Pemetrexed-Erlotinib, Pemetrexed Alone, or Erlotinib Alone as Second-Line Treatment for East Asian and Non-East Asian Never-Smokers with Locally Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer: Exploratory Subgroup Analysis of a Phase II Tri / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This subgroup analysis of a phase II trial was conducted to assess possible ethnicity-based trends in efficacy and safety in East Asian (EA) and non-EA populations with nonsquamous non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Never-smoker patients (n=240) with locally advanced or metastatic nonsquamous NSCLC included 133 EA patients randomized to pemetrexed supplemented with dexamethasone, folic acid, and vitamin B12 plus erlotinib (pemetrexed-erlotinib) (n=41), erlotinib (n=49), or pemetrexed (n=43), and 107 non-EA patients randomized to pemetrexed-erlotinib (n=37), erlotinib (n=33), or pemetrexed (n=37). The primary endpoint, progression-free survival (PFS), was analyzed using a multivariate Cox model. RESULTS: Consistent with the results of the overall study, a statistically significant difference in PFS among the three arms was noted in the EA population favoring pemetrexed-erlotinib (overall p=0.003) as compared with either single-agent arm (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29 to 0.79; p=0.004 vs. erlotinib; HR, 0.40; 95% CI, 0.23 to 0.70; p=0.001 vs. pemetrexed). The EA patients treated with pemetrexed-erlotinib achieved a longer median PFS (7.4 months) compared with erlotinib (4.5 months) and pemetrexed (4.0 months). The PFS results also numerically favored pemetrexed-erlotinib in the non-EA population (overall p=0.210) (HR, 0.62; 95% CI, 0.37 to 1.05; p=0.078 vs. erlotinib; HR, 0.75; 95% CI, 0.42 to 1.32; p=0.320 vs. pemetrexed) (median PFS: pemetrexed-erlotinib, 6.7 months; erlotinib, 3.0 months; pemetrexed, 4.4 months). CONCLUSION: The PFS results from this subset analysis in both EA and non-EA populations are consistent with the results in the overall population. The PFS advantage for pemetrexed-erlotinib is significant compared with the single agents in EA patients.

Definitive radiotherapy with or without chemotherapy for clinical stage T4N0-1 non-small cell lung cancer

PURPOSE: To determine failure patterns and survival outcomes of T4N0-1 non-small cell lung cancer (NSCLC) treated with definitive radiotherapy. MATERIALS AND METHODS: Ninety-five patients with T4N0-1 NSCLC who received definitive radiotherapy with or without chemotherapy from May 2003 to October 2014 were retrospectively reviewed. The standard radiotherapy scheme was 66 Gy in 30 fractions. The main concurrent chemotherapy regimen was 50 mg/m2 weekly paclitaxel combined with 20 mg/m2 cisplatin or AUC 2 carboplatin. The primary outcome was overall survival (OS). Secondary outcomes were failure patterns and toxicities. RESULTS: The median age was 64 years (range, 34 to 90 years). Eighty-eight percent of patients (n = 84) had an Eastern Cooperative Oncology Group performance status of 0-1, and 42% (n = 40) experienced pretreatment weight loss. Sixty percent of patients (n = 57) had no metastatic regional lymph nodes. The median radiation dose was EQD2 67.1 Gy (range, 56.9 to 83.3 Gy). Seventy-one patients (75%) were treated with concurrent chemotherapy; of these, 13 were also administered neoadjuvant chemotherapy. At a median follow-up of 21 months (range, 1 to 102 months), 3-year OS was 44%. The 3-year cumulative incidences of local recurrence and distant recurrence were 48.8% and 36.3%, respectively. Pretreatment weight loss and combined chemotherapy were significant factors for OS. Acute esophagitis over grade 3 occurred in three patients and grade 3 chronic esophagitis occurred in one patient. There was no grade 3-4 radiation pneumonitis. CONCLUSION: Definitive radiotherapy for T4N0-1 NSCLC results in favorable survival with acceptable toxicity rates. Local recurrence is the major recurrence pattern. Intensity modulated radiotherapy and radio-sensitizing agents would be needed to improve local tumor control.

