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Background: Artemis deficiency is an autosomal recessive disorder characterized by a combined immunodeficiency with increased cellular radiosensitivity. In this review, the clinical and genetic characteristics of 15 patients with DCLRE1C variants are presented., Methods: The demographic, clinical, immunologic, and genetic characteristics of patients with confirmed DCLRE1C variants diagnosed between 2013 and 2023 were collected retrospectively. Three patients were evaluated for radiosensitivity by the Comet assay, compared with age- and sex-matched healthy control., Results: Seven patients who had severe infections in the first 6 months of life were diagnosed with T-B-NK+ SCID (severe combined immunodeficiency). Among them, four individuals underwent transplantation, and one of those died due to post-transplant complications in early life. Eight patients had hypomorphic variants. Half of them were awaiting a suitable donor, while the other half had already undergone transplantation. The majority of patients were born into a consanguineous family (93.3%). Most patients had recurrent sinopulmonary infections (73.3%), and one patient had no other infection than an acute respiratory infection before diagnosis. Two patients (13.3%) had autoimmunity in the form of autoimmune hemolytic anemia. Growth retardation was observed in only one patient (6.6%), and no malignancy was detected in the surviving 11 patients during the median (IQR) of 21.5 (12-45) months of follow-up. Three patients who had novel variants exhibited increased radiosensitivity and compromised DNA repair, providing a potential vulnerability to malignant transformation., Conclusion: Early diagnosis, radiation avoidance, and careful preparation for transplantation contribute to minimizing complications, enhancing life expectancy, and improving the patient's quality of life., (© 2024 The Author(s). Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

We report the national data on the outcomes of hematopoietic stem cell transplantation (HSCT) for thalassemia major (TM) patients in Turkey on behalf of the Turkish Pediatric Stem Cell Transplantation Group. We retrospectively enrolled 1469 patients with TM who underwent their first HSCT between 1988 and 2020 in 25 pediatric centers in Turkey. The median follow-up duration and transplant ages were 62 months and 7 years, respectively; 113 patients had chronic graft versus host disease (cGVHD) and the cGVHD rate was 8.3% in surviving patients. Upon the last visit, 30 patients still had cGvHD (2.2%). The 5-year overall survival (OS), thalassemia-free survival (TFS) and thalassemia-GVHD-free survival (TGFS) rates were 92.3%, 82.1%, and 80.8%, respectively. cGVHD incidence was significantly lower in the mixed chimerism (MC) group compared to the complete chimerism (CC) group (p < 0.001). In survival analysis, OS, TFS, and TGFS rates were significantly higher for transplants after 2010. TFS and TGFS rates were better for patients under 7 years and at centers that had performed over 100 thalassemia transplants. Transplants from matched unrelated donors had significantly higher TFS rates. We recommend HSCT before 7 years old in thalassemia patients who have a matched donor for improved outcomes., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Genetic deficiencies of immune system, referred to as inborn errors of immunity (IEI), serve as a valuable model to study human immune responses. In a multicenter prospective cohort, we evaluated the outcome of SARS-CoV-2 infection among IEI subjects and analyzed genetic and immune characteristics that determine adverse COVID-19 outcomes., Methods: We studied 34 IEI patients (19M/15F, 12 [min: 0.6-max: 43] years) from six centers. We diagnosed COVID-19 infection by finding a positive SARS-CoV-2 PCR test (n = 25) and/or a lung tomography scoring (CORADS) ≥4 (n = 9). We recorded clinical and laboratory findings prospectively, fitted survival curves, and calculated fatality rates for the entire group and each IEI subclass., Results: Nineteen patients had combined immune deficiency (CID), six with predominantly antibody deficiency (PAD), six immune dysregulation (ID), two innate immune defects, and one in the autoinflammatory class. Overall, 23.5% of cases died, with disproportionate fatality rates among different IEI categories. PAD group had a relatively favorable outcome at any age, but CIDs and IDs were particularly vulnerable. At admission, presence of dyspnea was an independent risk for COVID-related death (OR: 2.630, 95% CI; 1.198-5.776, p < .001). Concerning predictive roles of laboratory markers at admission, deceased subjects compared to survived had significantly higher CRP, procalcitonin, Troponin-T, ferritin, and total-lung-score (p = .020, p = .003, p = .014, p = .013, p = .020; respectively), and lower absolute lymphocyte count, albumin, and trough IgG (p = .012, p = .022, p = .011; respectively)., Conclusion: Our data disclose a highly vulnerable IEI subgroup particularly disadvantaged for COVID-19 despite their youth. Future studies should address this vulnerability and consider giving priority to these subjects in SARS-Cov-2 therapy trials., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Hemoglobinopathies are the most common single-gene diseases and are estimated to affect millions of people worldwide. Thalassemia and sickle cell disease are the most prevalent diseases of this group. Today, despite the decreasing number of newborns diagnosed with a hemoglobinopathy, it remains an important health problem for many countries. Although regular red blood cell (RBC) transfusions, advanced iron chelation, and supportive therapy alternatives have improved life expectancy, allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option for patients with hemoglobinopathies to prevent irreversible organ damage. Modern transplantation approaches and careful posttransplantation follow-up of patients have improved survival outcomes, and HSCT has now been performed in several patients with hemoglobinopathies worldwide. Considering current experiences, hematopoietic stem cell transplantation is recommended in cases of β-thalassemia (β-thal) in the presence of a matched family or unrelated donor, without secondary organ damage due to transfusion. In patients with sickle cell anemia, transplantation indications include transfusion dependence and cases of secondary organ damage. Recently, gene therapy as a possible treatment option has yielded promising results, though it is not in routine clinical use at its current stage.

