Therapeutic Comparison of Chemotherapy and Surgery for Early Stage Diffuse Large B-cell Gastric Lymphoma

PURPOSE: The use of surgery versus stomach-preserving treatment for primary gastric lymphoma has caused controversy among doctors. This retrospective, single center study aims to evaluate the efficacy and benefit of stomach-preserving treatment against surgery for early stage diffuse large B-cell lymphoma of stomach. MATERIALS AND METHODS: From August 1991 to January 2006, 43 cases of early-stage diffuse large B-cell gastric lymphoma were reviewed. RESULTS: Eleven cases were treated with chemotherapy or chemotherapy plus radiation (CT +/- RT), 17 were treated with surgery alone (OP), and 15 were treated with surgery plus adjuvant chemotherapy (OP + CT). The complete remission and response rates were 63.6% and 90.9% in those treated with CT +/- RT (7 complete responders, 3 partial responders, 1 non-responder), 100% and 100% in those treated with OP, and 100% and 100% in those treated with OP + CT, respectively. Five-year overall survival rates were 85.7%, 87.5%, and 100% in those treated by CT +/- RT, OP, and OP + CT, respectively (p=0.76). The five-year disease free survival rates were 100%, 87.5% and 100% in those treated by CT +/- RT, OP, and OP + CT, respectively (p=0.99). There was no significant difference in overall survival and disease free survival between modalities. Even though there are no definite differences in the number of complications between those treated by CT +/- RT or OP, these facts reflect little concern on complications after surgery. CONCLUSION: In preventing morbidity arising from early or late complications from surgery and promoting quality of life, chemotherapy should be a primary consideration for early stage diffuse large B-cell lymphoma of the stomach.

Long-term Outcome after Prophylactic Lamivudine Treatment on Hepatitis B Virus Reactivation in Non-Hodgkin's Lymphoma

Hepatitis B virus (HBV) reactivation is the frequent complication after cytotoxic chemotherapy in HBsAg-positive non-Hodgkin's lymphoma (NHL) patients. Pre-chemotherapy viral load may be a risk factor and HBeAg-positive status is associated with increased viral load. The aim of this study was to investigate the long-term treatment outcome of lamivudine in preventing HBV reactivation and its associated morbidity according to HBeAg status. Twenty-four adult HBsAg-positive NHL patients were taken 100mg of lamivudine daily before the initiation of chemotherapy. The median duration of lamivudine therapy was 11.5 months (range: 1-54 months) and the median number of chemotherapy cycles was 6 (range: 1-16 cycles). The steroid containing chemotherapy regimens were used in 18 patients (75%), and the anti-CD20 monoclonal antibody containing chemotherapy regimen was used in 6 patients (25%). Four patients received autologous peripheral blood stem cell transplantation without resultant HBV reactivation. Hepatitis related to HBV reactivation was developed in 1 patient among 14 HBeAg-positive patients and no one among 10 HBeAg-negative. One patient developed HBV reactivation after lamivudine withdrawal, and 4 patients developed the YMDD (tyrosine-methionine-aspartate-aspartate) mutation during lamivudine therapy. There were no statistical differences in HBV reactivation rate during chemotherapy according to the HBeAg status. Our results demonstrate that lamivudine should be considered preemptively before the chemotherapy for all HBsAg-positive NHL patients to prevent HBV reactivation, regardless of pre-chemotherapy HBeAg status. Finally, compared with the chronic hepatitis B patients, similar rate of HBV reactivation after lamivudine withdrawal and development of YMDD mutation was observed in NHL patients.

Longlasting Remission of Primary Hepatic Mucosa-associated Lymphoid Tissue (MALT) Lymphoma Achieved by Radiotherapy Alone

Primary hepatic lymphoma is a rare disorder representing less than 1% of all extranodal lymphomas. Histological examination of a primary hepatic lymphoma usually reveals a diffuse large B-cell lymphoma; there have been few reports of primary hepatic mucosa-associated lymphoid tissue (MALT) lymphomas. A 67-year-old man was being treated for a duodenal ulcer; while receiving therapy for the ulcer, a liver mass was incidentally found on abdominal ultrasonography. The pathologic diagnosis of the hepatic mass was an extranodal marginal zone B-cell lymphoma of MALT. The patient underwent radiotherapy with a total of 4,140 cGy delivered. The patient achieved complete remission and has been followed for 6 years with no recurrence of the disease. This report reviews the case of a primary hepatic extranodal marginal zone B-cell lymphoma of MALT successfully treated by radiotherapy alone.

