GRISCELLI SYNDROME; A CASE REPORT AND REVIEW OF THE LITERATURE

Abstract:Griscelli syndrome (GS) is a rare disease first described in 1978. It is inherited in autosomal recessive pattern. This disease is characterized by partial albinism, pigmentation dilution, cellular immunodeficiency, neurological involvement & uncontrolled phases of macrophage & lymphocyte activation.We report a 5 months Old Iranian girl presenting with silver-gray hair,eyelashes and eyebrows, hepatosplenomegaly, pancytopenia, hemophagocytosis and progressive neurologic deterioration. Griscelli syndrome can be suggested according to her symptoms. The chemotherapy was not effective for her and she died due to multi organ failure.Key words:Griscelli syndrome, Hemophagocytosis, Albinism

Management of refractory/relapsed acute leukemia with heart limitation by anthracycline-free chemotherapy regimens in pediatric patients: New hypothesis and new approach

Background: Anthracycline therapy for acute leukemia may be associated with significant morbidity and mortality in children or elderly patients that have a degree of heart failure. Patients with prior anthracycline exposure, those with pre-existing heart disease, or who have received the total anthracycline dose present an increased risk for cardiotoxicity. Therefore, new chemotherapy regimens in these situations would be life saving for leukemia patients. We have conducted a systematic review of possible strategies for rescue regimens without anthracycline in refractory acute leukemia patients. Methods: We gathered the data from 5 creation databases and relevant website until August 2016. We selected randomized clinical trials or other studies that used anthracycline-free chemotherapy regimens to treat acute refractory leukemia in children and adults. The quality of the studies was evaluated according to the Cochrane risk of the polarization tool. All stages of the review were independently conducted by two authors. We obtained data from 75 main clinical trials. Results: There were 75 trials included from which 4 were considered to be at low risk for bias. Most trials showed that the improvement did not reach statistical significance. Conclusion: Evidence existed to support the use of the combination of fludarabine, cytarabine, and filgrastim, ICE-rituximab chemotherapy regimens, or monoclonal antibodies such as tyrosine kinase inhibitors (Sorafenib) useful for acute refractory/relapsed leukemia.These drugs are used as first salvage regimens or clofarabine and cladribine for acute myeloid leukemia in patients for whom combined anthracycline chemotherapy is inappropriate. © 2018, Shiraz University of Medical Sciences. All rights reserved

Management of refractory/relapsed acute leukemia with heart limitation by anthracycline-free chemotherapy regimens in pediatric patients: New hypothesis and new approach

Background: Anthracycline therapy for acute leukemia may be associated with significant morbidity and mortality in children or elderly patients that have a degree of heart failure. Patients with prior anthracycline exposure, those with pre-existing heart disease, or who have received the total anthracycline dose present an increased risk for cardiotoxicity. Therefore, new chemotherapy regimens in these situations would be life saving for leukemia patients. We have conducted a systematic review of possible strategies for rescue regimens without anthracycline in refractory acute leukemia patients. Methods: We gathered the data from 5 creation databases and relevant website until August 2016. We selected randomized clinical trials or other studies that used anthracycline-free chemotherapy regimens to treat acute refractory leukemia in children and adults. The quality of the studies was evaluated according to the Cochrane risk of the polarization tool. All stages of the review were independently conducted by two authors. We obtained data from 75 main clinical trials. Results: There were 75 trials included from which 4 were considered to be at low risk for bias. Most trials showed that the improvement did not reach statistical significance. Conclusion: Evidence existed to support the use of the combination of fludarabine, cytarabine, and filgrastim, ICE-rituximab chemotherapy regimens, or monoclonal antibodies such as tyrosine kinase inhibitors (Sorafenib) useful for acute refractory/relapsed leukemia.These drugs are used as first salvage regimens or clofarabine and cladribine for acute myeloid leukemia in patients for whom combined anthracycline chemotherapy is inappropriate. © 2018, Shiraz University of Medical Sciences. All rights reserved

Acute renal failure: A rare initial presentation of acute lymphoblastic leukemia

Acute lymphoblastic leukemia has several presentations associated with bone marrow and extramedullary involvement. The unusual presentation may be due to the infiltration of leukemic cells in any organ. An 11-year-old girl presented with fever and vomiting, since one day before admission after starfish biting during swimming. Her vital signs were: blood pressure 150/100 mmHg, pulse 98 beats per minute, respiration 18 breathes per minute, and temperature 37.2 °C (99 F). Laboratory work-up showed blood urea nitrogen 38 mg/dl and creatinine 2.8 mg/dl. In peripheral blood smear, few atypical cells, mild anemia (Hb: 9.2 g/dl), and mild thrombocytopenia (Platelet: 109,000/µL) were detected. Bone marrow aspiration and immunophenotyping were in favor of acute precursor B cell type lymphoblastic leukemia. The patient had a favorable response to treatment after initiating high-risk chemotherapy. Therefore, acute renal failure can be a rare initial presentation of acute lymphoblastic leukemia, and azotemia will improve with an early chemotherapy treatment

