Allogenic Hematopoietic Stem Cell Transplant in Iranian Patients With Congenital Sideroblastic Anemia: A Single-Center Experience.

Congenital sideroblastic anemia is characterized by anemia and intramitochondrial iron accumulation in erythroid precursors that form ring sideroblasts. The most common recessive forms are caused by sequence variations in the ALAS2 and SLC25A38 genes. In patients with transfusion-dependent and pyridoxine- resistant severe congenital sideroblastic anemia, hematopoietic stem celltransplantis the only curative option. Herein, we described successful implementations of allogeneic hematopoietic stem cell transplant in 4 Iranian children with congenital sideroblastic anemia. The patients had presented with clinical manifestations of anemia early in life, and the diagnoses of congenital sideroblastic anemia were established through blood tests and bone marrow aspiration. Congenital sideroblastic anemia was further confirmed by the identification of pathogenic variants in SLC25A38 in 2 patients. All 4 patients received allogeneic hematopoietic stem cell transplant with myeloablative conditioning regimen that included busulfan, cyclophosphamide, andrabbit antithymocyte globulin. A combination of cyclosporine A and methotrexate or mycophenolate mofetil was used for graft-versus-host disease prophylaxis. Bone marrow and peripheral blood from sibling or related donors with fully matched human leukocyte antigen profiles were applied. The outcomes of hematopoietic stem celltransplantin patients with congenital sideroblastic anemia were favorable. Three patients achieved full donor chimerism (>95%, 98%, and 100%), and the other patient showed mixed chimerism (75%). All patients remained transfusion independent. Hemato- poietic stem celltransplantis a curative treatmentthat can provide long-term survival for patients with congenital sideroblastic anemia, particularly when used in a timely manner. There remain ongoing challenges in various aspects of hematopoietic stem celltransplantin patients with congenital sideroblastic anemia, which remain to be elucidated.

Pattern of ABCC Transporter Gene Expression in Pediatric Patients with Relapsed Acute Lymphoblastic Leukemia.

BACKGROUND: Abnormal expression of ABCC transporter genes has been associated with treatment failure in pediatric patients with acute lymphoblastic leukemia (ALL). The aim of this study was to evaluate the expression pattern of ABCC1-6 and ABCC10 genes in Iranian pediatric patients with ALL relapse and determine the potential predictive value of determining ALL relapse from ABCC expression. METHODS: Patients with ALL were divided into two separate groups, either the case group with relapsed ALL or the control group in which ALL patients have been in progression-free survival for at least 3 years A total of thirty-nine participants (23 with relapsed ALL; 16 controls) were enrolled over 26 months. To determine the levels of ABCC1-6 and ABCC10 transporter gene expression RT-PCR was used. Cumulative doses of the chemotherapy drugs, VCR, DNR and L-ASP, were calculated for each patient. RESULTS: Our findings showed elevated expression of ABCC2-6 and decreased expression of ABCC1 and ABCC10 to be associated with an increased risk of ALL relapse. The mean-fold expression of ABCC2 was significantly increased in the ALL relapse group. Additionally, the expression pattern of the ABCC transporter genes was associated with high doses of three chemotherapy drugs, VCR, DNR and L-ASP. CONCLUSION: Evaluating the expression pattern of ABCC transporter genes may be a potential biomarker for predicting the occurrence of ALL relapse in Iranian pediatric patients and improve cancer prognosis.

Cost-utility of Protocols of BFM-ALL and UK-ALL for Treatment of Children with Acute Lymphoblastic Leukemia in Iran.

