Analysis of T Lymphocyte Subsets Following Antilymphocyte Globulin and Cyclosporine A Therapy in Patients with Aplastic Anemia / 대한혈액학회지

BACKGROUND: Immunosuppression of hematopoiesis has been regarded as one of the most important pathogenetic mechanisms of idiopathic aplastic anemia. This investigation intended to examine the immunological pathogenesis of aplastic anemia and discover the therapeutic mechanism and predictor factors for the combined therapy of antilymphocyte globulin (ALG) and cyclosporine A through observing the changes of T lymphocyte subsets in the peripheral blood before and after the combining therapy of ALG and cyclosporine A. METHODS: Comparisons and analyses were made after measuring CD4+ T-lymphocytes and CD8+ T-lymphocytes by the flow-cyto metry after gathering the peripheral blood from 17 aplastic anemia patients, who were treated with a combining therapy of ALG and cyclo sporine A at the Hematopoietic Stem Cell Transplatation Center of St. Mary's hospital, Catholic University, from August 2000 through November 2000. These were conducted prior to treatment, immediately after the therapy and 3 months later. Fifteen healthy bone marrow do nors were selected as a normal control group. RESULTS: With respect to comparing T lymphocyte subsets between the aplastic anemia patient group and the normal control group in the peripheral blood, the CD4+ T lymphocytes ratio and the absolute numbers decreased significantly for the aplastic anemia patient group, as opposed to that of the normal control group (P=0.0001, P=0.0003). The CD8+ T lymphocytes ratio and the absolute numbers increased significantly for the response group (complete response group and partial response group) than that of the control group (P=0.0003, P=0.0295). Regarding the ratio of CD4+ T lymphocytes to CD8+ T lymphocytes, the aplastic anemia patients group showed a significant decrease comparing to that of the control group with 0.79+/-0.32 and 1.41+/-0.24 respectively (P=0.0001). The therapyresponding rate for ALG and cyclosporine A was 70.59% (complete response rate, 23.53%; partial response rate, 47.06%). There were no critical complications to be considered as limiting factors for the therapy. The CD8+ T lymphocytes ratio and absolute numbers already increased before the therapy for the better response group (P=0.0001, r=0.791; P=0.008, r=0.616). The ratio between CD4+ T lymphocytes and CD8+ T lymphocytes was decreased comparing the other two groups as 0.57+/-0.18 in the complete response group before the treatment was implemented. However, there was no statistically significant difference (P=0.30). The ratio of CD8+ T lymphocytes 3 months after the therapy decreased by three-folds in the response group as compared with that of the non-response group before the therapy. The ratio between CD4+ T lymphocytes and CD8+ T lymphocytes improved more than that of the other two groups (1.00+/-0.70) for the complete response group (P=0.0046). CONCLUSION: The imbalance of the lympho cyte subset shown as the ratio between the CD4+ T lymphocytes and the CD8+ T lymphocytes decreased secondary to the decrease of CD4+ T lymphocytes as well as the increase of CD8+ T lymphocytes were believed to be the factors that caused marrow failure among others. The ratio between CD4+ T lymphocytes and CD8+ T lymphocytes can be improved by removing CD8+ T lymphocytes, which increased by the combining therapy of ALG and cyclosporine A. These results may help predict the therapeutic effects by way of analyzing the T-lymphocyte subsets in the peripheral blood prior to implementing the therapy.

Influence of Karyotype on Outcome of Allogeneic Bone Marrow Transplantation for Adults with Precursor B-Lineage Acute Lymphoblastic Leukemia in First or Second Remission / 대한혈액학회지

BACKGROUND: The discrepancy of therapeutic outcome between pediatric and adult patients with acute lymphoblastic leukemia (ALL) can be attributed in part to the higher frequency of adverse genetic abnormalities in adults. Several features such as age, leukocyte count, karyotype, and the rapidity of leukemic cell clearance have been noted to influence outcome of adult ALL in chemotherapy setting. However, the prognostic relevance of these factors has not been definitely evaluated in allogeneic BMT setting. METHODS: A total of 41 consecutive adults with precursor B-lineage ALL who had a successful karyotype and treated with allogeneic BMT while in first or second complete remission (CR) were entered onto the study. Cases known to be t(9;22) or t(4;11) were classified as unfavorable karyotype. RESULTS: There were 21 males and 20 females with median age 27 (range, 15~43) years. The distribution of FAB types was as follows : L1 26 cases (63.4%), L2 15 cases (36.6 %). Unfavorable karyotypes were identified in 12 patients (29.3%). Disease status at the time of transplant was first CR (n=37) or second CR (n=4). With a median follow-up of 26 months (range, 7~65 months), the probability of disease-free survival (DFS) was 66.5% and 49.9% at 2 and 5 years, respectively. In univariate analyses, characteristics predicting for worse DFS were FAB type (L2), pretransplant status (second CR) and unfavorable karyotype. Further multivariate analysis showed that the most powerful predictive factor for DFS was karyotype (P<0.01). CONCLUSION: Our clinical data shows that karyotype is the most important prognostic factor in adult precursor B-ALL after allogeneic BMT.