Background: Hematopoietic stem cell transplantation (HSCT) is a curative therapy option for hematologic malignancies. Iron overload is common in this patient group and can impact short-term and long-term nonrelapse mortality., Study Design: Retrospective observational cohort study., Aims: To evaluate the effect of iron load on early and late HSCT outcomes in patients with acute leukemia and myelodysplasia to assess the necessity of reducing iron load., Patients and Methods: Sixty patients who underwent HSCT in pediatric stem cell transplantation unit between 2000 and 2012 were evaluated retrospectively. The patients were divided into those with pretransplantation serum ferritin levels above and below the median value of 1299 ng/mL., Results: Forty-two (70%) of the patients were male, mean ages of the low and high ferritin groups were 85.43±9.42 and 118.56±10.04 months, respectively. Acute graft-versus-host disease (GVHD) within the first 100 days and acute liver GVHD were significantly more common in the high ferritin group (P<0.011 for both). Ferritin level was not associated with rates of engraftment syndrome, veno-occlusive disease, early/late infection, relapse, or overall and disease-free survival., Conclusions: In our study, significant result especially in terms of acute liver GVHD, was important to emphasize the need to be more careful in terms of acute liver GVHD risk in early liver pathologies in patients with high levels of ferritin after transplantation. In future large studies may be helpful to explain the relationship between acute liver GVHD and high ferritin levels.

