACKGROUND: Granulocytic sarcoma (GS) is an extramedullary solid tumor composed of immature myeloid cells. GS has been associated with acute myeloid leukemia (AML), myelodysplastic syndromes or myeloproliferative diseases. Although GS can affect various tissues of the human body, it has rarely been reported in other soft tissues such as the breast, gastrointestinal, respiratory and genitourinary tracts. We report a pediatric case diagnosed with granulocytic sarcoma of the bladder and concomitant AML. CASE: A twelve-year-old previously healthy girl was admitted to the pediatric urology clinic with a ten-day history of hematuria and pollakiuria. Laboratory examinations revealed anemia, thrombocytopenia and neutrophilic leukocytosis. Bone marrow aspiration results were consistent with acute myeloid leukemia -FAB subtype M2-. Abdominal magnetic resonance imaging (MRI) showed an irregularly bounded 12 cm mass on the right side of the bladder. Transurethral resection (TUR) pathology was consistent with granulocytic sarcoma. After a multimodal treatment approach, complete remission was achieved. CONCLUSIONS: Malignant bladder masses are rare causes of macroscopic hematuria in childhood. The diagnostic spectrum is wide, ranging from rhabdomyosarcoma to leukemia involvement. The bladder is a rare site of extramedullary involvement in pediatric patients with AML. Multimodal treatment should be considered on a per-patient basis.

How do the threshold values used in the decision on red blood cell and platelet transfusions comply with the guidelines?

OBJECTIVE: Blood transfusion is life-saving medical practice with significant risks. National and international guidelines have been established for indications related to blood use and threshold values for transfusions. In this study, we aimed to determine the erythrocyte and thrombocyte transfusion rates in surgical, internal, and emergency clinics in our hospital and to compare the threshold values before erythrocyte and platelet (PLT) transfusion among the clinics. METHODS: Red blood cell (RBC) and PLT transfusions in our hospital between January 2019 and June 2019 were retrospectively analyzed. Clinics were divided into three groups: surgical clinics, internal clinics, and emergency clinic. Demographic characteristics, pre-transfusion hemoglobin (Hb), and PLT values of patients were recorded. Data were analyzed statistically. RESULTS: During the 6-month study period, 5179 patients were transfused in 24,924 patients and the transfusion rate was 21%. In this period, a total of 14,518 units of blood products including 8369 units RBC suspension and 1390 units PLT suspension were transfused. The mean age of the patient was 50.32±28.88 years and the female/male ratio was 1.11. The most RBC transfusions were performed in the general internal medicine service in internal clinics and gynecology in surgical clinics. The most PLT transfusions were performed in the general medicine service in internal clinics and pediatric cardiovascular surgery in surgical clinics. ES transfusions were performed in the emergency medicine clinic with the lowest mean Hb value (Hb: 8.07±1.84 g/dl) and in the surgical clinics with the highest mean Hb value (Hb: 9.29±1.46 g/dl). TS transfusions were performed in internal clinics with the lowest mean PLT value (PLT: 44030±44075/mm3), while the highest mean PLT value (PLT: 97140±75782/mm3) was performed in surgical clinics. CONCLUSION: It was observed that threshold values in particular for PLT transfusions in our hospital were above the guideline recommendations. Our results suggest that the knowledge level of physicians about transfusion limits and practices should be increased.

Use of granulocyte transfusion in early period in life-threatening infections of pediatric hematology and oncology patients: A single-center experience.

Despite all the developments in medicine, infections continue to be one of the most important causes of mortality in pediatric hematology and oncology patients. The more severe the degree of neutropenia develops after intensive chemotherapy in cancer patients, and the longer the neutropenia duration, the higher the risk of infection. Granulocyte transfusion (GT) is used as supportive therapy in cases where the bone marrow needs time to recover in invasive bacterial or fungal infections along with severe neutropenia. The patients who had granulocyte transfusions in our clinic between June 2019 and June 2020 were reviewed retrospectively. A total of 15 units of granulocyte concentrate were used in 11 febrile neutropenia attacks of 9 patients. The demographic characteristics of the patients and features belonging to the period of GT were recorded. In our study, the clinical response rate after GT was 90.9 %, while the hematological response rate was 40 %. Most of the patients were treated succesfully, the mortality rate was 9%. We think that the most critical factor for success with GTs is determining the neutropenic patient in particular with a combination of high-risk malignancy and acute life-threatening infection for using GT. Also, early use of GT in those patients who do not recover despite appropriate antimicrobial and supportive treatment may contribute to improvement of the clinical conditon in a shorter period of time and reduction of repeated GTs.

