Abnormal frequency of the memory B cell subsets and plasmablasts in patients with congenital severe hemophilia A: correlation with "Inhibitor" formation.

BACKGROUND: Development of antibodies against infused Factor VIII (FVIII) or "inhibitors" represents a major challenge following FVIII replacement therapy in patients with hemophilia A (HA). Recent studies have shown that certain cellular compartments of the immune system contribute to the production of such antibodies. Herein, we determined the frequency of class-switched CD19+IgD-CD27+/non-class-switched CD19+IgD+CD27+ memory B cell subsets and CD19+CD27hiCD38hi plasmablasts in patients with severe HA and their association with the development of inhibitors in these patients. METHODS: This cross-sectional case-control study enrolled 32 patients with severe HA, including 8 with and 24 without inhibitors, and 24 healthy individuals. The frequencies of the memory B cell subsets and plasmablasts were determined using flow cytometry. RESULTS: The frequency of CD19+IgD+CD27+ non-class-switched memory B cells was significantly lower in patients with HA (including both patients with and without inhibitors) than in healthy controls. The percentages of both CD19+IgD-CD27+ class-switched and CD19+IgD+CD27+ non-class-switched memory B cells did not differ significantly between patients with and without inhibitors. HA patients with inhibitors had significantly higher proportions of CD19+CD27hiCD38hi plasmablasts than the control group as well as the inhibitor (-) ones. No significant correlation was observed between the inhibitor levels with the percentages of memory B cell subsets and plasmablasts. CONCLUSION: This study is the first to demonstrate a dysregulated proportion of CD19+IgD+CD27+ non-class-switched memory B cells and CD19+CD27hiCD38hi plasmablasts in patients with severe HA. Therefore, strategies targeting memory B-cell/plasmablast differentiation may have promising outcomes in the management of inhibitor formation in patients with severe HA.

Iron Overload in Children With Leukemia; Identification of a Cutoff Value for Serum Ferritin Level.

OBJECTIVE: To determine the prevalence of iron overload in children with acute lymphoblastic leukemia (ALL) after treatment cessation and establish a cutoff value for serum ferritin level as an indicator of iron overload. BACKGROUND: Early detection and monitoring of iron overload in patients with leukemia is crucial. METHODS: In this prospective cohort study, 66 pediatric patients with ALL who were treated at a tertiary referral center affiliated with Shiraz University of Medical Sciences in Shiraz, Southern Iran, were investigated from July 2020 to December 2022. Serum ferritin levels were measured 6 months after treatment completion. T2* magnetic resonance imaging of the liver and heart was done for all patients. The receiver operating characteristic curve was used to illustrate the area under the receiver operating characteristic curve to assess the diagnostic value of serum ferritin level and total transfusion volume. RESULTS: A total of 24 patients (36.4%) had iron overload in the heart or liver based on T2 magnetic resonance imaging findings. Serum ferritin level was a highly accurate diagnostic marker for iron overload in pediatric patients with ALL, with a sensitivity of 95.8%, and specificity of 85.7% for a cutoff value of 238.5 ng/mL. Also, blood transfusion was a good predictor of iron overload a sensitivity of 75% and specificity of 81% for a cutoff value of 28.3 mL/kg. CONCLUSION: We identified specific cutoff values for serum ferritin and blood transfusion volume to predict iron overload with high sensitivity and specificity. These markers offer a cost-effective and accessible approach for periodic screening of iron deposition, particularly in resource-constrained settings.