Treatment of Hodgkin's Disease: A Twenty-Year Follow-up of Patients at a Center in Korea

Hodgkin's disease (HD) is a hematologic malignancy which shows common features regardless of race, but racial differences may be considered with certain clinical characteritcs. HD in Korea shows somewhat different characteristics when compared to cases in Western countries. We evaluated the clinical and histopathologic characteristics of HD, the outcomes of various chemotherapy regimens, and prognostic factors of HD in Korea. One hundred and five patients with initial histopathologic diagnosis of Hodgkin's disease were retrospectively reviewed 20 years after diagnosis at Yonsei University College of Medicine. Nodular sclerosis was the most common histopathogic subtype (41%) and mixed cellularity was nearly as common (40%). The overall complete remission rate (CR) was 87.6%. The disease-free survival (DFS) and overall survival (OS) rate were 79.2% and 84.8% at 5-years, 70% and 79.2% at 10- and 20-years. There were no significant differences in CR rate and DFS, but OS rates were significantly higher in m-BACOP and ABVD regimen. Univariate analysis revealed that age, B-symptom, ECOG scale, Ann Arbor stage, international prognostic index, and serum beta2-microglobulin level were significant prognostic factors for both DFS and OS. Multivariate analysis demonstrated that age, B symptoms, and ECOG scale were significant prognostic factors for OS only. In conclusion, the survival rates of HD patients in our center were superior to those of previous reports in Korea and Western countries. Considering the higher OS rate and decreased incidence of side effects, the ABVD regimen may be recommended for the initial treatment of Hodgkin's disease.

Nine-Year Survival of Lymphoblastic Lymphoma Patients

This study aimed to analyze the overall survival period of adult lymphoblastic lymphoma patients treated with various therapeutic regimens, and to assess the determinants affecting survival outcome. Twenty-five adult patients with lymphoblastic lymphoma who had been treated at Severance Hospital, Yonsei University College of Medicine, Seoul, Korea from June 1996 to June 2005 were analyzed retrospectively. As an initial remission induction chemotherapy, the hyper-CVAD regimen was performed in eight patients, the Stanford/Northern California Oncology Group (NCOG) regimen in five, the CAVOP regimen in four, the m-BACOP regimen in three, and the CHOP regimen in one patient. Patients were divided into two groups according to their therapeutic modalities. Twenty patients received conventional chemotherapy alone and five received subsequent PBSCT after conventional chemotherapy. Four patients of the PBSCT group underwent autologous PBSCT and one underwent allogeneic PBSCT. The overall response rate was 80% (60% showing a complete response, 20% showing a partial response) and the relapse rate was 73.3%. The overall survival (OS) rate was 55.1% at 1 year, 31.5% at 5 years, and 23.6% at 9 years. The disease-free survival (DFS) rate was 46.7% at 1 year and 30.0% at 7 years. The 5-year OS rate in relation to the regimens was 60% with the Stanford/NCOG regimen, 50% with the CAVOP regimen, and 33.3% with the m-BACOP regimen. The patients treated with the hyper-CVAD regimen had an 18.2% 2-year OS rate, and other patients with CHOP or COPBLAM-V expired early in their course. The OS rate in patients treated with conventional chemotherapy alone was 19.8%, whereas patients treated with subsequent PBSCT after chemotherapy showed 50% overall survival (p=0.25). The age at presentation influenced the outcome of the patients (p=0.01). The Stanford/NCOG regimen is an effective initial choice of therapy for lymphoblastic lymphoma patients, and is superior to the hyper-CVAD regimen in complete response rate and overall survival rate (p=0.36). Addition of PBSCT after chemotherapy may be needed for achieving optimal outcomes.

