Isolated Extramedullary Relapse of Acute Myelogenous Leukemia as a Uterine Granulocytic Sarcoma in an Allogeneic Hematopoietic Stem Cell Transplantation Recipient

We report an unusual case of acute myelogenous leukemia in a patient who showed an extramedullary relapse in her uterus, without bone marrow recurrence, two years after an allogeneic bone marrow transplant. She complained of irregular vaginal spotting, and magnetic resonance imaging demonstrated a uterine mass. A biopsy revealed a massive infiltration of immature myeloid cells. A variable number of tandem repeats (VNTR) based on an examination of peripheral blood cells showed full donor chimerism. After receiving chemotherapy, her uterine mass had completely resolved. She has remained in complete remission for more than 6 months. This case suggests that physicians should be aware of the possibility of a uterine relapse in female bone marrow transplant recipients with acute myelogenous leukemia.

Akt Expression in Acute Leukemia Cells and Its Clinical Significance / 대한혈액학회지

BACKGROUND: Disturbances in apoptosis through phosphoinositide 3-kinase(PI3K)/Akt pathway is thought to be crucial in cancer cell immortality. Enhanced expression and activation of Akt was investigated in several malignancies but not in acute leukemia. We investigated the expression of Akt and phospho-Akt in acute leukemia cells and clinical characteristics of expression and non-expression group. METHODS: Bone marrow cells from patients who were newly diagnosed as acute leukemia and healthy volunteer were obtained and analyzed by Western blot analysis using monoclonal antibody against Akt, phospho-Akt (Ser473), and phospho-Akt (Thr308). Clinical data were obtained retrospectively. RESULTS: The expression of Akt was demonstrated in 27 of 43 cases (63%) and phospho- Akt(Ser473) was noted in 24 of 27 (54%) Akt-positive cases, respectively. Phospho-Akt (Ser473)-expression group showed significantly higher initial WBC counts compared to negative group (P=0.003). By chromosomal analysis, patients with Akt expression did not show any good prognostic karyotype (P=0.001). CONCLUSION: This result suggests that Akt overexpression and activation is detected in acute leukemia cells and might have a role in molecular pathogenesis of acute leukemia.

Biological Characteristics of AC133 Antigen-Positive Acute Leukemia / 대한혈액학회지

BACKGROUND: AC133 antigen is a cell surface antigen which is selectively expressed on hematopoietic stem and progenitor cells. It has been reported that AC133 antigen is expressed on the subsets of CD34+ acute leukemia, and occasionally on CD34- acute leukemia. We investigated the clinical and biological characteristics of AC133 antigen-positive acute leukemia. METHODS: Thirty-six adult acute leukemia patients were analyzed using a cut-off criterion of 20% or more gated leukemic blasts expressing the AC133 antigen for AC133+ leukemia. The biological characteristics focused on apoptosis were examined using multicolor flow cytometry and Western blot analysis. RESULTS: AC133 antigen was expressed in 12 cases (33.3%). Eleven of 21 (52.4%) acute myelogenous leukemia (AML) patients and 1 of 15 (6.7%) acute lymphoblastic leukemia patients were positive for AC133 antigen, and the difference was significant. None of the clinical prognostic markers were significantly different between AC133+ and AC133- AML. Median disease free and overall survival time were not significantly different between AC133+ and AC133- AML. The expression rate of CD34 was significantly higher in AC133+ AML patients compared to those of AC133- AML (P=0.045). Among the apoptosis-related proteins, the Fas expression on the leukemic blasts was higher in the AC133+ AML (P=0.048), but Fas ligand, Bcl-2, caspase-3 expression rates were not significantly different between AC133+ and AC133- AML. The apoptosis rate was significantly lower in the Ara-C treated AC133+ AML (P=0.049), but the apoptosis rates to other apoptosis-inducing agents (doxorubicin, TNF-alpha) were not different between AC133+ and AC133- AML cells. We thought that there were some associations between a trend toward higher caspase-3 expression rates and lower Ara-C induced apoptosis rates in the AC133+ AML. CONCLUSION: There was no significant correlation between AC133 antigen expression and various clinical characteristics of acute leukemia, but the AC133 antigen might provide different biological characteristics including apoptosis from other immature cell surface markers. However, to verify the prognostic usefulness of AC133 antigen and the basis of the biological characteristics of AC133 antigen-positive acute leukemia, further study is needed.