We conducted a prospective, phase II, multicenter, single-arm study to evaluate the efficacy and safety of deferasirox in patients age >2 to <18 years with β-thalassemia major (TM) who underwent hematopoietic stem cell transplantation (HSCT) and had evidence of iron overload (serum ferritin >1000 µg/L; cardiac MRI T2* <20 ms, or liver iron concentration [LIC; by MRI R2]  ≥5 mg/g). Patients received deferasirox at an initial dose of 10 mg/kg/day, with up-titration to a maximum of 20 mg/kg/day. The study continued for 52 weeks and included a total of 27 patients (mean age, 9.1 ± 3.8 years; 70.4% male). One patient (3.7%) was lost to follow-up. The majority of patients (n = 20; 74.1%) were able to achieve the intended dose of 20 mg/kg/day. No deaths occurred. A total of 134 adverse events (AEs) were reported in 25 patients (92.6%) during the study. The majority of patients had grade 1 or 2 AEs, with only 8 patients (29.6%) experiencing grade 3 AEs. Only 10 AEs occurring in 4 patients (14.8%) were suspected to be related to deferasirox (ALT/AST increase, n = 4; urinary tract infection, n = 1). The deferasirox dose had to be adjusted or interrupted for 6 AEs occurring in 4 patients (14.8%). A total of 6 serious AEs occurred in 3 patients (11.1%), none of which were suspected to be related to deferasirox. From baseline to week 52, there were decreases in median concentrations of alanine aminotransferase (ALT), from 30.0 to 17.0 IU/L, and aspartate aminotransferase (AST), from 35.5 to 26.0 IU/L. Median serum creatinine and cystatin C concentrations were similar at baseline and week 52. There was a continuous and significant decrease in median serum ferritin level from 1718.0 µg/L at baseline to 845.3 µg/L following 52 weeks of therapy (P < .001); 9 patients (33.3%) achieved a level of <500 µg/L. There was also a significant decrease in median LIC (from 8.6 to 4.1 mg/g; P < .001) and an increase in median cardiac T2* (from 26.0 to 28.0 ms; P = .520) from baseline to week 52. Our findings indicate that deferasirox treatment at doses up to 20 mg/kg/day reduces the iron burden in children with TM post-HSCT, with a manageable safety profile., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Recently, haploidentical transplantations have been performed with unmanipulated BM or PBSC. This approach is becoming more widely adopted with the use of PTCY. However, there is limited evidence about this approach in children. We present 15 children who received 16 haploidentical HSCT with unmanipulated BM or PBSC using PTCY for GVHD prophylaxis. Post-transplant CY(50 mg/kg IV) was given on the third and fifth day, and CsA or tacrolimus with MMF or MP was also used for GVHD prophylaxis. All patients engrafted at a median of 16 and 18 days for neutrophil and thrombocyte recovery, respectively. Grades II-III acute GVHD developed in seven patients, and mild chronic GVHD was found in two patients. Two patients died within the first 100 days due to sepsis (TRM 12.5%). Eleven patients are currently alive, with a median follow-up of 12 months (range 6-22 months). The 12-month OS and DFS were 75 ± 10.8% and 68.8 ± 11.6%, respectively. Our results with these high-risk patients are encouraging for haploidentical HSCT in pediatric patients. Future studies should continue to assess haploidentical HSCT, including comparison of other modalities, in a primary pediatric population., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Haematopoietic stem cell transplantation (HSCT) remains the best therapeutic option for many acquired and inherited paediatric haematological disorders. Unfortunately, the probability of finding an HLA matched donor is limited. An alternative technique is PGD combined with HLA matching, which offers the possibility of selecting unaffected embryos that are HLA compatible with the sick child, with the aim of possible use of stem cells from the resulting baby in future. Since the first successful report for Fanconi anaemia a decade ago, the therapeutic success of this technique was reported in a few cases and for a limited number of disorders. Here, we report full recovery of 44 sick children who received HSCT from healthy infants conceived after pre-implantation HLA matching for the following 10 indications; beta-thalassaemia, Wiskott-Aldrich syndrome, Fanconi anaemia, sickle cell anaemia, acute myeloid leukaemia, acute lymphoblastic leukaemia, Glanzmann's thrombasthaenia, Diamond-Blackfan anaemia, X-linked adrenoleukodystrophy and mucopolysaccharidosis type I. No serious complications were observed among recipients and donors. Graft failure occurred in four children with beta-thalassaemia where a second HSCT was planned. Preimplantation HLA matching is a reliable technique and provides a realistic option for couples seeking treatment for an affected child when no HLA-matched donor is available., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: A risk associated with the iron chelator deferiprone is the development of neutropenia or agranulocytosis. Accordingly, the product label recommends weekly blood monitoring and immediate interruption of treatment upon detection of an absolute neutrophil count (ANC) <1.5 × 10(9)/L, out of concern that continued therapy might lead to a more severe drop. However, it is uncertain how these recommendations are followed under real-life conditions and, if they are not followed, whether continuation of therapy results in increased incidence of agranulocytosis., Procedure: This non-interventional surveillance program assessed the monitoring of deferiprone therapy in clinical practice. A total of 294 patients with transfusion-dependent anemias received deferiprone, as monotherapy or with another chelator, for up to 1 year. The participating physicians were not given any instructions about treatment and monitoring beyond being referred to the information in the package insert., Results: ANC monitoring was conducted at an average interval of 5 ± 4 weeks, and deferiprone was not always interrupted upon detection of neutropenia. One patient (0.3%) experienced agranulocytosis, and nine others (3%) experienced a total of 11 episodes of neutropenia. All neutropenia episodes resolved; median time to resolution was similar whether or not treatment was interrupted; and no case of neutropenia progressed to agranulocytosis., Conclusions: These data indicate that less frequent ANC monitoring and continuation of deferiprone therapy during neutropenia are not associated with prolonged neutropenia or with progression to agranulocytosis., (© 2014 Wiley Periodicals, Inc.)

