Is supplementation efficacious in maintaining adequate plasma levels of vitamin A and E for thalassemic patients undergoing hematopoietic stem cell transplantation? a cross-sectional study

Thalassemia along with hematopoietic stem cell transplantation [HSCT] can lead to major oxidative stress. Vitamins A and E are antioxidants which protect membrane from lipid peroxidation. We sought to determine for the first time, whether vitamins A and E supplementation is efficacious in maintaining or increasing plasma level of these vitamins in thalassemic children undergoing HSCT. A cross-sectional study was performed on 50 children with beta-thalassemia major hospitalized for HSCT. Patients took a daily multivitamin. Plasma vitamins A and E levels were measured at four different times: on admission, HSCT day [day 0], day 7 and day 14 after HSCT. Plasma vitamin A and E were abnormal on admission in most patients [62.0% and 60.0% respectively]. Ratio of patient with normal to abnormal plasma level of the vitamins improved from baseline to a peak on day 7 then deteriorated afterward until day 14. There was an increasingly positive correlation between daily oral intake and plasma vitamin A at different times, but plasma vitamin E showed inverse correlation at first which tended towards no correlation subsequently. In multivariate analysis, supplementation significantly changed plasma level of vitamin A at different measurement time [P=0.001] within study subjects. But, plasma level of vitamin E showed no significant difference [P=0.2]. Our findings suggest that oral supplementation could have beneficial effects due to increasing plasma vitamin A level and preventing plasma vitamin E depletion

Changes of bone density in pediatric patients with beta-thalassemia major after allogenic hematopoietic stem cell transplantation

Thalassemia major and its treatment by stem cell transplantation can have deleterious effects on bone integrity. This study assesses the adverse effects of transplantation on growing bones of pediatric thalassemic patients. Bone mineral density [BMD] of 20 patients from three thalassemia classes whose mean [SD] age was 7.4 [3.8] years were tested with a Norland XR-46 device at baseline [before transplantation], 6 and 12 months after transplantation. At 6 and 12 months after transplantation we observed no significant changes in mean BMD. There were no Z-scores less than -2 among patients. Class 3 thalassemia did not negatively impact BMD. Calcium [Ca], phosphorous [P] and ferritin levels were not significantly related to patients' BMD scores. Transfusion duration and chelation therapy showed positive significant relationships to BMD [g/ cm2], but no significant relation with the BMD Z-score. The deleterious relation between corticosteroid use and changes in BMD was not significant. In contrast, patients who developed acute graft versus host disease [aGVHD] after transplantation showed significant adverse effects on BMD of their femur [P = 0.020] and spine [P = 0.027]. Stem cell transplantation in pediatric thalassemic patients who do not develop aGVHD does not appear to have any significant positive or negative effects on BMD

Comparison of qualitative PCR and pp65 antigenemia for the diagnosis of CMV infection in hematopoietic stem cell transplanted patients

Human cytomegalovirus [CMV] is a major life-threatening pathogen for hematopoietic stem cell transplant recipients. Specific tests are used for the diagnosis and monitoring of CMV infection in transplant patients. This study evaluates the performance of pp65 antigenemia and qualitative PCR assays for monitoring CMV in such patients. We analyzed 179 clinical samples from 41 patients by using a validated home-brewed qualitative PCR and a commercial antigenemia assay. The obtained results were evaluated using quantitative real-time PCR as the gold standard. CMV was observed in 26.8% of samples analyzed by the antigenemia assay and in 42.6% of the samples by qualitative PCR. Among 179 clinical samples, 50.8% were negative and 21.2% were positive by both assays. On the other hand, 26.3% were only positive by qualitative PCR whereas 1.7% were positive by the antigenemia assay. A comparison of the results with real-time PCR showed that qualitative PCR has a higher sensitivity than the antigenemia assay [98.7% vs. 45.7%]. The specificity of both assays was equal [96.8%]. Quantitative results of the antigenemia assay showed good correlation with real-time PCR [r=0.715; p<0.001] Both the qualitative PCR and antigenemia assays have special deficiencies for efficient diagnosis of CMV infection. Therefore, effective management of CMV infection in transplant patients requires the use of other sensitive quantitative methods such as qPCR

