RESULTS:In 221 cycles from 138 patients (104 cycles requiring HLA matching), 90.5% had embryo(s) biopsied for genetic testing. There were 119 embryo transfers for thalassemia (76) and thalassemia-HLA cases (43), respectively, resulting in overall clinical pregnancy rates of 54.6%, implantation rates of 45.7%, and live birth rates of 44.1%. Our dataset included fifteen PGD-HLA live births with successful HSCT in twelve affected siblings, 67% using umbilical cord blood stem cells (UCBSC) as the only SC source.CONCLUSIONS:We report favorable thalassemia PGD and PGD-HLA laboratory and clinical outcomes from a single center. The ultimate success in PGD-HLA is of course the cure of a thalassemia-affected sibling by HSCT. Our PGD-HLA HSCT series is the first and largest performed entirely in Asia with twelve successful and two pending cures and predominant UCBSC use.

To assess outcomes of hematopoietic cell transplantation (HCT) for thalassemias and hemoglobinopathies in a single medical center in Thailand.

A 15-year-old high functioning autistic boy with normal IQ was found to have episode of eyes rolling upwards followed by rhythmic body shaking and was unresponsive for 2 minutes

A β-thalassaemia mutation occurring from insertion of a duplicated 22-bp intron/exon junction of the β-globin gene has been characterised. The repeated 22-bp insertion causes duplication of a 3′ splice site at IVSI/exon 2 junction. Reverse transcription–polymerase chain reaction showed that the proximal 3′ splice site present in the duplicated gene is used, leading to a frameshift and a premature chain termination at codon 37. β-Globin messenger ribonucleic acid (mRNA) transcribed from the mutant gene was not detected, suggesting that the process of nonsense-mediated mRNA decay may be triggered by the premature stop codon.

β Thalassemia is a major public health concern in Southeast Asia. A prevention program has been implemented in Thailand comprising mass carrier screening and genetic testing. In this study, a Thai girl with severe β thalassemia/hemoglobin (Hb) E disease was born from the mother with Hb E trait and the genotypically normal father. DNA sequencing revealed novel 22‐bp tandem duplication in the paternal allele of β globin gene, producing a severely truncated product. A short recurring nucleotide at the insertion site suggested a predisposition to this mutation. Therefore, spontaneous β globin mutations occasionally occur in normal population. Its clinical significance is noteworthy in countries with high prevalence of β thalassemia. Am. J. Hematol 2007. © 2006 Wiley‐Liss, Inc.

