Sickle Thalassemia Research Articles

Clinicohematological profile of hemolytic anaemia in tertiary care hospital in rural Andhra Pradesh

Introduction: Hemolytic anaemias are a group of disorders that cause significant morbidity in children. Method: A cross sectional study was conducted at NRI Medical College for a period of 1 year. All cases of newly diagnosed and old cases of hemolytic anaemia on follow up were included. Results: The study showed beta thalassemia as the most common hemolytic anaemia; followed by malaria, sickle beta thalassemia, thalassemia intermedia, beta thalassemia minor, Sickle cell disease, sickle cell trait, auto immune hemolytic anaemia, and hereditary spherocytosis. The mean hemoglobin at presentation was 5.39 gm/dl. Anthropometric measurements in 32 cases of congenital hemolytic anaemias revealed height < 3rd centile in 9 cases. Weight less than 3rd centile was seen in 11 cases. 13 children had hemolytic facies. Massive splenomegaly causing discomfort, gall stones, heart failure were seen in 2 cases each. In thalassemia major, 10 cases required frequent transfusions, [10-12 per year]. 9 came for less frequent transfusions [6 per year]. Sickle thalassemia, thalassemia intermedia, required one transfusion every 1-2 years. Occasional transfusions were given in sickle cell anaemia, hereditary spherocytosis. Serum ferritin levels varied between 220-1427. Conclusion: Hemoglobin electrophoresis remains the main investigation of choice in diagnosis of hemolytic anaemia. Thalassemia major is the most severe among other hemolytic anaemias encountered in this series. The study emphasizes the need to improve awareness regarding hemoglobinopathies among population, prenatal screening, blood transfusion policies, chelation policies to prevent complications in transfusion dependent patients.

Spectrum of Sickle Cell Diseases in Patients Diagnosed at a Tertiary Care Centre in Karnataka with Special Emphasis on their Clinicohaematological Profile.

Sickle cell disease is a monogenic disorder with considerable clinical diversity and Sickle haemoglobin is responsible for wide spectrum of disorders which vary with respect to severity of anaemia, frequency of crises and duration of survival. As they are confused with many other clinically aggressive disorders, precision in diagnosis is essential both to proper clinical management and subsequent genetic counselling. Hence, this study was taken up in order to diagnose these conditions and administer suitable counselling measures to minimise the incidence of sickle cell disease in the future. The aim of this study was to identify the spectrum of all Sickle cell diseases diagnosed at a tertiary care centre in Bangalore, Karnataka, India who presented over a period of five years from 2009 to 2013 and also to screen the parents and siblings of the patients for their carrier status. We reviewed 26 cases of Sickle Cell Disease (SCD) and also 38 parents & 10 siblings of these children for their carrier status. Haemoglobin electrophoreses was performed by using alkaline gel method, followed by High Performance Liquid Chromatography when needed. A total of 26 children diagnosed with SCD were enrolled in the study. Most common entity was Sickle Cell Anaemia (SCA), followed by sickle thalassaemia and Sickle Cell Trait (SCT). Commonest clinical presentation was fever and pallor. Amongst the parents and siblings, sickle cell trait was the most common entity followed by thalassaemia trait. One interesting case of HbSE disease was encountered, which is a rare entity in India. This study brings out the total spectrum of SCDs in a tertiary care centre in Karnataka, with more emphasis on screening of the parents and siblings for their carrier status.