Prognostic factors for survival in children who relapsed after allogeneic hematopoietic stem cell transplantation for acute leukemia.

BACKGROUND: Post-transplant relapse has a dismal prognosis in children with acute leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Data on risk factors, treatment options, and outcomes are limited. PROCEDURE: In this retrospective multicenter study in which a questionnaire was sent to all pediatric transplant centers reporting relapse after allo-HSCT for a cohort of 938 children with acute leukemia, we analyzed 255 children with relapse of acute leukemia after their first allo-HSCT. RESULTS: The median interval from transplantation to relapse was 180 days, and the median follow-up from relapse to the last follow-up was 1844 days. The 3-year overall survival (OS) rate was 12.0%. The main cause of death was disease progression or subsequent relapse (82.6%). The majority of children received salvage treatment with curative intent without a second HSCT (67.8%), 22.0% of children underwent a second allo-HSCT, and 10.2% received palliative therapy. Isolated extramedullary relapse (hazard ratio (HR): 0.607, P = .011) and relapse earlier than 365 days post-transplantation (HR: 2.101, P < .001 for 0-180 days; HR: 1.522, P = .041 for 181-365 days) were found in multivariate analysis to be significant prognostic factors for outcome. The type of salvage therapy in chemosensitive relapse was identified as a significant prognostic factor for OS. CONCLUSION: A salvage approach with curative intent may be considered for patients with post-transplant relapse, even if they relapse in the first year post-transplantation. For sustainable remission, a second allo-HSCT may be recommended for patients who achieve complete remission after reinduction treatment.

A Very Rare Type of Leukemia in a Young Pediatric Patient Treated With Hematopoietic Stem Cell Transplantation: Blastic Plasmacytoid Dendritic Cell Neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a newly identified, very rare, highly aggressive hematopoietic neoplasm, primarily found in elderly males. They typically present in the form of skin involvement with a high frequency of lymph node and bone marrow involvement. BPDCN has a very poor prognosis, with no consensus on a widely accepted treatment modality. Here we present a very young patient with BPDCN, who presented with generalized lymphadenopathy, skin involvement, and leukemic blasts in the bone marrow. She was treated with high-risk acute lymphocytic leukemia protocol, followed by allogeneic hematopoietic stem-cell transplantation, and has been in clinical remission for 12 months.

Hematopoietic stem cell transplantation in CD40 ligand deficiency: A single-center experience.

Deficiency of the CD40L, expressed on the surface of T lymphocytes, is caused by mutations in the glycoprotein CD40L (CD154) gene. Resulting defective humoral and cellular responses cause a clinical presentation that includes recurrent sinopulmonary bacterial infections, opportunistic infections, sclerosing cholangitis, neutropenia, and autoimmune manifestations. HSCT represents the only curative treatment modality. However, the therapeutic decision to use HSCT proves challenging in many cases, mainly due to the lack of a phenotype-genotype correlation. We retrospectively reviewed patients with CD40L deficiency who were transplanted in Antalya and Göztepe MedicalPark Pediatric HSCT units from 2014 to 2019 and followed by Akdeniz University School of Medicine Department of Pediatric Immunology. The records of eight male cases, including one set of twins, were evaluated retrospectively. As two transplants each were performed on the twins, a total of ten transplants were evaluated. Conditioning regimens were predominantly based on myeloablative protocols, except for the twins, who received a non-myeloablative regimen for their first transplantation. Median neutrophil and platelet engraftment days were 13 (range 10-19) and 14 (range 10-42) days, respectively. In seven of ten transplants, a CMV reactivation was developed without morbidity. None of the patients developed GVHD, except for one mild case of acute GVHD. All patients survived, and the median follow-up was 852 days. Our data show that HSCT for patients with CD40 ligand deficiency is a potentially effective treatment for long-term disease control.

Role of a second transplantation for children with acute leukemia following posttransplantation relapse: a study by the Turkish Bone Marrow Transplantation Study Group.

We examined outcomes of 51 pediatric patients with relapsed acute leukemia (AL) who underwent a second allogeneic hematopoietic stem cell transplantation (alloHSCT). After a median follow-up of 941 days (range, 69-2842 days), leukemia-free survival (LFS) and overall survival (OS) at 3 years were 26.6% and 25.6%, respectively. The nonrelapse mortality rate (NMR) and cumulative incidence of relapse (CIR) were 36.4% and 42.4%, respectively. The Cox regression analysis demonstrated that the risk factors at second transplantation for predicting limited LFS were active disease (hazard ratio (HR) = 5.1), reduced intensity conditioning (RIC) (HR = 5.0), matched unrelated donor (MUD) (HR = 3.4) and performance score <80 (HR = 3.2). Pediatric patients with AL who relapsed after their first alloHSCT may survive with a second alloHSCT. Disease status, conditioning intensity, donor type, and performance score at the second transplantation are the relevant risk factors. A score based on these factors may predict the results of the second transplantation.