Two Cases of Crohn's Disease with Myelodysplastic Syndrome / 대한혈액학회지

Myelodysplastic syndromes (MDS) are bone marrow stem cell disorders characterized by dysplastic hematopoiesis leading to peripheral pancytopenias, and by a high risk of progression to acute myeloid leukemia. Several immunological disorders, particularly relapsing polychondritis, seronegative arthritis and cutaneous vasculitis have been described in association with MDS. Crohn's disease is an inflammatory bowel disease characterized by inflammatory, ulcerative bowel lesions and frequent association with systemic manifestations. Recently, some researchers have suggested that an association may exist between MDS and inflammatory bowel diseases, especially Crohn's disease, based on concomittant findings of both disorders in some reported patients. We report here two cases who developed MDS and Crohn's disease concurrently, and review previously reported literatures.

A Case of Serum Amino Acid Disturbance with Hyperammonemia in a Patient with Multiple Myeloma / 대한혈액학회지

Hyperviscosity and hypercalcemia are the common causes of disturbance of consciousness in patients with multiple myeloma (MM). However, there have been anecdotal reports of disturbance of consciousness in MM due to hyperammonemia and serum amino acid disturbance without possible causes such as liver failure. A 45-year-old female patient with MM was admitted due to general weakness. On 7th hospital day, she showed somnolence and disorientation. On the assumption of hyperviscosity syndrome, plasma exchange was performed immediately, but no effect. At that time, serum ammonia level was 431ng/dL, and serum glycine level was abnormally elevated. This type of serum amino acid disturbance was different from that usually found in chronic liver disease. After vincristine, adriamycin, and dexamethasone chemotherapy, serum ammonia level was restored to the normal range followed by improved mental status. We report, first in Korea, a case of MM with mental disturbance due to hyperammonemia and serum amino acid disturbance.

Therapeutic Outcome of Epstein-Barr Virus Positive T/NK Cell Lymphoma in the Upper Aerodigestive Tract

Expression of the natural killer (NK) cell antigen CD56 is uncommon in malignant lymphoma, but when it is, it is almost exclusively of the non-B cell lineage and show a preference for the nasal and nasopharyngeal region. T/NK cell lymphoma is known to be aggressive and refractory to treatment. It is highly associated with the Epstein-Barr Virus (EBV), but clinical investigations are rarely reported, that is until recently. We report here, on the clinical features and therapeutic outcomes of patients with T/NK cell lymphomas and its association with EBV. We reviewed fifty-four cases with peripheral T cell lymphomas in the upper aerodigestive tract between Jan. 1987 and Aug. 1998 from the Severance Hospital, Yonsei University College of Medicine. The diagnosis of T/NK cell lymphoma was made according to the expression of the NK cell markers, CD56 antigen and cytoplasmic CD3 epsilon, in tumor specimens, by immunohistochemistry. Epstein-Barr early region (EBER) RNA was detected using in situ hybridization on paraffin-embedded sections. Among the 54 cases with malignant lymphomas occurring in the upper aerodigestive tract, 20 had T/NK cell lymphoma (37%). The primary sites of T/NK cell lymphomas were the nasal cavity, 12 cases (60%), the tonsils, 4 cases (20%), the nasopharynx, 2 cases (10%), and the oropharynx, 2 case (10%). There were no differences between the features, at diagnosis or therapeutic modalities for patients with T/NK cell lymphoma and non-T/NK cell lymphoma. The complete remission rate of T/NK cell lymphomas was lower than non-T/NK cell lymphomas (65% vs 85%, p=0.02). The overall survival of T/NK cell lymphomas was 13 months (1-74 month), which was significantly lower than non-T/NK cell lymphomas [60.6% with a median follow up of 22 months (1-101 month, p=0.02)]. Disease free survival of T/NK cell lymphomas was 22 months (4-66 month), significantly lower than non-T/NK cell lymphomas [73.8% with a median follow up of 22 months (2-95 month), p=0.04]. The overall survival rates for T/NK cell lymphomas were significantly lower than for EBV positive non-T/NK cell lymphomas (p=0.018). EBER RNA was detected in the paraffin-embedded tissue sections of all T/NK cell lymphomas, compared to only 17.6% (6 of 34 cases) for non- T/NK cell lymphomas. In conclusion, as patients with T/NK cell lymphomas showed poor clinical outcomes, and a high association with EBV positivity, clinical trials with more investigational therapeutic strategies, and further research into the relationship of EBV infection with pathogenesis of T/NK cell lymphoma is warranted.