To describe the incidence, risk factors, and treatment of autoimmune diseases (ADs) occurring after cord blood transplantation (CBT), we analyzed both CBT recipients reported to EUROCORD who had developed at least 1 new AD and those who had not. Fifty-two of 726 reported patients developed at least 1 AD within 212 days (range, 27-4267) after CBT. Cumulative incidence of ADs after CBT was 5.0% +/- 1% at 1 year and 6.6% +/- 1% at 5 years. Patients developing ADs were younger and had more nonmalignant diseases (P < .001). ADs target hematopoietic (autoimmune hemolytic anemia, n = 20; Evans syndrome, n = 9; autoimmune thrombocytopenia, n = 11; and immune neutropenia, n = 1) and other tissues (thyroiditis, n = 3; psoriasis, n = 2; Graves disease, n 1; membranous glomerulonephritis, n = 2; rheumatoid arthritis, n = 1; ulcerative colitis, n = 1; and systemic lupus erythematosus, n = 1). Four patients developed 2 ADs (3 cases of immune thrombocytopenia followed by autoimmune hemolytic anemia and 1 Evans syndrome with rheumatoid arthritis). By multivariate analysis, the main risk factor for developing an AD was nonmalignant disease as an indication for CBT (P = .0001). Hematologic ADs were most often treated with steroids, rituximab, and cyclosporine. With a median follow-up of 26 months (range, 2-91), 6 of 52 patients died as a consequence of ADs. We conclude that CBT may be followed by potentially life-threatening, mainly hematologic ADs.

From January 1991 to June 2009, 245 children with beta thalassemia major who underwent their first allogeneic HSCT in Turkey and who were followed for a minimum of one yr post-transplantation were enrolled this study. The median age of the patients was 6.6 yr old (range, 1-22 yr). The distribution of Pesaro risk class I, II, and III categories was 41, 130, and 63 children, respectively. The median serum ferritin level was 2203 ng/mL. Eighty-eight patients received bone marrow (BM) stem cells; 137, peripheral blood (PB) stem cells; and 20, cord blood (CB) stem cells. The donors were HLA-matched siblings or parents. Median engraftment times were shorter in PBSCT patients compared with the BMT group (p < 0.001). Grade II-IV acute GvHD was observed in 33 children (13.5%), while cGvHD was observed in 28 patients (12.5%), eight of whom had the extensive form. Thalassemic reconstitution was observed in 43 (17%) of the transplant patients. Post-transplant aplasia occurred in three patients, and the TRM rate was 7.75%. Seventeen patients were lost after 100 days. The thalassemia-free survival and OS rates were 68% (95% CI, 61.8-74.2) and 85.0% (95% CI, 80.2-89.8), respectively. We believe that this study is important because it is the first multicenter national data for children with beta thalassemia major receiving HSCT., (© 2012 John Wiley & Sons A/S.)

A reciprocal translocation between chromosomes 9 and 22 creates oncogenic BCR/ABL fusion in the breakpoint region of the derivative chromosome 22. The aim of this study was to evaluate the importance of atypical fluorescence in situ hybridization (FISH) signal patterns in pediatric and adult acute lymphoblastic leukemia (ALL) cases. We evaluated t(9;22) translocation in 208 cases with ALL (294 tests), including 139 childhood and 69 adult cases by FISH technique using BCR/ABL extra signal (ES) probe. FISH signal patterns observed in pediatric ALL cases were as follows; Major-BCR/ABL (M-BCR/ABL) (1.4%), minor-BCR/ABL (m-BCR/ABL) (3.6%), trisomy 9 (4.3%), trisomy 22 (4.3%), trisomy or tetrasomy of both chromosomes 9 and 22 (2.9%), monosomy 9 (1.4%), monosomy 22 (0.7%), ABL gene amplification (1.4%), derivative chromosome 9 deletion (1.4%), and extra copies of the Philadelphia chromosome (1.4%). FISH signal patterns observed in adult ALL cases were as follows; M-BCR/ABL (5.8%), m-BCR/ABL (11.6%), two different cell clones with major and minor BCR/ABL signal pattern (2.9%), extra copies of Philadelphia chromosome (4.3%), derivative chromosome 9 deletion (1.4%), trisomy 9 (2.9%), tetraploidy (1.4%), monosomy 9 (1.4%), trisomy 22 (1.4%), and coexistence of both trisomy 22 and monosomy 9 (1.4%). Trisomy 9, trisomy 22, and polyploidy of chromosomes 9 and 22 were specific atypical FISH signal patterns for childhood B cell acute lymphoblastic leukemia (B-ALL) patients. However, monosomy 9 and ABL gene amplification were highly specific for childhood T cell acute lymphoblastic leukemia (T-ALL) patients. Our report presents the correlation between atypical FISH signal patterns and clinical findings of a large group of ALL cases.

