COVID-19 and Cancer: Questions to Be Answered / 한국호스피스완화의료학회지

The World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak to be a pandemic on March 12, 2020. In Korea, there have been 24,027 confirmed cases of COVID-19 and 420 deaths as of October 3, 2020. The clinical spectrum of COVID-19 ranges from asymptomatic infection to death. Cancer care in this pandemic has radically changed. The literature was reviewed. The COVID-19 pandemic has made it urgently necessary to profoundly re-organize cancer patients’ care without compromising cancer outcomes. Several important questions in regard to COVID-19 infection in cancer patients have emerged. Are patients with cancer at a higher risk of COVID-19 infection?Are they at an increased risk of mortality and severe illness when infected with COVID-19?Does anticancer treatment affect the course of COVID-19? Based on the existing research, cancer patients with immunosuppression are vulnerable to COVID-19 infection, and cancer patients are more likely to experience severe COVID-19. However, chemotherapy and major surgery do not seem to be predictors of hospitalization or severe disease. Korean background data on patients with cancer and COVID-19 are lacking. Prospective multicenter studies on the outcomes of patients with cancer and COVID-19 should be conducted.

Treatment Patterns and Changes in Quality of Life during First-Line Palliative Chemotherapy in Korean Patients with Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate chemotherapy patterns and changes in quality of life (QOL) during first-line palliative chemotherapy for Korean patients with unresectable or metastatic/recurrent gastric cancer (GC). MATERIALS AND METHODS: Thiswas a non-interventional, multi-center, prospective, observational study of 527 patients in Korea. QOL assessments were conducted using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-STO22 every 3 months over a 12-month period during first-line palliative chemotherapy. The specific chemotherapy regimens were selected by individual clinicians. RESULTS: Most patients (93.2%) received combination chemotherapy (mainly fluoropyrimidine plus platinum) as their first-line palliative chemotherapy. The median progression-free survival and overall survival were 8.2 and 14.8 months, respectively. Overall, “a little” changes (differences of 5-10 points from baseline)were observed in some of the functioning or symptom scales; none of the QOL scales showed either “moderate” or “very much” change (i.e., ≥ 11 point difference from baseline). When examining the best change in each QOL domain from baseline, scales related to some aspects of functioning, global health status/QOL, and most symptoms revealed significant improvements (p < 0.05). Throughout the course of first-line palliative chemotherapy, most patients' QOL was maintained to a similar degree, regardless of their actual response to chemotherapy. CONCLUSION: This observational study provides important information on the chemotherapy patterns and QOL changes in Korean patientswith advanced GC. Overall, first-line palliative chemotherapy was found to maintain QOL, and most parameters showed an improvement compared with the baseline at some point during the course.

Hospice Palliative Care in South Korea: Past, Present, and Future / 한국호스피스완화의료학회지

Hospice palliative care (HPC) in Korea has developed steadily since its introduction in 1965. Currently, HPC in Korea is targeted only towards terminal cancer patients and their families, and the national health insurance scheme covers only inpatient hospice care for said patients. In recent years, healthcare professionals and policy makers began to recognize the need for HPC services in diverse settings including outside hospital boundaries, and for all terminally-ill patients. A law on HPC passed in January 2016 allows terminally-ill patients to refuse life-sustaining treatments, and will likely facilitate further development of HPC services. It is critical for the government and all interested parties in the medical, academic and social sectors to collaborate to ensure its success once it takes effect in 2017. This article will briefly review the half-century history of HPC in Korea, and discuss how to prepare for and cope with death and, thereby, improve the quality of death.