A Case of Refractory Iron Deficiency Anemia / 대한혈액학회지

Iron deficiency is the most common cause of anemia worldwide. The goal of therapy for iron deficiency anemia (IDA) is to supply sufficient iron to repair the hemoglobin deficit and replenish storage iron, combined with correction of underlying conditions. The majority of patients with IDA respond well to oral or parenteral iron replacement therapy if appropriately prescribed, but some rare cases of IDA refractory to both oral and parenteral iron replacement therapy due to in-born error of iron metabolism have been reported previously. We report here a mysterious case of IDA refractory to both oral and parenteral iron therapy and even to red cell transfusions. A 21-year-old male patient was admitted to our hospital due to general weakness and dizziness. His hemogram, iron profiles and bone marrow study showed the findings compatible with IDA. We could not find any conditions that cause acute or chronic blood loss, or any evidence of in-born error of iron metabolism. In spite of adequate iron relplacement therapy via both oral and parenteral routes, and even with red cell transfusions, his hemogram and iron profiles were not improved.

Therapeutic Outcomes of Langerhans' Cell Histiocytosis / 대한혈액학회지

BACKGROUND: Langerhans' cell histiocytosis is a proliferative histiocytic disorder of unknown cause formerly referred to histiocytosis X, with pathologic characteristics of abnormal proliferation of histiocytes which belong to the mononuclear phagocytes. The clinical manifestations range in severity from solitary lytic bone lesions to fatal multisystem disease, typically with indolent clinical courses. The authors reported here, the clinical features and therapeutic outcomes of Langerhans' cell histiocytosis according to stage and prognostic features. METHODS: We reviewed the medical records of 38 cases with Langerhans' cell histiocytosis confirmed by biopsy from March 1983 to March 1998 in Severance hospital for disease course, treatment, and late sequelae. RESULTS: 1) Median age of the patients was 3 years-old, and the male to female ratio was 2.2:1. 2) Fifteen cases were less than 2 years of age, 21 had soft tissue involvements, 10 had more than 4 organ involvement, and 8 had involved organ dysfunction. 3) As for the clinical stages, 19 cases were in stage I, 9 in stage II, 4 in stage III, and 6 in stage IV. As for the pathologic stages, 15 had monostic disease, 2 had polyostic disease, and 21 had multisytemic disease. 4) The incidence of more than 4 organ involvement in cases or = 2 years [53.3% (8/15) vs 8.7% (2/23), P=0.004], and the incidence of organ dysfunction in cases or = 2 years [33.3% (5/15) vs 3% (3/23)], indicating that cases or = 15 years. There was a significant correlation between the presence of more than 4 organ involvement and organ dysfunction (P=0.041). 5) The response rate of all cases was 71% (27 cases), and the response rate of 25 cases who received chemotherapy was 60% (15 cases). There was no difference in the response rate according to the type of chemotherapy. Overall survival rate was 63.4% at 50 months, disease-free survival rate was 56.7% at 24 months. The disease free survival rate was significantly lower in cases younger than 2 years of age than cases older than 2 years of age (P=0.047), in cases with 4 or more organs involvement than 3 or less (P=0.0002), in cases with evidence of organ dysfunction than without evidence of organ dysfunction (P=0.082), and in cases with soft tissue involvement than with only bone involvement (P=0.043). There was significant differences in disease free survival rate according to clinical stage (P=0.001). The overall survival and disease free survival rate of the cases older than 15 years of age were similar to those of the cases younger than 15 years of age were similar to those of the cases younger than 15 years of age. 6) Five cases died during follow-up periods, organ involvement, and organ dysfunction were found to be important prognostic factors, and cases with lesions limited to skeletal system showed more than 90% of survival rate. In the future, clinical investigation enrolled with more cases about the difference of clinical features and therapeutic outcomes between adult patients and pediatric patients should be warranted.

