WITHDRAWN: Initial lymphocyte count in patients with acute immune thrombocytopenic purpura: Can it predict persistence of the disease?

Ahead of Print article withdrawn by publisher.

Direct short-term cytotoxic effects of BIBR 1532 on acute promyelocytic leukemia cells through induction of p21 coupled with downregulation of c-Myc and hTERT transcription.

Acute promyelocytic leukemia (APL) is characterized by specific t(15;17), distinct morphologic picture, and clinical coagulopathy that contribute to the morbidity and mortality of the disease. This study aims to investigate the effects of antitelomerase compound BIBR1532 on APL cells (NB4). BIBR 1532 exerts a direct short-term growth suppressive effect in a concentration-dependent manner probably through downregulation of c-Myc and hTERT expression. Our results also suggest that induction of p21 and subsequent disturbance of Bax/Bcl-2 balanced ratio as well as decreased telomerase activity may be rational mechanisms for the potent/direct short-term cytotoxicity of high doses of BIBR1532 against NB4 cells.

Outcome of primary childhood central nervous system tumors: results from a single center in Iran.

BACKGROUND: Childhood primary central nervous system (CNS) malignancies are one of the most important concerns in pediatric oncology. MATERIAL: In this historical cohort, 82 patients treated in Ali-Asghar Children's Hospital between 1996 and 2005 were evaluated for age, gender, type of treatment, tumor pathology, and survival. RESULTS: The records of 38 female (46.3%) and 44 male (53.7%) patients were included. The mean age was 6.8 ± 3.39 years (6 months to 14 years); the frequency of medulloblastoma was significantly more than others (p = 0.012). Complete resection, radiotherapy, and chemotherapy were done in 47.5, 82.9, and 97.56%, respectively. Estimated 5 years overall and event-free survivals (EFSs) were approximately 68.5 and 35%, respectively. The patients with complete resected tumors had significantly better outcome (p = 0.013). Also, low-grade versus high-grade astrocytoma was significantly a better outcome (p = 0.01). CONCLUSION: The poor EFS with consideration of high number of progressive disease among our patients (50% unresectable tumor) suggests that children in Iran with CNS tumors had high quality of care but availability of advanced treatment protocol and sharing of cooperative trial study is essential for survival improvement. In addition to use more advanced methods and equipments of radiotherapy and chemotherapeutic drugs, we should seriously consider development of better surgical techniques to increase the rate of complete resection of malignant CNS tumors.

Endocrinopathies in patients with transfusion-dependent beta-thalassemia.

Thalassemia is common in Iran. Appropriate therapy for this disease includes a regular blood transfusion and chelation therapy. However, in this approach patients will inevitably experience side effects, particularly iron overloads in critical organs, including heart, ductless glands, and liver. This study attempted to determine prevalence of adenoidal abnormality between Iranian thalassemia patients for prediagnosis and to offer necessary medical measures. This is a descriptive nonrandomized study and included all the patients suffering from thalassemia major referring to medical centers linked with the Iranian blood transfusion organization from January 2004 to January 2005. All patients were sampled for CBC, FBS, 2-h BS, HbAlC, liver function, renal function, and endocrine disease. Initially, reports of adenoidal experiments as well as other associated parameters were provided from medical records. A total of 437 patients enrolled in the study: 5.4% suffered from diabetes, 1% had hypothyroid, and 1 person showed hypoparathyroidism. The mean levels of ferritin in diabetic and nondiabetic groups and hypothyroid and nonhypothyroid groups were not significantly different. The mean levels of ferritin among various age groups also were not significantly different. Results of a comparison between present research and similar studies conducted throughout Iran and those performed abroad on adenoidal abnormalities in thalassemia patients show that subject patients of this study statistically suffered from fewer difficulties than diabetes patients in other studies.

Hodgkin lymphoma as second malignancy during continuing chemotherapy for childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most prevalent childhood malignancy in most parts of the world with a 5-year survival rate above 70%. Long-term survivors are at risk for treatment-related late effects and second malignant neoplasms (SMNs). SMNs occur with a mean latency of 6-6.7 years after ALL diagnosis but are rarely observed during maintenance chemotherapy (CT). Hodgkin lymphoma (HL) as a complication of ALL is very rare. We report two children with ALL who developed HL while receiving maintenance CT. Both received appropriate chemo- and radiotherapy (CT/RT) and have survived for more than10 years.