The efficacy of Allium ampeloprasum L. in reducing neutrophil recovery time in childhood cancer with febrile neutropenia: a randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Febrile neutropenia is a serious complication of cancer chemotherapy that can result in delays in treatment. This study evaluates the efficacy of A. ampeloprasum L. at neutrophil recovery time in children with chemotherapy-associated febrile neutropenia. METHODS: This single-center, parallel-group, double-blind, randomized clinical trial was conducted at an oncology hospital. Patients selected among childhood cancers with febrile neutropenia. Overall, 97 febrile neutropenic children were enrolled. The intervention group (n=49) was given A. ampeloprasum L. in capsules (500 mg twice daily) for seven days plus supportive care. The control group (n=48) was treated similarly with supportive care and placebo capsules. Total white blood cell (WBC) and absolute neutrophil counts (ANC) were checked daily and neutrophil recovery time in both groups was compared. RESULTS: Patients in the intervention group experienced shorter neutrophil recovery compared to the control group (4.02 ± 2.32 days vs. 6.38 ± 2.80 days, respectively, P less than 0.001). The intervention group was discharged from the hospital earlier than the control group with a mean of two days, but it did not reach statistical significance (P=0.133). Mean WBC and ANC were not significantly different in the two groups. Herbal medicine was well tolerated, and no adverse effect was reported. CONCLUSIONS: A fresh, lyophilized extract from deciduous leaves of A. ampeloprasum L. can effectively shorten the ANC recovery time leading to an earlier release from the hospital. The trial was registered in the Iranian Registry of Clinical Trials with registration No. IRCT2015051615666N2 (http://www.irct.ir/).

Skeletal complications in patients with hemophilia: a single-center experience.

BACKGROUND: Arthropathy is a common complication in patients with hemophilia. We examined the prevalence of this skeletal complication in patients with hemophilia who were registered at a Comprehensive Hemophilia Center in Shiraz, Southern Iran. MATERIALS AND METHODS: In this cross-sectional study, an orthopedic specialist visited 448 patients and conducted screenings for skeletal complications. The assessment included evaluating the type of hemophilia, disease severity, treatment modality, the presence of inhibitors, and the identification of skeletal complications. RESULTS: Ninety patients with hemophilia A, with a mean age (SD) of 31.6 (14.4) years, and 10 patients with hemophilia B, with a mean age of 30.5 (20.6) years, were assessed. The most frequently affected joints were the knee and ankle joints. In the univariate analysis, patients with severe disease were more likely to exhibit synovitis, a target joint, and bone disease compared to patients with non-severe disease. Additionally, a history of treated or active hepatitis and an annual bleeding rate showed significant associations with the target joint. In the multivariable logistic regression analysis, disease severity (OR 14.43, 95% CI 1.6-129.6) and a higher age at diagnosis (OR 1.06, 95% CI 1.00-1.13) increased the likelihood of developing osteoporosis. A history of hepatitis (OR 3.67, 95% CI 1.28-10.48) was identified as an independent risk factor for the target joint. CONCLUSION: Skeletal complications are a common occurrence in hemophilia. Regular consultations with orthopedic specialists, focusing on bleeding control and hepatitis prevention, are essential for reducing the impact of this debilitating complication.

Large Retroperitoneal Teratoma Presenting with Unilateral Hydronephrosis in an Infant: A Case Report and Review of the Literature.

Teratoma is a type of germ cell tumor layer that appears in the gonadal, sacrococcygeal, mediastinal, and retroperitoneal regions. Primary retroperitoneal teratoma is rare and asymptomatic but can present with symptoms due to a mass effect on neighboring organs. These tumors have to be considered in the differential diagnosis of a mass in the abdominal cavity of children to distinguish between Wilms' tumor, neuroblastoma, and other intra-abdominal lesions. We presented an infant boy with protrusion of the left upper quadrant of the abdomen and a palpable abdominal mass that had progressively enlarged. An abdominal computed tomography scan revealed a large retroperitoneal cystic, solid mass on the left side of the abdominal cavity, causing pressure on the left ureter. Also, hydronephrosis of the left kidney was seen with a decreased enhancement of the left kidney due to obstruction uropathy. The mass was suspicious on imaging for a retroperitoneal teratoma. The patient underwent laparotomy, and excision of the huge retroperitoneal mass was done. The final diagnosis was an immature teratoma grade 3, and the patient was discharged in good condition. Retroperitoneal teratomas are rare tumors in infants. These tumors would be an incident diagnosis or diagnosed by the mass effect of giant tumors on other organs. They must be considered in the differential diagnosis of intra-abdominal tumors in children. Hydronephrosis and obstructive uropathy can be rare consequences of the mass effects of these tumors.