Platelet Dysfunction in a Patient with Multiple Myeloma: A Case Report with a Literature Review / 대한내과학회지

Multiple myeloma is a monoclonal plasma cell proliferation disorder with various symptoms and signs caused by paraproteinemias. Among these signs, a bleeding tendency is one of the major fatal causes. However, significant severe bleeding is rare in most cases. In this study, we report a case of multiple myeloma in a patient who had a severe recurrent bleeding tendency due to platelet dysfunction caused by paraproteins. After being treated with therapeutic plasma exchange and chemotherapy, the patient's monoclonal protein level decreased and the bleeding stopped.

Phase II Study of S-1 Plus Either Irinotecan or Docetaxel for Non-small Cell Lung Cancer Patients Treated with More Than Three Lines of Treatment / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was designed to evaluate the efficacy of a combination treatment of S-1 plus either irinotecan or docetaxel for advanced/metastatic non-small cell lung cancer (NSCLC) patients who have already failed 3 or more lines of treatment. MATERIALS AND METHODS: This was a prospective single center phase II study. The eligible patients received S-1 40 mg/m2 twice a day orally on days 1 though 14 combined with irinotecan 150 mg/m2on D1 only or docetaxel 35 mg/m2 on D1 and D8. The treatment was repeated every 3 weeks until disease progression, unacceptable toxicity, or patient refusal. The choice between the two regimens was made at the discretion of the treating physician. RESULTS: A total of 14 patients participated in the study. There were 3 patients with squamous cell carcinoma, 9 with adenocarcinoma, and 2 with NSCLC, NOS. Eight of the patients were male. There were 8 patients with an Eastern Cooperative Oncology Group (ECOG) of 1, and 6 patients with an ECOG of 2. All the patients had already been treated with platinum-based chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitor therapy. Out of the 14 patients, 10 received irinotecan and S-1 and the other 4 received docetaxel and S-1. Twelve patients had also received pemetrexed. Disappointingly, there were no response from 2 patients with a stable disease, and therefore, as per the protocol, we stopped the study early. With a median follow-up time of 49 months, the median survival time was 5.6 months (95% confidence interval, 4.3 to 6.9 months). CONCLUSION: S-1 containing doublets did not show activity in this population as a salvage treatment and further investigation cannot be recommended.

False-Positive Hypermetabolic Lesions on Post-Treatment PET-CT after Influenza Vaccination

We report a case of a 59-year-old man with testicular germ cell tumor who showed new hypermetabolic lesions at the left axillary lymph nodes on a post-treatment positron emission tomography-computed tomography (PET-CT) scan. The hypermetabolic lesions were found to be caused by an influenza vaccination 10 days prior to the PET-CT scan and disappeared without additional treatment. To date, he is alive with complete remission.

Modified Number of Extranodal Involved Sites as a Prognosticator in R-CHOP-Treated Patients with Disseminated Diffuse Large B-Cell Lymphoma

BACKGROUND/AIMS: Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP) has improved survival in patients with diffuse large B-cell lymphoma (DLBCL) and weakened the prognostic power of the international prognostic index (IPI). We evaluated the efficacy of the IPI and revised IPI (R-IPI) in patients with DLBCL who were treated with R-CHOP, focusing on extranodal site number (ENS) because extranodal involvement occurs frequently in Koreans. METHODS: A total of 126 R-CHOP-treated patients with stage III/IV DLBCL were analyzed. We performed a retrospective analysis of the clinicopathologic factors and verified the predictive power of the standard IPI and R-IPI. Various numbers of extranodal sites were analyzed for further stratification, and we set the extranodal site-modified IPI (E-IPI) as the IPI when the number of extranodal sites was stratified as or = 3. RESULTS: A univariate analysis showed that ENS was associated with complete response (CR, p = 0.04), event-free survival (EFS, p = 0.01), and overall survival (OS, p or = 3. A multivariate analysis revealed that an ENS > or = 3 remained associated with EFS (p or = 3, rather than the original or = 2, was the most significant prognostic factor for EFS and OS. All three indices were predictive, but only the E-IPI identified the high-risk group of R-CHOP-treated Korean patients with disseminated DLBCL.

