Frequency of bcl-2 mbr/JH Rearrangement and Prognostic Implication of bcl-2, c-myc Protein Expression in Non-Hodgkin's Lymphoma / 대한혈액학회지

BACKGROUND: Deregulated bcl-2 appears to prolong cell survival and to cooperative with c-myc in promoting cell proliferation. We investigated whether there is any clinicopathologic correlation between the survival and the frequency of bcl-2/JH rearrangement and bcl-2, c-myc protein expression in non-Hodgkin's lymphoma. METHODS: We conducted a study for bcl-2 mbr/JH rearrangement with polymerase chain reaction and for bcl-2, c-myc expression with immunohistochemical staining in 46 formalin-fixed, paraffin-embedded non-Hodgkin's lymphoma tissues of patients treated with CHOP chemotherapy including 37 specimens of diffuse large cell type. RESULTS: The bcl-2 mbr/JH rearrangement was positive in 13% (6/46) of non-Hodgkin's lymphoma specimens. For bcl-2, strong positive reaction (3+) and 2+ positive reaction were seen in 16 (35%) and 16 cases (35%), respectively; while 3+ and 2+ reactions were found in 20 (44%) and 16 cases (35%), respectively, for c-myc by immunohistochemistry. Eighty one percent of positive cases for bcl-2 were also positive for c-myc simultaneously. The 6 cases with bcl-2 mbr/JH rearrangement were weakly positive at 3 cases and strong positive at 3 cases for bcl-2 by staining. In cases of diffuse large cell lymphoma, high expression (3+) of bcl-2 & c-myc protein tended to have a shorter 2 year survival, though it was statistically not significant. CONCLUSION: High expression of bcl-2 and c-myc protein suggest that bcl-2 cooperate with c-myc in tumorigenesis of aggressive non-Hodgkin's lymphoma. The prognostic implication of bcl-2 and c-myc expression in diffuse large cell lymphoma patients needs to be evaluated in a larger, prospective cohort to draw a definitive conclusion.

Treatment of Acute Promyelocytic Leukemia (APL) by a Combination of All-Trans Retinoic Acid (ATRA) and Chemotherapy / 대한혈액학회지

BACKGROUND: All-trans-retinoic acid (ATRA) induces complete remission (CR) in the great majority of patients with PML/RAR -positive acute promyelocytic leukemia (APL). However, it is associated with a rapid rise in leukocytes in one third to half the patients, with potentially fatal "ATRA syndrome". Furthermore, most of the patients relapse with maintenance therapy using ATRA alone or low-dose chemotherapy. In this study, we have analyzed the outcome for APL patients who were treated with ATRA alone or combined with low-dose chemotherapy followed by postremission chemotherapy in Chonnam University Hospital from April 1993 to December 1997. METHODS: Sixteen patients with newly diagnosed APL were eligible to analysis. Patients received 45mg/m2 ATRA until CR occurred. If initial WBC were above 5,000/microliter, low-dose chemotherapy was concomitantly given, and if during the ATRA therapy WBC were above 5,000/microliter by day 5 or 10,000/microliter by day 10, or 15,000/microliter by day 15, low-dose chemotherapy was added. Four polychemotherapy cycles or allogeneic bone marrow transplantation were given as postremission therapy. RESULTS: Median age was 34 years (range, 17 to 67). Of 16 APL patients, 15 (93.8%) achieved CR and 1 (6.2%) died of intracerebral hemorrhage. After a median follow-up of 11.5 months (range, 0 to 47), the Kaplan-Meier estimated overall survival (OS) rate was 87.1 +/- 8.6% at 3 year, the event-free survival (EFS) rate was 87.1 +/- 8.6%, 58.0 +/- 24.4% and 29.0 +/- 23.9% at 1 year, 2 year and 3 year, and the disease-free survival (DFS) rate was 92.9 +/- 6.9%, 69.6 +/- 20.7% and 46.4 +/- 23.5% at 1 year, 2 year and 3 year, respectively. CONCLUSION: The present study suggests that ATRA with or without low-dose chemotherapy followed by postremission chemotherapy is a well-tolerated and effective regimen that is shown to improve the CR rate, reduce a early mortality rate and considerably prolong the overall survival in patients with newly diagnosed APL.

