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Quantitative real-time PCR (qPCR) assay is accepted as the method of choice for monitoring human cytomegalovirus (HCMV) infection in hematopoietic stem cell transplant recipients, but the high cost of commercial kits has hampered its use in many developing countries. In this study, an affordable in-house qPCR was used to manage HCMV infection in pediatric patients and the diagnostic value of this method was compared with the conventional pp65 antigenemia assay. A total number of 1179 samples from 82 recipients were used in this study, and the effect of some potential risk factors on HCMV reactivation was evaluated. The qPCR was able to detect HCMV reactivation earlier and with higher sensitivity than antigenemia assay. Forty-six episodes of reactivation were detected in 39 patients, of which all were detected by the qPCR assay, while only 21 episodes were diagnosed by antigenemia. The DNAemia level of 1284 IU/ml plasma was defined as the optimal cutoff value for starting pre-emptive therapy. It was shown that the acute GVHD severity and the relationship of donor and recipient are the most significant risk factors for HCMV reactivation. The data suggest that the antigenemia method for monitoring HCMV reactivation could be substituted by the qPCR assay., (© 2015 Steunstichting ESOT.)

Liver biopsy has been performed for many decades for classifying the patients with TM. Meanwhile, using non-invasive methods such as T2* MRI technique has been recently much more considered to determine the hepatic iron overload. Ninety-three pediatric HSCT candidates with TM who underwent liver biopsy were included in this study. Hepatic T2* MRI values and serum ferritin concentrations were assessed to investigate and determine the useful method in detection of patients with TM class III whom received different conditioning regimens, in comparison with class I and II. Twenty (21.5%) patients were categorized as class III. Hepatic T2* MRI could detect TM class III patients with 60% sensitivity and 87.67% specificity (LR+: 4.867, accuracy: 81.72%), while predictive feature of ferritin values for distinguishing patients with TM class III was not statistically significant (p-value >0.01). Combination of T2*MRI with age (T2*-age) could detect TM class III with 85% sensitivity and 72.6% specificity (LR+: 3.1, accuracy: 75.27%).T2*-age may be considered as an alternative and non-invasive method to liver biopsy for differentiation and classification of patients with TM before transplantation., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Beta thalassemia major is a genetic hemoglobin disorder that affects bone density. The disease leads to deteriorating bone structure but can be treated with hematopoietic stem cell transplant. We aimed to assess bone mineral density changes in pediatric beta thalassemia major patients who had undergone a hematopoietic stem cell transplant compared with similarly affected patients who had not undergone a hematopoietic stem cell transplant., Materials and Methods: Forty beta thalassemia major patients, 20 transplant and 20 nontransplant, younger than 16 years of age were enrolled. The mean age of transplant patients was 8.15 years and nontransplant patients was 9.5 years (P = .242). The female:male ratio was 1:1 in both groups. None of the patients reached puberty during this study. Bone mineral density was evaluated in transplant patients before and 1 year after hematopoietic stem cell transplant. Bone mineral density of nontransplant patients also was evaluated 1 year after their initial bone mineral density test. A Norland XR-46 densitometer was used to make all bone mineral density measurements. None of the patients had a z score < -2., Results: Mean bone mineral density changes in the femur and spine during this study were 0.008 ± 0.075 g/cm2 and 0.048 ± 0.045 g/cm2 in transplant patients and 0.045 ± 0.072 g/cm2 and 0.036 ± 0.058 g/cm2 in nontransplant patients. No significant differences between bone mineral density changes in transplant and nontransplant patients were detected during the study., Conclusions: No significant effects on bone mineral density were detected in hematopoietic stem cell transplant pediatric beta thalassemia major patients compared with similarly affected nontransplant patients. Studies of longer duration may be required to identify significant changes in bone mineral density in hematopoietic stem cell transplant patients.