Clinicopathologic Characteristics of T-cell Non-Hodgkin's Lymphoma: A Single Institution Experience

BACKGROUND/AIMS: Although the incidence of T-cell non-Hodgkin's lymphoma (NHL) is higher in Far East Asia than in Western countries, its incidence and clinical course in Korea are not well-defined. Therefore, we assessed the relative frequency and clinical features of T-cell NHL in Korea. METHODS: We performed a retrospetcive analysis of 586 patients with NHL. RESULTS: 101 (17.2%) had T-cell NHL. The most frequent subtypes of T-cell NHL were extranodal NK/T-cell lymphoma, nasal type (NASAL), peripheral T-cell lymphoma, unspecified type (PTCL-U), and anaplastic large cell lymphoma, T/null cell, primary systemic type (ALCL). The seven pathological subtypes could be classified into three prognostic subgroups. When patients with the three most frequent subtypes were grouped together, their survival was reflected in the International Prognostic Index (IPI) scores. Univariate analysis of IPI elements and other clinical features showed that clinical stage and extranodal sites were significant predictors of survival. Cox multivariate analysis showed that the number of extranodal sites was the only independent prognostic indicator. CONCLUSIONS: The relative frequency of T-cell NHL seems to be decreasing in Korea, although NASAL remains frequent. Korean patients with ALCL appear to have an unfavorable prognosis. Large-scale studies are warranted for Korean patients with T-cell NHL.

Peritoneal Dissemination from Malignant Fibrous Histiocytoma of the Buttock: Unusual Metastases from a Rare Tumor

We report a case of malignant fibrous histiocytoma (MFH) of the right buttock with multiple metastases to the lung, bone, and small intestine. He received resection and end-to-end anastomosis of the jejunum for the jejunal metastatic tumor, and mass excision of the metastatic tumor of the left femur followed by closed reduction and internal fixation and palliative radiotherapy. In addition, he received palliative radiotherapy to the metastatic pulmonary tumor with suspicious invasion into the thoracic aorta. However, one month after the completion of the aggressive local treatments, metastatic tumors recurred in the abdominal cavity, an extremely unusual site, resulting in peritoneal dissemination. He died of progressive disease 5 months after the initial diagnosis.

A Phase II Study of Cetuximab (Erbitux(R)) plus FOLFIRI for Irinotecan and Oxaliplatin-refractory Metastatic Colorectal Cancer

We have evaluated the efficacy and safety of cetuximab plus FOLFIRI for irinotecan and oxaliplatin-refractory colorectal cancers. From September 2004 to February 2006, 31 patients with metastatic colorectal cancer were treated with cetuximab (400 mg/m2 intravenously [IV] over 2 hr on day 1 followed by weekly 1-hr infusions of 250 mg/m2) plus bi-weekly FOLFIRI (irinotecan 150 mg/m2 IV over 90 min, and leucovorin 100 mg/m2 IV over 2 hr, followed by 5-FU 400 mg/m2 IV bolus on day 1, and followed by 5-FU 2,400 mg/m2 by continuous IV over 46 hrs). Patients received a median of four cycles (range: 1-23). Eight (25.8%) patients had confirmed partial responses and 10 (32.2%) had stable disease. After a median follow-up of 13.2 months for surviving patients, the median time to progression was 2.9 months, the median duration of response was 5.4 months, and the median overall survival was 10.9 months. Skin toxicity was observed in 25 patients (80.4%) including grade 3 in 6 patients (19.4%). Other common non-hematologic toxicities of all grades were mucositis (32.3%), asthenia (22.6%), diarrhea (12.9%), and paronychial cracking (12.9%). The combination of cetuximab with FOLFIRI was effective and tolerable in colorectal cancer patients heavily pretreated with a number of chemotherapy regimens.

Gemcitabine Single or Combination Chemotherapy in Post Anthracycline and Taxane Salvage Treatment of Metastatic Breast Cancer: Retrospective Analysis of 124 Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the efficacy of gemcitabine- based chemotherapy, particularly in patients with anthracycline- and taxane-pretreated 2(nd)-line or greater metastatic breast cancer, and to compare gemcitabine monotherapy (G) with two gemcitabine-based doublets, gemcitabine/ vinorelbine (GV) and gemcitabine/capecitabine (GX). MATERIALS AND METHODS: Of 124 consecutive patients who progressed after anthracycline- and taxane-containing chemotherapy, 58 received G alone, 38 received GV, and 28 received GX; their outcomes were analyzed retrospectively. RESULTS: The median number of prior metastatic chemotherapy regimens was 2 (range 0~4). Visceral metastases were observed in 65 patients (51.4%). The overall response rate was 19.3% (21 partial responses). After a median follow-up period of 21.4 months, the overall survival was 7.6 months (95% CI: 5.5~9.6 months) and the median time to progression was 3.1 months (95% CI: 2.0~4.2 months). Compared with monotherapy (G), combination therapy with vinorelbine or capecitabine (GV/ GX) was associated with a significantly higher response rate (8.2% vs. 28.3%, p=0.008) and a significantly longer median time to progression (2.8 vs. 3.5 months; p=0.028), but overall survival did not differ between the groups (7.4 vs. 8.2 months, respectively; p=0.54). Most of the adverse treatment-related events were mild to moderate in intensity. The most common adverse event was hematologic toxicity. Multivariate analysis showed that poor performance status and a short disease-free interval were independent prognostic factors for impaired overall survival. CONCLUSIONS: The combination of gemcitabine with vinorelbine or capecitabine was an active and well-tolerated treatment option for taxane- and anthracycline-pretreated 2(nd)-line or greater metastatic breast cancer patients, and gemcitabine-based doublets were more beneficial than gemcitabine monotherapy in alleviating symptoms for these patients.