High Dose Chemotherapy and Autologous Stem Cell Transplantation in Non-Hodgkin's Lymphoma: an Eight-Year Experience

Autologous stem cell transplantation (ASCT) is commonly used in relapsed or refractory non-Hodgkin's lymphoma (NHL). Several trials report the role of ASCT for high risk patients. We evaluated the results and the prognostic factors influencing the therapeutic effects on the patients who were treated with high dose chemotherapy (HDC) and autologous peripheral stem cell transplantation. We analyzed the data of 40 cases with NHL who underwent ASCT after HDC. Twenty- four patients had high-risk disease, 12 cases sensitive relapse, and two cases resistant relapse or primary refractory each. The median age of patients was 34 years (range, 14-58 years). The median follow-up duration from transplantation was 16 months (range, 0.6-94 months). Estimated overall survival and progression-free survival at 5 years were 40% and 30%, respectively. Poor prognostic factors for survival included older age (> or = 45 years), poor performance status in all patient analysis, and a longer interval between first complete remission and transplantation in high risk patients. In high risk NHL patients, transplantation should be done early after first complete remission to overcome chemo-resistance.

A Case of Serum Amino Acid Disturbance with Hyperammonemia in Patient with Primary Amyloidosis / 대한혈액학회지

There have been reports that hyperammonemia and amino acid disturbance can cause loss of consciousness in patients with multiple myelomas and normal liver function. We experienced a case of a 71-years-old female patient with amyloidosis, who had shown disturbance of consciousness. At that time, the serum ammonia level was elevated; serum amino acids disturbance was also noted. In particular, the decrease in branched-chain amino acids and increase in aromatic amino acids results in a low Fisher ratio. The Fisher ratio, the ratio of branched-chain to aromatic amino acids, has been suggested as an important indicator of consciousness disturbance. We report, for the first time in Korea, a case of amyloidosis, with mental disturbance due to serum amino acid disturbance.

Two Cases of Acquired Hemophilia A Successfully Treated with Oral Steroid or Danazol / 대한혈액학회지

Acquired Hemophilia A is a rare and considerably life-threatening coagulopathy, which is caused by the development of autoantibodies against factor VIII (FVIII) in non-hemophilic adults. Acquired FVIII inhibitors can be associated with diverse conditions, such as malignant disorders, medications, autoimmune diseases, postpartum states and others. These autoantibodies inhibit normal coagulation, had results in bleeding complications, which can contribute to mortality in a high percentages of cases. Effective control of the disorder can be achieved by prompt diagnosis and appropriate managements. Generally, the managements of acquired hemophilia A are aimed at treating the acute bleeding and eliminating inhibitors by immunosuppression. Although a range of treatment options exists for patients with acquired hemophilia A, there is no consensus with regard to the optimal therapies for this disorder. Herein, two cases, an 82-year-old man and a 78-year-old man who were successfully treated by steroid or danazol, which is a relatively mild immunosuppressive agent, are reported.

A Case of Acute Respiratory Distress Syndrome by Nosocomial Mycoplasma Pneumonia Associated with Cold Agglutinin Disease in Primary CNS Lymphoma

Although Mycoplasma pneumonia is frequently observed in immunocompromized patient if, rarely results in acute respiratory distress syndrome (ARDS). The cold agglutinin is positive in 33-76% of patients with M. pneumonia infection. We experienced a case of ARDS due to mycoplasma pneumonia associated with cold agglutinin disease in primary CNS lymphoma. He was a 60-year old primary CNS lymphoma patient with mycoplasma pneumonia and cold agglutinin disease who rapidly progressed to ARDS after 1 cycle of chemotherapy. He completely recovered with roxithromycin, levofloxacin, and ventilator supports. After recovery 2nd cycle of combination chemotherapy and brain radiation therapy was given and, CNS lymphoma is in complete remission until now.

A Case of Acute Respiratory Distress Syndrome by Nosocomial Mycoplasma Pneumonia Associated with Cold Agglutinin Disease in Primary CNS Lymphoma

Although Mycoplasma pneumonia is frequently observed in immunocompromized patient if, rarely results in acute respiratory distress syndrome (ARDS). The cold agglutinin is positive in 33-76% of patients with M. pneumonia infection. We experienced a case of ARDS due to mycoplasma pneumonia associated with cold agglutinin disease in primary CNS lymphoma. He was a 60-year old primary CNS lymphoma patient with mycoplasma pneumonia and cold agglutinin disease who rapidly progressed to ARDS after 1 cycle of chemotherapy. He completely recovered with roxithromycin, levofloxacin, and ventilator supports. After recovery 2nd cycle of combination chemotherapy and brain radiation therapy was given and, CNS lymphoma is in complete remission until now.