Transplantation of peripheral blood stem cells mobilized by intensified consolidation and granulocyte colony-stimulating factor in acute leukemia

The purpose of this study was to evaluate the feasibility and efficacy of autologous transplantation of peripheral blood stem cells (PBSC) mobilized with high-dose consolidation chemotherapy and granulocyte colony-stimulating factor in patients with acute myelogenous leukemia (AML). Twenty patients received myeloablative chemotherapy or chemo-radiotherapy including total body irradiation followed by the infusion of PBSC. PBSC were collected by large-volume leukaphereses. The mean number of mononuclear cells and CD34-positive cells infused were 7.2 x 10(8)/kg (range, 2.2-16.6), and 6.6 x 106/kg (range, 2.1-27.7), respectively. Engraftment failure was not seen in the enrolled patients. The median time to neutrophil (> or = 500/microL) and platelet recovery (> or = 50,000/microL) from the transplant was 12 days (range, 8-20) and 28 days (range, 10-600), respectively. The 2-year probability of disease-free survival (DFS) and relapse were 43% and 57% for patients with AML transplanted in first complete remission (CR1). The outcome of the patients transplanted in the advanced status was significantly worse than the patients transplanted in CR1 (P=0.04). Most relapses occurred within 1 year after transplantation. Fatal hepatic veno-occlusive disease was observed in one case. Other transplantation-related toxicities were mild. Our results demonstrated that autologous transplantation of high-dose consolidation chemotherapy-mobilized peripheral blood progenitor cells is feasible in the patients with AML in CR1. To further reduce the risk of leukemia relapse, much effort should be contributed to the field of ex vivo purging and post-transplant immunotherapy.

Non-Hodgkin's lymphoma & primary biliary cirrhosis with Sjogren's syndrome

Sjogren's syndrome (SS) is an autoimmune disease characterized by a lymphocytic infiltration of the salivary and lacrimal glands leading to a progressive destruction of these glands due to the production of autoantibodies. This disorder is either isolated (primary SS) or associated with other systemic diseases (secondary SS). The occurrence of B-cell non-Hodgkin's lymphoma (NHL) represents the major complication in the evolution of SS patients. The risk of developing NHL, which is equivalent for both primary and secondary SS, was estimated to be 44 times greater than that observed in a comparable normal population. NHLs in SS patients occur preferentially in the salivary glands and in other mucosa-associated lymphoid tissues (MALT). However, it can also occur in the lymph nodes or bone marrow. We documented a case of low-grade B-cell lymphoma of MALT in the right eyelid and primary biliary cirrhosis (PBC) of a patient with SS. To the best of our knowledge, this is the first case reported in Korea.