Altered frequency of FOXP3+ regulatory T cells is associated with development of inhibitors in patients with severe hemophilia A.

INTRODUCTION: The development of anti-factor VIII (FVIII) antibodies or "inhibitors" is a major complication following FVIII replacement therapy in patients with severe hemophilia A (HA), rendering the treatment inefficient. Data on the role of regulatory T cells (Tregs) in inhibitor formation in these patients are rare. Herein, we aimed to investigate whether a difference in the FOXP3+ Tregs is linked to the formation of the inhibitors in severe HA patients. METHODS: In this cross-sectional study, 32 patients with severe HA (8 patients with inhibitors and 24 without inhibitors) and 24 healthy controls were enrolled. The frequency of FOXP3+ Tregs was determined using multicolor flow cytometry method. RESULTS: Our results showed that the median level of CD4+ CD25+ FOXP3+ Tregs did not significantly differ between HA patients and healthy controls and between HA patients with and without inhibitors (P > 0.05). However, patients with inhibitors had significantly lower amounts of CD4+ CD25- FOXP3+ Tregs compared to those without inhibitors as well as healthy controls (*P = 0.012 and *P = 0.004, respectively). The frequency of CD4+ CD25+ T cells was significantly higher in HA patients who developed inhibitors compared to the inhibitor-negative ones whereas they were lower in inhibitor-negative patients compared to the healthy controls (*P = 0.013 and *P = *0.029, respectively). The percentages of CD4+ CD25+ T cells were positively correlated with the levels of inhibitors in HA patients (r = 0.45, *P = 0.021). CONCLUSION: Our data demonstrated for the first time that the CD4+ CD25- FOXP3+ Tregs might be implicated in the prevention of inhibitor formation in severe HA patients.

Cardioprotective effects of deferoxamine in acute and subacute cardiotoxicities of doxorubicin: a randomized clinical trial.

BACKGROUND: Cardiotoxicity is a major concern following doxorubicin (DOX) use in the treatment of malignancies. We aimed to investigate whether deferoxamine (DFO) can prevent acute cardiotoxicity in children with cancer who were treated with DOX as part of their chemotherapy. RESULTS: Sixty-two newly-diagnosed pediatric cancer patients aged 2-18 years with DOX as part of their treatment regimens were assigned to three groups: group 1 (no intervention, n = 21), group II (Deferoxamine (DFO) 10 times DOX dose, n = 20), and group III (DFO 50 mg/kg, n = 21). Patients in the intervention groups were pretreated with DFO 8-h intravenous infusion in each chemotherapy course during and after completion of DOX infusion. Conventional and tissue Doppler echocardiography, serum concentrations of human brain natriuretic peptide (BNP), and cardiac troponin I (cTnI) were checked after the last course of chemotherapy. Sixty patients were analyzed. The level of cTnI was < 0.01 in all patients. Serum BNP was significantly lower in group 3 compared to control subjects (P = 0.036). No significant differences were observed in the parameters of Doppler echocardiography. Significant lower values of tissue Doppler late diastolic velocity at the lateral annulus of the tricuspid valve were noticed in group 3 in comparison with controls. By using Pearson analysis, tissue Doppler systolic velocity of the septum showed a marginally significant negative correlation with DOX dose (P = 0.05, r = - 0.308). No adverse effect was reported in the intervention groups. CONCLUSIONS: High-dose DFO (50 mg/kg) may serve as a promising cardioprotective agent at least at the molecular level in cancer patients treated with DOX. Further multicenter trials with longer follow-ups are needed to investigate its protective role in delayed DOX-induced cardiac damage. Trial registration IRCT, IRCT2016080615666N5. Registered 6 September 2016, http://www.irct.ir/IRCT2016080615666N5 .