Successful ambulatory treatment of Hodgkin's disease in Iranian children based on German-Austrian DAL-HD 85-90: single institutional results.

BACKGROUND: Hodgkin's disease (HD) accounts for 7.5% of childhood malignancies in Iran. In order to minimize chemotherapy toxicity and avoid eventual hospitalization and psychological and financial burdens we have applied since 1988, for the first time in Iran, a treatment regimen based on subsequently revised DAL-HD 85-90 and later GPOH-HD 95 protocols. PATIENTS AND METHODS: During the period 1988-2004, 40 children with HD received DAL/GPOH-HD-adapted treatment; 25 males (62.5%) and 15 females (37.5%) (male/female ratio 1.7; age 4-14 years, mean 8.8). Clinical evaluation and staging was performed in all patients. Constitutional symptoms: 24 patients were asymptomatic (A; 60%) and 16 had constitutional complaints (B; 40%). Staging was as follows: stage I; seven (17.5%); II, 11 (27.5%); III, 11 (27.5%); and IV, 11 (27.5%). Histopathology: 22 patients had mixed cellularity (MC; 55%), 13 nodular sclerosis (32.5%), four lymphocyte predominance (LP; 10%) and one patient lymphocyte depletion (2.5%). Stage IA and IIA patients (n = 15) received either OPA x2 (vincristine, prednisolone, doxorubicin) or OPPA x2 or OPEA x2 (vincristine, prednisolone, procarbazine and doxorubicin), the latter receiving etoposide instead of procarbazine, and applied to males. Stages IIB, IIIA/B and IV received OPPA x2, followed by CO(P)P x4 (cyclophosphamide, vincristine, prednisolone in alternate courses and procarbazine). Twenty nine patients (72.5%) received radiotherapy (20-25 Gy); four to the involved field (stage I), 25 to the upper mantel (stage II and also III with either residual or mediastinal mass) and three additionally to spleen and para-aortic lymph nodes. Eleven patients received only chemotherapy. RESULTS: All patients achieved complete remission (CR). Relapse occurred in eight patients (20%); seven stage IV (MC) and one stage IA (LP) with progression to IIIB. Salvage chemotherapy consisted of MOPP/ABVD hybrid; six patients achieved a second sustained remission and three patients died: two due to relapse and progressive disease and the third one in CR, owing to thrombocytopenic hemorrhage and foudroyant pneumonia. The achieved overall and event-free survival was 88.1% and 75.4%, respectively. Aside from minor acute toxicities, three patients demonstrated azoospermia at the age of 18 years and one of these patients suffered non-Hodgkin lymphoma as a second malignancy. HD occurred as a second malignancy in two patients with acute lymphoblastic leukemia. Both received appropriate treatment and are over 10 years in CR. CONCLUSIONS: The DAL/GPOH-HD-based treatment approach proved to achieve long-term sustained cure even in children with advanced HD disease. The essentially outpatient diagnosis and treatment modus did not compromise the disease outcome, and was well tolerated and accepted by the patients and their parents. The employed drugs are easily available and affordable. This treatment approach is suitable for ambulatory use in developing countries. However, male infertility remains the major obstacle to procarbazine and cyclophosphamide use.

Hodgkin disease in Iranian children.

The epidemiological pattern of Hodgkin disease (HD) was studied in 139 Iranian children with an age range of 2.5-15 years (mean age 8.3) over a 17-year period (1972-1989). The main features observed were: a high male to female ratio of 3.2:1, a high frequency of HD in toddlers and young school children (73%), the prevalence of mixed cellularity subtype (74.5%) and rare occurrence of lymphocyte depletion subtype (2%) the high occurrence of constitutional symptoms (57%) and the high rate of stage III and IV patients (73.5%). Response to the treatment consisting mainly of chemotherapy and/or radiotherapy was favourable and overall and disease-free survival rates of 91.4% and 74.2% were achieved over a follow up period of 6 months-17 years. According to these findings the epidemiological pattern of Iranian children with HD is similar to that occurring in rural areas of developed countries.

