Primary Systemic Anaplastic Large Cell Lymphoma in a Single Korean Institution: Clinical Characteristics and Treatment Outcome

Despite advances in the characterization of anaplastic large cell lymphoma (ALCL), little data is available on Asian patients. We report here upon single Korean institution's experience regarding the clinical characteristics and outcomes of ALCL. We performed a retrospective study of 32 adults with ALCL. Most of the patients received anthracycline-based chemotherapy. Ann Arbor stage III-IV, B symptoms, high-intermediate/ high International Prognostic Index (IPI), and extranodal disease at diagnosis were present in 56%, 44%, 41%, and 63%, respectively. Compared with Western studies, the male/female ratio (4.3) was markedly higher and skin (9%) and bone involvement (9%) were less frequent. The staining results for anaplastic lymphoma kinase were positive in 6 (33%) of 18 cases available. The complete response (CR) rate was 62% (95% CI, 44-80%). With a median follow-up of 51.0 months, 5 yr overall survival was 40+/-11%. The 3 yr relapse-free survival for the 18 patients who achieved CR was 74+/-12%. Age, performance status, lactate dehydrogenase, extranodal disease sites number, and IPI were correlated with treatment response and survival. Our data suggest that Korean ALCL patients appear to have a higher male/female ratio, less frequent skin/bone involvement, and lower CR rate compared with those of Western studies.

Detection of IgH and Cyclin D1 gene Rearrangement with Interphase FISH in Multiple Myeloma / 대한진단검사의학회지

BACKGROUND: The t(11;14)(q13;q32) is known to be one of the most frequent chromosomal abnor-malities found in multiple myeloma (MM). However, studies on t(11;14) in MM have been problemat-ic due to the fact that MM cells proliferate poorly in vitro. The purpose of our study is to evaluate inci-dence, clinical, and hematologic findings of MM with IgH and cyclin D1 gene rearrangement and to investigate the usefulness of interphase FISH (fluorescence in situ hybridization). METHODS: The study group included 36 patients (23 newly diagnosed MM, 8 relapsed MM, 5 per-sistent MM after treatment) admitted to Mokdong and Gil Hospital from November 1998 to July 2002. Interphase FISH was performed with IGH/CCND1 dual color, dual fusion translocation probe (Vysis Inc, Downers Grove, IL USA), using bone marrow mononuclear cells. RESULTS: Incidence of IgH and cyclin D1 gene rearrangement by interphase FISH was 19%. One patient with normal karyotype and another patient without any metaphase cells showed IgH and cyclin D1 gene rearrangement with interphase FISH. The lambda light chain subtype was more frequently found in patients with rearrangement (4/5, 80%) than those without rearrangement (6/23, 26%) (P<0.05). No significant differences were found in other clinical and hematologic findings in the two groups. CONCLUSIONS: We suggest that MM with IgH and cyclin D1 gene rearrangement is associated with the expression of lambda light chain. Interphase FISH may be helpful in samples with normal karyotype or no metaphase cells for detection of gene rearrangement of MM.

Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia / 대한혈액학회지

BACKGROUND: The outcome of hematopoietic stem cell transplantation (HSCT) for patients with severe aplastic anemia (SAA) in Seoul National University Hospital was analyzed retrospectively. METHODS: Between January, 1990 and March, 1999, 25 patients with SAA underwent HSCT. Their medical records were reviewed. Statistical analyses were done about survival and complication after HSCT. RESULTS: The median age of patients was 22 (range, 14~43) and male to female ratio was 18 : 7. Twenty two were HLA matched non- identical siblings. Three were one identical twin, one one-locus mismatched father and one HLA matched unrelated donor, respectively. Conditioning regimens were CY/TLI (cyclophosphamide, total lymphoid irradiation) for 18 patients, CY/ATG (CY, antithymocyte globulin) for 3, CY/ buffy (CY, unirradiated buffy- coat) for 2, CY/ ATG/TLI for 1, BU/CY (busulfan, CY) for 1. For prophylaxis of graft-versus-host disease (GVHD), cyclosporine and methotrexate were used in all patients except for identical twin. The median nucleated cell dose given to patients was 4.5x108/kg (range, 2.0~5.9). All evaluable patients achieved absolute neutrophil count of 500/microliter after median 17 days of HSCT (range, 12~27) and untransfused platelet count over 20,000/microliter after median 21 days of HSCT (range, 13~67). Six patients (24%, grade I : 3, II : 1, III : 1, IV : 1) developed acute GVHD and 8 (32%, limited : 4, extensive : 4) developed chronic GVHD. Hepatic venoocclusive disease (VOD) occurred in 2 patients (8%). Rejection occured in 4 patients (16 %), but among 22 allogeneic transplant recipients from HLA matched siblings, only one (5%) lost graft. After a median follow-up of 32 months (range 9~120 months), 5 year overall survival of all patients was 87%, and that of 22 allogeneic recipients from HLA matched sibling donors was 95%. Four patients (16%) died. Causes of death were VOD in one case, rejection with pneumonia one, acute GVHD one. One died from traffic accident in a cured state. CONCLUSION: Experiences from our center suggest that HSCT is an effective treatment for patients with severe aplastic anemia. Long- term survival is especially excellent for patients who have matched related donors.

