Clinical Impact of Prognostic Nutrition Index for Advanced Gastric Cancer Patients with Peritoneal Metastases Treated Nivolumab Monotherapy / 전남의대학술지

Although nivolumab shows survival benefits for patients with advanced gastric cancer (AGC), predictive biomarkers for nivolumab treatment in AGC remain unclear, especially in the case of peritoneal metastases. This study investigated the clinical significance of the prognostic nutrition index (PNI), reflecting the host nutritional status and immunity, in AGC patients undergoing nivolumab monotherapy. This study retrospectively analyzed 53 AGC patients who received nivolumab between October 2017 and February 2021. Among them, 35 patients with peritoneal metastases were reviewed to investigate the relationship between the PNI and oncological outcomes. The PNI was calculated as 10×serum albumin level (g/dl)+0.005×total lymphocyte count (per mm3 ) at the first administration of nivolumab. With a median follow-up duration of 2.0 (0.3-13.5) months, the median overall survival (OS) was 2.0 months. The overall response and disease-control rates were 0.0% and 20.0%, respectively. Among the 35 patients, 13 patients were identified as a high-PNI group. In the univariate analysis, the high-PNI group showed a significantly longer PFS and OS than the low-PNI group. In the multivariate analysis, the high-PNI was independently associated with a longer PFS (p=0.021) and OS (p=0.022). The PNI can be useful for predicting PFS and OS in AGC patients with peritoneal metastases. However, further studies are required to validate these results in AGC and new strategies are needed to improve the outcome for AGC patients with peritoneal metastases.

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.

Clinical Usefulness of Hydromorphone-OROS in Improving Sleep Disturbances in Korean Cancer Patients: A Multicenter, Prospective, Open-Label Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the efficacy of hydromorphone-OROS (HM-OROS) in reducing sleep disturbance and relieving cancer pain. MATERIALS AND METHODS: One hundred twenty cancer patients with pain (numeric rating scale [NRS] > or = 4) and sleep disturbance (NRS > or = 4) were evaluated. The initial HM-OROS dosing was based on previous opioid dose (HM-OROS:oral morphine=1:5). Dose adjustment of the study drug was permitted at the investigator\'s discretion. Pain intensity, number of breakthrough pain episodes, and quality of sleep were evaluated. RESULTS: A total of 120 patients received at least one dose of HM-OROS; 74 of them completed the final assessment. Compared to the previous opioids, HM-OROS reduced the average pain NRS from 5.3 to 4.1 (p < 0.01), worst pain NRS from 6.7 to 5.4 (p < 0.01), sleep disturbance NRS from 5.9 to 4.1 (p < 0.01), incidence of breakthrough pain at night from 2.63 to 1.53 times (p < 0.001), and immediate-release opioids use for the management of breakthrough pain from 0.83 to 0.39 times per night (p = 0.001). Of the 74 patients who completed the treatment, 83.7% indicated that they preferred HM-OROS to the previous medication. The adverse events (AEs) were somnolence, asthenia, constipation, dizziness, and nausea. CONCLUSION: HM-OROS was efficacious in reducing cancer pain and associated sleep disturbances. The AEs were manageable.

Mycoflora and Enzymatic Characterization of Fungal Isolates in Commercial Meju, Starter for a Korean Traditional Fermented Soybean Product

Mycoflora was assessed in the commercial meju from four well-separated geographic origins. A total of 112 fungal isolates were identified by phenotypic characteristics and molecular taxonomy using sequencing the internal transcribed spacer of the rDNA and revealed 19 species from 13 genera. Enzymatic characteristics of protease and amylase, and mycotoxin production were analyzed.

Arsenic trioxide induces depolymerization of microtubules in an acute promyelocytic leukemia cell line

BACKGROUND: Arsenic trioxide (As2O3) is a well-known and effective treatment that can result in clinical remission for patients diagnosed with acute promyelocytic leukemia (APL). The biologic efficacy of As2O3 in APL and solid tumor cells has been explained through its actions on anti-proliferation, anti-angiogenesis, and apoptotic signaling pathways. We theorize that As2O3 activates a pathway that disrupts microtubule dynamics forming abnormal, nonfunctioning mitotic spindles, thus preventing cellular division. In this study, we investigated how As2O3 induces apoptosis by causing microtubule dysfunction. METHODS: Cultured NB4 cells were treated with As2O3, paclitaxel, and vincristine. Flow cytometric analysis was then performed. An MTT assay was used to determine drug-mediated cytotoxicity. For tubulin polymerization assay, each polymerized or soluble tubulin was measured. Microtubule assembly-disassembly was measured using a tubulin polymerization kit. Cellular microtubules were also observed with fluorescence microscopy. RESULTS: As2O3 treatment disrupted tubulin assembly resulting in dysfunctional microtubules that cause death in APL cells. As2O3 markedly enhanced the amount of depolymerized microtubules. The number of microtubule posttranslational modifications on an individual tubulin decreased with As2O3 concentration. Immunocytochemistry revealed changes in the cellular microtubule network and formation of polymerized microtubules in As2O3-treated cells. CONCLUSION: The microtubules alterations found with As2O3 treatment suggest that As2O3 increases the depolymerized forms of tubulin in cells and that this is potentially due to arsenite's negative effects on spindle dynamics.