Hydroxyurea in the treatment of major beta-thalassemia and importance of genetic screening.

Efforts have been undertaken to find an alternative approach to packed red cell transfusion (PRCT) in major beta-thalassemia. Augmentation of fetal hemoglobin (HbF) by hydroxyurea (HU) has been reported to be less effective in this condition as compared to sickle cell anemia due to molecular heterogeneity of the former disease. HU efficacy and its relation to Xmn1 polymorphism and IVSII-1 mutation was evaluated in major beta-thalassemics. Forty-five patients, M/F ratio 0.8, aged 6-33 years, received oral HU, 20 mg/kg per day, 4 days per week and daily1 mg folic acid. Thirty-six patients were PRCT dependent (group A) and nine independent (group B). The aim was to stabilize or increase pre-PRCT Hb over 10.0+/-0.5 g/dl and to reduce the need or cease the PRCT in group A and to increase Hb level and curb the ineffective erythropoesis, e.g., splenomegaly, facial bone deformity, in group B. HU was administered for at least 6 months (mean: 9 months) and discontinued in case of response failure. Screening for Xmn1 polymorphism and IVSII-1 mutation was carried out in most patients. In group A, 25 patients have become PRCT independent for a period of 2.5-7.3 years (mean: 4 years). The mean Hb, pre-HU 10.0 and post-HU 10.7 g/dl (range: 8.8-13.7 g/dl), mean serum ferritin pre- and post-HU was1877 and 525 ng/ml. The PRCT requirement was reduced in one patient, and ten patients did not respond. In group B HU has been given over 3.3 years (range: 2.8-4.8 years), Hb increased from 9.3 to 10.4/dl, and there was no tangible progression of ineffective erythropoesis. Responders in both groups expressed more comfort with this regimen. Xmn1 and IVSII-1 (homo- and/or heterozygosis) are relevant markers in most responding patients. Molecular determination of genetic markers in early childhood will help to identify candidates for pharmacological HbF switching by HU.

Human testosterone-oestradiol binding globulin in health and disease.

Levels of testosterone-oestradiol binding globulin (TeBG) were measured by a precipitation technique in terms of dihydrotestosterone-5alpha (DHT) binding capacity in children, adult males and females, pregnant and hirsute women and women with various trophoblastic disorders. It was found that TeBG levels in children of either sex (1.92 +/- 0.16 mug DHT bound/100 ml serum) approached the normal female range (2.31 +/- 0.11) and were distinctly higher than those of the adult male (1.04 +/- 0.09). In both pregnancy and trophoblastic disease (hydatidiform mole and choriocarcinoma but not metastatic choriocarcinoma) TeBG levels were elevated (17.5 +/- 0.70 and 14.9 +/- 1.49, respectively). In hirsutism TeBG was depressed (1.17 +/- 0.09) and comparable with the levels in normal male subjects. A number of other parameters, HCG, oestradiol-17 beta, testosterone and progesterone were measured and found to be similar to those previously reported in the literature. It appears that TeBG titre might provide an additional index in following the prognosis of trophoblastic disorders, besides HCG measurement.

Localization of the thiamine-responsive megaloblastic anemia syndrome locus to a 1.4-cM region of 1q23.

Thiamine-responsive megaloblastic anemia (TRMA) is a rare autosomal recessive syndrome characterized by megaloblastic anemia, deafness, and diabetes mellitus. A genome scan previously established linkage of this disorder to 1q23 and haplotype analysis defined a 16-cM critical region. Molecular genetic analyses of four unrelated multiplex Iranian families inheriting TRMA confirmed linkage to the same region and identified recombinant chromosomes which permitted refinement of the critical region to a narrow 1.4-cM interval. The haplotypes of the families differed, consistent with at least two independent mutational events. This refinement of the TRMA locus to less than 10% of that previously published should markedly facilitate the identification and evaluation of positional candidate and novel genes which may cause this disorder.