The survival of childhood leukemia: An 8-year single-center experience.

BACKGROUND: The survival of childhood leukemia has improved. We aimed to report the survival rate and the associated factors in children with acute leukemia during an 8-year follow-up. AIMS: This study investigates the 8-year survival rates of children with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in Shiraz, the largest oncology center in Southern Iran. We also aimed to assess the independent factors associated with higher mortality in childhood leukemia. METHODS: Children 0-18 years with acute leukemia were followed from 2013 to 2021 in Shiraz, Iran. The 8-year overall survival (OS) and event-free survival (EFS) rates were estimated by the Kaplan-Meier method. Independent factors associated with survival were assessed by the Cox regression hazard modeling. RESULTS: We included 786 children, with 43.5% female, and a mean age of 6.32 ± 4.62 years. Patients with AML compared to ALL experienced more relapse (34.6% vs. 22.5%, p = .01) and death (31.7% vs. 11.3%, p < .001). The cumulative 8-year OS and EFS were 81% (95% confidence interval (CI), 74.3% to 86.1%) and 68.3% (95% CI, 63.5% to 72.7%) in ALL patients and 63.5% (95% CI, 52.1% to 72.9%) and 43% (95% CI, 33.1% to 52.6%) in AML patients. Multivariable analysis revealed that hepatomegaly (hazard ratio = 4, 95% CI, 1.0 to 22.3, p = .05) was the main independent risk factor of death in ALL patients. No definite risk factor was defined for AML patients. CONCLUSION: The survival of childhood leukemia has recently increased dramatically in low-middle income countries. Hepatomegaly was introduced as a potential risk factor for lower survival in ALL patients. Further multicenter studies are needed to confirm the validity of this association.

Prognosis and Overall Survival of Thalassemia Patients using Semi-Parametric Mixture Cure-Rate Model: a 30-Year Retrospective Cohort Study.

BACKGROUND: Understanding the determinants of long-term overall survival (OS) of thalassemia patients (TPs) is the mainstay of care. METHODS: As a retrospective survey, we assessed the data of 769 TPs who had regular follow-up and blood transfusion for at least 30 years from 1990 - 2019. We utilized semi-parametric proportional hazards mixture cure-rate regression to discover the factors with a significant effect on short- and long-term OS separately. RESULTS: The 25- and 30-year OS for the TPs were calculated to be 98.7% and 90.4%, respectively. Each five-year age escalation was associated with a 30% decrease in the probability of being short-term survivors (HR = 1.06, p = 0.047). Parental family relationship influenced both cured (OR = 3.00, p = 0.017) and uncured (HR = 0.50, p = 0.046) TPs. Moreover, the type of iron chelation drug, liver iron concentration, and normal EF results had a significant effect on long-term OS. Aging, parental consanguinity, liver and cardiac siderosis, higher ferritin levels, and low hemoglobin level were associated with poorer prognosis in TPs. CONCLUSIONS: However, deferoxamine followed by multiple drugs as iron chelation, severe liver siderosis, and abnormal EF declined the probability of long-term OS among TPs. This can be considered by health policy decision-makers to enforce the screening program more strictly.

Efficacy and safety of fibrinogen concentrate for perioperative prophylaxis of bleeding in adult, adolescent, and pediatric patients with congenital fibrinogen deficiency: FORMA-02 and FORMA-04 clinical trials.