Risk Factors in Anticancer Chemotherapy Induced Thrombocytopenia Requiring Platelet Transfusion / 대한암학회지

PURPOSE: Severe thrombocytopenia is a rare but life threatening side effect of anticancer chemotherapy. This study is for delineating risk factors for anticancer chemotherapy induced thrombocytopenia requiring platelet transfusion in cancer patients. MATERIALS AND METHODS: Ninety seven cases of cancers (stomach cancer 37, lung cancer 31 and breast cancer 29) were included in this study design. Complete blood cell counts were done at day 1 and then twice a week to find lowerest thrombocyte count in each cycle. Discriminant analysis of risk factors for chemotherapy induced thrombocytopenia requiring platelet transfusion were performed. RESULTS: Anticancer chemotherapy induced thrombocytopenia less than 150,000/ microliter developed in 18 cases (20.0%) at day 20.6 8.0 and mean platelet count was 111,060 35,360/ microliter. Thrombocytopenia less than 100,000/ microliter developed in 10 cases (10.3%) at day 20.2 6.9 and mean platelet count was 56,200 30,460/ microliter. Among them platelet transfusions were needed in 6 cases (6.2%). Using discrininant analysis, day 1 platelet count less than 150,000/ microliter with total lymphocyte count less than 900/ microliter were identified as risk factors for anticancer chemotherapy induced thrombocytopenia requiring platelet transfusion. CONCLUSION: Thrombocytopenia less than 150,000 microliter with total lymphocyte count less than 900/ microliter before administrating anticancer drugs are high risk factors for platelet transfusion, and needed proper managements.

Acute tumor lysis syndrome in patients with non-Hodgkin's lymphoma / 대한내과학회지

BACKGROUND: Acute tumor lysis syndrome(TLS) has been defined as the metabolic abnormalities that occur after rapid tumor breakdown. In this study, we have evaluated the types or degrees of metabolic abnormalities and clinical characteristics in patients with non-Hodgkin's lymphoma(NHL) who developed TLS. METHODS: Patients were considered to have 'laboratory TLS(LTLS)' if any two of the following metabolic abnormalities occurred spontaneously or within 4 days of treatment: hyperphosphatemia, hyperkalemia, hyperuricemia, azotemia, and hypocalcemia. 'Clinical TLS(CTLS)' was defined as LTLS plus one of the following: a serum potassium level greater than 6.0mEq/L, a creatinine level greater than 2.5mg/dL, a calcium level less than 6.0mg/dL, the development of a life-threatening arrhythmia, or sudden death. RESULTS: Of 111 cases with NHL, TLS occurred in 16(14.4%), LTLS in 11(9.9%), and CTLS in 5(4.5%). There was a significant difference of gender, histologic type, clinical stage, performance status, extranodal involvement, serum lactate dehydrogenase(LDH), LDH index, beta2-microglobulin, uric acid, and blood urea nitrogen(BUN) level in the TLS versus control group. In multiple regression analysis, TLS occurred more frequently in patients with pre-treatment azotemia, aggressive histologic type, and elevated serum LDH level(p< 0.05, respectively). Pre-treatment and post-treatment TLS occurred in 8 cases(50%) respectively. The common metabolic abnormalities included hyperphosphatemia(87.5%), azotemia(81.3%), and hypocalcemia(75%). Of 11 cases with conservative care, 8 cases recovered within several days, but 3 cases died with multi-organ failure from disease progression. All 5 cases after hemodialysis for TLS recovered without any significant complications. CONCLUSION: The current study suggests that all patients with high-grade lymphomas and pre-treatment azotemia or a high serum LDH level be carefully monitored for at least 4 days after chemotherapy.

A Case of Hypertrophic Gastropathy and Early Gastric Cancer Associated with Pachydermoperiostosis / 대한소화기내시경학회지

Pachydermoperiostosis is a rare hereditary syndrome characterized by finger clubbing, periosteal new bone formation of tubular bones, and hypertrophic skin changes (pachydermia). This syndrome is known to be associated with a variety of diseases such as cranial suture defect, female escuchen, bone marrow failure and autonomic nervous system symptoms such as facial flushing and hyperhidrosis. There are just a few reports documenting gastric ulcer, hypertrophic gastropathy and Crohn's disease as associated diseases. A case is herein reported of pachydermoperiostosis accompanied by hypertrophic gastropathy and early gastric cancer.

