Myelodysplastic syndromes in Thailand: a retrospective pathologic and clinical analysis of 117 cases.

To gain more insight into the understanding of myelodysplastic syndromes (MDS) as they occur in Thailand, a retrospective clinicopathologic analysis was conducted in patients (age > 15 years) diagnosed as MDS from January 1992 to December 1996 at the five major medical centers in various geographic regions of the country. The central reviewers independently examined the bone marrow and peripheral blood smears of all the patients and classify the disease according to the French-British-American (FAB) classification. There were a total of 117 eligible patients. The median age of the patients was 56 years (range 16-86). The male:female ratio was 1:1. Thirty-two percent of the patients were younger than 40 years. The frequency of the FAB subtypes was RA/RARS, 54.7; RAEB, 23.1; CMML, 9.4; and RAEB-T, 12.8%. Anemia was the most common symptom presenting in 84.6% of the patients. In the 34 patients in whom the cytogenetics in the bone marrow were analysed, 44.1% revealed abnormalities. Of these, monosomy 7 and trisomy 8 were the most common aberration, each being detected in 26.7% of the patients. Transfusions were the main therapeutic modality in 80% of the patients. Kaplan-Meier analysis revealed a 5 year survival rate of 29% for the whole group with a median survival of 24 months. Twenty-five percent of the patients had progressed to acute myelogenous leukemia (AML) with a median time to disease-progression of 23 months. The median survival for RA/RARS, RAEB, CMML and RAEB-T were 58.4, 19.9, 10.7 and 8.7 months, respectively (P < 0.001). The stepwise Cox regression analysis revealed the percentage of blasts in the bone marrow as the only parameter significantly associated with survival and disease progression. On comparison with data from other countries, the age of Thai patients with MDS is considerably lower than the western population but is comparable to other asian countries. The distribution of the FAB subtypes and the survival of the patients are similar. The major prognostic features, however, lie in the percentage of blasts in the bone marrow rather than the degree of the observed cytopenia.

Allogeneic stem cell transplantation in a patient with refractory Burkitt's lymphoma using non-myeloablative conditioning regimen.

We have performed an allogeneic stem cell transplant in an 18-year-old male patient who had Burkitt's lymphoma. The patient had disease which was refractory to conventional intensive chemotherapy and radiation therapy. High-dose chemotherapy with autologous stem cell rescue was given but the patient relapsed within 2 months after transplantation. He was then treated with allogeneic stem cell transplantation using a fludarabine, busulfan and anti-thymocyte globulin-based conditioning regimen. His GVHD prophylaxis included mycophenolate and tacrolimus. The patient had engraftment within 14 days. Investigation by FISH showed more than 95% of his peripheral blood nucleated cells to be of donor origin since day +14. He is now alive and well and remains disease-free 6-months after the transplant. A graft-versus-lymphoma effect is thought to be one of the factors contributing to his remission.

Successful treatment of refractory autoimmune haemolytic anaemia in a post-unrelated bone marrow transplant paediatric patient with rituximab.

Here, we report a case of paediatric beta-thalassaemia major patient who underwent unrelated T cell-non- depleted bone marrow transplantation and developed a complication of autoimmune haemolytic anaemia (AIHA) refractory to corticosteroid and intravenous immunoglobulin therapy. After this child received two doses (375 mg/m2/dose) of rituximab (anti-CD20 monoclonal antibody), his AIHA was resolved.

Full chimerism in nonmyeloablative stem cell transplantation in a beta-thalassemia major patient (class 3 Lucarelli).

Bone marrow transplantation is the only therapeutic option that can eliminate thalassemic disease. Early results indicated that children in class 3 Lucarelli had a much worse outcome because of high nonrejection mortality and high rejection rate. We therefore tried to investigate a nonmyeloablative stem cell transplantation (NST) approach for such a disease in order to reduce mortality and rejection. We report here the case of successful NST in a 10-year-old girl who had class 3 Lucarelli beta-thalassemia major. The conditioning regimen consisted of busulfan, fludarabine, antilymphocyte globulin and total lymphoid irradiation. Her GVHD prophylaxis included mycophenolate mofetil and cyclosporin. The patient had full donor engraftment without acute and chronic GVHD. She is now alive and well and remains disease-free 1 year after transplant.