A Case-Control Study to Identify Risk Factors for Totally Implantable Central Venous Port-Related Bloodstream Infection / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To date, the risk factors for central venous port-related bloodstream infection (CVP-BSI) in solid cancer patients have not been fully elucidated. We conducted this study in order to determine the risk factors for CVP-BSI in patients with solid cancer. MATERIALS AND METHODS: A total of 1,642 patients with solid cancer received an implantable central venous port for delivery of chemotherapy between October 2008 and December 2011 in a single center. CVP-BSI was diagnosed in 66 patients (4%). We selected a control group of 130 patients, who were individually matched with respect to age, sex, and catheter insertion time. RESULTS: CVP-BSI occurred most frequently between September and November (37.9%). The most common pathogen was gram-positive cocci (n=35, 53.0%), followed by fungus (n=14, 21.2%). Multivariate analysis identified monthly catheter-stay as a risk factor for CVP-BSI (p=0.000), however, its risk was lower in primary gastrointestinal cancer than in other cancer (p=0.002). Initial metastatic disease and long catheter-stay were statistically significant factors affecting catheter life span (p=0.005 and p=0.000). Results of multivariate analysis showed that recent transfusion was a risk factor for mortality in patients with CVP-BSI (p=0.047). CONCLUSION: In analysis of the results with respect to risk factors, prolonged catheter-stay should be avoided as much as possible. It is necessary to be cautious of CVP-BSI in metastatic solid cancer, especially non-gastrointestinal cancer. In addition, avoidance of unnecessary transfusion is essential in order to reduce the mortality of CVP-BSI. Finally, considering the fact that confounding factors may have affected the results, conduct of a well-designed prospective controlled study is warranted.

Trends in the Aggressiveness of End-of-Life Care for Advanced Stomach Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: It is important to balance the appropriateness of active cancer treatments and end-of-life care to improve the quality of life for terminally ill cancer patients. This study describes the treatment patterns and end-of-life care in terminal gastric cancer patients. MATERIALS AND METHODS: We retrospectively analyzed the records of 137 patients with advanced gastric cancer receiving chemotherapy and dying between June 1, 2006 and May 31, 2011. We recorded interval between last chemotherapy dose and death; frequency of emergency room visits or admission to the intensive care unit in the last month before death; rate of hospice referral and agreement with written do-not-resuscitate orders; and change in laboratory values in the last three months before death. RESULTS: During the last six months of life, 130 patients (94.9%) received palliative chemotherapy; 86 (62.7%) during the final two months; 41 (29.9%) during the final month. During the final month, 53 patients (38.7%) visited an emergency room more than once; 21 (15.3%) were admitted to the intensive care unit. Hospice referral occurred in 54% (74 patients) of the patients; 93.4% (128 patients) gave written do-not-resuscitate orders. Platelets, aspartate aminotransferase and creatinine changed significantly two weeks before death; total bilirubin, one month before; and C-reactive protein, between four and two weeks before death. CONCLUSION: Our results demonstrated that a significant proportion of gastric cancer patients received palliative chemotherapy to the end of life and the patients who stopped the chemotherapy at least one month before death had a lower rate of intensive care unit admission and longer overall survival than those who sustained aggressive chemotherapy until the last months of their lives.

Withdrawal of life prolonging treatment, and palliative care

Hospice palliative care does not aim at the artificial prolongation or artificial hastening of human lives. It helps terminal patients to face the natural end of their lives comfortably, by controlling the suffering of the patients and family members. Hospice in Korea was started in 1965 by Roman Catholic sisters from Australia without successive development, but it has been actively developed since the 1990s. Nevertheless, many tasks remain to be addressed before reasonable and sufficient palliative care can be provided to provide a high quality of life for terminal patients. Laws and regulations for hospice and palliative care should be established and reimbursement from the National Medical Insurance for palliative care also needs to be initiated. In addition, efforts should be made for the education of specialists and lay people to increase the acceptance of hospice and palliative care in Korean society. Ethical issues involved in terminal care, such as the withdrawal of futile treatment and use of advance medical treatment, should be widely discussed within Korean society until a broad consensus is reached.

Numb Chin Syndrome with Concomitant Painful Ophthalmoplegia Leading to a Diagnosis of Diffuse Large B Cell Lymphoma / Journal of the Korean Cancer Association, 대한암학회지

Painful ophthalmoplegia (PO) and concomitant numb chin syndrome (NCS) is a very rare event. There are a few reports in the literature about PO and concomitant NCS that have preceded the diagnosis of a malignancy. In this report, we describe a patient with diffuse large B cell lymphoma who presented with PO and concomitant NCS as the initial symptom of the disease.