We investigated prospectively factors influencing the safety of hematopoietic stem cell (HSC) collection in 453 pediatric donors. The children in the study donated either BM or peripheral blood stem cells (PBSCs) according to center policy. A large variability in approach to donor issues was observed between the participating centers. Significant differences were observed between BM and PBSC donors regarding pain, blood allotransfusion, duration of hospital stay, and iron supplementation; however, differences between the groups undergoing BM vs PBSC donation preclude direct risk comparisons between the 2 procedures. The most common adverse event was pain, reported mainly by older children after BM harvest, but also observed after central venous catheter (CVC) placement for PBSC collection. With regard to severe adverse events, one patient (0.7%) developed a pneumothorax with hydrothorax after CVC placement for PBSC collection. The risk of allotransfusion after BM harvest was associated with a donor age of < 4 years and a BM harvest volume of > 20 mL/kg. Children < 4 years were at higher risk than older children for allotransfusion after BM harvest and there was a higher risk of complications from CVC placement before apheresis. We conclude that PBSC and BM collection are safe procedures in children.

Background: The aim was to evaluate the feasibility of donor lymphocyte infusion (DLI) in transplanted patients with thalassemia who were at imminent risk of graft rejection (GR)., Procedure: We retrospectively evaluated outcomes in a cohort of 19 patients with thalassemia who received DLI following 21 transplantations. Patients were divided into three groups depending on indication and time of DLI: group I, mixed chimerism-level-3 (MC-level-3) within 2 months and subsequently receiving DLI; group II, MC-level-3 within 2 months and receiving deferred DLI beyond post-transplant 2.5 months; group III, receiving DLI because of a gradual decrease in both donor cells and hemoglobin levels without MC-level-3 within 2 months., Results: Three patients evolved to compete chimerism (16%), 9 patients had MC with transfusion independency (47%) and 7 had GR (37%). Three of 7 patients in group I, 1 of 4 patients in group II and 8 of 10 patients in group III preserved the graft. Although significant increases in the percentage of donor cells were not detected in group III, hemoglobin levels improved (median, 6.8-8.8 g/dl, P = 0.002)., Conclusion: The risk of GR is high in patients with thalassemia who have MC-level-3 within 2 months after transplantation. DLI is a feasible method for converting unstable MC towards stable MC or full donor chimerism, but its efficacy is partially related to the percentage of residual host cells at the time of infusion. Serial chimerism studies can identify unstable MC earlier and may guide the proper timing of intervention., (Copyright © 2011 Wiley Periodicals, Inc.)

Allogeneic hematopoetic stem cell transplantation (HSCT) is the only radical cure of beta-thalassemia. However, iron overload remains a cause of morbidity and mortality in posttransplant period. The authors present 7 patients as a preliminary report who underwent bone marrow transplant (BMT) and received oral chelating therapy (deferasirox) because of poor compliance to phlebotomy and desferrioxamine. The patients investigated mainly for possible side effects of deferasirox. No negative effect was seen in aspartate aminotransferase (AST), alanine aminotransferase (ALT), hemoglobin (Hb), and donor chimerism of the patients while serum ferritin levels significantly reduced (P = .018). Although serum creatinin significantly increased (P = .034), it was in normal limits in all patients. The authors believe that this report shows promising findings to plan further studies to clarify clinical safety and efficacy of deferasirox in posttransplant period.

SCN is an inherited hematological disorder with severe neutropenia and recurrent infections. Although there are some reports that recombinant rhG-CSF improves clinical outcome, allogeneic HSCT appears to be the only curative treatment for these patients. We report here two children with SCN successfully treated by CBT from unrelated donors. They were refractory to rhG-CSF treatment and have no identical family donor. Bu + CY were given as conditioning. Case 1 and Case 2 received 6/6 and 5/6 HLA-matched unrelated umbilical cord blood, respectively. The number of infused nucleated cells was 6, 18 x 10(7)/kg and CD34(+) cell number was 3, 74 x 10(5)/kg in Case 1. Those cell numbers were 8, 8 x 10(7)/kg and 5, 34 x 10(5)/kg for Case 2, respectively. Neutrophil/platelet engraftments were 45/49 days in Case 1 and 24/36 days in Case 2. Grade II cutaneous acute GVHD was seen in Case 2 that was treated successfully with prednisolone. Both patients are well with normal hematological findings and full donor chimerism for post-transplant 20 and 24 months, respectively. We conclude that UCB can be considered as a safe source of stem cell in patients with SCN who need urgent HSCT.