Characterization of Peripheral Blood CD34+ Cells Mobilized by Recombinant Human Granulocyte-Colony Stimulating Factor in Healthy Adult Donors / 대한혈액학회지

BACKGROUND: CD34+ cells are capable of engraftment and hematopoietic reconstitution. However, expression patterns of other surface antigens such as CD13, CD33, CD38 and HLA-DR on CD34+ cells in mobilized peripheral blood have remained unclear. This study analyzed the expansion kinetics of the CD34+ cells and subsets in the peripheral blood of healthy donors treated with recombinant human Granulocyte Colony-Stimulating Factor (rhG-CSF), the relative composition of CD34+ subsets in mobilized peripheral blood and apheresis product, the yield of apheresis product. METHODS: The 6 peripheral blood stem cell donors received a daily dose of 500 microgram (8.1~10 microgram/kg) of rhG-CSF subcutaneously for 6 or 7 days. The hematologic parameters and the number of CD34+ cells and subsets in peripheral blood were recorded at baseline and daily for a total 6 to 7 days. With monoclonal antibodies which were designed for two color direct immnunofluorescence (IF) analysis with combination of fluorescence isothiocyanate (FITC) and phycoerythrin (PE) conjugated, CD34CD38, CD34HLA-DR, CD34CD13, and CD34CD33 surface antigens were analyzed by flow cytometry. RESULTS: The number of CD34+ cells mobilized to peripheral blood peaked at day 4 or 5 with rhG-CSF treatment. Circulating CD34+ cell expanded by 11.5-fold from 4.5 +/- 1.8x106/L before rhG-CSF treatment to maximal increment 51.9 +/- 13.4x106/L after mobilization. Subsets of CD34+CD38-, CD34+HLA-DR-, CD34+ CD13-, and CD34+CD33- (in % ofthe CD34+ cell) were all decreased and subsets of CD34+CD38+, CD34+HLA-DR+, CD34+CD13+, and CD34+CD33+ were all increased after mobilization, so that the numbers of early committed and myeloid committed progenitors were higher than the those of multipotent stem cells in mobilized peripheral blood and leukapheresed products. Each apheresis product yielded a mean of 451.6x106 (7.7x106/kg of RBW) CD34+ cell and 172.3x105 (2.9x105/kg of RBW) CFU-GM. CONCLUSION: Sufficient amount of CD34+ cells capable of engraftment and hematopoietic reconstitution can be mobilized by administration of rhG-CSF to healthy adult donor. Subsets of mobilized CD34+ cells were mainly composed of early committed and myeloid committed progenitors, although absolute numbers of all progenitor cells including multipotent stem cells were significantly increased.

A case of chronic graft-versus-host-disease following allogeneic peripheral blood stem cell rescue for poor graft function after bone marrow transplantation

To overcome poor graft function after allogeneic bone marrow transplantation (BMT), the use of peripheral blood stem cells (PBSC) instead of bone marrow is gaining more popularity because of its advantages. There may, however, be an increased risk of graft-versus-host-disease (GVHD) because of the large number of lymphocytes present in a leukapheresis product. An 18-year-old man with severe aplastic anemia underwent an allogeneic BMT using his HLA-identical sister. After initial excellent graft take for 8 months, his blood counts gradually decreased to 2.8 x 10(9)/L of white cells and 28 x 10(9)/L of platelets with marrow cellularity of < 10%. After allogeneic granulocyte-colony stimulating factor mobilized PBSC rescue, the patient's blood counts recovered satisfactorily. Around 1 year after the boost, he developed chronic GVHD that responded to prednisolone and cyclosporin A. He is now well on low-dose steroids at day +1055 after PBSC rescue. The present case is the first experience of a long-term follow-up who underwent allogeneic PBSC rescue in Korea.

A case of Marfan syndrome with acute monoblastic leukemia

We report on an 18-year-old man who had both acute monoblastic leukemia and Marfan syndrome. A diagnosis of Marfan syndrome was established by those characteristics of arachnodactyly, ectopia lentis, mitral valve prolapse, and mitral regurgitation. Findings on bone marrow examination of the patient showed that most of nucleated cells were monoblasts and immunophenotype of those cells showed CD13+, CD33+, CD56+, and HLA-DR+. To our knowledge, this is the second report of leukemia in Marfan syndrome in the world.

A Case of AML Atypical M2 with Granulocytic Sarcoma in the Meninges Induced Remission by All-Trans Retinoic Acid and Combined Chemotherapy / 대한혈액학회지

We repoarted a rare case of AML atypical M2 who developed granulocytic granulocyte sarcoma in the meninges which was induced complete remission with all-trans retinoic acid (ATRA), daunorubicin and cytosine arabinoside (Ara-C). Morphological and immunophenotypic study of leukemic cells in this patient suggested acute promyelocytic leukemia. However, leukemic clees lacked both t (15;17) and PML-RARalpha gene rearragement, rather showed t (8;21). The patient was diagnosed as AML atypical M2.