Sjögren-like syndrome after bone marrow transplantation.

OBJECTIVE: To study the incidence of dry eye in Sjögren-like syndrome, graft-versus-host disease (GVHD) in hematological patients undergoing bone marrow transplantation (BMT). MATERIAL AND METHOD: Prospective, cross-sectional study in twenty-six patients that were planned for BMT (group I). Twenty-nine patients undergoing BMT before study were classified as group II no GVHD (9), and group III with GVHD (20). Thirty-two normal subjects were controls. All subjects were examined by slit lamp biomicroscopy and had their tear samples analyzed about tear osmolarity. They were also evaluated for aqueous tear production by phenol red thread test, Schirmer test without anesthesia, tear film stability by tear break-up time (TBUT), and rose bengal staining 2 weeks before BMT (for group I) as well as 6 weeks, 3 months, and 6 months after BMT. The patients with GVHD were followed up 1 month later. Main outcome measures were amount of tear production, tear film stability, and dry eye symptoms. RESULTS: Average aqueous tear production in group III was less than control and group II (p < 0.001). Mean TBUT in group III was faster than control (p < 0.001) and group I before BMT (p = 0.001). Mean score of rose bengal staining in group III was more than control and group I before BMT (p < 0.001). Keratoconjunctivitis sicca and red eye developed in 27.5%, and 20% of group III, with incidence of dry eye by Schirmer test without anesthesia (67.5%). This compares with group II having incidence of dry eye of 16.7%. However, 42.3% of group I before BMT had dry eye compared with 9.4% in the controls (p < 0.001). CONCLUSION: Trend of dry eye in patients with BMT and GVHD were higher than no-GVHD group. Doctors should be aware of ocular symptoms and signs of dry eye in patients with BMT and follow-up for proper management.

Monosomy 7 in patients with aplastic anemia and paroxysmal nocturnal hemoglobinuria with evolution into acute myeloid leukemia.

We report two cases of Thai patients with aplastic anemia/paroxysmal nocturnal hemoglobinuria (AA/PNH) who subsequently developed acute myeloid leukemia (AML) at their terminal phase. Monosomy 7 was demonstrated upon karyotypic analysis of bone marrow in both cases at the time leukemia developed The first patient was a 25-year-old man diagnosed with AA at age 14, recovered from AA at age 15, developed PNH at age 21 and turned into AML at age 25. The second patient was a 27-year-old man diagnosed with PNH at age 22, developed severe AA at age 25 and turned into AML at age 27. This latter patient received anti-lymphocyte globulin when he developed severe AA but did not respond well whereas the first patient fully recovered from AA with anabolic hormone treatment. Time to diagnosis of AML in the patient who received immunosuppressive therapy was strikingly shorter than that who received conventional androgen therapy (2 years vs 11 years after AA, respectively). The presence of monosomy 7 in leukemic cells of both patients emphasizes its central role in the development of AML from AA/PNH. However, other factors such as choice of AA/PNH therapy and patients response may modulate the time to emergence of monosomy 7-carrying AML clone and frank leukemia. Further studies into the biologic and genetic mechanisms involved in the development of leukemic clone arising from AA/PNH should be explored.

Collection and processing of umbilical cord blood for cryopreservation.

Umbilical cord blood (UCB) is being increasingly used as an alternative source of hematopoietic stem cells for allogeneic bone marrow transplantation. UCB transplantation has been successfully used to treat a variety of genetic, hematological, and oncological disorders in children and adults. The objectives of this study was to establish a closed-system technique for UCB collection and buffy coat separation by Optipress I device. Thirty-four UCB were collected by triple-bag system from pregnant mothers whose fetuses were not affected by thalassemic diseases after prenatal diagnosis. The mean volumn of UCB collection were 120 +/- 5 ml (range 65-180 ml). Total WBC, CD34+ cells, the progenitor cell erythroid burst-forming unit (BFU-E) and granulocyte-macrophage colony-forming unit (CFU-GM) in the UCB units were (9.36 +/- 0.84) x 10(8), (3.61 +/- 0.52) x 10(6), (9.12 +/- 1.60) x 10(5), and (5.32 +/- 1.23) x 10(5), respectively. Good correlation between the nucleated cell and net cord blood volume could be demonstrated (p < 0.0001). The correlation between CD34+ cells and the following parameters: nucleated cell, BFU-E or CFU-GM were also demonstrated (p = 0.001, 0.0105 or 0.0001, respectively). Buffy coat was subsequently separated from 18 UCB units by Optipress I device. 70 +/- 3 ml of buffy coat were collected and cryoprocessing was done by automatic controlled-rate freezer. Good recovery of total WBC, CD34+ cells, progenitor cells BFU-E and CFU-GM after buffy coat separation were observed 89 per cent, 95 per cent, 109 per cent, and 102 per cent respectively. There was no aerobic bacterial or fungal contamination in the separated blood products. By using this technique, the UCB units were easily collected, rapidly separated within one hour, and high recovery of the hematopoietic progenitor cells could be obtained.