An Unusual Case of Spontaneous Remission of Hodgkin's Disease after a Single Cycle of COPP-ABV Chemotherapy Followed by Infectious Complications

Advanced Hodgkin's disease is usually treated with six or more cycles of combination chemotherapy. Spontaneous regression of the cancer is very rarely reported in patients with Hodgkin's disease. We present an unusual case of a patient with Hodgkin's disease who experienced complete remission with a single cycle of chemotherapy, followed by pneumonia. The case was a 36-year-old man diagnosed with stage IVB mixed cellularity Hodgkin's disease in November 2000. After treatment with one cycle of COPP-ABV (cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine) chemotherapy without bleomycin, the patient developed interstitial pneumonia and was cared in the intensive care unit (ICU) for two months. Follow-up chest computerized tomography (CT), performed during the course of ICU care, revealed markedly improved mediastinal lymphomatous lesions. Furthermore, follow-up whole body CT and 18-fluorodeoxyglucose positron emission tomography showed complete disappearance of the lymphomatous lesions. Four years later, the patient is well and without relapse. This report is followed by a short review of the literature on spontaneous regression of Hodgkin's disease. To the best of our knowledge, this is the first case report of spontaneous remission of Hodgkin's disease in Korea.

Clinical characteristics and treatment outcome of primary mediastinal lymphoma / 대한내과학회지

BACKGROUND: The primary mediastinal lymphoma (PML) is defined as the non-Hodgkin's lymphoma that presents primarily within the mediastinum, and primary mediastinal diffuse large B cell lymphoma (PMLBL) is defined as primary mediastinal lymphoma of which histology shows diffuse large B cell lymphoma. There is no available clinical study yet about the clinical characteristics and treatment outcome of PMLBL in Korea. Here the authors report our experience of 21 cases of PML including 11 cases of PMLBL. METHODS: The authors reviewed retrospectively medical records of 21 cases with PML from January 1992 to January 2003, and analyzed clinical characteristics, response to induction therapy, and survival. The authors subsequently performed subset analysis in 11 cases with PMLBL. Median follow-up period was 16 months (range, 4~80 months). RESULTS: Male to female ratio was 8:13 and the median age of 21 PML cases was 33.5 years. Of 21 PML cases, histology of most cases was diffuse large B cell lymphoma (11/21) and lymphoblastic lymphoma (8/21). Cell lineage was B cell in 13 cases (61.9%). Thirteen cases (62.0%) were in stage I and II. Initial induction therapy was chemotherapy alone in 19 cases, combined chemoradiotherapy in 1 case and no treatment in remaining 1 case. Response rate to initial therapy was 70% in 20 PML cases (complete response [CR] 50%, partial response 20%) with CR of 50% in 10 PMLBL. Median progression-free survival and overall survival for 11 PMLBL cases were 11 months and 16 months, respectively. CONCLUSION: Incidence of PML showed slight predominance in female and in relatively young age with median age of less than 40 years. Most patients presented with a chief complaint of superior vena cava syndrome including dyspnea. The most common histology of PML was diffuse large B cell lymphoma. PMLBL represented low complete response rate to conventional chemotherapy, low progression-free and overall survival rates compared with peripheral diffuse large B cell lymphoma by historical review.

Three Cases of Diffuse Large B-Cell Lymphoma Presenting as Primary Splenic Lymphoma

Primary splenic lymphoma (PSL) is often defined as generalized lymphoma with splenic involvement as the dominant feature. It is a rare disease that comprises approximately 1% of all malignant lymphomas. We investigated three cases of non-Hodgkin's splenic lymphoma that had different clinical features on presentation. The patients' survival times from diagnosis ranged from 59 to 143 months, without evidence of relapse after splenectomy and chemotherapy, with or without radiotherapy. This data suggest that PSL is potentially curable. Further studies are needed to evaluate the impact that different treatment modalities without splenectomy have on patient survival.