A Phase 2 Study of VP-16 , Ifosfamide , and Cisplatin ( VIP ) Combination Chemotherapy Plus Concurrent Thoracic Irradiation for Limited Small Cell Lung Cancer / 대한암학회지

PURPOSE: A phase II study of etoposide, ifosfamide, cisplatin combination chemotherapy and concurrent thoracic irradiation in patients with untreated limited small cell lung cancer (SCLC) was conducted to assess toxicities, response rate, response duration, and median survival. MATERIALS AND METHODS: Patients with histologically confirmed SCLC with a ECOG criteria 2 and adequate renal function and bone marrow reserve were eligible. Each cycle consisted of VP-16 100 mg/m i.v, days 1-3, ifosfamide 1,200 mg/m i.v. days 1-3 with Mesna, and cisplatin 30 mg/m i.v. days 1-3. Cycles were repeated every 21 days. Concutrent thoracic itradiation was given as total 40-45 Gy for 4-5 weeks beginning within 24 hours of the third cycle. Patients with complete remission received prophylactic cranial irradiation after the 6th cycle. RESULT: Forty two patients with limited SCLC were treated at Seoul National University Hospital between December 1993 and August 1996. Three patients were not evaluable because of lost to follow up (2 patients) and one treatment-related early death. Of 39 evaluable patients, responses were seen in 38 (97%) patients including 22 (56%) complete responses and 16 (41%) partial responses. The median remission duration was 65 wks. The median disease free survival was 60 wks. The median overall survival was not reached and 2-year survival was 69% with median duration of follow up of 63.5 wks. Hematologic side effects (WHO Gr>III/IV) of evaluable 228 cycles of chemotherapy were leukopenia in 34%, thrombocytopenia in 16%. One patient expired after prolonged leukopenia and sepsis. Nonhematologic side effects (WHO Gr>II) included nausea and vomiting (17%) and peripheral neuropathy (2%). CONCLUSION: VIP combination chemotherapy with concurrent thoracic irradiation is effective and tolerable in limited SCLC.

Allogeneic Bone Marrow Transplantation for Acute Myelogenous Leukemia: Retrospective Analysis in a Single Institution / 대한혈액학회지