Although liver biopsy is an invasive procedure, it remains the gold standard technique for the evaluation of hepatic fibrosis in different patients, including those with major thalassemia (MT). Recently, noninvasive imaging techniques, such as transient elastography, have emerged. We investigated the effectiveness of TE, in comparison to liver biopsy, for the evaluation of liver fibrosis in pediatric patients with MT who were candidates for hematopoietic stem cell transplantation (HSCT). Eighty-three pediatric MT patients (48 boys and 35 girls), who were candidates for HSCT, were included in this study. The median age was 8 years. Liver stiffness was assessed for all patients, before transplantation, using both TE, measured in kilopascals (kPa) and liver biopsy, based on the Metavir score. The diagnostic accuracy of TE and liver biopsy were estimated using linear discriminated analysis (the area under the receiver operating characteristic curves [AUROCs]). The median TE score was 4.3 kPa (range, 3.5 to 5.2). The TE value did not differ among patients with different ferritin levels (P = .53). TE increased proportionally to Metavir fibrosis stages (P < .001) and the necro-inflammatory grade (P < .001). The TE score also correlated to liver iron content (P < .001), liver size (P < .003), and Lucarelli risk classification (LRC) (P < .001). ROC curve analysis revealed moderate accuracy of the TE score for the diagnosis of fibrosis (AUROC = 73%) and for distinguishing individuals with a LRC III from those classified as I and II (AUROC = 82%). The TE score was also superior to Fibrosis-4 (AUROC = 61%) for the assessment of liver fibrosis and LRC differentiation. The results of this study demonstrated that TE can be a valuable method for assessing liver fibrosis and differentiating LRC III from the other 2 classes in pediatric patients with MT who have been selected for HSCT., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

The clinical outcome of hematopoietic stem cell transplantation (HSCT) for patients with β-thalassemia major (β-TM) can be affected by several factors. We investigated the influence of β-globin gene mutation in patients with β-TM on the clinical outcome of HSCT and conducted a prospective study of consecutive β-TM patients who underwent allogeneic HSCT at our center. Among 87 included patients, 62 (71%) had homozygous and 25 (29%) had compound heterozygous β-globin gene mutations. Intervening sequence II-1 appeared to be the most common mutation, with an occurrence rate of 33% in β-globin alleles. With a median follow-up of 12 months, the thalassemia-free survival and overall survival probabilities were 83% (standard error, 4%) and 90% (standard error, 3%), respectively. Overall survival was not found to be associated with the β-globin gene mutation status, but thalassemia-free survival was significantly improved in patients with homozygous mutations compared with patients with compound heterozygous mutations in univariate (91.2% versus 64.0%, P = .009) and multivariable (hazard ratio, 3.83; P = .014) analyses. This is the first report on the impact of β-globin mutation status on the outcome of β-TM after allogeneic HSCT and helps to better illustrate the course and prognosis of β-TM after transplantation., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Non-invasive methods like MRI-based techniques have been considered recently for assessment of liver and heart status in patients with thalassemia major (TM). The purpose of this study is to examine the alterations of hepatic and myocardial T2(∗) MRI values in TM patients after hematopoietic stem cell transplantation (HSCT) just before starting chelation therapy., Procedure: The study included fifty-two TM patients with mean age of 7.6years who were referred to our center for HSCT. Before HSCT, patients underwent liver biopsy to determine fibrosis stage based on the Lucarelli classification. Hepatic and myocardial T2(∗) values before and 6months after transplantation were measured and analyzed., Results: There was not a statistically significant increase in myocardial T2(∗) values after HSCT (p-value=0.35). Hepatic T2(∗) values significantly decreased after HSCT (p-value <0.001), showing the liver status has been worsened. In subgroup analysis, post-HSCT hepatic T2(∗) values (adjusted for baseline values) were significantly higher in patients with graft-versus-host disease (GvHD) compared to non-GvHD patients (p-value=0.04)., Conclusions: The issue of iron overload is still remained as the main problem in ex-thalassemic patients after HSCT. We found T2(∗) MRI technique a quite beneficial method for following up the patients after transplantation. Obviously, planning large controlled trials associated with liver biopsy results after transplantation is required., (Copyright © 2014 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.)