A Case of Primary Peripheral T-cell Lymphoma of the Stomach with Cytotoxic Phenotype / 대한소화기내시경학회지

Primary gastric lymphoma is the most common form of extralymphatic non-Hodgkin's lymphoma (NHL). Most cases are of B-cell origin and few cases of lymphoma of T-cell origin have been reported. Peripheral T cell lymphoma is a lymphoma of extrathymic origin. Expression of T-cell intracellular antigen (TIA)-1 can be detected in all cytotoxic cells, and the expression of this cytotoxic protein is associated with extranodal presentation. We report a case of primary peripheral T cell lymphoma of the stomach with cytotoxic T-cell phenotype in a 70-year-old male presenting with upper gastrointestinal bleeding.

Complete Resolution of Posttransplant Lymphoproliferative Disorder (Diffuse Large B-cell Lymphoma) with Reduction of Immunosuppressive Therapy

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation. PTLD is the disorder arising from the combined effects of Epstein-Barr virus associated lymphoid proliferation with the disruption of the normal immune control by the cytotoxic T cells. The treatment for PTLD is one of the most controversial topics in solid organ transplantation. It is well known that the initial management of PTLD is a reduction of immunosuppression. Early diagnosis and the early reduction in immunosuppression are essential even for monomorphic lymphoma. We report here on a case of the complete resolution of PTLD (diffuse large B cell lymphoma) which occurred after a drastic reduction of immunosuppression in a renal transplant recipient.

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.

A Case of Leukemia Cutis Associated with B-cell Chronic Lymphocytic Leukemia / 대한혈액학회지

Leukemia may be accompanied by two types of skin lesion. One is nonspecific lesion, called leukemids and the other is leukemia cutis, which is generally regarded as being a specific sign of dissemination of aggressive systemic leukemia to the skin. It is known to be associated with poor prognosis. Although some cases of leukemia cutis have been reported in Korea, however, there has been reported few cases of leukemia cutis which occurred in chronic lymphocytic leukemia (CLL). Recently we have experienced a case of leukemia cutis associated with CLL, so report this case with review of literatures.

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.

Primary lymphoma of genitourinary tract / 대한내과학회지

BACKGROUND: The primary lymphoma of genitourinary tract is very rare and reported sporadically in Korea. Therefore the aim of this study is to evaluate the clinical characteristics with therapeutic outcome in 15 cases of primary lymphoma of genitourinary tract. METHODS: Reviewed retrospectively medical records of 15 cases with primary lymphoma of genitourinary tract who had been diagnosed from January, 1990 to May, 2002, we analysed the clinical characteristics, stage, disease free survival and overall survival. RESULTS: There were 8 cases of lymphoma of testis, 3 cases of uterine cervix and body, 1 case of ovary, 1 case of vagina, and 2 cases of kidney. The histologic types were all diffuse large B cell, except 5 cases (3 cases T/NK cell, 1 case low grade MALT lymphoma, and 1 case precursor B cell lymphoblastic lymphoma). The median survival duration of all cases is 8.0 months, showing the similarity to that of testis lymphoma (7.0 months). CONCLUSION: In comparison with the prognosis of the lymphomas in uterine body and cervix, it was worse for the testicular and renal lymphoma, even though 3 cases of T/NK cell lymphoma impacted on the prognosis of testicular lymphoma. Therefore, with simultaneous elucidation of the prognostic factors systemically, therapeutic strategy must be continuously sought.

Eleven-Year Experience of Low Grade Lymphoma in Korea (Based on REAL Classification)

Low grade lymphomas are malignancies of predominantly small lymphocytes that typically have long median survival periods due to low proliferative rates. It is considered an indolent disease, but patients with low grade lymphoma can almost never be cured with conventional treatment. New low-grade lymphoma entities have been classified by the International Lymphoma Study Group (ILSG) and are also categorized into the Revised European American Lymphoma (REAL) classification. The REAL classification utilizes a multiparameter definition of clinico-pathologic and biologic entities. According to this classification, we investigated the incidence, various clinical characteristics, treatment outcome and prognostic factors of low grade lymphoma. Many clinical characteristics of low grade lymphoma in Korea differed from those of Western countries, especially in the incidence, therapeutic outcome and prognostic factors. In Korea, although the general incidence of low grade lymphoma is relatively low, the relative number of mucosa-associated lymphoid tissue lymphoma (MALToma) is very high, and the overall survival rate is better than that reported of Western countries. Thus, further investigation on treatment outcome and prognosis of low grade lymphoma entities, other than mucosa-associated lymphoid tissue lymphoma, are warranted.