Two cases of syndromic neutropenia with a report of novel mutation in G6PC3

Severe congenital neutropenia [SCN] is a rare primary immunodeficiency. Different genes are found to be associated with SCN, including ELA2, HAX1, WAS, GFI1, G-CSFR. Also, recently G6PC3 as a rare gene in SCN has been reported. Patients with G6PC3 often have cardiac and/or urogenital malformations. Two patients with persistent severe neutropenia, recurrent infections and maturation arrest at promyelocyte-myelocyte stage in their bone marrow were assessed in this study. Both patients showed structural heart disease and one of them also showed urogenital anomaly. Sequence analyses of G6PC3 in 2 patients revealed two different homozygous mutations, one in exon 6 [Asn 313 fs], and the other in exon 3 [Ser 139 Met], the latter is a new mutation which has not been reported in previous studies. It can be concluded that G6PC3 is one of the responsible gene for SCN in Iranian patients. Based on the results, a new mutation in G6PC3 observed in one patient

Hematopoietic stem cell transplantation in acute promyelocytic leukemia, experience in Iran

Acute promyelocytic leukemia is a rare indication for hematopoietic stem cell transplantation. Usually it is indicated as consolidation of salvage regimens following relpase. Here we report our experience with stem cell transplantation in acute promyelocytic leukemia patients. Between 1989 and 2011, we performed 40 hematopoietic stem cell transplantation in first complete remission or relapsed acute promyelocytic leukemia patients. Median age of patients was 23.5 years. Patients received 11 autologous and 29 allogeneic hematopoietic stem cell transplantation from their HLA fully-matched sibling donors. Different conditioning regimens were applied. A total of 24 patients received hematopoietic stem cell transplantation who were in first complete remission and the remainder with a second or more complete remission. Hematopoietic stem cell engraftment was observed in all cases. There were no deaths prior to 100 days after hematopoietic stem cell transplantation. Acute graft versus host disease was mild to moderate in the majority of patients, whereas it was grade III in 4 patients. Chronic graft versus host disease was extensive in 2 cases. With a 4-year median follow up, the relapse rate was 25%. A total of 26 patients are alive. Five year overall survival was 65.5% and 46.8% for allogeneic and autologous hematopoietic stem cell transplantation, respectively. Hematopoietic stem cell transplantation is an acceptable treatment for acute promyelocytic leukemia. Although there is a statistical difference for overall survival between allogeneic or autologous hematopoietic stem cell transplantation, the choice between autologous or allogeneic transplantation needs to have reliable methods for the detection of molecular remission before hematopoietic stem cell transplantation as well as close, reliable follow up of patients with clinical and molecular parameters

Long-term results of non-fludarabine versus fludarabine-based stem cell transplantation without total body irradiation in Fanconi anemia patients

Hematopoietic cell transplantation [HCT] is the only therapeutic modality capable of correcting the hematologic manifestations of Fanconi anemia [FA]. The development of well-tolerated immunosuppressive conditioning regimens for FA patients undergoing HCT has proven to be a challenging task for hematologists. Retrospective, patients referred to the hematology, oncology and stem cell transplantation research center. We analyzed the outcome of 53 FA patients who had undergone HCT between 1992 and 2010. The median age at transplantation was 9 years. Patients received transplants from an HLA-identiccal sibling [n=39] or matched relative [n=9] and one-antigen locus mismatched other relative/sibling [n=5]. All of the patients underwent transplantation with fludarabine and non-fludarabine-based conditioning regimens. No radiation therapy was given. The median follow-up period for survivors was 13.5 months [range, 3 months-13.5 years]. The 3-year overall survival [OS] was 60.6%. The 3-year OS for patients who did or did not receive fludarabine-based preparative regimens for the allograft was 36.4%, and 70%, respectively. However, there were no statistically significant differences in OS rates between these two groups [P=.112]. Graft failure occurred in 4 patients [7.5%]. All of these 4 patients had received fludarabine-based conditioning regimens. The incidence of acute GVHD after fludarabine-based regimens was 45% versus 79% in non-fludarabine-based regimens [P=.03]. Despite the high incidence of acute GVHD [78.6%] in the non-fludarabine group, which ressulted in the death of some patients, the OS rate was significantly better than in fludarabine recipients. Therefore, in spite of the fact that recent studies advocate the fludarabine-based conditioning regimens, we propose to conduct a multicenter, prospective study to evaluate the outcomes of regimens employed in FA patients