A Case of Leukemic Pleural Infiltration in Atypical Chronic Myeloid Leukemia

Pleural effusion in chronic myeloid leukemia (CML) is poorly understood and rarely reported in the literature. When the pleural effusion is caused by leukemic pleural infiltration, the differential white blood cell count of the effusion is identical to that of the peripheral blood, and the fluid cytology reveals leukemic blasts. We report here a case of bilateral pleural involvement of atypical CML in an 83-yr old male diagnosed with pancreatic cancer with abdominal wall metastasis and incidental peripheral leukocytosis. Based on bone marrow examination, chromosome analysis and polymerase chain reaction he was diagnosed with Philadelphia chromosome negative, BCR/ABL gene rearrangement negative CML. Following 3 months of treatment with gemcitabine for pancreatic cancer, he developed bilateral pleural effusions. All stages of granulocytes and a few blasts were present in both the pleural fluid and a peripheral blood smear. After treatment with hydroxyurea and pleurodesis, the pleural effusion resolved.

Concurrent Male Gynecomastia and Testicular Hydrocele after Imatinib Mesylate Treatment of a Gastrointestinal Stromal Tumor

We report a gastrointestinal stromal tumor (GIST) patient with male gynecomastia and testicular hydrocele after treatment with imatinib mesylate. A 42 yr-old male patient presented for management of hepatic masses. Two years earlier, he had undergone a small bowel resection to remove an intraabdominal mass later shown to be a GIST, followed by adjuvant radiation therapy. At presentation, CT scan revealed multiple hepatic masses, which were compatible with metastatic GIST, and he was prescribed imatinib 400 mg/day. During treatment, he experienced painful enlargement of the left breast and scrotal swelling. Three months after cessation of imatinib treatment, the tumors recurred, and, upon recommencing imatinib, he experienced painful enlargement of the right breast and scrotal swelling. He was diagnosed with male gynecomastia caused by decreased testosterone and noncommunicative testicular hydrocele. He was given androgen support and a hydrocelectomy, which improved his gynecomastia. The mechanism by which imatinib induces gynecomastia and hydrocele is thought to be associated with an inhibition of c-KIT and platelet-derive growth factor. This is the first report, to our knowledge, describing concurrent male gynecomastia and testicular hydrocele after imatinib treatment of a patient with GIST.

Three Cases Treated with High-dose Cytarabine and Etoposide followed by Autologous Stem Cell Transplantation for Relapsed Primary CNS Lymphoma / 대한혈액학회지

The treatment outcomes with conventional second-line chemotherapy or radiotherapy aregenerally very poor for patients with relapsed primary CNS lymphoma (PCNSL). We treated three relapsed PCNSL patients with high-dose cytarabine plus etoposide (CYVE) chemotherapy, and this was followed by autologous stem cell transplantation (ASCT). The salvage CYVE chemotherapy consisted of cytarabine 2g/m2/d on days 2 to 5 in a 3-hour infusion and 50mg/m2/d on days 1 to 5 in a 12-hourinfusion, and etoposide 200mg/m2/d on days 2 to 5 in a 2-hour infusion. After two cycles of CYVE chemotherapy, two patients achieved a complete response (CR), and one patient achieved a partial response (PR). All three patients experienced febrile neutropenia and grade 4 thrombocytopenia with the CYVE chemotherapy. However, the hematologic toxicities were well managed without any complications. The conditioning regimen for ASCT consisted of BCNU 300mg/m2 on day -7, etoposide 100mg/m2 on days -6 to -3, cytarabine 100mg/m2 on days -6 to -3, and cyclophosphamide 35mg/kg on days -6 to -3 (BEAC). After ASCT, the patient who initially showed a PR with CYVE chemotherapy then achieved a CR. At the time of this report, one patient remained alive in CR for 41 months after CYVE chemotherapy. The remaining two patients experienced relapse 5 months and 4 months after ASCT, respectively, and they ultimately died of disease progression 18 months and 8 months after ASCT, respectively. In our cases, the CYVE chemotherapy+ASCT was well tolerated, and this induced the complete disappearance of the tumor, and one patient showed prolonged disease-free survival. CYVE chemotherapy+ASCT could be a treatment option for relapsed PCNSL.