MIBG is an effective component in treatment of neuroblastoma. Furthermore, MIBG scintigraphy is an imaging modality in primary assessments. None of the previous studies have evaluated the role of pretransplant MIBG scintigraphy in decision making for neuroblastoma treatment. We selected therapeutic regimen based on pretransplant (131) I-MIBG scintigraphy. Twenty high-risk patients were enrolled. On day -30, patients underwent diagnostic MIBG scintigraphy. Patients were then subdivided into two groups (10 cases in each arm). MIBG-avid subgroup received MIBG (12 mCi/kg), etoposide (1200 mg/m2), carboplatin (1500 mg/m2), and melphalan (210 mg/m2). Non-MIBG-avid subgroup received etoposide (600 mg/m2), carboplatin (1200 mg/m2), and melphalan (150 mg/m2). Patients received CRA after ASCT. Mean age at diagnosis was 42.5 months (range, 17-65) in MIBG-avid and 38.9 months (range, 18-65) in non-MIBG-avid patients. Mean age at diagnosis and transplantation did not reveal significant difference between two subgroups. In MIBG-avid patients, the three-yr OS was 66 ± 21%. In MIBG-non-avid subgroup, the three-yr OS was 53 ± 20%. In MIBG-avid and non-MIBG-avid subgroups, the three-yr EFS were 66 ± 21% and 47 ± 19%, respectively. These findings may suggest an effective role in selecting the therapeutic strategy for pre-ASCT MIBG scintigraphy in high-risk neuroblastoma. MIBG-avid subset may benefit from the combination of therapeutic MIBG and high dose of chemotherapy., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Primary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition that clinically characterized by fever, hepatosplenomegaly, and cytopenia. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment option for patients diagnosed with primary HLH., Methods: In this prospective study, we analyzed the outcome of 10 pediatric patients with primary HLH who had received HSCT, using reduced-intensity conditioning (RIC) regimen from 2007 to 2012. The median age at transplantation was 22.6 months (range: 6-60). All of the patients received the same RIC regimen based on the use of fludarabine in combination with melphalan and horse antithymocyte globulin (ATG). Cyclosporine and methylprednisolone were used as graft-vs.-host disease (GvHD) prophylaxis., Results: Hematopoietic engraftment occurred in all patients. At the present time, 8 patients with a median follow-up of 39 months are still alive and all of them are disease free. Acute and chronic GvHD developed in 6 and 2 patients, retrospectively. Two patients died of sepsis and chronic GvHD during the study., Conclusion: Because of pretransplant infections caused by underlying immunodeficiency in patients with primary HLH, the use of less toxic regimen with RIC seems to be highly effective in this regard. Recipients of RIC transplant, with either full or mixed chimerism, had a long-term survival rate with no manifestation of primary HLH symptoms., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: 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., Methods: A cross-sectional study was performed on 50 children with β-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. Findings : 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)., Conclusion: Our findings suggest that oral supplementation could have beneficial effects due to increasing plasma vitamin A level and preventing plasma vitamin E depletion.

Partial albinism with variable immunodeficiency are the two major characteristics of Griscelli syndrome type 2 (GS-2). This syndrome is usually associated with a high mortality rate and commonly results in early childhood death. Patients suffer from different infections and experience crisis of HLH. HSCT remains the sole curative treatment for GS-2. We prospectively analyzed the outcomes of transplantation with RIC regimen in five patients. The median age at transplantation was 21.6 months (range: 12-30). All of the patients underwent HSCT from HLA-matched related donors. Currently, four patients are cured, and symptoms of recurrent infections and HLH crisis are not seen in them. The only patient who died had undergone HSCT in the accelerated phase of HLH. One patient who developed acute GvHD had a favorable response to therapy. No chronic GvHD occurred in patients. It seems that the use of RIC regimen as a method of transplant preparation is effective and tolerable in this group of patients with various comorbidities. It is recommended to carry out HSCT in these patients at lower ages, before presentations of different infections and HLH crisis., (© 2013 John Wiley & Sons A/S.)