Hematopoietic stem cell transplantation in the eastern mediterranean region [EMRO] 2008-2009: report on behalf of the eastern mediterranean bone marrow transplantation [EMBMT] group

The Eastern Mediterranean Bone Marrow Transplantation [EMBMT] Group has accumulated over 25 years of data and experience in hematopoietic stem cell transplantation [HSCT], most particularly in he-moglobinopathies, severe aplastic anemia [SAA], and inherited metabolic and immune disorders, in addition to hematologic malignancies peculiar to the region and where recent updates in trends in activities are warranted. To study trends in HSCT activities in the World Health Organization-Eastern Mediterranean [EM] region surveyed by EMBMT between 2008 and 2009. STUDY DESIGN: Retrospective analysis of the survey data, mainly of the cumulative number of transplants, types of transplants [autologous vs. allogeneic], types of conditioning as myeloablative [MAC] vs. reduced intensity conditioning [RIC] and trends in leukemias, hemo-globinopathies, SAA, inherited bone marrow failure syndromes amongst others. Fourteen teams from ten Eastern Mediterranean Region Organization [EMRO] countries reported their data [100% return rate] to the EMBMT for the years 2008-2009 with a total of 2608 first HSCT [1286 in 2008; 1322 in 2009]. Allogeneic HSCT represented the majority [63%] in both years. The main indications for allogeneic HSCT were acute leukemias [732; 44%], bone marrow failure syndromes [331, 20%], hemoglobinopathies [255; 15%] and immune deficiencies [90; 5%]. There was a progressive increase in the proportions of chronic myeloid leukemia [CML] cases transplanted beyond the first chronic phase [3; 7% of all CML cases in 2008 vs 13; 29% in 2009]. The main indications for autologous transplants were plasma cell disorders [345; 36%] Hodgkin disease [256; 27%], non-Hodgkin lymphoma [207; 22%] and solid tumors [83; 9%]. RIC continued to show a progressive increase over the years [7% in 2007, 11% in 2008 and 13% in 2009], yet remained relatively low compared to contemporary practices in Europe published by EBMT. The vast majority [95%] of allo-HSCT sources were from sibling donors with a continued dominance of peripheral blood [PB] [1076; 63%], while cord blood transplant [CBT] increased to 83 [5% of allo-HSCT], matched unrelated donor [MUD] remained underutilized [1; 0%] and there were no haploidentical transplants reported. Large centers with >50 HSCT/year showed a plateau of the total number of allo-HSCT over the last 5 years that may be related to capacity issues and needs further study. There is an overall increased rate of HSCT in the EMRO region with a significant increase in utilization of CBT and allogeneic PB-HSCT as a valuable source. However, further research on outcome data and development of regional donor banks [CB and MUD] may help facilitate future planning to satisfy the regional needs and increase collaboration within the group and globally

[Griscelli syndrome: report of an Iranian case]

In this study, we report a patient who was afflicted by Griscelli syndrome [GC] type II. GS II is an autosomal recessive disorder that is associated with silver-gray sheen of the hair and immunodeficiency. Mutation in RAB27A gene is responsible for this type of GS. The aim of this study is to investigate mutations in the RAB27A gene in a 3-year-old boy who was referred to our center with immunodeficiency, silvery gray sheen of the hair, fever and accelerated phase. He was the third child of consanguine parents. The first child is a 6-year-old healthy girl and the second one was a boy who had the same clinical features as the proband, and he died when he was 13-month-old. So far the most of Iranian patients have had mutation in exon 6 of RAB27A gene and this mutation we report has been seen just in Iranian patients