Modified FOLFIRI as Second-Line Chemotherapy after Failure of Modified FOLFOX-4 in Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate efficacy and toxicity of irinotecan, leucovorin and 5-fluorouracil (FOLFIRI) as second-line treatment after failure of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) for advanced gastric cancer. MATERIALS AND METHODS: Patients who received modified FOLFOX-4 as first-line treatment and then received sequential modified FOLFIRI for disease progression were included in this study. The modified FOLFIRI regimen consisted of irinotecan 150 mg/m2 in a 90-minute intravenous infusion on day 1, leucovorin (LV) 20 mg/m2 and 5-fluorouracil (5-FU) 400 mg/m2 as a bolus followed by 600 mg/m2 as a 22-hour infusion on days 1 and 2 with the same dose of 5-FU/LV of modified FOLFOX-4 every 2 weeks. RESULTS: A total of 32 patients received 126 courses of FOLFIRI chemotherapy. No complete response was achieved. Three patients (9.4%; 95% confidence interval [CI], 0 to 20.1%) achieved partial response, whereas 11 (34.4%; 95% CI, 17.0 to 51.8%) patients showed stable disease. Disease control rate (complete response, partial responses and stable diseases) was 43.8% (95% CI, 25.6 to 61.9%) and median follow up duration was 11.3 months (range, 2.23 to 37.9 months). Median time to progression was 2 months (95% CI, 1.49 to 2.51 months), and median overall survival from the start of FOLFIRI was 5.84 months (95% CI, 4.34 to 7.34 months). Toxicities were tolerable. CONCLUSION: Modified FOLFIRI as second-line chemotherapy after failure of the modified FOLFOX-4 in advanced gastric cancer was tolerable but showed a lower response rate. Further study about retrying 5-FU/LV with irinotecan after failure of the 5-FU/LV combined regimen is necessary in advanced gastric cancer.

Modified FOLFIRI as Second-Line Chemotherapy after Failure of Modified FOLFOX-4 in Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate efficacy and toxicity of irinotecan, leucovorin and 5-fluorouracil (FOLFIRI) as second-line treatment after failure of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) for advanced gastric cancer. MATERIALS AND METHODS: Patients who received modified FOLFOX-4 as first-line treatment and then received sequential modified FOLFIRI for disease progression were included in this study. The modified FOLFIRI regimen consisted of irinotecan 150 mg/m2 in a 90-minute intravenous infusion on day 1, leucovorin (LV) 20 mg/m2 and 5-fluorouracil (5-FU) 400 mg/m2 as a bolus followed by 600 mg/m2 as a 22-hour infusion on days 1 and 2 with the same dose of 5-FU/LV of modified FOLFOX-4 every 2 weeks. RESULTS: A total of 32 patients received 126 courses of FOLFIRI chemotherapy. No complete response was achieved. Three patients (9.4%; 95% confidence interval [CI], 0 to 20.1%) achieved partial response, whereas 11 (34.4%; 95% CI, 17.0 to 51.8%) patients showed stable disease. Disease control rate (complete response, partial responses and stable diseases) was 43.8% (95% CI, 25.6 to 61.9%) and median follow up duration was 11.3 months (range, 2.23 to 37.9 months). Median time to progression was 2 months (95% CI, 1.49 to 2.51 months), and median overall survival from the start of FOLFIRI was 5.84 months (95% CI, 4.34 to 7.34 months). Toxicities were tolerable. CONCLUSION: Modified FOLFIRI as second-line chemotherapy after failure of the modified FOLFOX-4 in advanced gastric cancer was tolerable but showed a lower response rate. Further study about retrying 5-FU/LV with irinotecan after failure of the 5-FU/LV combined regimen is necessary in advanced gastric cancer.

The Role of Korean Hospice Care in the Asia Pacific Hospice Palliative Care Society / 한국호스피스완화의료학회지

Korean hospice care has been greatly developed in a short period of time, thanks to help of foreign specialists and aids from developed countries. With enormous growth in economy, Korea which once received foreign aids now give help to other countries. It is the time for the Korean hospice society to consider ways to make an international contribution. That way, Korea could help terminal patients both in Korea and neighboring countries overcome sufferings, maintain their dignity as human beings until the end of their lives and have a comfortable moment of death. Thus, we need to think about ways to contribute to the international hospice society and make related plans.

Knee Pain as an Initial Symptom of Colon Cancer / 대한내과학회지

Knee pain is rarely an initial symptom of colon cancer, because most bone metastases develop in the late stage of cancer. Therefore, patients with colorectal cancer usually present with gastrointestinal symptoms. Recently, we experienced a 46-year-old female with rectal cancer that presented as knee pain due to tibial metastasis without other organ metastasis. She was evaluated for knee pain and diagnosed with a rectal cancer after biopsies of the tibial and rectal masses. We report the first such case in Korea with a review of the literature.