Managing the patient with haemoglobinopathy and multiple red cell antibodies

Background and ObjectivesSickle cell disease (SCD) and thalassaemia, particularly the β‐type, represent major sources of morbidity. Recommended treatment includes regular blood transfusion following highly uniform strategies across thalassaemia units and monitoring related complications including alloimmunization. This complex problem depends on donor–recipient antigenic diversity, the patient's immune status and specific circumstances such as pregnancy.Materials and MethodsWe examined alloimmunization against RBC antigens and autoimmunization in 983 patients with thalassaemia and SCD in Greece, in relation to applied RBC antigen matching policies and other factors possibly relevant in reducing the rate of alloimmunization and delayed haemolytic transfusion reaction (DHTR).ResultsUp to 2010, 11.6% of all patients had history of alloimmunization and 7.3% of autoimmunization. Frequency was highest in thalassaemia intermedia followed by sickle–thalassaemia and thalassaemia major. New alloimmunization was low at 1.4% after 2010, corresponding to a risk of 1:9405 units of RBCs transfused. Despite the very high transfusion burden in the chronically transfused patients, the use of extended matched donor blood is proven effective in reducing the rate of alloimmunization.ConclusionMultiple RBC alloantibodies represent a small but difficult to manage risk for responders prone to combination with autoimmunization. DHTR with hyperhaemolysis is a major clinical problem in haemoglobinopathies, especially during the gestational period and delivery in patients who escape expert medical follow‐up. Progress in the safety and quality of blood transfused in these patients is expected to contribute to prolongation of their life expectancy and to reproduction. Investigation of HLA and other antibodies in patients prone to developing RBC antibodies is suggested.

Serum ferritin as a biomarker in hematological conditions

Objective: This study is to evaluate significance of serum ferritin in differentiating between different hematological conditions. Methods: This is a prospective study conducted on children aged between 1 to 12 years attending Pediatric OP and IP of Navodaya Medical College, Raichur for period of one year. 200 children who fulfilled WHO criteria for anemia were taken as cases and 200 normal healthy children of same demographic data were taken as controls. Serum ferritin levels were compared between the normal healthy children and children with different types of anemias. Results: The mean value of serum ferritin in normal controls (106.8 ± 38.0ng/ml), in IDA (5.1 ± 2.3ng/ml), in Dimorphic anemia (330±40ng/ml), in Sickle cell anemia (430±83ng/ml), in Thalassemia major (1520±230 ng/ml), and in leukemias (1550±140ng/ml) Conclusion: Serum ferritin is moderately raised in dimorphic anemia, in Sickle cell anemia, Thalassemia and leukemias it is significantly raised. And we found that serum ferritin is the most sensitive and reliable parameter compared to other parameters in iron profile in evaluating both iron deficient and iron overload conditions. Keywords: Serum Ferritin, Thalassemia, Sickle cell anemia, Dimorphic anemia, leukemia

Urinary Transforming Growth Factor β-1 as a Marker of Renal Dysfunction in Sickle Cell Disease

Sickle cell disease (SCD) is a genetic disorder that results in deformity of red blood cells. Renal dysfunction affects 5-18% of patients with SCD. To date, few studies have described urinary levels of transforming growth factor β-1 (TGF-β1), which is a marker of fibrosis, as a biomarker in identifying patients at risk of developing renal disease in SCD. The aim of this study is to determine prevalence of sickle cell nephropathy in Egyptian SCD patients. We aimed also to evaluate the association of urinary TGF-β1 with other conventional biomarkers of renal damage in SCD patients to identify a novel renal biomarker for early diagnosis of sickle nephropathy. We examined 40 SCD patients, 21 with sickle cell anemia, 16 sickle thalassemia, and three with sickle trait. We compared them to 20 control children with matched age and sex. The study was held in the time period between May 2013 and December 2013 in the Hematology Clinic, New Cairo University Children Hospital, Cairo, Egypt. Urinary excretion of TGF-β1 was 7.07±1.91ng/mL in SCD patients versus 2.23±0.76ng/mL in control children (p < 0.001). SCD patients had elevated estimated glomerular filtration rate (177.44±35.6mL/min/1.73m(2)), denoting a state of glomerular hyperfiltration. 47.5% of SCD patients had microalbuminuria. Urinary TGF-β1 correlated positively with microalbuminuria and estimated glomerular filtration rate (p=0.001 and p=0.018, respectively). We concluded that urinary TGF-β1 may serve as a marker of early renal injury in SCD.