Allogeneic umbilical cord blood stem cell transplantation (CBT) has been accepted worldwide for curative therapy of many serious hematologic disorders for nearly two decades. To evaluate efficacy and outcomes of unrelated versus related donor CBT in Thai children with non-malignant diseases and to assess feasibility of using cord blood (CB) units cryopreserved in Thai National Cord Blood Bank, we retrospectively reviewed all children undergoing such transplants in our institute from February 2002 to July 2006. There were eligible 11 patients categorized into unrelated group (n=4, 3 male and 1 female) and related donors group (n=7, 6 male and 1 female). Median age and weight were 4 years 9 months (range 1 year 3 months-11 years 9 months), 17.3 kg (range 7.8–55 kg) and 7 years (range 1 year 6 months-14 years 10 months), 19.6 kg (range 13.1–30 kg), respectively. There were 2 cases of β-thalassemia/hemoglobin E, 1 of Wiskott-Aldrich syndrome (WAS), and 1 of severe aplastic anemia (SAA) in unrelated donors group, while every case in related group was diagnosed β-thalassemia/hemoglobin E. 4 unrelated donors consisted of 2 one-HLA-A-allele, 1 one-HLA-B-antigen, and 1 two-HLA-A-B-antigen mismatched cord blood units, while 7 related donors consisted of 5 HLA-identical, 1 two-allele mismatched, and 1 haploidentical siblings. Myeloablative conditioning regimen consisted of busulfan, cyclophosphamide, and anti-thymocyte globulin (ATG) for WAS and thalassemia patients. Fludarabine, ATG, and melphalan were used for the SAA girl because of precedent multiple transfusion received. Cyclosporine was used as graft-vs-host disease (GvHD) prophylaxis in every case. Median numbers of infused mononuclear cells and CD34+ cells of the unrelated donors group were 3.3×10 7 /kg (range 2.4–44) and 2.75×10 5 /kg (range 2.26–25), compared to 1.9×10 7 /kg (range 1.5–3.4), and 1.06×10 5 /kg (range 0.2–5.3) of the related group. Median times to neutrophil and platelet engraftments in each group were 15 and 37 days, compared to 22 and 43 days, respectively. 6 complete donor engraftments were achieved from 3 unrelated CB units and from 3 related sibling donors, however 2 mixed-chimerism status with donor predominance were present from related group. The remaining 1 case of the unrelated group and 2 of the related group did not engrafted, subsequently one case (thalassemia) resumed autologous recovery and unfortunately two cases (thalassemia and SAA) died due to neutropenic septicemia. Acute GvHD occurred in 2 unrelated (skin, gut, liver involvement grade IV (n=1); skin, gut grade II (n=1)) and 1 related (skin involvement grade II) CBT recipients. After immunosuppressive therapy the GvHD lesions were completely resolved in all but one thalassemia boy who suffered from severe fatal grade IV GvHD and eventually died. Median follow-up time for surviving patients was 30 months (range 4–53). Overall and disease-free survival in unrelated donor CBT (n=4) recipients were 50% (n=2) and 50% (n=2), compared to in related donor (n=7) 85.71% (n=6) and 71.43% (n=5), respectively. To date the boy with WAS has been cured by unrelated CBT for more than 4 years. Umbilical cord blood provides a reasonable option for source of hematopoietic stem cells to do transplantation for treatment non-malignant hematologic diseases and the outcome in our study is relatively well and comparable to other studies.

Background: Allogeneic hematopoietic stem cell transplantation (SCT) has been established as a curative therapy for β-thalassemia major which is prevalent among Thais. Donors are usually patients' siblings but the chance to find an optimal HLA-identical is just about 30%. Thus clinical trial using alternative donors such as partially-mismatched related donors or matched unrelated donors could be a good choice.

The authors evaluated the outcome of ten children given hematopoietic stem cell transplantations from Thai unrelated donors (URD-HSCT) selected using DNA high-resolution typing of both HLA class I and II loci. Six patient/donor pairs (60%) were fully matched; four (40%) were 5/6 matched. Patients had either non-malignant (n=9) or malignant (n=1) diseases. In most cases, graft-versus-host disease (GVHD) prophylaxis composed of cyclosporine and short-term methotrexate. The probability of hematopoietic recovery at day 30 was 90%. The cumulative probability of acute GVHD and of chronic GVHD equaled 44.4 and 0%, respectively. Three patients died of transplant-related complications. The probability of transplant-related mortality (TRM) at 30, 100, and 180 days were 10, 30, and 30%, respectively. The overall and disease-free survival rates were 70 and 70%, respectively. URD-HSCT with donor selection based on high-resolution HLA typing is associated with a low incidence of both severe acute GVHD and graft failure. The observed outcome is comparable to that of children transplanted from HLA-identical siblings.

Allogeneic bone marrow transplantations (BMT) from HLA-matched siblings have been successfully used for treatment of patients with high-risk hematological malignancies, genetic immunodeficiencies, metabolic disorders, or marrow failure syndromes. Unfortunately, most of patients lack matched related donors. Over the past decade clinicians have explored the suitability of umbilical cord blood (CB) as an alternative source for hematopoietic stem cell transplantation. Since the first related cord blood transplantation (CBT) was performed successfully for a child with Fanconi Anemia in 1988, there have been many children undergoing CBT from related donors. The further experience suggests that CB donation is a safe procedure for both mother and newborn. Subsequently, several quality CB banks were established worldwide with requirement of specific issues including donor recruitment, CB collection and processing, histocompatibility testing, infectious and genetic disease testing, transportation of CB, and protection of confidentiality of donors and recipients. The clinical data showed that unrelated donor CBT had comparable survival results to unrelated donor BMT CB offers many potential advantages such as it is readily available, its collection causes no harm to the donor and minimal HLA-disparity is acceptable. However there are some disadvantages due to the volume and cell dose of each collected CB is limited, thus methods to enhance the number or quality of stem cells in CB are needed. At present the world's experiences suggest that CB is an acceptable alternative to bone marrow.