Prognostic Factors in Non-Hodgkin's Lymphoma Patients Treated by Autologous Stem Cell Transplantation: A Single Center Experience / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Autologous stem cell transplantation (ASCT) is increasingly used in patients with non-Hodgkin's lymphoma (NHL). Various clinical parameters-were evaluated to obtain significant predictors of the outcome following ASCT in patients with NHL. MATERIALS AND METHODS: Between April 1994 and December 2003, ASCT was performed on 80 patients with NHL at the Asan Medical Center. RESULTS: Patients had various histological subtypes and disease status. The two year progression free survival (PFS) and overall survival for all patients were 34 and 31%, respectively. A univariate analysis showed the performance status, stage, modified extranodal involvement category, International Prognostic Index (IPI) at mobilization, disease status at mobilization, and history of radiation prior to mobilization as significant predictors of the outcome following ASCT. Four risk groups, with different 2 year PFS, were identified by the age adjusted IPI at mobilization (mAAIPI): low risk 44%; low intermediate risk 40%; high intermediate risk 19%; and high risk 0% (p=.0003). A multivariate analysis revealed 3 significant factors for the PFS: disease status, prior RT and mAAIPI. CONCLUSIONS: The mAAIPI was found to be an independent predictor of the outcome of NHL patients undergoing ASCT. This powerful prognostic tool should be used to evaluate potential candidates for ASCT.

Efficacy and Safety Study of Docetaxel as Salvage Chemotherapy in Metastatic Gastric Cancer Failing Fluoropyrimidine and Platinum Combination Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Fluoropyrimidine (F) and platinum (P) combination chemotherapy has been widely used for the first line treatment of advanced gastric cancer (AGC). Docetaxel (D) has shown promising activity in this disease. The present study retrospectively investigated the efficacy of D monotherapy as salvage chemotherapy for AGC that is failing F and P combination chemotherapy. MATERIALS AND METHODS: A total of 34 patients, fitting the eligibility criteria, were included in this study. D was administered at a dose of 75 mg/m2 IV every 3 weeks, with dexamethasone prophylaxis. Twenty-nine patients had measurable lesions. The median treatment-free interval was 38.5 days, and 91.2% of patients had progressed within 4 months of withdrawal of the first line chemotherapy. RESULTS: A total of 133 cycles of D were administered, with a median of 3.5 (1~8) cycles. From an intention-to-treat analysis, 6 patients achieved partial responses (PR), with a response rate of 20.7% (95% CI, 6.0~35.4). The duration of objective PRs in these six were 2.3+, 2.5+, 2.9, 3.0+, 6.2 and 6.8 months, respectively. Six patients showed a stable disease, but 15 showed progression. The median time to progression was 4.2 months (95% CI, 2.8~5.5), with a median overall survival since the start of D monotherapy of 8.4 months (95% CI, 5.5~11.3). Grade 3/4 neutropenia and febrile neutropenia occurred in 12.9% of patients and 3.1% of cycles. The incidence of grade 3 or worse non-hematological toxicities were as follows; peripheral sensory neuropathy 9.7%, asthenia 3.2% and allergic reaction 2.7%. CONCLUSION: Docetaxel, 75 mg/m2, is active in AGC as second-line chemotherapy after failure of prior exposure to the F and P combination chemotherapy, with a favorable toxicity profile.