HSCT is the only proven treatment option for CML, a rare disease in children. Recently, there are promising reports on the advantageous effect of imatinib mesylate for pediatric patients with CML. We conducted a retrospective study on 33 pediatric patients suffering from CML. Fourteen underwent HSCT and the rest were treated with imatinib. With a median follow-up of 24 months, the two-yr OS in the HSCT group and the imatinib group was 84% and 87%, respectively (p = 0.714). The probabilities of two-yr DFS were 59% in the HSCT group and 82% in the imatinib group, either (p = 0.880). Relapse occurred in 5 (35.7%) patients of the HSCT group, and 8 (42.1%) patients showed relapse in the imatinib group. Among nine patients who died, five were in the HSCT group and the rest were in the imatinib group. The probability of relapse in the patients of the imatinib group followed up for several consecutive years may be higher than observed in the HSCT group, so we cannot easily conclude which way is more reliable., (© 2013 John Wiley & Sons A/S.)

Idiopathic CD4+ lymphocytopenia (ICL) is a rare immunodeficiency disease with severe CD4 T-cell depletion, leading to serious opportunistic infections. The optimal treatment of ICL has not been determined, especially in severe form of the disease. Here, we report an eight-yr-old girl with ICL who was successfully treated with fludarabine-based conditioning HSCT. To the best of our knowledge, this is the first pediatric ICL case that was treated by HSCT. Allogeneic HSCT with a reduced intensity condition (RIC) regimen may be a feasible and curative treatment option in ICL patients with recurrent life-threatening complications., (© 2013 John Wiley & Sons A/S.)

Severe congenital neutropenia (SCN) is a rare primary immunodeficiency disease. Different genes are found to be associated with SCN, including ELA2, HAX1, WAS, GFI1, G-CSFR and G6PC3. The aim of this study was to find different gene mutations responsible for SCN in Iranian patients. Twenty-seven patients with SCN referred to Immunology, Asthma and Allergy Research Institute during a five year priod 5 years (May 2007 and May 2012), were included in this study. Neutropenia related exons and flanking regions of ELA2, HAX1, WAS, GFI1, G-CSFR and G6PC3 were amplified by PCR and the sequences were analyzed. The results showed different mutations including 4 ELANE mutations, 11 HAX1 mutations and 2 G6PC3 mutations. None of the patients had GFI1 mutation and also one mutation was found in G-CSFR in a patient with ELANE mutation. Ten patients had unknown genetic diagnosis which was compatible with other studies. According to these results, most of the patients showed HAX1 mutations and this finding which significantly differed from other reports, might be related to differences in Iranian ethnicity and also in high rate of consanguineous marriages in Iran.

Background: 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., Methods: 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., Results: 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/cm(2)), 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)., Conclusion: 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.

Wiskott-Aldrich syndrome (WAS) is a life-threatening X-linked recessive immunodeficiency disease described as a clinical triad of thrombocytopenia, eczema, and recurrent infections, caused by mutations of the WAS protein (WASP) gene. The milder form of this disease is X-linked thrombocytopenia (XLT) that presents only as platelet abnormalities. Mutation analysis for 15 boys with Wiskott-Aldrich syndrome was performed. Five previously reported mutations and six novel mutations including G8X, R41X, D283E, P412fsX446, E464X, and AfsX358 were detected.