BACKGROUND: Congenital fibrinogen deficiency (CFD) is a rare coagulation disorder placing patients at increased bleeding risk. Human fibrinogen concentrate (HFC) represents current standard of care for fibrinogen replacement in CFD, however, limited data are available on HFC for prophylactic administration before/during surgery. Here, we report results and dosing considerations for HFC treatment in perioperative bleeding management in adult, adolescent, and pediatric patients with CFD. STUDY DESIGN AND METHODS: FORMA-02/FORMA-04 were multinational, prospective, open-label, uncontrolled Phase 3 HFC efficacy/safety studies for surgical bleeding prophylaxis in adult/adolescent (≥12 years) and pediatric patients (<12 years) respectively. HFC dosing was calculated to achieve pre-established target fibrinogen plasma levels. Overall hemostatic efficacy was assessed as success/failure by an Independent Data Monitoring and Endpoint Adjudication Committee (IDMEAC) according to objective criteria. RESULTS: Twelve patients (≥12 years, N = 9; <12 years, N = 3) received HFC for surgical prophylaxis (15 surgeries; 13 minor, 2 major). Eleven minor surgeries in patients aged ≥12 years required a median of 1 infusion (range; 1-5), with a mean (±SD) dose of 93.50 mg/kg [±41.43] and two minor surgeries in patients <12 years required 1 infusion (91.55 mg/kg [±23.40]). The major surgery in an adult patient required eight infusions (225.3 mg/kg total dose). The major surgery in a pediatric patient required six infusions (450.4 mg/kg). All surgeries were rated successful by the IDMEAC. DISCUSSION: In adults/adolescents and pediatric patients with fibrinogen deficiency, HFC treatment for hemostatic management during/after minor and major surgery was successful, with efficacy comparable across the different age groups.

Optical coherence tomography findings in patients with transfusion-dependent ß-thalassemia.

BACKGROUND: Structural ophthalmologic findings have been reported in patients with ß-thalassemia due to chronic anemia, iron overload, and iron chelation therapy toxicity in few previous studies. We aimed to investigate structural ocular findings and their relationship with hematological parameters in patients with transfusion-dependent ß-thalassemia (TDT). METHODS: In this cross-sectional study, from January 2018 to January 2019, 39 patients with TDT over the age of 18 participated. Multicolor fundus imaging, optical coherence tomography (OCT), and blue light fundus autofluorescence imaging were performed for all patients and 27 age- and sex-matched controls. RESULTS: The mean age of patients was 28.6 ± 6.2 years. The central macular thickness and macular thicknesses in all quadrants were significantly thinner in patients than controls (P<0.05). None of the retinal nerve fiber layer (RNFL) measurements were significantly different between TDT patients and controls. There was a significantly negative correlation between hemoglobin with central macula thickness (r=-0.439, P=0.005). All measurements of macular subfield thickness were insignificantly thinner in patients with diabetes mellitus (DM) compared to the non-DM subgroup. CONCLUSIONS: Macular thickness was significantly thinner in central macula and entire quadrants in TDT patients compared to healthy individuals; however, all RNFL measurement thicknesses were comparable between the two groups. Close monitoring of TDT patients by periodic ophthalmologic examinations with more focus on diabetic patients, patients with severe anemia and iron overload should be warranted.

Atopy manifestations in pediatric patients with acute lymphoblastic leukemia: correlation assessment with interleukin-4 (IL-4) and IgE level.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common type of cancer in the age range of under 15 years old and accounts for 25-30% of all childhood cancers. Although conventional chemotherapy regimens are used to improve the overall survival rate, it has been associated with some complications, amongst which allergic manifestations with unknown mechanisms are more common. METHODS: Our study compared serum IgE and IL-4 concentration, as a hallmark of allergic responses in pediatric ALL patients before and after 6 months of intensive (high-dose) chemotherapy, to show whether changes in the level of these markers may be associated with atopy. Serum level of IL-4 and IgE was measured using enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The results showed that the level of IgE and IL-4 increased following chemotherapy in both ALL patients with and without atopy. In addition, post-chemotherapy treatment IgE and IL-4 levels were significantly elevated in patients with atopy compared to those without it. The difference between baseline and post-chemotherapy level of IgE and IL-4 was significantly higher in patients with atopy compared to those without it. CONCLUSIONS: To the best of our knowledge, this is the first study that showed a connection between post-chemotherapy allergic manifestations in pediatric ALL patients and IL-4 and IgE level. Flow cytometry analysis of the T-helper 2 (Th2) lymphocytes and other allergy-related T cell subsets like Tc2 and Th9 as well as the study of the genetic variations in atopy-related genes like IL-4/IL-4R, IL-5, IL-9, IL-13, and high affinity FcεRI IgE receptor and also HLA genes is necessary to clearly define the underlying mechanism responsible for post-chemotherapy hypersensitivity reaction in pediatric ALL patients.