Busulfan, thiotepa, and melphalan as a conditioning regimen for allogeneic bone marrow transplantation in patients with acute myelogenous leukemia / 대한내과학회지

BACKGROUND: The purpose of this study was to evaluate the toxicity and efficacy of high-dose chemotherapy with busulfan, thiotepa and melphalan (BTM) as a myeloablative regimen in allogeneic bone marrow transplantation (allo-BMT) for patients with acute myelogenous leukemia (AML). METHODS: Twenty-seven patients with AML were enrolled; Sixteen patients had standard risk (SR) diseases (first complete remission (CR1) and de novo AML) and eleven patients had high risk (HR) diseases (second, or subsequent remission, secondary AML, relapsed, or refractory AML, CR marrow with persisting extramedullary manifestation (chloroma), or hypoplastic acute leukemia). The conditioning regimen included busulfan 4 mg/kg/day for a total dose of 12 mg/kg; thiotepa 250 mg/m2/day for a total dose of 500 mg/m2; and melphalan 50 mg/m2/day for a total dose of 100 mg/m2. Cyclosporine A and short-course methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. RESULTS: The median time to recovery a granulocyte count of 0.5 x 109/L was 14 days (range 10~25 days) and platelet transfusion independence was 30 days (range 12~49 days). The major regimen-related toxicities were gastrointestinal-related symptoms including oral mucositis, nausea, vomiting, and diarrhea. All patients experienced oral mucositis (> or = grade 1) and the patients with oral mucositis of equal and greater than grade 3 were 44% in SR and 45% in HR. The toxicities associated with lung, skin, heart and brain were minimal. Three (11%) patients had severe or fatal veno-occlusive disease (VOD). There were five treatment-related death (19%) (hepatic VOD with multiorgan failure (n=3), pneumonia and ARDS (n=2)) within the first 100 days after allo-BMT. There was not a significant difference between SR and HR group (p=0.167). The incidence of acute GVHD equal or greater than grade II was less than 10%. The actual survival at 2 year was 70.4%(95% confidence interval (CI), 54.7%~86.1%)(SR; 81.3% (95% CI; 63.4~99.1%) vs HR; 54.6% (95% CI; 28.7~80.4%), p=0.154). After a median follow-up of 630 days, 18 of 27 (67%, 355~1062 days) patients are alive without evidence of disease. Three of the 27 patients relapsed (SR; 0% vs HR; 55.6% (95% CI; 19.6~71.3%), p=0.004). CONCLUSION: The BTM regimen followed by allo-BMT is associated with acceptable toxicity and appears to have significant activity in patients with AML. It should be used with caution in patients with prior hepatopathy or refractory state who have an increased risk of severe VOD. Busulfan, thiotepa, and melphalan is an effective and alternative myeloablative regimen for patients with AML.

An unusual case of acute multifocal bacterial nephritis / 대한내과학회지

Acute multifocal bacterial nephritis is a severe form of acute renal infection in which heavy leucocytic infiltrates occurs throughout kidney. Therefore, in contrast to uncomplicated acute pyelonephritis, it frequently causes acute renal failure. We here report an unusual case of acute multifocal bacterial nephritis which caused acute real failure and massive proteinuria. A 44-year old man was referred to our hospital because of high fever and both flank pain and non-oliguric acute renal failure. He had pyuria and massive proteinuria(5.87g/day), and serum creatinine level of 3.6mg/dL. We initially suspected hemorrhagic fever with renal syndrome. But immunofluorescent antibody for Hantavirus was negative and E. coli was isolated at urine. Computed tomography showed multifocal areas of wedge-shaped low densities in both kidneys. Kidney biopsy revealed tubulointerstitial infiltration of leucocyte without glomerular change. After treatment of antibiotics, proteinuria completely disappeared and serum creatinine level decreased to 1.0mg/dL.

Acute Renal Failure in Children: Underlying Disease and Management according to Age

PURPOSE: It has been stressed that age itself as well as multiple organ failure are important prognostic factors in acute renal failure (ARF) in children. This study was performed to find out the significance of age factor and underlying disease of ARF in children. METHODS: We tried to review 58 pediatric ARF cases, retrospectively, in the pediatric intensive care unit (excluding the neonatal and surgical intensive care unit cases) of the Samsung Seoul Hospital of Sung Kyun Kwan University from Sept., 1994. to Dec., 1996. RESULTS: We classified the enrolled 58 cases into 5 age groups and more than half were younger than 1 year old. As underlying causes, heart and gastrointestinal disease were predominant in less than 1 month of age group. After 1 year of age, intrinsic renal disease was the most common cause (43-50%). Among the renal disease, systemic lupus erythematosus (10-15 year group), hemolytic uremic syndrome (1-10 year group), and obstructive uropathy (less than 1 year age group) were common etiologies. The mortality was the highest (46.7%) in less than 1 year group and lowest (21.4%) in 10-15 year age group. CONCLUSION: The underlying disorders of ARF in children were different among the age group. Among intrinsic renal diseases, hemolytic uremic syndrome was the most common cause. The difference in the mortality was dependent on age and underlying disease.

A Case of Multiple Splenic Infarction in Polycythemia Vera treated with Phlebotomy alone / 대한내과학회지

Polycythemia vera (PV) is a chronic myeloproliferative disease characterized by an increase in the total mass of red cells. Leukocyte and platelet counts are often elevated as well. The most common complication is thrombosis, which usually involves brain, heart, gastrointestinal tract, and kidneys, but rarely involves spleen. The cornerstone of therapy for this disease is phlebotomy and it is associated with an increased risk of thrombosis, especially for patients older than 70 years, those with a history of thrombosis, and those requiring an increased frequency of phlebotomy. Concurrent treatment with myelosuppressive agents decreases the risk of thrombotic complications.Recently we experienced a case of multiple splenic infarction in PV treated phlebotomy alone in a 42-year old woman who had complained of massive splenomegaly, left upper quadrant abdominal pain and fever. CT scan of abdomen showed multiple hypodense areas suggesting splenic infarction. She was managed with hydroxyurea and salicylate instead of phlebotomy and showed a clinical improvement with lowering the platelet count and reducing splenomegaly. PV with a assive splenomegaly is prone to thrombosis and phlebotomy in such patients may contribute to the thrombotic complications by increasing platelet counts. When it is necessary to lower the platelet count or reduce splenomegaly, hydroxyurea may be more useful than phlebotomy.