Outcome of transplantation with unrelated donor bone marrow in children with severe thalassaemia.

SUMMARY: We conducted a study of unrelated donor bone marrow transplantation (BMT) in 11 children with severe thalassaemia. The conditioning regimen consisted of busulphan, cyclophosphamide and antilymphocyte globulin. All received T-cell nondepleted bone marrow. The median marrow-nucleated cell dose was 4.9 x 10(8) /kg (range; 3.5-8.0 x 10(8) /kg). Median time of granulocyte recovery was 16 days (range; 13-21 days), and of platelet recovery was 39 days (range; 14-196). Grade 2-4 acute graft-versus-host disease (GVHD) developed in six patients (54%), and grade 3-4 in one patient (9%). Three (27%) of 11 evaluable patients had chronic GVHD (limited stage). All 11 patients are alive without thalassaemia after a median follow-up time of 397 days (range; 171-814 days). This study lends support to consideration of unrelated donor BMT as an acceptable therapy to cure severe thalassaemia especially in patients who are young and do not yet show irreversible severe complications of iron overload.

HIV infection after autologous bone marrow transplantation despite HIV-antibody and HIV-antigen screening.

We report a 41-year-old woman who underwent ABMT for non-Hodgkin's lymphoma during her third CR. Her post-transplant course was complicated by interstitial pneumonitis, hemorrhagic cystitis, cytopenia and episodes of infection from herpes zoster virus and Staphylococcus aureus. She required prolonged blood product support and was later found to be seropositive for anti-HIV on day +191 despite HIV-antibody and HIV-antigen screening of blood donors.

Quality of life in Thai patients after bone marrow and peripheral blood stem cell transplantation: a comparison study with patients treated with conventional chemotherapy.

This study of adult patients of Thai cultural background compared the quality of life (QOL) of patients undergoing bone marrow and peripheral blood stem cell transplantation (BMT/PBSCT) with that of patients treated with conventional chemotherapy (CT). The study population comprised 59 patients who were transplant recipients (29 allogeneic, 29 autograft, and one syngeneic BMT/PBSCT) and 24 patients treated with CT for various hematologic malignancies. The participants completed a 50-item structured QOL questionnaire sent by mail. No significant differences were found between the two patient groups regarding their psychological, social, and treatment-related well-being or their overall QOL; all scores were above 75% of the total. The mean score regarding the physical domain, however, was significantly lower in BMT/PBSCT patients. Areas of highest concern in both groups were sexuality and financial burden. Happiness, functional ability, financial burden, and the degree of familial acceptance were the most important predictors of the self-rated QOL in BMT/PBSCT patients. Seventy-five percent of BMT/PBSCT patients would be willing to undergo the procedure again under the same circumstances. These results indicated that the QOL of Thai patients undergoing BMT/PBSCT was in general satisfactory and comparable to patients treated with conventional CT.

Acute nonlymphocytic leukemia with a translocation (1;3)(p36;q21) in an XYY man.

Neoplastic disease is quite rare in an XYY syndrome. We report the fifth known case, who suffered from acute nonlymphocytic leukemia (ANLL). Cytogenetic study of his bone marrow revealed a new chromosomal translocation (1;3)(q36;q21), which has only recently been described in patients with myelodysplastic syndrome.

A prospective randomized study of Chop versus Chop plus alpha-2B interferon in patients with intermediate and high grade non-Hodgkin's lymphoma: the International Oncology Study Group NHL1 Study .

UNLABELLED: The addition of a brief alpha interferon regimen to each CHOP induction cycle, plus one year of alpha interferon thrice weekly maintenance therapy, has no early effect on response rates or survival in patients with Intermediate or High grade cell NHL. BACKGROUND: The CHOP (Cyclophosphamide, Adriamycin. Vincristine, Prednisone) regimen is the most widely used first-line therapy for patients with Intermediate or High Grade (IG/HG) non-Hodgkin's lymphoma (NHL). Alpha 2b interferon (INF) enhances response rates and improves survival in low-grade NHL. The International Oncology Study Group (IOSG) conducted a prospective randomized study comparing CHOP alone or combined with INF in patients with IG/HG-NHL. The primary study aim was to compare the objective response rates in these patient cohorts. PATIENTS AND METHODS: Patients with a confirmed diagnosis of measurable NHL of International Working Formulation (IWF) groups D to H histology were randomized to receive CHOP alone or CHOP with 5Mu INF s.c. for 5 days on days 22 to 26 of each 28 day cycle with INF 5 million units (Mu) given three times per week subcutaneously for 52 weeks in those patients who responded to CHOP plus INF. RESULTS: The overall response rates were equivalent in both groups: CHOP alone (214 patients) 81% (complete 55%, partial 26%); CHOP plus INF (221 patients) 80% (complete 54%, partial 26%). At 36 months, the actuarial survival rate was equivalent in both groups. CONCLUSIONS: There is no apparent early advantage in terms of response or survival conferred by adding the study INF regimen to CHOP therapy for patients with IG/HG-NHL.