Elevated CD9 expression as a potential biomarker for diagnosis of Bernard-Soulier syndrome.

Diagnosis of inherited platelet glycoprotein disorders is based on specific laboratory techniques such as aggregometry and flow cytometry. Flowcytometry is a powerful method, but equivocal results are produced in some cases. New cluster of differentiation markers could resolve the diagnostic dilemmas. Abnormal expression of CD9 in Bernard-Soulier syndrome (BSS) is recently reported. We aimed to determine the diagnostic significance of CD9 expression in a cohort of Iranian patients with inherited platelet glycoprotein defects. Twelve BSS, 21 Glanzmann thrombasthenia and 16 healthy controls were included in the present study. Flowcytometric diagnosis of BSS and Glanzmann thrombasthenia was made by analysis of CD41/61 and CD42a/42b CD markers. Moreover, phycoerythrin-labelled anti CD9 was examined in patients and healthy controls. The mean fluorescence intensity (MFI) of CD9 among the three groups was compared using suitable statistical methods and a P value of less than 0.05 considered statistically significant. Mean MFI of CD9 was 990.0 in BSS patients versus 421.2 and 317.3 in individuals with Glanzmann thrombasthenia and healthy controls, respectively (P < 0.05). Between the two-group comparison of means by the Mann-Whitney test revealed a P value of less than 0.001 for BSS group versus GT (2.4-fold) and BSS versus healthy controls (2.9-fold). CD9 molecule also expressed differently in patients with Glanzmann thrombasthenia in comparison with healthy controls (P < 0.001), although with a less magnitude (1.3-fold). According to our findings, CD9 is a potential biomarker for laboratory diagnosis of inherited glycoprotein defects, especially to elucidate the ambiguous results in BSS cases.

Case reports of invasive mucormycosis associated neutropenic enterocolitis in leukemic children: diagnostic and treatment challenges and review of literature.

BACKGROUND: Bacterial enterocolitis is one of the most common neutropenic fever complications during intensive chemotherapy. Despite aggressive antibacterial treatments, this complication usually imposes high morbidity and mortality in cancer patients. Management of bacterial neutropenic enterocolitis are well known; however, management of fungal neutropenic enterocolitis may be more challenging and needs to be investigated. Prompt diagnosis and treatment may be life-saving, especially in patients at risk of mucormycosis-associated neutropenic enterocolitis. CASE PRESENTATION: We report two mucormycosis-associated neutropenic enterocolitis cases in pediatric leukemic patients receiving salvage chemotherapy for disease relapse. Both patients' clinical signs and symptoms differ from classical bacterial neutropenic enterocolitis. They were empirically treated as bacterial neutropenic enterocolitis with anti-gram-negative combination therapy. Despite broad-spectrum antimicrobial treatment, no clinical improvement was achieved, and both of them were complicated with severe abdominal pain necessitating surgical intervention. Mucormycosis is diagnosed by immunohistopathologic examination in multiple intraoperative intestinal tissue biopsies. Both patients died despite antifungal treatment with liposomal amphotericin-B and surgical intervention. CONCLUSION: Mucormycosis-associated neutropenic enterocolitis is one of the most unfavorable and untreatable side effects of salvage chemotherapy in leukemic children with disease relapse. This report could be of considerable insight to the clinicians and scientists who counter the enigma of fungal infections during febrile neutropenia and help to understand better diagnosis and management.