Premarital screening of college students for carrier detection in thalassemia and sickle cell disease: need of the hour

Background: Hemoglobinopathies are a group of inherited conditions characterized by quantitative and qualitative abnormalities in the synthesis of hemoglobin. In India, the most prevalent hemoglobinopathies are thalassemia and sickle cell anemia. To reduce the burden of highly prevalent monogenic disorders, it is essential that disease progression be halted at the carrier stage. This can be done by carrier detection and genetic counseling in young individuals. In Central India, where prevalence of thalassemia and sickle cell anemia is high, premarital screening is being implemented for the first time in medical students for identification of asymptomatic carriers of these hemoglobinopathies and possible prevention of future high-risk marriages by genetic counseling. Objectives: The objectives of this study were to (1) determine the prevalence of asymptomatic carriers of sickle cell disease and thalassemia in first-year MBBS students; and (2) know the frequency of hemoglobinopathy carriers in different ethnic groups of this study group. Materials and Methods: This study was conducted at a Regional Hemoglobinopathy Detection and Management Centre of a tertiary-care hospital in central India in newly admitted medical students and was approved by the institutional ethics committee. Venous blood samples were analyzed for blood counts and solubility test positivity. Electrophoresis for pattern analysis and high-performance liquid chromatography for confirmation of diagnosis were used on each student. Results were analyzed with the help of statistical analysis. Results: Overall prevalence of hemoglobinopathies was 10%. Beta-Thalassemia trait was the most prevalent hemoglobinopathy followed by sickle cell trait. Presence of hemoglobinopathies was seen in varied ethnic groups. Conclusion: Importance of screening in young asymptomatic individuals is highlighted.

Overview of Chelation Recommendations for Thalassaemia and Sickle Cell Disease

The long term consequences of iron toxicity are mostly reversible with effective iron chelation therapy. Recommendations for use of chelation therapy in transfusion dependent thalassaemia (TDT), sickle cell disease (SCD) and non transfusion dependent thalassaemia (NTDT) continue to evolve as our knowledge and clinical experience increases. Improved chelation options including drug combinations and a better understanding of condition specific factors may help to improve efficiency of chelation regimens and meet the needs of patients more effectively.

Hepatocellular carcinoma in thalassaemia: an update of the Italian Registry.

The risk of developing hepatocellular carcinoma (HCC) in patients with thalassaemia is increased by transfusion-transmitted infections and haemosiderosis. All Italian Thalassaemia Centres use an ad hoc form to report all diagnoses of HCC to the Italian Registry. Since our last report, in 2002, up to December 2012, 62 new cases were identified, 52% of whom were affected by thalassaemia major (TM) and 45% by thalassaemia intermedia (TI). Two had sickle-thalassaemia (ST). The incidence of the tumour is increasing, possibly because of the longer survival of patients and consequent longer exposure to the noxious effects of the hepatotropic viruses and iron. Three patients were hepatitis B surface antigen-positive, 36 patients showed evidence of past infection with hepatitis B virus (HBV). Fifty-four patients had antibodies against hepatitis C virus (HCV), 43 of whom were HCV RNA positive. Only 4 had no evidence of exposure either to HCV or HBV. The mean liver iron concentration was 8 mg/g dry weight. Therapy included chemoembolization, thermoablation with radiofrequency and surgical excision. Three patients underwent liver transplant, 21 received palliative therapy. As of December 2012, 41 patients had died. The average survival time from HCC detection to death was 11·5 months (1·4-107·2 months). Ultrasonography is recommended every 6 months to enable early diagnosis of HCC, which is crucial to decrease mortality.

G248(P) Growth pattern in Sickle Cell Disease (SCD) children

AimTo study growth pattern of children with sickle cell disease as growth deficit experienced by these children remain a problem with clinical significance and intangible consequence.MethodRetrospective cross sectional growth pattern...