BACKGROUND: There is a requirement to assess the effectiveness and resources used in two protocols United Kingdom (UK-ALL) and Berlin-Frankfurt-Munster (BFM-ALL) that are most commonly used to treatment of ALL patients by oncologists in Iran. Accordingly, we analyzed the cost of treatment and utility of children treated with two protocols in Iran. METHODS: The entire medical direct costs of patients in "BFM ALL" protocol and "UK ALL" protocol in multi-centers calculated from Apr 2010 to Jun 2015. For calculating utility and Quality Adjusted Life Year (QALY) of the patients, we used standard questionnaire Health Utilities Index 3 (HUI3). The patients and their parents were interviewed. Data were analyzed using software SPSS18 and EXCEL. RESULTS: The average direct medical cost for each patient for BFM-ALL was 15026 USD and UK-ALL was 8282 USD which showed a significant difference in the total cost of the treatment in the two protocols (P≤0.02). Finally, there was a significant difference in the utility score of the maintenance phase of these two methods (P≤0.003). CONCLUSION: UK-ALL is dominant and BFM protocol is dominated by both sides total costs and utility and QALY. Mainly, more hospital stay in "BFM ALL" protocol is the cause of raised costs in this protocol. Consequently, by considering different QALYs in the methods and low costs in "UK ALL" protocol, "UK ALL" protocol is more preferred.

Evaluation of humoral immune function in patients with chronic idiopathic thrombocytopenic purpura.

Coincidence of autoimmune diseases such as immune thrombocytopenic purpura (ITP) with immunodeficiencies has been reported previously in patients who suffered from primary antibody deficiency (PAD). But there is no original study on immunological profiles of ITP patients to find out their probable immune deficiency. In this case-control study, ITP patients' humoral immunity was investigated for diagnosis of PAD in comparison with normal population. To evaluate the humoral immune system against polysaccharide antigens, patients' serum immunoglobulin levels were measured and a 23-valent pneumococcal capsular polysaccharide vaccine (PPV23) was administrated to evaluate the antibody response to vaccination. In this study, 14 out of 36 patients (39%) were diagnosed with antibody mediated immune deficiency including 2 patients (5.5%) with immunoglobulin class deficiency and 4 (11%) with IgG subclass deficiency. The remaining patients suffered from specific antibody deficiency. The most frequent deficiency in ITP patients was specific antibody deficiency.Therefore, immunological survey on ITP patients may be important especially for those who have undergone splenectomy.

Immunogenicity of trivalent influenza vaccine in children with acute lymphoblastic leukemia during maintenance therapy.

PURPOSE: The aim of this study was to assess the immune response of children with acute lymphoblastic leukemia (ALL) to influenza vaccine and to compare it with healthy controls. PROCEDURE: Thirty-two children aged 1-18 years with ALL on maintenance therapy and 30 healthy sibling controls were enrolled in the study. All children were vaccinated with trivalent inactivated influenza vaccine. Hemagglutinin-inhibition (HI) antibody titers were determined in sera of both patient and control groups just before and 4 weeks after vaccination. The ability of each group to mount a protective (> or =40) and/or fourfold titer was measured. RESULTS: The protective response for virus subunits among patients and healthy controls were 43.4% versus 88% for H1N1 (P = 0.04), 63.3% versus 80% for H3N2 antigens (P = 0.06), and 26% versus 73% for B antigen (P = 0.001). Responses for H1N1 and B subunits were significantly lower in patients than controls. In the patient group, the significant response to each virus was demonstrated in the analysis of pre- and post-vaccination geometric mean titer (GMT) (P = 0.001). The percentage of patients and controls with fourfold increase in HI titers were 56.2% versus 80% for H1N1 (P = 0.04), 40.6% versus 53.3% for H3N2 (P = 0.31), and 59.4% versus 83.3% for B (P = 0.038). Immune responses for H1N1 and B subunits were significantly lower in patients than controls. CONCLUSIONS: Influenza vaccine is tolerated well in ALL patients with acceptable but limited immune response compared to healthy controls. These findings support the recommendation for annual influenza vaccination in children with ALL.

Hydroxyurea-induced hematological response in transfusion-independent beta-thalassemia intermedia: case series and review of literature.