Treatment outcome and survival rate of primary cutaneous lymphomas / 대한내과학회지

BACKGROUND: Primary cutaneous lymphomas are very rare type of malignant lymphomas. They represent a heterogeneous group of T-cell and B-cell lymphomas with considerable variations in clinical presentation, histopathology, immunophenotype, and prognosis. In this report, we evaluated the clinical characteristics of primary cutaneous lymphoma according to their clinical stages and histopathologic types. METHODS: From January, 1985 to Jun, 1999, 23 patients with histopathologic diagnosis of primary cutaneous lymphoma were evaluated retrospectively. RESULTS: The mean age was 48.5 years at the time of diagnosis of primary cutaneous lymphomas, and the most frequent form of cutaneous involvement was nodule(35%). The average duration from the occurrence of cutaneous lesion to the diagnosis of primary cutaneous lymphoma was 29.8 months. There were 20 cases(87%) of primary cutaneous T cell lymphomas, whereas primary cutaneous B cell lymphomas were seen in 3 cases(13%). The patients with stage I were 9 cases(39%), whereas the patients with stage IV were 10 cases(43%). Complete remission rate was 29% and partial remission rate was 57%. Median disease-free survival duration was 7 months and median overall survival duration was 33 months. One-year overall survival rate was 63.3% and 3-year overall survival rate was 56.3%. CONCLUSION: Primary cutaneous lymphomas were usually diagnosed at a far-advanced stage, and showed poor treatment results. Therefore early diagnosis is important to improve the survival rate. There should be carefully follow-up and repeated tissue diagnosis of the skin lesions which had a suspicion of primary cutaneous lymphoma and had not responded to conservative treatment.

A Case of Mucormycosis in a Patient with Myelodysplastic Syndrome and Review of the Literature in Korea / 감염

BACKGROUND: Mucormycosis is a highly virulent and rapidly progressive infectious disease caused by Mucorales. Immunocompromised hosts, such as patients with poorly controlled diabetes mellitus or diabetic ketoacidosis, patients receiving long-term deferoxamine therapy, and patients with hematologic malignancy, are predisposed to mucormycosis. We presented a case of brain abscess in a patient with myelodysplastic syndrome, and reviewed the cases of mucormycosis reported in Korea. METHODS: Relevant reports on mucormycosis were collected by searching the Korean database of medical literature. A total of 57 cases from 41 reports in Korea were reviewed as to clinical types, predisposing factors, treatments, and outcomes. RESULTS: The male to female ratio was 1.2:1. The mean age was 44 (range 1-72) years. The most frequent predisposing factor was diabetes mellitus (40 %), followed by the use of immunosuppressive agents (21%), and hematologic malignancies (16%). The most frequent clinical type was rhinocerebral (65%), followed by gastrointestinal (12%), pulmonary (9%), cutaneous (7%), and disseminated type (5%). The overall mortality rate was 33.3%, and the mortality rate in patients treated with surgical debridement was lower that in patients treated medically. The mortality rate in patients receiving surgical debridement only 13.3%, surgical debridement plus amphotericin B 26.9%, amphotericin B only 44.4%, and supportive care only 85.7%. Patients with disseminated type had a higher mortality rate than the other types. Conclusions:Early diagnosis of mucormycosis followed by the removal of predisposing factors and aggressive management, such as early surgical debridement and use of amphotericin B greatly affect therapeutic outcome. Therefore, much attention to the clinical features and identification of the organism are warranted. Collaborative evaluation through the collection of more cases with mucormycosis may be required in order to clarify the characteristics of mucormycosis in Korea.