Double Autologous Stem Cell Transplantation for Multiple Myeloma: A Korean Single Center Study

BACKGROUND: Although high dose chemotherapy coupled with an autologous stem cell transplantation (ASCT) is widely accepted as effective therapy for multiple myeloma (MM), few reports are available in Korea, especially in the area of double ASCT. We present the results of an institutional retrospective study of 12 patients with MM treated by double ASCT. METHODS: Eligible patients received induction therapy using vincristine, adriamycin, dexamethasone (VAD), and mobilization was performed using cyclophosphamide plus lenograstim. High-dose melphalan (total 200 mg/m2) was used to condition the ASCT. RESULTS: The median interval from diagnosis to ASCT was 6 months (range, 1.8-15.3 months). The median interval between the 1st and 2nd ASCT was 4.4 months (range 2.1-48.7 months). The median follow up was 18.3 months (range 8.1-50.5 months) for the nine surviving patients. No therapy-related mortality occurred. Following induction chemotherapy, two patients experienced CR. Following double ASCT, eight patients experienced CR. The 5 year OS was 59%. The median duration of event free survival was 2.13 years (95% CI, 0.84-3.42). CONCLUSION: Although the results of study did not demonstrate the advantage of double ASCT, this is the first report to outline the outcome of double ASCT for Korean MM patients.

Clinical Value of Cyclooxygenase-2 Expression in Human Breast Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To determine whether COX-2 expression is associated with clinicopathological parameters, including c-erb-B2 overexpression and angiogenesis, and the disease- free survival of patients with operable breast cancer. MATERIALS AND METHODS: Paraffin-embedded tissue samples were selected from 205 patients surgically resected for breast cancer, between 1991 and 1997, and followed- up for at least 4 years. Samples were immunohistochemically stained with antibodies to COX-2, c-erb-B2 and CD34. RESULTS: COX-2 and c-erb-B2 expressions were detected in 118/205 (57.6%) and 58/205 (28.3%) patients, respectively. COX-2 expression was significantly higher in c-erb-B2 positive than c-erb-B2 negative tumors (75.9% vs. 49.7%, p-value 0.001). COX-2 expression was positively correlated with microvessel count (13.3+/-8.0 vs. 6.6+/-7.0, p-value 0.050), but not with other clinicopathological characteristics, including tumor size, involved axil lary lymph nodes and estrogen or progesterone receptor status. Although COX-2 expression itself was not a prognostic marker, breast cancer patients with tumors that co-expressed both COX-2 and c-erb-B2 had a poorer 5-year disease-free survival rate than those that did not (60.2% vs. 78.3%, p-value 0.0527). CONCLUSION: Our data suggest that COX-2 expression occurs frequently in c-erb-B2 positive breast cancer, and co-expression of COX-2 and c-erb-B2 may be a useful prognostic marker in patients with operable breast cancer.

An Improved Outlook for Patients with Acute Leukemia over the Last 14 Years: A Perspective from a University Hospital / 대한혈액학회지

BACKGROUND: To see whether there has been improvement in the survival of patients with acute leukemia over the last 14 years, a retrospective analysis was performed. METHODS: Clinical and laboratory data were obtained form the medical records. Patient survival data was obtained from the hospital records, national cancer registry or by direct phone contacts. RESULTS: Between June, 1989 and August 2002, 714 adult patients were diagnosed with acute leukemia at Asan Medical Center in Seoul. Fourteen patients were lost to follow-up within 100 days of the diagnosis and excluded. There were 535 patients with acute myelogenous leukemia (AML) and 165 with acute lymphoblastic leukemia (ALL). There were 65 patients with acute promyelocytic leukemia (APL) among 535 patients with AML. Patients with non-APL AML and ALL were divided into 3 cohorts according to the year of the diagnosis: cohort I, 1989~1994; cohort II, 1995~1998; cohort III, 1999~2002. Patients with APL were also divided into 3 cohorts: cohort I, pre-all-transretinoic acid (ATRA) period (1989~1994. 2); cohort II, ATRA with or without chemotherapy (1994. 3~2000. 8); and cohort III, ATRA plus idarubicin (2000. 9~2002). Univariate analysis showed significant improvement in patient survival in non-APL AML (4-year projected survival rates of 10%, 19%, and 33% for cohorts I, II, and III, respectively, P=0.0000), in ALL (27%, 28%, and 52%, P=0.03), and in APL (36%, 56%, and 80%, P=0.04). Multivariate analysis showed that the year of diagnosis was a significant independent variable for patient survival in non-APL AML and ALL. CONCLUSION: Our study showed significant survival improvement in acute leukemia over the last 14 years. This improvement is not likely due to change in patient demographics. Rather, it is likely that introduction of newer methods of treatment of acute leukemia, such as multi-cycle combination chemotherapy for ALL, high dose cytarabine consolidation for AML, ATRA for APL, and wider application of allogeneic hematopoietic cell transplantation, has resulted in a better patient survival.