Serum Angiogenin Level in Sickle Cell Disease and Beta Thalassemia Patients

Introduction: Angiogenesis has been investigated in different kinds of anemia. However, its role as a marker of angiogenesis has not been investigated in thalassemia or sickle cell disease (SCD). Objectives: We aimed to investigate serum angiogenin level in children and adolescents with beta thalassemia or SCD and its relation to possible risk factors of angiogenesis. Materials and Methods: This study included; 32 β-thalassemia major (β-TM) patients aged 14.2 ± 3.8 years, 20 β-thalassemia intermedia (β-TI) patients aged 14.3 ± 4.8 years, 20 SCD patients aged 14.1 ± 2.4 years; 8 with (HbSS) and 12 with sickle thalassemia (HbS/β-thalassemia) and 35 age and sex-matched controls. Data collected regarding; age, sex, disease duration, blood transfusion frequency, transfusion index, chelation type and duration, CBC, Hb electrophoresis, serum ferritin and serum angiogenin level (by ELISA). Results: Angiogenin level was significantly higher in patients with SCD [250 (100–300) pg/mL] compared to β-TM [180 (140–230) pg/mL] and controls [89 (80–103) pg/mL] (P < .001) especially those with HbSS (P = .06). There was a significant negative correlation between serum angiogenin and age of patients, age of onset and duration of chelation in β-TM (P < .01, P < .001, P = .003) and β-TI (P = .009, P = .03, P < .001) and with serum ferritin in β-TI group (r = −0.573, P = .008). In SCD, angiogenin level was negatively correlated with both frequency of blood transfusion (r = −0.731, P < .001) and duration of hydroxyurea therapy (P = .017). Conclusions: High angiogenin level detected among patients with SCD may be negatively influenced by regular blood transfusion and hydroxyurea therapy, while; early onset of chelation therapy may decrease angiogenin level in β-TM.

Clinical profile of sickle cell syndromes: Experience at a tertiary care centre in South India

Background: Sickle cell syndromes are commonly encountered inherited haematological disorders regarding which sparse published data are available from Telangana State. Methods: Prospective study of 55 patients diagnosed to have sickle cell syndromes at our tertiary care teaching hospital in Hyderbad, Telangana State, South India. Results: Their mean age was 19.9 (range 3-48) years; there were 35 males. Consanguinity was noted in 31%. History of cholecystectomy was evident in 5 cases. Blood transfusions were received in the past in 52% of cases. Symptoms at presentation were jaundice (85%), pain (80%), fatiguability (60%), pallor (30%), dyspnoea (29%), lump abdomen (7%) and leg ulcer (3%). Acute chest syndrome was seen in 10.9% cases. Physical examination revealed pallor (90%), icterus (80%) hepatomegaly (49%) and splenomegaly (41%). Mean haemoglobin at presentation was 8.3 g/dL. Sickle cells were seen in peripheral smear in 51%. Sickling test was positive in all after induction. Characterization of haemoglobin by high performance liquid chromatography revealed homozygous sicke cell anaemia was evident in 22/43 (51.2%), sickle thalassemia in 16/43 (37.2 %) and sickle cell trait in 5/43 (11.6 %). Conclusions: Sickle cell disease should be considered in the differential diagnosis while evaluating patients presenting with anaemia and skeletal pains. Prompt recognition and management improves survival and eventual prognosis in these patients.

Haemoglobinopathies: genetic and clinical aspects with an impact on blood transfusion