A Case of Mucormycosis in a Patient with Myelodysplastic Syndrome and Review of the Literature in Korea / 감염

BACKGROUND: Mucormycosis is a highly virulent and rapidly progressive infectious disease caused by Mucorales. Immunocompromised hosts, such as patients with poorly controlled diabetes mellitus or diabetic ketoacidosis, patients receiving long-term deferoxamine therapy, and patients with hematologic malignancy, are predisposed to mucormycosis. We presented a case of brain abscess in a patient with myelodysplastic syndrome, and reviewed the cases of mucormycosis reported in Korea. METHODS: Relevant reports on mucormycosis were collected by searching the Korean database of medical literature. A total of 57 cases from 41 reports in Korea were reviewed as to clinical types, predisposing factors, treatments, and outcomes. RESULTS: The male to female ratio was 1.2:1. The mean age was 44 (range 1-72) years. The most frequent predisposing factor was diabetes mellitus (40 %), followed by the use of immunosuppressive agents (21%), and hematologic malignancies (16%). The most frequent clinical type was rhinocerebral (65%), followed by gastrointestinal (12%), pulmonary (9%), cutaneous (7%), and disseminated type (5%). The overall mortality rate was 33.3%, and the mortality rate in patients treated with surgical debridement was lower that in patients treated medically. The mortality rate in patients receiving surgical debridement only 13.3%, surgical debridement plus amphotericin B 26.9%, amphotericin B only 44.4%, and supportive care only 85.7%. Patients with disseminated type had a higher mortality rate than the other types. Conclusions:Early diagnosis of mucormycosis followed by the removal of predisposing factors and aggressive management, such as early surgical debridement and use of amphotericin B greatly affect therapeutic outcome. Therefore, much attention to the clinical features and identification of the organism are warranted. Collaborative evaluation through the collection of more cases with mucormycosis may be required in order to clarify the characteristics of mucormycosis in Korea.

Effects of Low-Dose Cytosine Arabinoside Plus Granulocyte-Macrophage Colony-Stimulating Factor and the Changes of Peripheral Blood Lymphocytes and Bone Marrow Clonogenic Assay in Myelodysplastic Syndrome / 대한혈액학회지

BACKGROUND: In vitro data indicate that granulocyte-macrophage colony-stimulating factor (GM-CSF) induces leukemic clonogenic cells to proliferate, thereby enhancing preferentially the cytotoxicity of the cell cycle-specific drug cytosine arabinoside (Ara-C) when compared with normal hematopoietic progenitor cells. We evaluated the therapeutic outcomes of low-dose Ara-C (LD Ara-C) plus GM-CSF for the patients with high-risk myelodysplastic syndrome (MDS). At the same time we evaluated the lymphocyte subset of peripheral blood and the bone marrow clonogenic assay of those patients. METHODS: Thirteen patients of MDS were treated with combination therapy composed of LD Ara-C and GM-CSF. The proportion of peripheral blood CD4, CD8 T-lymphocytes and natural killer (NK) cells were enumerated by flow cytometric direct immunofluorescence method. Clonogenic assays were done by methylcellulose culture system. Those laboratory parameters were analyzed with regard to the therapeutic responses. RESULTS: The subtypes according to the FAB classification included 8 patients of refractory anemia with excess of blasts (RAEB), 4 RAEB-transformation (RAEBT) and 1 chronic myelomonocytic leukemia (CMML). Five cases (38.5%) achieved complete remission after this type of treatment, two (15.4%) had a partial remisison and six (46.2%) had no response. The treatment was generally tolerable. There was no early toxic death. The median disease-free survival of the complete responders was 6 months. Three cases had a progression to acute leukemia. The proportion of pre-treatment CD4-positive T-lymphocytes in non-responders was significantly lower than that of complete responders (P<0.05). Eight cases (61.5%) showed "leukemic" growth pattern in clonogenic assay. The proportion of the "nonleukemic" growth in the complete responders was higher than that of nonresponders. CONCLUSION: The combined treatment of LD Ara-C and GM-CSF was tolerable for the patients with high-risk MDS. The immunologic parameters and in vitro growth pattern were thought to be associated with therapeutic responses. Further studies for the large number of patients will be required.