A novel frame-shift deletion in FANCF gene causing autosomal recessive Fanconi anemia: A case report

Background: Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by congenital anomalies, early-onset bone marrow failure, and a high predisposition to cancers. Up to know, different genes involved in the DNA repair pathway, mainly FANCA genes, have been identified to be affected in patients with FA. Case presentation: Here, we report clinical, laboratory and genetic findings in a 3.5-year-old Iranian female patient, a product of a consanguineous marriage, who was suspicious of FA, observed with short stature, microcephaly, skin hyperpigmentation, anemia, thrombocytopenia and hypo cellular bone marrow. Therefore, Next Generation Sequencing was performed to identify the genetic cause of the disease in this patient. Results revealed a novel, private, homozygous frameshift mutation in the FANCF gene (NM-022725: c. 534delG, p. G178 fs) which was confirmed by Sanger sequencing in the proband. Conclusion: Such studies may help uncover the exact pathomechanisms of this disorder and establish the genotype-phenotype correlations by identification of more mutations in this gene. It is the first report of a mutation in the FANCF gene in Iranian patients with Fanconi anemia. This new mutation correlates with a hematological problem (pancytopenia), short stature, and microcephaly and skin hyperpigmentation. Until now, no evidence of malignancy was detected

Termination of pregnancy due to Thalassemia major, Hemophilia, and Down's Syndrome: the views of Iranian physicians

<p>Abstract</p> <p>Background</p> <p>Genetic disorders due to <b>kindred </b>marriages are common medical conditions in Iran; however, the legal aspects of abortion remain controversial. This study was undertaken to determine physicians' opinions regarding the termination of pregnancy for three genetic diseases: thalassemia major, hemophilia, and Down's syndrome.</p> <p>Methods</p> <p>A questionnaire was administered to selected physicians by stratified random sampling to determine the following: age, gender, knowledge about prenatal diagnosis of diseases in high risk pregnancies, agreement with abortion, recommended gestational age for abortion, and, if opposed to abortion, the reason.</p> <p>Results</p> <p>Of 323 physicians, who participated in the study, 91.3(295), 40.6(131), and 78.6%(254) were in agreement and 8.7(28), 59.4(192), and 21.4%(69) were opposed to abortion for thalassemia major, hemophilia, and Down's syndrome, respectively. Among 289 physicians opposed to abortion in respect of each of all three conditions, the following reasons were cited: religion, 18; emotional, 10; quality of care, 23; hope to find a new treatment option in the future, 103; miscellaneous reasons, 6; and a combination of these reasons, 129. Among 680 physicians in agreement with abortion in relation to all of the diseases, 4.6%(31) were agreed with abortion in less than 12 weeks gestation, 79.2%(538) in less than 16 weeks gestation, 5.6%(38) in less than 20 weeks gestation, 2.2%(15) in less than 24 weeks gestation, and 8.4%(58) were agreed with beyond the 24 weeks of gestational age.</p> <p>Conclusion</p> <p>The majority of physicians were in agreement with abortion for thalassemia major and Down's syndrome because of the overall prognosis, but opposed to abortion for hemophilia.</p

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

Survival rate among children with acute lymphoblastic leukemia based on their relapse status in Shiraz Shahid Faghihi hospital during 2004-9

Background: Relapse in leukemic patients is considered as a major cause of treatment failure and a decrease in patient survival rate. This study was conducted to determine the survival rate of patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) based on their relapse status.Materials and Methods: This retrospective cohort study was performed on a total of 243 cases of leukemia aged less than 15 years in Shiraz Shahid Faghihi hospital. Data were analyzed using Kaplan-Meier method, log-rank test and Cox regression model.Results: The 1- and 5-year survival rates for patients without relapsed leukemia were 96.9 and 76.9 and for relapsed leukemia were 82.4 and 28.6, respectively. Therefore, there was a significant relationship between the relapse occurrence and survival rate among the patients (P=0.001). Conclusion: The relapse occurrence is one of the main effective factors in survival rate of leukemic patients a five-year survival rate in the patients is less than 30 percent in this center

Successful treatment of refractory metastatic neuroblastoma with panobinostat in combination with chemotherapy agents and iodine-131-meta-iodobenzylguanidine therapy

Introduction: Neuroblastoma commonly required multimodal therapy containing surgery, chemotherapy, radiotherapy, and immunotherapy. Case report: In our case, who had refractory metastatic neuroblastoma, we use histone deacetylase inhibitor (panobinostat) in combination with chemotherapy agents and iodine-131-meta-iodobenzylguanidine (MIBG) therapy. Management and outcome: This approach leads to successfully treat the patient. MIBG scan and bone marrow examination after therapy revealed no evidence of tumor. Now, she underwent autologous transplantation six months ago and free of tumor. Conclusion: Panobinostat can cause apoptosis induction in refractory metastatic neuroblastoma in combination with MIBG therapy and chemotherapy