The haemoglobinopathies are autosomal recessive genetic disorders resulting in qualitative or quantitative change in the haemoglobin (Hb) molecule. HbS, the most widespread structural haemoglobin variant, hinders microcirculation by causing a sickle shape of red cells. In sickle cell disease, blood transfusion should be done only for strict indications. In thalassaemias, Hb synthesis is impeded by defective production of globin chains. The commonest types of clinical importance are α‐, βδ‐ and β‐thalassaemia. Compound heterozygotes for thalassaemia and Hb variants may have varying clinical impact.Morbidity is related to the anaemia, complications of blood transfusions including iron overload and transfusion transmissible infections, and splenectomy.Treatment of homozygous β‐thalassaemia is based on regular blood transfusion from early childhood, placing a major workload for blood transfusion services. Stringent quality measures are necessary to ensure that the transfused product meets requirements.Greece's national registry records 4,506 thalassaemia major and intermedia, “Η” haemoglobinopathy and sickle cell disease patients. Thalassaemia patients consume 18% of total RBC supply. Incidence of transfusion associated adverse reactions is 250:100 000 units of RBCs. Allergic (87.6:100 000) and NHFTR (89.9:100 000) are most common. One sickle thalassaemia patient died of hyperhaemolysis syndrome. Eight patients died of HCV hepatocellular carcinoma. HIV was transmitted to one patient during the window period.

Bone-Marrow or Cord-Blood Transplantation for Hemoglobinopathies?

There is currently considerable interest in attempting to cure sickle cell disease (SCD) and thalassemia major (TM) by transplantation of healthy

Sickle cell and thalassaemia posts are good value and need protecting.

Genetic blood disorders sickle cell and thalassaemia affect 12,500 and 800 people respectively in England.

Pulmonary Hypertension: An Emerging Risk in Hemoglobin Disorders

Pulmonary hypertension (PH) is one of the main cardiovascular complications in haemoglobinopathies and is considerably implicated in patients’ morbidity and mortality. In thalassemia intermedia, PH is found in about 60% of traditionally managed patients and represents the main cause of heart failure. In sickle cell anemia, PH is encountered in one third of patients and has been found to be a strong and independent predictor of mortality, while in sickle thalassemia, PH is generally less frequent and severe. The pathophysiology of PH in haemoglobinopathies is multifactorial and several mechanisms seem to be implicated, including a complex vasculopathy, hypercoagulability and elastic tissue defects, all associated with chronic hemolysis, high output state due to chronic anemia, as well as left heart dysfunction, pulmonary disorders and thromboembolic complications. Echocardiography is the most useful tool for patients’ screening on a regular basis, while the diagnosis of PH should always be confirmed by right cardiac catheterization. The proper management of the disease itself with haematological modalities such as blood transfusions combined with iron chelation or hydroxyurea, is the most effective approach for the prevention and treatment of haemoglobinopathy-associated PH. Antithrombotic agents should also be considered while the value of novel agents used in the treatment of pulmonary arterial hypertension, including endothelin antagonists or phosphodiesterase-5 inhibitors, is not yet established in patients with haemoglobinopathies.

‘He's the dad isn't he?’ Gender, race and the politics of prenatal screening

Background. Men's involvement in prenatal screening is becoming increasingly important. However, despite the potentially significant role of fathers in haemoglobinopathy screening, their participation is under researched. Furthermore, the portrayal of Black and minority ethnic (BME) fathers tends to be based on persisting stereotypes of men as either absentee parents with limited roles in screening or as controlling decision-makers. Objective. To describe the influence of ethnicity and gender on the process of participation of men in antenatal screening for sickle cell and thalassaemia. Design. A qualitative study, using in-depth interviews and focus groups with 22 pregnant women from a range of socio-economic and ethnic backgrounds, 16 male partners and 15 midwives in a northern city in the UK. Results. Men from BME groups take a pragmatic and equitable role in screening with their partners. White British men on the other hand, while willing to participate in screening, take a more casual view of their own direct participation. Accounts from hospital midwives supported these findings. Conclusions. While acknowledging the importance of material connections between certain BME groups and blood disorders, two key issues are raised. First, BME men's involvement contribute a challenge towards existing assumptions often made about BME fathers. Second, White British men's participation can be useful in determining the genetic status of the foetus and therefore their role should not be neglected. Screening research and practice need to broaden out their focus on issues of gender, ethnicity and screening.

The role of pDC, recipient T(reg) and donor T(reg) in HSC engraftment: Mechanisms of facilitation.