The Effect of Recombinant Fibronectin Fragment (Retronectin) and Cytokines during deltaLNGFR Retroviral Transduction of CD34+ Cells / 대한혈액학회지

BACKGROUND: Hematopoietic stem cells (HSC) remain one of the most promising target cells for gene therapeutic approaches, but is currently limited by a number of issues, including the low gene transfer efficiency. METHODS: We evaluated the effect of recombinant fibronectin fragment (retronectin) and cytokines during retroviral transduction of CD34+ cells and analyzed the characteristics of transduced cells. To rapidly characterize and isolate transduced cells, we used a retroviral vector coding for the truncated form of the low-affinity nerve growth factor receptor (delta LNGFR). RESULTS: The total number of CD34+ cells (1.5~6.3-fold) and the amount of cycling (S+G2/M) cell fractions (2~6-fold) were increased after cytokine prestimulation, especially using thrombopoietin (TPO)-based cytokines. The immunophenotype of CD34+ cells showed no significant differences according to the cytokines. However, CD34+AC133+ cells were more effectively maintained in the presence of TPO. The transduction efficiency of CD34+ cells was significantly increased in the presence of retronectin (6.7+/-2.3% vs 23.1+/-4.4%). Immunomagnetic selection of the transduced cells allowed us to enrich these effectively (6.7+/-2.3% --> 86.3+/-6.5%). Compared with control, delta LNGFR transduction did not influence on the immunophenotype and cloning efficiency of CD34+ cells. Among the delta LNGFR+/-derived colonies, 85.0% were shown to contain an integrated delta LNGFR gene. CONCLUSION: These data show that retronectin and TPO-based cytokines can be used to facilitate retroviral transduction of CD34+ cells. Also, delta LNGFR transduced cells could be rapidly characterized by FACS analysis and effectively enriched by immunomagnetic selection method. Further improvement of transduction conditions for stimulation of HSC proliferation without differentiation and development of new vectors that obviate the requirement for cell division are likely to enhance transduction of primitive HSC.

A Case of Colonic Perforation associated with CMV Colitis in a Patient with Non-Hodgkin's Lymphoma / 대한혈액학회지

Cytomegalovirus (CMV) disease in gastrointestinal tract is common among immunocompromised host. Ulcer, hemorrhage and perforation are manifestations of CMV infection in gastrointestinal tract and the most common site of intestinal perforation is the colon, followed by the distal ileum. Early diagnosis and preemptive therapy of CMV infection in the gastrointestinal tract should be warranted to prevent intestinal perforation, one of life-threatening complications of CMV colitis. We report a case of CMV colitis leading to colonic perforation in a patient with non-Hodgkin's lymphoma (T/NK cell lymphoma). Immunohistochemical stain of surgical specimen revealed positive, followed by positive EA-IPA and PCR for CMV antigen. He survived after successful left hemicolectomy and intravenous ganciclovir therapy.

A Case of Pleural Involvement in Patient with Waldenstr m's Macroglobulinemia / 대한혈액학회지

Waldenstr m's macroglobulinemia (WM) is a rare lymphoproliferative disorder characterized by lymphocytic tumor infiltration of the bone marrow and monoclonal IgM gammopathy. There had been anecdotal reports of pleural involvement in WM. We experienced a case of WM with pleural involvement and reported here for the first time in Korea with review of literature. A 73-year-old male patient was admitted to our hospital due to dizziness and general weakness. Serum protein electrophoresis showed M-peak in the gamma-globulin region, which was revealed as IgM kappa macroglobulin by serum and urine immunoelectrophoresis. He complained headache, visual disturbance and epistaxis associated with hyperviscosity syndrome and plasma filtration and combination chemotherapy was performed immediately. Symptoms and laboratory parameters such as serum IgM level and globulin fraction were markedly improved thereafter. But during the treatment, insidiously progressive exertional dyspnea was developed and the chest X-ray showed bilateral pleural effusion. The pleural fluid contained abundant plasmacytoid lymphocytes with reactive mesothelial cells. His dyspnea was completely resolved with clearing of the radiographic pleural effusion after continued steroid therapy.