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.

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.

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.

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.

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.

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.

Assessment of 17 Pediatric Cases With Colchicine Poisoning in a 2-Year Period.

AIM: The aim of the study is to discuss clinical effects, treatments, and outcomes of pediatric colchicine poisoning. METHOD: This study was designed as an observational case series study. The medical records of children aged between 0 and 18 years, who were hospitalized for colchicine poisoning at the Department of Pediatric Intensive Care Unit, Cumhuriyet University Faculty of Medicine, between January 2010 and January 2012, were retrospectively evaluated. RESULTS: We presented 17 children with colchicine poisoning. The mean (SD, range) age of patients was 71.5 (69.19, 18-204) months. The period to apply to the hospital after taking the medications was 7.3 hours (7.97, 30 minutes-26 hours) on average. The use of colchicine was due to diagnosis of Familial Mediterranean fever (FMF) in the families of 8 patients, diagnosis of Behçet disease in 1 patient's father, diagnosis of Behçet disease in 1 patient herself, and diagnosis of FMF in 6 patients themselves. Thirteen patients had taken colchicine at the dose of less than 0.5 mg/kg known as subtoxic and 1 patient had taken colchicine at the dose of greater than 0.8 mg/kg, and doses taken by 3 patients were not known. Fourteen patients (82.4%) had involuntary drug intake. Fifty percent of them were symptomatic at the moment of application and all had gastrointestinal complaints. All patients were observed in intensive care unit upon first admission and received supportive care. One of patients showed total alopecia, one showed leucocytosis, and another one showed acute abdomen picture. None of the patients showed mortality. CONCLUSIONS: Mortality of colchicine toxicity is high and quick assessment is absolutely required. In regions where FMF is common and the use of colchicine is high, clinicians should pay attention to symptoms and findings related to colchicine intoxication and keep them in mind in differential diagnosis.

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.

Assessing anxiety levels and empathic tendency in blood and platelet donors.

In spite of a constantly-increasing requirement for blood transfusion in the world, blood donation does not exhibit an increase at the same rate. In Turkey with a population of 74 million, only 15 per 10,000 people donate blood regularly and rate of voluntary blood donation is very low compared to developed countries. The aim of this study is to determine empathic level of donors and anxiety levels of blood and platelet donors and also to enable comfort and motivation of donors by taking precautions for reducing their anxieties. This prospective and descriptive study was conducted with 100 voluntary donors (50 blood donors, 50 platelet donors) who admitted to Blood Centre of Cumhuriyet University Hospital between 15 March 2012 and 30 April 2012. Average age of these donors was 27 (19-48)years. The mean scores of donors from Empathic Tendency Scale (ETS), State Anxiety Invertory (SAI) and Trait Anxiety Inventory (TAI) were 70 (49-83), 40 (33-45) and 34 (30-44), respectively. ETS score of those donating blood/platelet for the first time was low, >1 is higher in those who donated previously. SAI and TAI scores of blood donors were higher than those of platelet donors (p<0.001) and TAI score was higher in those who donate for the first time (p<0.007) compared to previously donated precipitants. In conclusion, this study underscores that the request of the donor to help others is the most important factor for donation. People frequently donate blood to unfamiliar people and recurring blood donations increase the level of empathy. Donation made during the continuous disclosure is an important factor for being a donor.

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.

Screening survivors of childhood acute lymphoblastic leukemia for obesity, metabolic syndrome, and insulin resistance.

Acute lymphoblastic leukemia (ALL) survivors were screened for risk factors of cardiovascular disease. Forty-four ALL survivors in first remission were enrolled. Twenty-six also received 12-18 Gy cranial radiotherapy (RT). Patients' body mass indexes (BMIs) at dignosis and during the study were compared. Metabolic syndrome (MS) evaluation was performed in patients, parents, and siblings older than 6 years. Homeostasis Model Assessment (HOMA) index of the survivors was also calculated. In survivors with impaired fasting glucose levels, oral glucose tolerance test (OGTT) was performed. Thyroid functions and IGF-1 and/or IGFBP-3 levels of the survivors who received cranial RT were evaluated. Median age of the survivors was 11.5 years (6-23). At diagnosis, mean BMI percentile was 46.7 (3-95) and mean z-score was -0.09 ± 1.14; during the study, these values rose to 71.1 ± 25.6 (3-100) and 0.8 ± 0.94, respectively (P < .001). One patient (2.2%) and nine survivors (20%) were obese at diagnosis and during the study, respectively (P = .005). Survivors had significantly higher BMI percentile and BMI z-score compared to their siblings (P = .006 and P = .011, respectively). The study group was small and we could not show a correlation of the patients' obesity with RT, thyroid functions, IGF-1, and IGFBP-3 levels. In three survivors (6.8%), there was MS. Maternal and paternal MS was not found as a risk factor for MS of the survivors (P = .1, P = .5, respectively). The HOMA index revealed insulin resistance (IR) in 12 (27.2%) of the survivors, whereas OGTT revealed abnormal glucose regulation and/or IR in four. As a conclusion, ALL survivors have high risk for obesity and MS.

The prevalence and outcomes of thrombocytopenia in a neonatal intensive care unit: a three-year report.

