The First Asian, Single-Center Experience of Blastocyst Preimplantation Genetic Diagnosis with HLA Matching in Thailand for the Prevention of Thalassemia and Subsequent Curative Hematopoietic Stem Cell Transplantation of Twelve Affected Siblings.

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.

Outcome of pediatric hematopoietic stem cell transplantations from Thai unrelated donors matched with high-resolution HLA typing.

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.

Clinical use of cord blood for stem cell transplantation.

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.

Umbilical cord blood transplantation in children with beta-thalassemia diseases.

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.

Efficacy and safety of meropenem as an empirical treatment for febrile neutropenia in children with cancer.

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.

Cord blood collection for the National Cord Blood Bank in Thailand.

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.