Hematopoietic stem cell transplantation (HSCT) has been utilized for treatment of many hematologic malignancies, genetic and metabolic disorders, and hemoglobinopathies such as sickle cell disease and thalassemia. It also induces donor-specific tolerance to organ and tissue transplants. The widespread success of HSCT is hampered by the toxicities of immunosuppression and development of graft-versus-host disease (GVHD). The mechanism of induction of transplantation tolerance (reciprocal donor/host) is still an elusive challenge in allogeneic HSCT. An understanding of the mechanisms for induction of tolerance and the critical cells involved in this process has resulted in novel cell-based therapies poised to be translated to clinical application. The focus of this review is those cells of interest.Bone marrow-derived plasmacytoid dendritic cells induce naïve T cells to differentiate to become antigen-specific regulatory T cells (T(reg)), creating a milieu for the induction of transplantation tolerance. Recently, CD8(+)/TCR(-) facilitating cells (FC), a novel cell population in mouse bone marrow, have been shown to potently enhance engraftment of allogeneic HSC without causing GVHD. The predominant subpopulation of FC resembles plasmacytoid precursor dendritic cells. FC induce antigen-specific T(reg) in vivo. Notably, FC address one major concern that has prevented the implementation of T(reg) cell therapy in the clinic: to expand T(reg) and have them remain tolerogenic in vivo. FC are novel in that they induce an antigen-specific regulatory milieu in vivo. The discovery of FC has opened new alternatives to expanded criteria in bone marrow transplantation that were previously restricted to human leukocyte antigen-matched recipients. The focus of this review is to cover what is currently known about the mechanism of FC action in inducing tolerance and preventing GVHD and hostversus-graft reactivity.

Outcome of patients (pts) with renal medullary carcinoma (RMC) treated in the era of targeted therapies (TT): A multicenter experience.

386 Background: RMC is a rare, highly aggressive primary neoplasm of the kidney that almost exclusively afflicts young black pts with sickle cell hemoglobinopathies, primarily sickle cell trait. The primary objectives of this study were to evaluate the clinical characteristics and treatment outcome of RMC pts. Methods: We retrospectively reviewed the medical records of pts diagnosed with RMC at four US institutions between 2000 and 2010. Overall survival (OS) was determined from initial diagnosis to date of death or last follow up (F/U). The time interval from date of metastasis to death or last F/U (OSm) was also determined. Kaplan-Meier methods were used to estimate OS and OSm. Results: 20 RMC pts were identified. All pts were black; 14 (70%) were males; 18 had sickle cell trait, 1 had sickle thalassemia and 1 not tested. 19 presented with stages III or IV; 7 (35%) had nephrectomy. Nineteen pts had ≥ 2 metastatic sites. Twelve pts had performance status [PS] 0/1; eight pts had PS 2/3. For the OS analysis, data on 16 pts were available and for the OSm analysis, data on 20 pts were available. The median follow up time for the OS analysis was 722 days. Thirteen of 16 pts died with median OS of 421 days [95%CI: 225–546]. Sixteen of 20 pts died in the OSm analysis with median OSm of 378 days [95%CI: 225–487]. Frontline therapy consisted of TT [sunitinib (5), bevacizumab + erlotinib (1), imatinib (2)], chemotherapy (C) [platinum/gemcitabine or taxane (7), gemcitabine/doxorubicin (2)], C + TT [gemcitabine/cisplatinum/bevacizumab (2), imatinib/doxorubicin (1)]. Three pts achieved a partial response (PR) in first-line (2 with C, 1 with C + TT). Twelve pts received second-line systemic therapies; 4 achieved PR (1 with bevacizumab/erlotinib, 2 with C, 1 with C + TT). Among 15 pts who had TT at any time during their treatment course, only 1 pt had PR. Conclusions: The prognosis of RMC pts remains poor despite initial palliation with systemic therapy. Collaborative multi-institutional efforts are needed to better understand the biology of this disease and improve treatment strategies. No significant financial relationships to disclose.

Anaerobic storage of red blood cells.