Prognostic Significance of Glycolytic Metabolic Change Related to HIF-1alpha in Oral Squamous Cell Carcinomas

BACKGROUND: Growing tumors adapt to a hypoxic environment and increase anaerobic glycolysis. This metabolic switch is related to aggressive behavior. We investigated the relationship between glycolytic metabolism biomarkers associated with hypoxia-inducible factor (HIF)-1alpha and prognosis. METHODS: We performed immunohistochemical staining of HIF-1alpha, pyruvate dehydrogenase kinase (PDK) 1 and lactate dehydrogenase (LDH) 5 in 74 patients with oral squamous cell carcinoma (SCC) who had received curative radical resection. RESULTS: High reactivity of HIF-1alpha, PDK 1 and LDH 5 was observed in 29 (39.2%), 32 (43.2%) and 54 (73.0%) patients, respectively. Expression levels of the three biomarkers were significantly correlated. All three markers were highly expressed in 16 (21.6%) patients. Elevated expression of the three markers was associated with increased invasiveness (p = 0.043) and recurrence (p = 0.017) of tumors. In survival analysis, upregulation of the three markers was additionally associated with shorter disease free survival (DFS, p = 0.001) and overall survival (OS, p = 0.002). High expression of all three markers was a strong independent prognostic factor for DFS (p = 0.030) and OS (p = 0.026). CONCLUSIONS: Oral SCC with altered glycolytic metabolism exhibits a more invasive and aggressive phenotype. Our results indicate that glycolytic metabolism biomarkers related to HIF-1alpha may be independent prognostic factors in patients with oral SCC.

Distribution of Dendritic Cells and Regulatory T-Cells in Cutaneous Lymphomas

BACKGROUND: Dendritic cells (DCs) play an important role in immune reactions. This study was designed to identify the distribution patterns of DCs and regulatory T-cells (Tregs) in cutaneous lymphomas. METHODS: Immunohistochemistry was used to determine langerin expression on Langerhans cells, CD11b on inflammatory DCs, CD209 and CD11c on dermal DCs, CD303 on plasmacytic DCs, and Foxp3 on Tregs in 81 cases of cutaneous lymphomas. RESULTS: Various DCs and Tregs were identified in most cutaneous lymphomas. Plasmacytic DCs, inflammatory DCs and Tregs were identified mainly in tumor areas, whereas dermal DCs were distributed both in the tumor and stromal areas. Among DCs, dermal DCs were most prominently identified in the cutaneous lymphomas not only in the tumor area but also in the stroma. The intense stromal infiltration of dermal DCs was consistent finding in T-cell lymphomas. Diffuse large B-cell lymphoma (DLBCL), not otherwise specified also showed intense stromal infiltration of dermal DCs, but stromal infiltration in DLBCL, leg type was relatively scant. CONCLUSIONS: The results suggest that all types of DCs and Tregs are involved in cutaneous lymphoma tumor immunity. Among them dermal DCs may play a dominant role.

A Case of a Synchronous Peripheral T-cell Lymphoma in a Patient with Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) patients tends to have a higher risk of developing lymphoid malignancies. The majority of such tumors are of a B cell origin. However, it is known that the T cell lymphoma subtypes in SLE patients are quite rare. Here, we describe a case of peripheral T cell lymphoma, unspecified (PTCL-U) that occurred in a 50-year-old female SLE patient. The lymphoma was located at the bilateral cervical and mediastinal lymph nodes. The staging workup revealed no evidence of any other organ involvement. Epstein-Barr virus messenger RNA was detected in the serum, but not in the lymph nodes. She received front-line chemotherapy with the CHOP regimen and she achieved complete remission. She then subsequently received high-dose chemotherapy with autologous peripheral stem cell transplantation. The patient currently remains in a clinical and serological state of remission for the SLE and PTCL until the time of this report 18 months after chemotherapy, and this was followed by autologous peripheral blood stem cell transplantation.

Past, Present and Future of Hospice in Korea

Hospice in Korea was started by Sisters of 'Little Company of Mary' came from Australia in 1965, and has been developed mostly by the efforts of some nurses, priests, and sisters of catholic church, ministers of protestant church, and some devoted physicians. Now Korean hospice is in the stage where the active participation of physicians is essential for the facilitation of the development, and the people's need for the maintenance of high level of 'Quality of Life' urges it. To accomplish this need, we should start the laws and regulations for hospice as well as the reimbursement system for hospice care from the National Medical Insurance, we should develop education systems for physicians and medical students, and we should start subspecialty of Palliative Medicine. We also need to increase the level of social and medical acceptance for the use of narcotics for pain control of terminal cancer patients. Finally we need to perform clinical trial as well as the basic research associated with hospice care, and these data can be the basement of hospice development in Korea.