Daclizumab, a humanized MoAB to IL-2Ra, has been found to be safe and effective in adults with refractory GvHD; however, data in children are limited. The aim of this prospective study was to evaluate the long-term safety and efficacy of daclizumab in children with steroid-refractory GI aGvHD. This study included 13 children who developed steroid-refractory GI GvHD between 2007 and 2009. When first-line treatment failed, daclizumab was given in a regimen of 1 mg/kg intravenously and then repeated on a 10- to 14-day interval for maximum five doses if necessary. Daclizumab was well tolerated, but infections were common. Ten patients responded to daclizumab completely, one patient responded partially, and two patients failed to respond. With a median follow-up of 630 days, 10 patients were alive and free of severe infections, but among them, four patients were suffering from cGvHD. Of the three remaining patients, one died because of bacterial meningitis, and the other two patients died because of severe refractory GI GvHD. This long-term evaluation showed that daclizumab could be an effective and relatively safe treatment in most of the pediatric patients with severe steroid-refractory GI GvHD., (© 2012 John Wiley & Sons A/S.)

Quantitation of human cytomegalovirus (HCMV) DNA is used to monitor immunocompromised patients in order to identify patients for preemptive therapy. Although several commercial qPCR assays are available for quantitation of HCMV, their major disadvantage is the high cost. In the present study, an internally controlled quantitative real-time PCR assay based on hydrolysis probe technology was developed for detection and quantitation of HCMV DNA in plasma samples. To demonstrate its performance characteristics, a total of 178 plasma samples from 102 kidney and hematopoietic stem cell transplanted patients were tested. The assay showed good precision and reproducibility, and an analytical sensitivity of 288.5 copies/ml or 17.6 copies/reaction. A sensitivity of 93.1% and a specificity of 96.6% were determined by examining clinical samples. Analysis of a panel containing potentially interfering viruses demonstrated no cross-reactivity with the assay. A strong correlation was observed between this qPCR method and the commercial Artus(®) CMV RG PCR kit (R=0.948; P=0.000). These results indicate that the affordable internally controlled qPCR method described will be useful for monitoring HCMV infection in plasma samples of immunocompromised patients., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Severe congenital neutropenia is one of primary immunodeficiency disorders that characterized by severe neutropenia and is associated with severe systemic bacterial infections from early infancy. Granulocyte colony stimulating factor (GCSF) is clinically used as a treatment for congenital and acquired neutropenia. The aim of this study was evaluation of GCSF (PD- Grastim) in treatment of these patients. Patients with severe congenital neutropenia referred to Immunology, Asthma and Allergy Research Institute between Jan 2007 and Dec 2010 enrolled the study. Other causes of neutropenia were excluded by serial CBC and bone marrow studies, medical and drug histories and immunological tests. Patients were visited and examined monthly to evaluate their CBC and ANC (absolute neutrophil count), GCSF side effects and dosage adjustment. Cytogenetic studies were being done for all the patients for early detection of progression to AML/MDS. From twenty two patients who enrolled this study, 16 patients regularly evaluated. They were ten males and six females, range in age from 2 to 18 years old. Two patients failed to continue our follow up unfortunately and four patients died due to disease complications. Patients were followed for 24 to 48 months. In a period of 12-24 months before treatment, the mean of hospitalization frequency was 3.1 times and duration was 10 days; while during receiving treatment, they decreased to 0.2 times and 3 days, respectively (p<0.01). Also significant increase in mean ANC was observed during follow up (315/µl before treatment versus 1749/µl after 12 month regular treatment). Bone pain was the most common side effect. There have been no evidences of developing AML/MDS up to present time. Treatment with GCSF significantly reduced the duration and the frequency of hospitalization. Because of plausible progression to AML/MDS, regular follow-up of patients should be continued.