Anaerobic storage of red blood cells.

Allogeneic Stem Cell Transplantation in Congenital Hemoglobinopathies – A Curative Approach When Performed as a Primary Therapeutic Modality: A Single Center Experience.

Abstract 1144Poster Board I-166Allogeneic stem cell transplantation (SCT) is the only curative treatment for congenital hemoglobinopathies. To date, hundreds of patients (pts) were transplanted using different conditioning regimens and different sources of stem cells harvested from matched family donor (MFD), matched unrelated donor (MUD) and cord blood. The experience of a single center, the Rambam Medical Center, Haifa, Israel, performing 32 transplants in 31 pts with congenital hemoglobinopathies is presented herein. During the years 2000- 2008, 32 SCT were performed in 31 pts. Median age was 8 years (10 months-22 years). Median follow up was 5.5 years (7 months-9.5 years). Twenty seven pts were transplanted due to thalassemia major, 1 for sickle thalassemia (transplanted twice), 1 with chronic hemolysis, and 2 for sickle cell disease. Distribution of thalassemic pts (including sickle thalassemia) according to the Pesaro risk classification included: 7 in class I, 2 in class II and 20 in class III. There were 29 transplants from MFD while 3 transplants from MUD SCT. Twenty seven pts underwent first transplant while 5 pts received second transplant after rejecting the first one. One patient received 2 transplants in our center while the other 4 received their first transplant in another center. Different conditioning protocols, all based on busulfan (Bu) and cyclophosphamide (Cy), were used according to risk classifications, donor type, first or second transplant and type of disease. Pts with class I thalassemia who had MFD received Bu, Cy, fludarabine and ATG followed by moderate T cell depleted graft (Elhasid et al, 2007). Pts with class III thalassemia received protocol P26 including hydroxyurea, azathioprine, Bu, Cy, fludarabine (Sodani et al, 2004). Protocol P26.1, based on protocol P26 with the addition of thiotepa and ATG, was used for second transplant (Gaziev et al, 2008). Sickle cell disease pts received P26 based protocol. In order to prevent graft versus host disease (GvHD), moderate T cell depletion (TCD) (105/kg T cells) using positive selection of CD34 cells, was planned for all pts who had MFD. Since graft rejection occurred in 2 pts with class III thalassemia receiving protocol P26 and moderate TCD, an amendment modified use of this protocol only in class I thalassemia pts in the setting of MFD transplantation. Twenty eight out of 31 pts survived with overall survival (OS) of 90%. Three pts, all class III thalassemia, died. One patient died after first transplant due to severe hemorrhagic cystitis and multi-organ failure and 2 pts died after second transplant. Twenty six out of 27 pts who had only one transplant survived with OS of 96%. Four pts rejected the graft (12.9%); 1 with sickle cell disease, 2 with class III thalassemia and 1 with class I thalassemia after unrelated CBT. Twenty five out of 28 pts (89%) who survived are ex-thalassemic or sickle cell disease (table 1). No acute GvHD occurred in pts with class I thalassemia who received moderate TCD while the incidence of acute GvHD was 20% in the rest of the pts. Chronic GvHD occurred in 20% of pts regardless of TCD. Although most of our pts were classified as class III thalassemia, OS as well as disease free survival were 90% and 89%, respectively. No acute GvHD occurred in pts with class I thal major transplanted from MFD using moderate TCD. The efficacy and safety of this when used as a primary therapeutic modality is emphasized. Risk-adapted conditioning regimens, including novel ones that do not use post-transplant immunosuppression, improve transplant outcome in congenital hemoglobinopathies.Table 1nTRMOverall survivalDisease free survivalAll pts313/31 (9.6%)28/31 (90%)25/28 (89%)Class I thalassemiaModerate TCDno GvHD prophylaxis60/6 (0%)6/6 (100%)6/6 (100%) DisclosuresRowe:Teva Pharmaceuticals: Consultancy; EpiCept Corporation: Consultancy.