Comparison of the clinical features and outcome of children with hemophagocytic lymphohistiocytosis (HLH) secondary to visceral leishmaniasis and primary HLH: a single-center study.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive inflammation. We aimed to describe the clinical and laboratory findings of HLH patients secondary to Visceral leishmaniasis (VL) and their treatment outcome during a 4-year follow-up period compared to primary HLH. METHOD: Forty children with primary HLH confirmed by genetic study and 20 children with HLH secondary to VL confirmed by a blood or bone marrow polymerase chain reaction from 2014 to 2018 in Shiraz, Fars province, Southern Iran, were enrolled. RESULTS: The median age at diagnosis was 11.5 months (range 1-170), and 56.7% were male. Fever and splenomegaly were the most frequent clinical presentations. 93.3% of the subjects had an HScore > 169, which had a good correlation with HLH-2004 criteria (r = 0.371, P = 0.004). Patients with primary HLH experienced more thrombocytopenia (P = 0.012) and higher alanine transaminase (P = 0.016), while patients with VL-associated HLH had higher ferritin (P = 0.034) and erythrocyte sedimentation rate (P = 0.011). Central nervous system (CNS) involvement occurred in 38.3% of patients. The mortality rate was higher in patients with CNS disease (61% vs. 35%, P = 0.051). The 3-yr overall survival rate was 35.9%. (24% in primary HLH and 100% in VL-associated HLH, P < 0.001). In Cox regression analysis, platelet count < 100,000/ µ l (hazard ratio 4.472, 95% confidence interval 1.324-15.107, P = 0.016) correlated with increased mortality in patients with primary HLH. CONCLUSION: VL is a potential source of secondary HLH in regions with high endemicity. Treatment of the underlying disease in VL-associated HLH is sufficient in most cases, with no need to start etoposide-based chemotherapy.

Trace Elements in Children with Acute Lymphoblastic Leukemia.

OBJECTIVE: Although combined chemotherapy regimen leads to 80% remission in children with acute lymphocytic leukemia (ALL), malnutrition and altered serum trace elements as a consequence of chemotherapy agents, have become the new issue to deal with. With the aim to evaluate each trace element in childhood ALL, we investiguâtes six main trace elements before and after induction chemotherapy while considering age, gender and chemotherapy protocol as confounding factors. METHODS: Thirty-six newly diagnosed ALL children were recruited, and trace elements were assessed by atomic absorption spectrometry technique. Trace elements (Zinc, Copper, Manganese, Magnesium, Chromium and Iron) decreased significantly after induction chemotherapy. RESULTS: Considering the confounding factors, mean difference of elements decreased significantly, except for Chromium. Its mean difference was only significant in children younger than 10 and those who had received standard risk chemotherapy. CONCLUSION: In conclusion, all the studied trace elements decreased significantly after induction chemotherapy session in ALL children. This highlights the importance of complementary and supplementary management. A larger cohort study with longer follow up is warranted to elucidate the long-term effect of chemotherapy on these trace elements on the general health status, quality of life or risk of relapse in ALL children.

Bayesian spatial modeling of transfusion-dependent ß-thalassemia incidence rate in Fars Province, Southern Iran.

BACKGROUND: Using maps and spatial analysis are technologies to evaluate the magnitude and spatial distribution of disease in epidemiology investigations. We aimed to conduct a Bayesian spatial analysis on epidemiologic data of transfusion-dependent ß-thalassemia (TDT) patients. METHODS: In this cross-sectional study, data of all TDT patients diagnosed during 1955-2018 in all counties of Fars Province were obtained from data registry of the Organization of Special Diseases of Shiraz University of Medical Sciences in Shiraz, Fars Province, Iran. Besag, York, and Mollie's (BYM) model was used for mapping. RESULTS: The estimated relative risk ranged from 0.23 to 1.66 for TDT patients. The highest and lowest relative risks of TDT were observed in Larestan located in Southern and Abadeh in Northern Fars Province respectively. CONCLUSIONS: Determining the accurate geographical distribution of a chronic disease such as ß-thalassemia can be an essential prerequisite in allocation of regional health system resources.