BACKGROUND: Hydroxyurea (HU) may improve the symptoms in thalassemia patients by increasing gamma-globin chain expression. However, the efficacy of HU in beta-thalassemia intermedia (TI) is unclear. METHODS: The authors treated 16 transfusion-independent TI patients (8 males) aged 10.7 +/- 5.0 years with HU, 20 mg/kg/day 4 days per week, for 6 months. Hemoglobin (Hb) and HbF levels were measured prior to treatment, during the treatment period (monthly), and following the completion of treatment. Mutations in the beta-globin gene as well as the XmnI polymorphism were determined. RESULTS: Treatment was well tolerated. There was a significant increase in both Hb and HbF (p < .001), and the increments were strongly correlated (r = .94; p < .001). XmnI polymorphism was not correlated with hematological response. Hb (p = .026) and HbF (p = .046) showed a more significant rise in patients with a Fr8/9 allele than those with one or two IVS-II-1 alleles. CONCLUSION: HU therapy was associated with a significant hematological response in our TI patients. The Fr8/9 mutation, but not the XmnI polymorphism, was a predictor of good hematological response. Studies with larger sample sizes are needed to confirm the results obtained in this study.

Intravenous immune globulin versus intravenous anti-D immune globulin for the treatment of acute immune thrombocytopenic purpura.

OBJECTIVE: The purpose of this study was to compare the efficacy and side effects of intravenous immunoglobulin (IVIG) with intravenous anti-D immunoglobulin for treatment of newly diagnosed acute childhood Idiopathic thrombocytopenic purpura (ITP). METHODS: Children (6 months to 14 years) with newly diagnosed acute ITP and platelet count below 20,000/ microL were randomized to receive single dose intravenous 75 microg/kg anti-D or 1g/kg IVIG for two consecutive days (total dose 2 g/kg). Response rate defined as a platelet count over 20,000 / microL 72 hours after initial treatment. RESULTS: Eighty one patients (52 male and 29 female) with mean age of 5 years and 3 months randomly divided in anti-D group (n=42) and IVIG group (n=39). Mean baseline (pretreatment) platelet counts were 15406 / microL and 15230/ microL in anti-D and IVIG group, respectively. The response rate in IVIG group (98%) was more significant than anti-D group (76%); (P = 0.017). After 7 days the platelet counts of all patients in IVIG group were more than 20,000/ microL while in anti-D group 12% had platelet counts below 20,000/ microL. CONCLUSION: In acute childhood ITP, initial treatment with IVIG (2g/Kg in divided dose) increased platelet count more rapidly and more significant than intravenous anti-D (single dose of 75 microg/kg) within the first 72 hours.

The relation between left ventricular diastolic indices and serum ferritin in thalassemia major.

Iron-induced heart failure is the primary cause of death in thalassemia major patients who receive continuous transfusions. Recent studies have suggested that diastolic function is impaired prior to systolic function in process of hemochromatosis, but they did not come to agreement on the first impaired diastolic index. Additionally, serum ferritin concentration is not a reliable indicator of body iron storage since it increases in any simple inflammation. Accordingly, the authors undertook this study to assess any association between left ventricular diastolic indices and serum ferritin in thalassemic patients with normal systolic function to estimate the true amount of body iron storage and correct it in earlier stages. Serum ferritin concentration and diastolic indices were measured in 29 patients with normal left ventricular systolic function. Linear regression test was used to find any association between hematological and cardiac factors. No significant association was found between diastolic indices and serum ferritin concentration. But the results were quite different in patients above and below 15 years of age; standardized coefficients (r) for peak of E and A were increased in patients above 15, and the significance was close to .05, unlike those of younger group. Although no correlation was found between serum ferritin and diastolic indices, the results were noteworthy in patients above 15. To appropriately judge this relation, the study must be continued with a bigger sample size and having patients' mean serum ferritin concentration during the 2 past years.