Background: BK virus-associated hemorrhagic cystitis (BKV-HC) is a severe complication after allogeneic hematopoietic stem cell transplantation (HSCT), but antiviral treatment for this condition has not been evaluated., Methods: We conducted a retrospective survey on the safety and outcome of cidofovir treatment for patients with BKV-HC in centers affiliated with the European Group for Blood and Marrow Transplantation., Results: From 1 April 2004 to 31 December 2007, 62 patients received a diagnosis of BKV-HC after a median interval of 35 days after HSCT (range, 3-577 days). Fifty-seven patients (92%) received intravenous cidofovir, whereas 5 patients received cidofovir intravesically. Complete response (CR) was recorded in 38 (67%) of 57 patients with HC treated with intravenous cidofovir, whereas partial response (PR) was documented in 7 patients (12%). CR was documented in 3 patients and PR in 1 patient with HC treated with intravesical cidofovir. A reduction of 1-3 logs in BKV load was documented in 8 of the 10 patients achieving CR. Mild-to-moderate toxic effects were recorded in 18 of 57 patients who received intravenous cidofovir administration. In a multivariate analysis, the factors significantly associated with response to cidofovir were the stem cell source (P = .01) and the use of total body irradiation (P = .03). After a median follow-up of 287 days, overall survival and total treatment-related mortality rates were 63% and 40% for patients achieving CR, compared with 14% and 72% for patients with PR or no response to cidofovir, respectively (P = .001 and P = .001, respectively)., Conclusions: Cidofovir may be a potentially effective therapy for BKV-HC, but evidence supporting its use requires randomized controlled trials.

Several investigators have been looking for less toxic conditioning regimen for stem cell transplantation in Fanconi anemia (FA) patients because of sensitivity to DNA cross-linking agents and tendency to malignancy. We report 16 multitransfused FA patients who underwent peripheral stem cell transplantation from 13 related and 3 unrelated donors. Although the first 6 patients received thoraco-abdominal irradiation + cyclophosphamide + antithymocyte globulin (regimen A) for conditioning, fludarabine (FLU) + cyclophosphamide + antithymocyte globulin (regimen B) were used in the last 10 patients in which 3 of them received unrelated graft. Cyclosporin A was given alone for the related allografts but also included mycophenolate mofetil for the unrelated allograft as graft versus host disease prophylaxis. We observed a lower risk of peritransplant morbidity and mortality with fewer and milder graft versus host disease in FLU based group. We lost 3 patients in regimen A group and 1 of them from secondary acute myeloid leukemia. Three patients are alive with transfusion independent. In regimen B group, 9 of 10 patients are alive with normal hematologic parameters and full donor chimerism. The longest follow-up durations are 90 and 60 months in regimen A and B, respectively. In conclusion, FLU based conditioning is more effective and successful with lower toxicity in multitransfused FA patients. However, it needs more experience and longer follow up duration.

beta-Thalassemia (thal) and sickle cell disease are the most common genetic diseases worldwide. Although supportive therapies such as regular transfusion and chelation for beta-thal and hydroxyurea (HU) for sickle cell disease have significantly improved clinical manifestations and the quality of life, they cannot eliminate disease and therapy-related complications. Today, hematopoietic stem cell transplantation (HSCT) is the only curative treatment for patients with hemoglobinopathies. The first successful HSCT was reported in 1981. At that time, more than 1,000 patients underwent HSCT in Pesaro, Italy. Sixty beta-thal patients underwent HSCT at the Department of Pediatric Hematology-Oncology, Akdeniz University School of Medicine, Antalya, Turkey between 1998 and 2006. We found stable mixed chimerism in 14 patients out of 45 (31%) in our transplanted thalassemia patients. The thalassemia free survival and overall survival rates were found to be 84.0 and 91.0%, respectively. The literature and our results indicate that HSCT can offer a cure for hemoglobinopathy patients.

BACKGROUND AND METHODS. Growth and endocrine disturbances are still important problems for patients with thalassemia major, which is a major health problem in southern part of Turkey. In the present study 71 thalassemia major patients over 3 years of age were evaluated for physical and sexual maturation status. RESULTS AND CONCLUSION. Twenty-three patients (32.4%) were below the third centile for height. Growth retardation was more pronounced in patients 10 years of age and up according to height and weight standard deviation scores (SDS). Delay in bone age SDS was found in almost all patients, and 74.5% of our patients over 12 years of age had not yet entered puberty. These results show that growth and endocrine disturbances have significant negative effects in the quality of life of thalassemic patients. More detailed studies will help to solve these problems.