Background: Chronic granulomatous disease (CGD) is a rare immunodeficiency due to a genetic defect in one of the NADPH-oxidase components. We studied CGD inheritance forms (autosomal recessive (AR) or X-linked (XL)) and AR-CGD subtypes in Iran., Methods: Clinical and functional investigations were conducted in 93 Iranian CGD patients from 75 families., Results: Most of the patients were AR-CGD (87.1%). This was related to consanguineous marriages (p = 0.001). The age of onset of symptoms and diagnosis were lower in XL-CGD compared with AR-CGD (p < 0.0001 for both). Among AR-CGD patients, p47phox defect was the predominant subtype (55.5%). The most common clinical features in patients were lymphadenopathy (65.6%) and pulmonary involvement (57%). XL-CGD patients were affected more frequently with severe infectious manifestations., Conclusions: Although XL-CGD is the most common type of the disease worldwide, only 12 patients (12.9%) were XL-CGD in our study. The relatively high frequency of AR-CGD is probable due to widely common consanguineous marriages in Iran.

Background: 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., Methods: 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., Results: 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., Conclusion: 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.

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.

LAD-I is a rare, autosomal recessive, primary immunodeficiency in which phagocyte adhesion and chemotaxis are impaired. Multiple infections in the absence of pus accumulation and persistent elevated peripheral blood neutrophil counts are the hallmark of LAD-I. Allogeneic HSCT is the only treatment proved to be potentially curative for phagocyte adhesion impairment in LAD-I. Here, we report on a case of a 30-month-old girl with LAD-I, in whom peripheral blood stem cell from a genotypically identical sibling resulted in mixed chimerism., (© 2009 John Wiley & Sons A/S.)

Background and Objective: 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., Design and Settings: Retrospective, patients referred to the hematology, oncology and stem cell transplantation research center., Patients and Methods: 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-identical 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., Results: 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)., Conclusion: Despite the high incidence of acute GVHD (78.6%) in the non-fludarabine group, which resulted 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.

Background: 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 hemoglobinopathies, 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., Objectives: 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, hemoglobinopathies, SAA, inherited bone marrow failure syndromes amongst others., Results and Discussion: 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., Conclusions and Recommendations: 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.

High-dose Busulfan in combination chemotherapy has been used commonly for hematopoietic stem cell transplantation. It crosses the blood-brain barrier and could cause seizure. Benzodiazepines have been used as anticonvulsant prophylaxis. This is a prospective study using oral lorazepam together with busulfan-based conditioning regimen in 30 children undergoing hematopoietic stem cell transplantation. The dose of lorazepam used ranged from 0.017 to 0.039 mg/kg (median = 0.026 mg/kg) per dose. None of the patients developed seizure while receiving oral lorazepam or within 72 hours of the last dose of Busulfan. Oral lorazepam was tolerated by the patients, but all patients needed dose reduction due to some adverse effects. In the authors' experience, oral lorazepam is a useful anticonvulsant prophylaxis for children receiving high-dose busulfan.

Pancreatoblastoma (PB) is a rare malignant neoplasm of the pancreas, which occurs mostly during childhood. Presently, the optimal treatment strategy is neither clear nor uniform for patients in advanced stages, in particular those with metastasis, inoperable, or recurrent tumors. To our knowledge, until now, only one patient with PB has been treated with hematopoietic stem cell transplantation (HSCT) following aggressive chemotherapy and surgical resection. Here we report the second case of PB who was treated with aggressive chemotherapy combined with autologous peripheral blood stem cell transplantation., (2010 Wiley-Liss, Inc.)

Sickle cell hemoglobin D disease is a rare variant of sickle cell disease. Affected patients suffer from episodes of acute exacerbation of clinical course with a wide range of manifestations such as acute chest syndrome, stroke, painful vaso-occlusive crises, acute sequestration crises, joint necrosis, organ failure, infections, and temporary aplastic crises, collectively called sickling crises. Conventional treatments for patients with sickle cell disease include hydroxyurea therapy and prophylactic red blood cell transfusion. However, morbidity and mortality rates remain high with these remedies. In this article, we report hematopoietic stem cell transplantation as an alternative treatment in children with high-risk factors. According to our knowledge and an extensive review of the literature, stem cell transplantation in sickle cell hemoglobin D disease previously has not been reported in any published study and our patient is the first case.