Clinical Significance of Vascular Endothelial Growth Factors (VEGF)-C and -D in Resected Non-Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Lymphatic spread of tumor is an important prognostic factor for patients with non-small cell lung carcinoma (NSCLC). Vascular endothelial growth factor-C (VEGF-C) and VEGF-D play important roles in lymphangiogenesis via the VEGF receptor 3 (VEGFR-3). We sought to determine whether VEGF-C, VEGF-D and VEGFR-3 are involved in the clinical outcomes of patients with resected NSCLC. MATERIALS AND METHODS: Using immunohistochemical staining, we investigated the protein expressions of VEGF-C, VEGF-D and VEGFR-3 in the tissue array specimens from patients who underwent resection for NSCLC. The immunoreactivity for p53 was also examined. The clinicopathological implications of these molecules were statistically analyzed. RESULTS: Analysis of a total of 118 specimens showed that VEGF-C, VEGF-D and their co-expression were significantly associated with more advanced regional lymph node metastasis (p=0.019, p=0.044 and p=0.026, respectively, N2 versus N0 and N1). A VEGFR-3 expression had a strong correlation with peritumoral lymphatic invasion (p=0.047). On the multivariate analysis for survival and recurrence, pathologic N2 lymph node metastasis was the only independent prognostic factor, but none of the investigated molecules showed any statistical correlation with recurrence and survival. CONCLUSIONS: The present study revealed that high expressions of VEGF-C and VEGF-D were strongly associated with more advanced regional lymph node metastasis in patients with resected NSCLC.

Treatment Outcome of Cisplatin-based Concurrent Chemoradiotherapy in the Patients with Locally Advanced Nasopharyngeal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The standard treatment of locally advanced nasopharyngeal cancer is a concurrent chemoradiotherapy (CCRT), and cisplatin has been used as the most popular chemotherapeutic agent. But many different doses and schedules for cisplatin administration such as daily, weekly and 3 week cycles have been proposed. We compared and analyzed the tumor response, the overall survival, the toxicity and the chemotherapy dose intensity in the patients with locally advanced nasopharyngeal cancer who were treated with CCRT. MATERIALS AND METHODS: We performed a retrospective study on 55 patients with locally advanced nasopharyngeal cancer, and they were treated with CCRT as a front-line treatment from Jan 1996 to Jun 2007 at Kangnam Saint Mary's Hospital. RESULTS: The patients had a median age of 53 years (range: 19~75 years). Of the total 55 patients, a 3-week cycle of 100mg cisplatin was administered in 31 patients and 30 mg weekly cisplatin was administered in 24 patients combined with radiotherapy. Twenty one patients had a complete response and four patients had a partial response for a response rate of 71.4% (95% CI: 59.5~83.3) after CCRT and followed by adjuvant chemo-therapy. The complete response rates for the 30 mg and 100 mg cisplatin groups were 72.7% (95% CI: 54.9~90.5) and 54.2% (95% CI: 36.7~71.7), respectively (p= 0.23). The duration of CCRT in the 100mg cisplatin group was significantly longer than that of the 30mg cisplatin group (11.1+/-2.9 weeks vs. 9.0+/-1.2 weeks, p= 0.003). The major deviation group, which was defined as prolongation of the radiotherapy duration for more than 2 weeks, had a significantly lower objective response rate than did the non-deviation group (56.3% vs 84.2%, respectively, p= 0.002). The major severe toxicities were leucopenia (49.1%), pharyngoesophagitis (49.1%), anorexia (43.6%), nausea (41.8%) and vomiting (40%). CONCLUSIONS: Weekly 30mg cisplatin-based CCRT is a practical, feasible cisplatin schedule for the patients with locally advanced nasopharyngeal cancer in regard to decreasing the interruption of radiation treatment and decreasing the treatment-related acute toxicities.