BACKGROUND: Acute myelogenous leukemia (AML) is the most common cause of leukemia in adults. Allogeneic bone marrow transplantation (BMT) for the treatment of AML is done worldwide now. METHODS: Between November 1987 and June 1998, we performed allogeneic BMT for 27 patients with AML from HLA-identical sibling donors. We reviewed medical records of these patients. RESULTS: The median age of patients was 31 (range, 15~43) and male to female ratio was 18 : 9. Conditioning regimens were BU/CY (busulfan, cyclophosphamide) for 22 patients, TBI/CY (total body irradiation, cyclophosphamide) for 3 patients, and TBI/VP/CY (TBI, VP-16, cyclophosphamide) for 2 patients. Cyclosporine and methotrexate were used in 18 patients for prophylaxis of graft-versus-host disease (GVHD), and cyclosporine and methyl-prednisolone were used in 9 patients. The median nucleated cell dose given to patients was 4.1x108 /kg. All evaluable patients achieved absolute neutrophil count of 500 /microliter after median 15 days after BMT (range, 11~45 days). Twenty-five percent of patients developed acute GVHD (> or = grade II) and there was no patient with grade IV acute GVHD. Twenty-nine percent developed chronic GVHD. Hepatic venoocclusive disease (VOD) occurred in 7 patients (26%). At the time of BMT, 16 patients were in the first remission status and 11 patients were in the advanced disease status. After a median follow-up of 27 months (range 7~127 months), the actuarial disease-free survival at 5 years was significantly higher in the first remission group than the others (44% vs. 9%; P=0.05). The difference of 5 year overall survival between these two groups approached statistical significance (50%for the first remission group and 12% for the others; P=0.13). There were 17 deaths. The causes of death were relapse (8 patients, 47%), VOD (3 patients, 18%), sepsis (2 patients, 12%), interstitial pneumonia (2 patients, 12%), chronic GVHD (1 patient, 6%), and drug-toxicity (1 patient, 6%). Eary deaths (<100 days) occurred in 6 patients (22%). CONCLUSION: Allogeneic BMT for patients with AML was most successful when done during the first remission. Clinical features of patients with AML treated with allogeneic BMT were similar to those from Western countries, but the incidence and severity of acute GVHD seem to be lower.

High Dose Chemotherapy Using CD34+ Hematopoietic Stem Cells / 대한혈액학회지

BACKGROUND: Recently, CD34 antigen expressed on hematopoietic stem cells which is not detected on non-Hodgkin lymphoma (NHL), multiple myeloma and most solid tumors, is identified. In autologous bone marrow transplantation (BMT), positive selection of CD34+ cells may be used to provide hematopoietic stem cells capable of engraftment but depleted of tumor cells. And it can be used to depletion of T lymphocytes to prevent the graft versus host disease (GVHD) in allogeneic BMT. So we performed this study to evaluate the efficacy of purification of CD34+ stem cells with CEPRATE SC Stem Cell Concentration System (CellPro Inc.) and to assess the influence of CD34+ stem cells on engraftment. METHODS: Peripheral blood stem cells were mobilized with cyclophosphamide (except one patient with malignant lymphoma) and G-CSF and harvested using CS-3000 (Fenwall). CD34+ stem cells counted by FACScan (Becton-Dickinson). The conditioning regimens were ICE (Ifosphamide/Carboplatin/Etoposide) in breast cancer, high dose melphalan in multiple myeloma, BEAC (BCNU/Etoposide/Ara-C/Cyclophosphamide) in NHL, TBI (total body irradiation) with cyclophosphamide in acute lymphocytic leukemia (ALL) and busulfan with cyclophosphamide in myelodysplastic syndrome (MDS). We used G-CSF (10 microgram/kg) after transplantation in all patients. RESULTS: Eleven patients, six with high risk or metastatic breast cancer, one with refractory multiple myeloma, one with acute lymphocytic leukemia (transformed from lymphoblasticlymphoma), two with relapsed malignant lymphoma, one with myelodysplastic syndrome (HLA one-locus mismatched allogeneic BMT case, for T lymphocyte depletion) were treated. Hematopoietic stem cells were harvested from autologous peripheral blood in all patients except one patient with MDS whose stem cells were harvested from allogeneic bone marrow. Median duration and number of peripheral blood stem cell (PBSC) harvest were 15 days (13~22) and 3 times (2~8), respectively. The mean number of total stem cells and CD34+ stem cells harvested per pheresis were 204.8 (17.4~797.9)x106/kg and 3.0 (0.3~11.9)x106/kg, respectively. The mean efficacy of CD34+ hematopoietic stem cell selection by CEPRATE SC Stem Cell Concentration System was 47.7% (1.4~99.0%). The number of infused CD34+ stem cells per patient ranged from 0.34 to 4.8x106/kg (mean 2.3x106/kg). After transplantation, the median day of achieving granulocyte counts of >0.5x109/L was 10.5 days and platelet counts of >50x109/L was 14 days. CONCLUSION: CD34+ stem cells separated with CEPRATE SC Stem Cell Concentration System provided reliable and timely hematopoietic reconstitution.