Association of HFE Gene Mutations With Serum Ferritin Level and Heart and Liver Iron Overload in Patients With Transfusion-dependent Beta-Thalassemia.

OBJECTIVE: This study was performed on patients with transfusion-dependent beta-thalassemia (TDT) to investigate the effect of HFE gene mutations of iron overload in a large group of patients with TDT major and its relationship with heart and liver T2* magnetic resonance imaging (MRI) level. MATERIALS AND METHODS: In a cross-sectional study, a total of 253 patients with TDT who had regular blood transfusion were included in this study. HFE gene mutations including H63D and C282Y were evaluated in all patients through molecular assay. Heart and liver T2* MRI results, types, duration of iron therapy, and the demographic data including age, gender, serum ferritin level, blood transfusion, and splenectomy history of the included participants were also collected, using a questionnaire. RESULTS: Homozygous and heterozygous H63D mutation was found in 39.5% of the patients and C282Y mutation was found only in 1 patient. Ferritin level was significantly higher in patients with H63D mutation in comparison with patients without this mutation (P=0.036). Although heart T2* MRI and also the liver T2* MRI in the patients with H63D was slightly higher, the difference was not statistically significant. No significant correlation was observed between serum ferritin level and heart and liver T2* MRI, and iron chelation regimen. DISCUSSION: Heart and liver iron overload was not significantly different between patients with and without H63D mutation. As for serum ferritin, it was significantly higher among patients with H63D mutation compared with patients without this mutation. Hence, it is recommended to consider HFE gene mutations among patients with thalassemia to reach a better iron overload evaluation and management.

Efficacy and safety of fibrinogen concentrate for on-demand treatment of bleeding and surgical prophylaxis in paediatric patients with congenital fibrinogen deficiency.

BACKGROUND: Congenital fibrinogen deficiency (CFD) is a rare, inherited disorder affecting normal blood clotting function, where patients can experience severe and/or frequent bleeding episodes (BEs). Treatment with human fibrinogen concentrate (HFC) can prevent/arrest bleeding. There is a need for more data on the efficacy, pharmacokinetics (PK) and safety of HFC treatment in paediatric patients with CFD. METHODS: Haemostatic efficacy of HFC (Fibryga® , Octapharma AG) for on-demand treatment of bleeding and surgical prophylaxis in patients <12 years old was assessed by investigators and an Independent Data Monitoring and Endpoint Adjudication Committee (IDMEAC) based on an objective 4-point efficacy scale. Maximum clot firmness (MCF; surrogate marker of haemostatic efficacy), single-dose PK and safety were also assessed. RESULTS: Of 14 patients receiving HFC (median [range] age 6.0 years [1.0-10.0]), eight received HFC for 10 BEs, three for surgical prophylaxis and 13 for PK. The IDMEAC rated haemostatic efficacy as 100% successful for on-demand BE treatment (95% CI 69.15-100.00) and surgical prophylaxis (95% CI 29.24-100.00). After a mean first dose of 70.78 mg/kg for BEs, mean (±SD) MCF significantly increased from pre-treatment to 1-hour post-infusion (3.3 mm [±1.77]; P = 0.0002), coinciding with haemostatic efficacy. PK parameters were favourable. Two possibly related adverse events occurred, including one serious (portal vein thrombosis). No allergic/hypersensitivity reactions or deaths were observed. CONCLUSION: HFC treatment for on-demand treatment of BEs and surgical prophylaxis was efficacious for this ultra-rare paediatric population with congenital afibrinogenaemia and showed a favourable PK and safety profile.