Immunophenotypic profile of adult acute myeloid leukemia (AML): analysis of 267 cases in Thailand.

Little data exists in Thailand and other Southeast Asian countries regarding the biological characteristics of adult acute myeloid leukemia (AML). In this study, we performed a flow cytometric analysis of 267 Thai adult AML cases to delineate the pattern of leukemic cell surface antigens. Forty-eight cases (18%) were identified as acute promyelocytic leukemia (M3) and 219 cases as non-M3. The most frequent subtype of AML in Thailand was M1/M2 and the least frequent was M7. M3 immunophenotypes were characterized by their unique lack of expression of CD34 and HLA-DR as contrast to the high mean expression of 50% and 70%, respectively, in non-M3. Overall, 60% of cases expressed CD34. Aberrant lymphoid antigens were uniquely seen in specific subtypes of Thai AML, including CD19 (33% of non-M3 vs 23% of M3) and CD2 (12% of M3 vs 2% of non-M3). CD56 was frequently expressed in both M3 and non-M3 while CD16 appeared to be associated with M4/M5 (24% of cases) and CD7 with M1/M2 (21% of cases). Eighty-one percent of non-M3 expressed CD38 while only 53% of M3 did. We found that most Thai adult AML patients were on average 15-20 years younger than those of the West or Japan with only 25% of Thai cases over 60 years of age, although the immunophenotypes were not markedly different. Biological studies of acute leukemia in various countries should help to provide epidemiological clues that play a role in the pathogenesis of leukemia in different geographic regions of the world. Our study represents the largest series of AML ever investigated in the Southeast Asian region.

Preliminary clinical evaluation of a protein chip for tumor marker serodiagnosis of various cancers.

This preliminary study aimed to investigate sensitivity and specificity of a protein chip system for multi-tumor marker serodiagnosis of ten types of cancers, and to understand the possible clinical applications of this protein chip for the Thai population. The specific cancers diagnosed by this protein chip are lung, breast, liver, cervix, colo-rectal, stomach, ovary, esophagus, prostate and pancreas cancers. We analyzed 215 serum samples of which 165 were obtained from clinically confirmed cancer patients and 50 from healthy people with no evidence of cancer. The sensitivity and specificity of the protein chip were 82.4% and 94.0%, respectively. The success rate of the protein chip for detecting all 10 types of cancers varied from 57% to 100%. The value of the simultaneous measurement of multiple tumor markers using the protein chip for cancer screening lied in the higher sensitivity compared to using single tumor markers for each type of cancer. In short, protein chips may be useful in mass screening for cancer during health checkups as well as for metastasis follow-up of cancer patients.

Reversal of marrow fibrosis in agnogenic myeloid metaplasia by allogeneic peripheral blood stem cell transplantation.

Agnogenic myeloid metaplasia (AMM) is a clonal hematopoietic stem cell disorder characterized by bone marrow fibrosis, extramedullary hemopoiesis, splenomegaly and a leukoerythroblastic blood picture. Current standard therapies using hydroxyurea, interferon, androgens or corticosteroids have not shown to prolong survival of patients with AMM. In this study, we performed a curative approach using an HLA-matched sibling as a donor for allogeneic peripheral blood stem cell transplantation (PBSCT) for a 45-year-old woman with AMM. Busulfan and cyclophosphamide were given as a conditioning regimen from day -7 to day -2 with cyclosporinA and methotrexate as post-transplant immunosuppressive therapy. Donor PBSCs were mobilized by G-CSF at 16 microg/kg/day for five days and transplantation was performed on March 2-3, 2000. The patient rapidly engrafted within 2 weeks after PBSC infusion without evidence of graft versus host disease. Her blood counts and bone marrow 2 years after transplantation were normal with full donor pattern by molecular analysis. In conclusion, marrow fibrosis can be reverted to normal by allogeneic PBSCT. Allogeneic PBSCT should thus be offered to AMM patients if an HLA-matched sibling is available. This report represents the first SCT for AMM in Thailand.

Nutritional support for children underwent bone marrow transplantation.

Nutritional support for children underwent bone marrow transplantation was studied by comparing parenteral nutritional support and oral intakes. During 1988-1991 a total of 15 recipients, 10 boys and 5 girls, ages ranging 1-12 years from the Department of Pediatrics, Faculty of Medicine, Siriraj Hospital were studied. The patients were classified according to underlying diseases into 3 groups; Group I (thalassemia), Group II (aplastic anemia) and Group III (malignancy). The results indicate that Group I required less parenteral support than the other groups. Group III required the most parenteral support. Complications from bone marrow transplantation support among the 3 groups were similar. Therefore the requirement for nutritional support depend on the type of hematologic disease from which the patient is suffering.