Pure red cell aplasia in Thailand: report of twenty four cases.

Twenty four cases of pure red cell aplasia were reported. No underlying diseases were found in two cases. Of the 22 cases with secondary form, 10 were from infections, mostly gram negative organisms. Three cases had systemic lupus erythematosus, two had autoimmune hemolytic anemia. The following conditions were found in one each: thymoma, thyroid carcinoma, protein calorie malnutrition, rheumatoid arthritis, non-Hodgkin lymphoma and Sheehan's syndrome. Three patients died, two from uncontrolled infection, the other from uncontrolled SLE and subsequently systemic fungal infection. Only one of the 2 primary cases responded to immunosuppressive drugs. The majority of patients with underlying infections, PRCA resolved after the infections were treated. This is the first reported series of PRCA in Thailand.

Detection of BCR/ABL fusion gene in CML: a preliminary report.

The BCR/ABL fusion gene in 31 patients with chronic myeloid leukemia (CML) was detected by RT/PCR. In 18 cases of Ph' positive patients, 13 had BCR 3/ABL II rearrangement, 1 had BCR 2/ABL II rearrangement and 4 had both rearrangements. One case with complex translocation: 46,XY,t(9;9;22), had BCR 3/ABL II rearrangement. In 8 cases of Ph' negative patients, 4 had BCR 3/ABL II rearrangement, 3 had both rearrangements while 1 had no BCR/ABL rearrangement. Interestingly, in 4 patients who had no cytogenetic result, we could observe BCR 3/ABL II rearrangement in 3 cases and both rearrangements in 1 case. The results suggest that this procedure is sensitive and independent of the presence or absence of an identifiable Ph' chromosome.

Serum erythropoietin levels in thalassemia major and intermedia.

Serum erythropoietin (EPO) levels were determined by enzyme linked immunosorbent assay (ELISA) in 61 thalassemic patients, consisting of 23 thalassemia major (TM) patients with multiple transfusion, 38 patients with thalassemia intermedia (TI). Thirty-two normal controls were also studied. The mean serum EPO levels were significantly higher in both groups with TM (165.96 +/- 17.31 mlU/ml) and TI (126.43 +/- 50.56 mlU/ml) compared with the control group (8.33 +/- 3.91 mlU/ml). The mean value of hematocrit (Hct) in the patients with TM (18.70 +/- 3.51%) was lower than those with TI (25.24 +/- 4.19 %) whereas the mean serum EPO level were significantly higher in TM than TI patients. An inverse correlation between the serum values of EPO and Hct was observed in both TI and TM patients, however this correlation was significant only in TI (r = -0.61, p<0.001). These data showed that serum EPO levels increased in all thalassemia patients despite repeated transfusion. Multiple transfusion may modulate the response of serum EPO to the degree of anemia, resulting in increased EPO levels and independent anemia in the TM patients.

Acute massive intravascular hemolysis and disseminated intravascular coagulation.

Two cases of acute intravascular hemolysis complicating acute disseminated intravascular coagulation were presented, one after normal delivery and the other after group A beta hemolytic streptococcal septicemia complicating acute myelomonoblastic leukemia. Neither case received heparin therapy. The first one survived while the latter succumbed. Intravascular hemolysis may not be a bad prognostic sign in such a condition.

The value of HLA-ABC common typing tray in relation to bone marrow transplantation.