Neonatal thrombocytopenia is one of the most common hematologic disorders in neonatal intensive care units (NICUs). The purpose of this study was to determine the prevalence of thrombocytopenia and whether thrombocytopenia has an effect on the occurrence of intraventricular hemorrhage (IVH) ≥ grade 2 and on mortality rate. This study was carried out retrospectively in neonates admitted to NICU of Cumhuriyet University in Sivas, Turkey, between 2009 and 2012. Among 2218 neonates evaluated, 208 (9.4%) developed thrombocytopenia. The prevalence of IVH ≥ grade 2 was more in infants with thrombocytopenia (7.2%) than in those without thrombocytopenia (4.4%), although this was not statistically significant (P = .08). In univariate analysis, IVH ≥ grade 2 was higher in cases with very severe thrombocytopenia (35.7%, n = 5) than in those with mild (2.1%, n = 2), moderate (4.7%, n = 3), and severe thrombocytopenia (15.2%, n = 5) (P = .04). Multivariate logistic regression analysis showed that birth weight <1500 g (OR 6.2, 95% CI 3.4-9.8; P = .0001), gram-negative sepsis (OR 2.5, 95% CI 1.8-4.2; P = .01), very severe thrombocytopenia (OR 1.3, 95% CI 1.1-2.1; P = .03), and platelet transfusion ≥2 (OR 7.3, 95% CI 4.1-12.1; P = .001) were significant risk factors for mortality. The results of our study suggest that outcomes of neonates with thrombocytopenia depend not only on platelet count but also on decreased gestational age or birth weight, prenatal factors, and sepsis.

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.

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.

Piperacillin/tazobactam monotherapy versus piperacillin/tazobactam plus amikacin as initial empirical therapy for febrile neutropenia in children with acute leukemia.

The purpose of this study is to compare the efficacy and safety of piperacillin/tazobactam (PIP/TAZO) versus PIP/TAZO plus amikacin in febrile neutropenic children with acute leukemia (AL). Children with AL who had febrile neutropenic episodes were randomized to treatment with PIP/TAZO versus PIP/TAZO plus amikacin. Modification was defined as addition of other antimicrobials and/or antifungal agents to the empirical therapy. Protocol failure was defined as withdrawal of the empirical regimen and introduction of other antimicrobials due to failure in controlling infection. Seventy-two febrile episodes of 42 patients with a median age of 4.5 years (3.5 months to 19 years) were evaluated. There were 37 and 35 episodes in PIP/TAZO and combination arms, respectively. Success without modification, with modification, protocol failure, duration of treatment were 45.9%, 35.1%, 18.9%, and 10 days in PIP/TAZO arm and 42.9%, 37.1%, 20%, and 12 days in combination arm, respectively (P > .05). There was no significant difference between the empirical therapy arms regarding median duration of neutropenia and defervescence of fever. Empirical therapy was substituted by other drugs in 6 and 5 episodes in PIP/TAZO and combination arms, respectively. There was no infection-related death. There was reversible increase in serum creatinine in 1 episode on the combination arm. Monotherapy with PIP/TAZO was effective and safe for initial empirical treatment of febrile neutropenic episodes in children with AL. However, local bacterial resistance patterns should be considered in daily practice. Combination of amikacin with PIP/TAZO did not improve treatment success, but it may increase nephrotoxicity.

A child with severe form of dyskeratosis congenita and TINF2 mutation of shelterin complex.

A 26-month-old male presented with bone marrow failure and dystrophic nail lesions mimicking onychomycosis. There was no skin finding. Treatment with androgen and methylprednisolone was started due to unavailability of a matched-related hematopoietic stem cell donor. After 30 months, transfusion support was required. TINF2 mutation was identified at the age of five and dyskeratosis congenita (DC) was confirmed. TIN2 mutation analysis must be carried out in patients younger than 10 years presenting with bone marrow failure even if characteristic physical anomalies of DC is missing. Genetic confirmation of DC prevents ineffective immunotherapy with misdiagnosis of acquired aplastic anemia.

Hemophilia-Specific Quality of Life Index (Haemo-QoL and Haem-A-QoL questionnaires) of children and adults: result of a single center from Turkey.

The aim of this study is to describe the health status, health care received, and their impact on the quality of life in patients with hemophilia. Patients with severe factor VIII or IX deficiency without inhibitors or other chronic disease were enrolled. Turkish version of the Hemophilia-Specific Quality of Life Index (Haemo-QoL) questionnaire was administered to the pediatric patients aged 4 to 16 years and Haem-A-QoL to the adult patients. Joints were evaluated according to the World Federation of Hemophilia (WFH) orthopedic joint scores.Thirty-nine children/adolescents and 31 adult patients were enrolled. Mean Haemo-QoL scores were 39.6 +/- 15.0 for the children and mean Haem-A-QoL 47.4 +/- 14.1 for the adult patients, respectively. Internal consistency reliability was generally sufficient. Total Cronbach's alpha coefficient was >.70 (range .77-.96) in all the age groups. Mean total WFH orthopedic joint scores were 1.83 +/- 2.7, 4.9 +/- 4.96, and 6.94 +/- 6.15 in 4-7, 8-12, and 13-16-year-old groups, respectively. They were more impaired in the adult patients (16.23 +/-14.12). These results show that the Turkish version of the Haemo-QoL and Haem-A-QoL are reliable instruments to measure the quality of life in the pediatric and adult patients with severe hemophilia. When compared to the Haemo-QoL scores of an international multicenter West European study of children, quality of life in the Turkish patients were more impaired in the subscales of physical health, feeling, view, school and sport, and treatment as well as more impaired WFH joint scores. The authors recommend primary factor prophylaxis and encouraging the patients to learn home treatment to improve joint scores and quality of life.