Discrepant Views of Korean Medical Oncologists and Cancer Patients on Complementary and Alternative Medicine / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was designed to evaluate the communication gap between Korean medical oncologists and cancer patients on complementary and alternative medicine (CAM). MATERIALS AND METHODS: Cross sectional studies utilized the responses of 59 medical oncologists and 211 patients. To understand the communication gap, perceived reasons and nondisclosure of CAM use, reactions of physicians to disclosure, and expectations for CAM were analyzed. Data were compared with use of the chi- squared test. RESULTS: Both medical oncologists and patients were in accord that CAM use would privde the patients with a feeling of hope. The medical oncologists believed more often than patients to attribute CAM use for control over medical care decisions, for the treatment of an incurable disease or as a nontoxic approach (p<0.05). Regarding reasons for nondisclosure, medical oncologists were morelikely to think that physicians would not understand the use of CAM, discontinue treatment or disapprove of the use of CAM (p<0.0001). Patients attributed nondisclosure mainly to the lack of questioning about CAM. Medical oncologists were more likely to warn of the risks with CAM use and less likely to encourage the use of CAM than perceived by patients (p=0.01). Patients expected that CAM could cure disease, extend survival, relieve symptoms and improve the immune system or quality of life more often than medical oncologists (p<0.05). CONCLUSION: Given the discrepant views of medical oncologists and patients on the use of CAM, medical oncologists should be aware of the discrepancies and attempt to resolve any differences.

Mucin Phenotype and CDX2 Expression as Prognostic Factors in Gastric Carcinomas

Background : Mucin phenotypic markers and CDX2 are widely expressed in gastric carcinomas, however, recent studies have produced conflicting results regarding whether the expression patterns of these markers have clinicopathologic significance. Methods : We examined samples from 217 gastric carcinoma patients immunohistochemically to determine if the expression of mucin phenotypic markers and CDX2 was correlated with postoperative survival and other clinicopathologic factors. Results : All tumors were phenotypically classified as gastric (type G, 81 cases), gastric and intestinal mixed (type GI, 55 cases), intestinal (type I, 43 cases), or unclassified (type U, 38 cases). The occurrence of type G and GI tumors was positively correlated with tumor progression whereas that of type U tumors was negatively correlated with tumor progression. CDX2 expression was correlated with type I tumors. Tumors that expressed MUC5AC or MUC6 had a better prognosis than those that did not. When the relationship between phenotype and prognosis was considered, type GI had the best prognosis, followed by type G, then type U. Conclusions : The mucin phenotypic markers may be useful for predicting tumor progression and survival in patients with gastric carcinomas. Additionally, CDX2 may play an important role in gastric carcinogenesis of type I tumors.

Autologous Stem Cell Transplantation using a Modified TAM Conditioning Regimen for Clinically Aggressive Non-Hodgkin's Lymphoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: High-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) have been used for the treatment of clinically aggressive non-Hodgkin's lymphoma (NHL). However, the superiority of specific conditioning regimens has not yet been established. The present study evaluated the efficacy and toxicity of a conditioning regimen involving fractionated total body irradiation (TBI), and the use of Ara-C and melphalan (TAM) for clinically aggressive NHL. MATERIALS AND METHODS: Between March 2002 and December 2004, 31 patients with aggressive NHL received fractionated TBI with a dose of 12 Gy over 3 days, and were administered 9 g/m2 Ara-C and 100 mg/m2 melphalan followed by autologous peripheral blood stem Cell Transplantation at the Catholic Hematopoietic Stem cell transplantation Center Korea. Patients that responded to first line chemotherapy and achieved complete remission (CR), or were in a first sensitive relapse were defined as having less advanced disease, while the other patients were defined as having more advanced disease. RESULTS: Objective responses were obtained in 24 of 31 patients (77.4%), comprising complete remission in 19 patients (61.3%) and partial remission in 5 (16.1%) patients. The median follow-up time was 28 months (range 1~62 months). At 3 years, the overall survival and event-free survival (EFS) rates were 62.3% and 47.3%, respectively. Patients with less advanced disease and more advanced disease showed 3-year EFS rates of 73.3% and 22.5 %, respectively (p=0.006). Early (within the first 100 days) treatment-related mortality occurred in 3 (9.7%) patients. Of the 31 total patients, 15 (48.4%) developed grade 3 mucositis, 22 (70.9%) developed neutropenic fever, and two (6.5%) developed interstitial pneumonia syndrome >grade 3. CONCLUSION: The modified TAM conditioning regimen and ASCT appear to be a feasible treatment regimen for clinically aggressive NHL, particularly for patients with less advanced disease.