To evaluate factors affecting the outcome of sibling and unrelated donor umbilical cord blood transplantation (CBT) in Thai children with beta-thalassemia diseases. The case-series study of all children undergoing such transplants in our institute was conducted Six children with thalassemia major were diagnosed at a median age of 1.5 years and CBT was performed at a median age of 5.5 years (range 2-15). Six donors consisted of three HLA-identical siblings, one two-allele, one three-antigen mismatched sibling, and one one-allele mismatched unrelated cord blood. The median number of nucleated cells infused was 2.83 x 10(7)/kg (range 1.49-5.3); the median number of CD34+ cells infused was 1.94 x 10(5)/kg (range 0.2-5.3). In all, two patients had complete donor engraftment; three had mixed chimerism (MC); one patient died of cerebral thrombosis and neutropenic septicemia. Of the two complete donor-engrafted patients, two developed grade 2 acute graft-versus-host disease (GVHD) which responded well to immunosuppressive therapy. Of the three mixed-chimeric patients, two were clinically cured. With a median follow-up of 7 months (range 2-30), five children survived and have done well with transfusion-independent. Umbilical cord blood provides a reasonable option for hematopoietic stem cell source to transplant for beta-thalassemia diseases and the outcome in the present study was good.

Umbilical cord blood is an effective alternative source of hematopoietic stem cells transplantation in children and adolescents. However, the efficacy and safety of cord blood transplantation correlates with the quantity and quality of cord blood. To evaluate the collection systems and processing of cord blood donations, a pilot research program to optimize recruitment, collection and processing of cord blood donations was developed. The present results showed that the quality of the cord blood (volume, total white blood cells (WBC) count, CD34+ and sterility control) collected was satisfactory and discard rate of collecting units (24.2%) were comparable with data reported from other cord blood banks. To find the optimal mode of collection, comparison of 3 cord blood collection methods (Method 1 = Hanging method after delivering the placenta, Method 2 = Aspiration from in utero placenta, Method 3 = Aspiration from in utero placenta and Syringe-assisted aspiration) using the closed system showed that method 3 was the best method but it required more trained personnel and involved a complicated procedure. The National Cord Blood Bank started its activity in 2002 after several years of pre-clinical studies. To date, a number of transplants using cord blood from related and unrelated cord blood (first report in Thailand) donors have been successfully performed.

Meropenem is a promising carbapenem antibiotic as an empirical monotherapy in patients with febrile neutropenia (FN). With the limited data of the therapy in pediatric patients, the authors conducted this study to evaluate the efficacy and safety of meropenem as empirical antibiotic therapy in 30 pediatric cancer patients with FN (mean age = 7.5 years), who were admitted to King Chulalongkorn Memorial Hospital from May 2000 to December 2001. Meropenem 60 mg/kg/day was given intravenously every 8 hours. The efficacy of meropenem was assessed as successful, inconclusive and failure on days 3 and 5 of the therapy and compared to that of other empirical antibiotics used from January 1997 to April 2000. The study showed that six blood culture specimens (20%) grew organisms, half of which were considered to be contaminants, and six urine culture specimens (20%) grew gram negative rod bacteria. On day 3 and 5 of the therapy, the success rate of meropenem was higher than that of comparatives (30.0% vs 17.6% on day 3, 50.0% vs 39.3% on day 5). The use of meropenem appeared safe, with minimal side effects. In conclusion, the present study showed that meropenem was safe and tolerable in children. The efficacy as an empirical monotherapy in pediatric cancer patients with FN was satisfactory, with a failure rate of 23.3 per cent on day 5 of treatment.