Bone marrow transplantation (BMT) is one of the most effective procedures to cure the previously uncured hematologic diseases. However, it is costly and HLA typing to select the compatible donors contributed to its cost. A total of 53 prospective patients for BMT and their 114 siblings were analyzed to evaluate the use of locally prepared HLA-ABC common typing tray (ABCCT) during Mar 1988-Mar 1992. The 16, 9, 7, 5, 5 and 12 patients were diagnosed as aplastic anemia, CML, thalassemia, ALL, ANLL and other blood diseases, respectively. It was found that 18 patients were HLA-identical (HLA-ID) with one of their siblings except one patient had 2 HLA-ID sibs. All of those who appeared to be HLA-ID were further tested for the HLA-ABCDR typings. It was observed that 16 (88.89%) of 18 patients and 17 (89.47%) of 19 sibs were confirmed as HLA-ID. After careful clinical screening, only 13 HLA-ID pairs were able to proceed to the mixed lymphocyte culture and confirmed their status of HLA-ID by this test. Finally, only 6 (46.15%) of 13 patients received BMT with a high rate of success, ie all patients have survived with bone marrow engraftment. Thus, ABCCT is very useful for related BMT. It was highly efficient to exclude HLA-non-ID and haplo-ID yet the cost and workload were greatly reduced.

Experience with factor VIII: C inhibitors and acquired von Willebrand's disease in an adult at Ramathibodi Hospital.

Eleven cases of acquired inhibitors against factor VIII: C and von Willebrand's factor (vWF) seen at the Department of Medicine, Ramathibodi Hospital from 1979 to 1991 were reviewed. Factor VIII: C inhibitor was found in 6 of 36 patients (17%) with hemophilia A (median age 18 years). Three patients each were weak (titer < 10 Bethesda units/ml), and strong antibody producers. Two cases of weak antibody producers had spontaneous disappearance of inhibitor, while all 3 strong antibody producers required specific treatment (corticosteroids, immunosuppressive drugs, and plasmapheresis). The inhibitor level temporarily declined in 2 patients, and disappeared in one. Spontaneous acquired inhibitor to factor VIII: C was seen in 3 patients. One each respectively had pemphigus vulgaris and bullous pemphigoid, autoimmune disease, and NIDDM. They were characterized by older age (median age 54 years), frequent skin and soft-tissue hematoma, but less hemarthroses. Inhibitor titer ranged from 15-280 Bethesda units/ml. Disappearance of the inhibitor after treatment with corticosteroids and immunosuppressive drugs were observed in all patients. Acquired von Willebrand's disease developed in 2 previously healthy patients. One patient was in the postpartum period, while the other had simultaneous acute viral hepatitis A infection. Both presented with the recent onset of spontaneous severe gingival bleeding, and demonstrated a prolonged bleeding time, reduced vWF:Ag (F VIIIR:Ag), and ristocetin cofactor (F VIIIR:vWF). Treatment with cryoprecipitate and corticosteroid resulted in remission of bleeding symptoms. Despite the rarity of these disorders, the recognition and proper management are of importance.

Study of hematopoietic progenitor cells, hematological values and lymphocyte subsets in cord blood: application for cord blood transplantation.

Hematological values, lymphocyte subsets and hematopoietic progenitor cells from normal term cord blood samples were studied, compared with normal adult blood, and analysed to determine whether a single collection of cord blood is sufficient for transplantation in adults. The parameters were assayed by automatic cells counter, flow cytometry and semisolid cell culture. All of the hematological values except RBC and MCHC were higher than in normal adult blood. Sex had an influence on RBC, Hb, Hct, Plt and reticulocyte counts. For lymphocyte subsets, all of the absolute CD3+, CD4+, CD8+ counts and T helper: suppressor ratio were higher than those of adult blood. All of the hematopoietic progenitor cells in cord blood were also higher than in adult blood. The mean volume of cord blood for each collection was 80.75 +/- 4.81 ml and the mean numbers of nucleated cells, CFU-GM and CD34+ were 13.51 +/- 0.38 x 10(8) cells, 4.33 +/- 0.66 x 10(5) colonies and 42.65 +/- 7.00 x 10(5) cells respectively. This 80 ml of cord blood would contain sufficient marrow repopulating cells for a recipient weighing about 20 kg. Recently developed technology, including ex vivo expansion may even permit transplants in adults.

Alpha chain disease in the Thai man.