Ruxolitinib salvage therapy is effective for steroid-refractory graft-versus-host disease in children: A single-center experience.

BACKGROUND: Despite the increasing performance of allogeneic hematopoietic cell transplantation over the last decades, graft-versus-host disease (GVHD) remains the main cause of morbidity and mortality. The efficacy of ruxolitinib against GVHD has been demonstrated in adult studies; however, very few studies have been conducted in children. PROCEDURE: This study aimed to evaluate the efficacy of ruxolitinib in 29 children with steroid-refractory acute or chronic GVHD. Twenty-five (87%) patients received at least three different immune modulator agents, including methylprednisolone, before initiating ruxolitinib. RESULTS: All grade 2 acute GVHD patients completely responded to ruxolitinib treatment; 82% of high-grade (3-4) acute GVHD patients and 80% of chronic GVHD (moderate-severe) patients had at least a partial response. Of seven patients with bronchiolitis obliterans, five had a partial response after ruxolitinib. Of 29 patients, 22 were administered steroids at any time in the first month of acute GVHD or the first three months of chronic GVHD during ruxolitinib usage, which was significantly tapered by the end of the observation period. CONCLUSION: Steroid-refractory acute and chronic pediatric GVHD patients treated with ruxolitinib had a high overall response rate, with the additional benefit of steroid sparing.

Haploidentical hematopoietic stem cell transplantation with post-transplant high-dose cyclophosphamide in high-risk children: A single-center study.

BACKGROUND: Post-Cy administration for GVHD prophylaxis in unmanipulated haploidentical HSCT has resulted in improved outcomes in recent years. Studies in children are lacking and accordingly we present the outcomes of 62 haploidentical transplantation for high-risk children. PROCEDURE: We retrospectively assessed 62 transplants in 60 patients who underwent haploidentical-related HSCT with unmanipulated stem cells and for whom Post-Cy was used for GVHD prophylaxis. RESULTS: Myeloid reconstitution was achieved on day + 30 for 57 of the 62 patients. The median follow-up of the surviving 39 patients (63%) was 26 months, with a range of 6-57 months. The OS and EFS at 2 years were 64.6% (52.0%-77.2%, 95% CI) and 58.9% (46.1%-71.7%, 95% CI), respectively. The only factor in our multivariate analysis that contributed to an inferior EFS was a poor remission status prior to HSCT (HR, 8.30; 1.08-63.56; P = 0.041, 95% CI). CONCLUSION: The results of T-cell replete haploidentical transplantation with Post-Cy GVHD prophylaxis in high-risk pediatric patients are promising. However, further research is needed to determine the factors that have affect HLA compatibility for predicting the success of haploidentical transplantations.

Risks and outcomes of invasive fungal infections in pediatric allogeneic hematopoietic stem cell transplant recipients receiving fluconazole prophylaxis: a multicenter cohort study by the Turkish Pediatric Bone Marrow Transplantation Study Group.

Invasive fungal infections (IFIs) are a major cause of infection-related morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Data from pediatric settings are scarce. To determine the incidence, risk factors and outcomes of IFIs in a 180-day period post-transplantation, 408 pediatric patients who underwent allogeneic HSCT were retrospectively analyzed. The study included only proven and probable IFIs. The cumulative incidences of IFI were 2.7%, 5.0%, and 6.5% at 30, 100, and 180 days post-transplantation, respectively. According to the multivariate analysis, the factors associated with increased IFI risk in the 180-day period post-HSCT were previous HSCT history (hazard ratio [HR], 4.57; 95% confidence interval [CI] 1.42-14.71; P = .011), use of anti-thymocyte globulin (ATG) (HR, 2.94; 95% CI 1.27-6.80; P = .012), grade III-IV acute graft-versus-host-disease (GVHD) (HR, 2.91; 95% CI 1.24-6.80; P = .014) and late or no lymphocyte engraftment (HR, 2.71; 95% CI 1.30-5.62; P = .007). CMV reactivation was marginally associated with an increased risk of IFI development (HR, 1.91; 95% CI 0.97-3.74; P = .063). IFI-related mortality was 1.5%, and case fatality rate was 27.0%.The close monitoring of IFIs in pediatric patients with severe acute GVHD who receive ATG during conditioning is critical to reduce morbidity and mortality after allogeneic HSCT, particularly among those with prior HSCT and no or late lymphocyte engraftment.