The Risk of Cytomegalovirus Infection in Non-myeloablative Peripheral Stem Cell Transplantation Compared with Conventional Bone Marrow Transplantation

Non-myeloablative allogeneic peripheral stem cell transplantation (NST) is a novel therapeutic strategy for patients with hematologic malignancies. Whether non-myeloablative transplants are associated with increased risk of cytomegalovirus (CMV) infections is unknown. To clarify this issue, we compared the outcome of CMV infection following 24 allogeneic non-myeloablative peripheral blood stem cell transplants and 40 conventional bone marrow transplants (CBT). The NST regimen consisted of busulfan (4mg/kg/day), fludarabine (30mg/m2) and anti-thymocyte globulin (10mg/kg). Twelve patients (50%) in the NST group and 17 (43%) in the CBT group developed positive antigenemia before day 100 (p=0.60). The time to the first appearance of positive antigenemia was not different between these two groups (p=0.40), and two groups showed similar initial and maximal antigenemia values (p=0.56 and p=0.68, respectively). Only one case of CMV colitis developed in the CBT group whereas CMV disease did not develop in the NST group. Although statistically insignificant, the treatment response against CMV antigenemia using ganciclovir was in favor of NST group. In conclusion, there was no difference in the risk of CMV infection between NST group and CBT group. Further prospective and controlled study is needed to clarify the impact of non-myeloablative procedure on the outcome of CMV infection.

Preliminary Results of the Prospective Randomized Phase III Trial on the Induction Chemotherapy in the Concurrent Chemoradiotherapy for the Locally Advanced Non-small Cell Lung Cancer

PURPOSE: To investigate the role of induction chemotherapy in relation to the treatment results and toxicities of concurrent chemoradiotherapy (CCRT) for locally advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with unresectable and pathologically confirmed Stage III NSCLC were eligible. According to the stage and pathological subgroup, the patients were randomized into two arms. Arm A received two cycles of the induction chemotherapy composed of gemcitabine, 1,000 mg/m2 (D1 and D8), and cisplatin, 70 mg/m2 (D1), followed by CCRT with weekly paclitaxel, 50 mg/m2, and cisplatin, 20 mg/m2. Arm B received immediate CCRT without the induction chemotherapy. A daily 2.2 Gy radiation dose was delivered to the isodose line covering the planned target volume, which was defined as the gross tumor volume plus a 1.0 cm margin from the planning CT, using a 3-D conformal radiation therapy technique. RESULTS: Between May 2003 and 2004, 63 patients were enrolled. Forty four patients (Arm A 23, Arm B 21) were evaluable, with follow-up periods exceeded 1 month after the end of the assigned treatment. The median follow-up periods were 6 and 7 months for Arms A and B, respectively. The patients' characteristics, including gender, age, weight loss, performance status, pulmonary function and stage, were well balanced between the two arms. The median largest tumor diameters were 4.8 cm (3.0~15 cm) and 5.0 cm (2.5~10 cm) for Arms A and B, respectively. The one-year survival rates were 58 and 63% for Arms A and B respectively, which showed no statistical significance (p=0.6667). The compliance of the induction chemotherapy was 96% (22/23 patients), and those of the CCRT were 86% for both arms (18/21 patients). The response rate of the induction chemotherapy was 64% (14/22 patients) and those of the CCRT were 83 (15/18 patients) and 89% (16/18 patients) for Arms A and B, respectively, which showed no statistical significance (p=0.630). In the 23 patients of Arm A, 8 (35%) suffered grade 3~4 neutropenia during the induction chemotherapy and 1 expired due to sepsis. CCRT caused grade 3~4 neutropenia in 6 and 1 patients of Arms A (29%) and B (5%), respectively, showing statistical significance (p=0.038). Grade 3~4 radiation pneumonitis developed in 2 and patients from Arms A (10%) and B (5%), respectively, (p=0.464) and grade 3~4 acute esophagitis developed in 7 (Arm A) and 5 patients (Arm B) (p=0.495). CONCLUSION: Both treatment schemes showed acceptable treatment compliance and toxicities. However, the induction chemotherapy resulted in a higher incidence of severe neutropenia. The treatment outcomes, as yet, have shown no statistical significance. To evaluate the role of induction chemotherapy on the survival prolongation in CCRT for locally advanced NSCLC, more patients and a longer follow-up are mandatory