A 61-year-old Thai man presented with a history of chronic diarrhoea of 1-2 years duration. Stool examination revealed a heavy parasitic infection. Several anthelminthics were given without benefit, despite disappearance of the intestinal parasites. Serum protein studies revealed abnormal alpha heavy chain. Two courses of cyclophosphamide, vincristine and prednisolone were followed by a brief remission in his symptoms. A 21 day course of tetracycline was then given, resulting in an improvement in his condition. He is still symptom free nine months after confirmation of the diagnosis, without any further treatment. Serum protein studies should be included in laboratory investigations of a patient with chronic diarrhoea.

Interferon alpha-2a to control thrombocytosis in chronic myelogenous leukemia and essential thrombocythemia.

Four patients with chronic myelogenous leukemia and thrombocytosis and one patient with essential thrombocythemia were treated with purified recombinant human interferon alpha-2a (IFN-alpha 2a). Significant decline in platelet counts, from a mean ( +/- SE) of 1.396 +/- 0.265 x 10(6)/mm3 to a mean of 0.396 +/- 0.04 x 10(6)/mm3 (p less than 0.05), was observed in all patients. The platelet count remained normal for 15, 21 and 30 days after discontinuation of IFN-alpha 2a in 3 patients. In 2 patients the platelet count began to rise slowly two weeks after discontinuation of IFN-alpha 2a. Our preliminary observations suggest that purified recombinant human IFN-alpha 2a may effectively control progressive thrombocytosis in advanced chronic myelogenous leukemia and essential thrombocythemia.

Effect of G-CSF on peripheral blood progenitor cell mobilization and collection from healthy donors.

We studied granulocyte colony-stimulating factor (G-CSF) mediated peripheral blood progenitor cells (PBPC), which were mobilized and collected from healthy donors for allogeneic transplantation. A total of 26 donors, age ranged from 21-41 years were mobilized with G-CSF at a dose of 7.5 microg/kg/day subcutaneously for 5 days and the collection was started on day 5. The CD34 cell counts reached a maximum on day 5 and subsequently declined despite continually given G-CSF. White blood cells (WBC), absolute neutrophil counts (ANC), absolute lymphocytes (AL) and their subsets, absolute mononuclear cells (AMNC), colony-forming unit-granulocyte, macrophage (CFU-GM) and CD34+ cells were increased about 6, 9, 2, 3, 34 and 40-fold, respectively, but red blood cells (RBC), hematocrit (Hct) and platelets (Pit) decreased on day 5 when compared to day 0. All parameters decreased after stem cell collection. For stem cell collection by Cobe Spectra, we used a blood volume of 19.27 +/- 4.65 liters, flow rate of 60.53 +/- 10.03 ml/minute, acid citrate dextrose solution (ACD)/blood ratio of 1:13.31, the final product volume was 314.14 +/- 72.24 ml, collection time was 325.40 +/- 73.36 minutes and one or two procedures were sufficient. The correlation between the number of CD34+ cells/kg, CFU-GM/kg and MNC/kg found in the harvested product and CD34 cells can be used for determining the necessary amount of progenitor cells for transplantation.

Angioimmunoblastic lymphadenopathy with dysproteinemia in Thailand.

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a disease of unknown etiology and pathogenesis. It has the features of hyperimmunity and immune deficiency, and its behavior resembles malignant lymphoma. We report a review of 16 patients with AILD seen at Ramathibodi Hospital from 1982 to 1986. Thirteen patients had fever and seven had pruritus and rashes. Lymphadenopathy was found in all 16 cases; generalized in 14 and localized in 2. Hepatomegaly was present in 14 patients while only 7 had splenomegaly. Laboratory findings included autoimmune hemolytic anemia, lymphocytosis and polyclonal hypergammaglobulinemia. Pulmonary involvement was seen in 5 cases, and bone marrow showed the characteristic features of the disease in 9 cases. Two patients went on to develop diffuse lymphocytic, poorly differentiated lymphoma. Fourteen patients were treated with prednisolone initially. Five responded with complete recovery, eight responded with partial recovery, and one died with extensive involvement of the disease. Six of the patients that recovered partially were later treated with cyclophosphamide, vincristine and prednisolone. One patient recovered completely and two partially. Three died from extensive involvement. Two patients with malignant lymphoma were treated by combination chemotherapy. One case went to complete remission while the other died from infection. One patient was lost to follow up before any treatment was started.