Follicular Dendritic Cell Sarcoma: A Case Report and Review of the Literature / Journal of the Korean Cancer Association, 대한암학회지

Follicular dendritic cells (FDC) are non-lymphoid, non-phagocytic accessory cells of the immune system and these cells are essential for antigen presentation and regulation of the reactions in germinal centers. Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm that shows a low-to-intermediate malignant potential. The most commonly involved sites are the lymph nodes, but FDCS may also occur at a variety of extranodal sites, including the oral cavity, tonsils, gastrointestinal tract and liver. We describe here a 79-year-old woman who had FDCS with extensive lymph node involvement, dry cough, and an itching sensation. The patient improved after systemic chemotherapy.

Outpatient-basis Chemotherapy of Oxaliplatin, 5-fluorouracil, and Leucovorin as First-line Treatment for Patients with Metastatic or Recurrent Colorectal Cancer

The objectives of the present study were to evaluate the efficacy and safety of an outpatient-basis chemotherapy of oxaliplatin, 5-fluorouracil, and leucovorin as the first-line treatment for patients with advanced colorectal cancer. Forty-three histologically confirmed patients with metastatic or recurrent colorectal cancer were enrolled. The chemotherapy consisted of oxaliplatin 85 mg/m2 as a 2-hr infusion on day 1, plus leucovorin 30 mg/m2 over 10 min, followed by bolus 5-fluorouracil 400 mg/m2 and an 8-hr infusion of 5-fluorouracil 600 mg/m2 on days 1 and 2 (modified FOLFOX4), all of which were administered on an outpatient basis every 2 weeks. The median age was 58 yr (range 33-72 yr), and 25 (58.1%) patients had metastatic diseases. Eventually, 39 patients were assessable for efficacy and all assessable for toxicity. Four (9.3%) complete responses and 11 (25.6%) partial responses were confirmed, giving an overall response rate of 34.9% (95% CI; 20.0-49.7%). The median time to progression and median overall survival for all patients was 6.1 months and 17.4 months, respectively. Grade 3/4 neutropenia occurred in 2 patients (4.7%) and febrile neutropenia was observed in 1 patient (2.3%). Modified FOLFOX4, an outpatient-basis regimen, was found to be well-tolerated and effective as the firstline chemotherapy in patients with advanced colorectal cancer.

Unpredicted Severe Toxicity after 5-Fluorouracil Treatment due to Dihydropyrimidine Dehydrogenase Deficiency

Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU). Thus, patients with a DPD deficiency are at risk of developing severe 5-FU-associated toxicity. A 37-year-old female with gastric cancer underwent a curative operation, followed by adjuvant chemotherapy consisting of 5-FU and epirubicin. After the first cycle of chemotherapy, the patient manifested grade 2 mucositis and febrile neutropenia, and when her treatment was subsequently continued with doxifluridine she developed severe mucositis and febrile neutropenia. A PCR study revealed that her DPD mRNA level was lower than that in a control group. Thus, when considering the routine use of 5-FU for the treatment of cancer patients, an analysis of DPD activity or screening for DPD mutations is warranted in confined patients who experience unpredicted severe toxicity after initial 5-FU administration, even though DPD deficiency is a rare metabolic defect.

Clinical Significance of Platelet Count at day +60 After Allogeneic Peripheral Blood Stem Cell Transplantation

Thrombocytopenia (TP) is a frequent complication after allogeneic stem cell transplantation (SCT) and regarded as a poor prognostic factor, especially in patients with chronic graft-versus-host disease (GVHD), although various factors were related to the development of TP after allogeneic SCT. Sixty-three patients receiving allogeneic peripheral blood stem cell transplantation (PBSCT) were stratified according to platelet count (PC) at day +60 and analyzed in terms of overall survival (OS) and the incidence of non-relapse mortality (NRM). Ten patients (15.9%) were stratified in group 1 (PC or =80 x 10(9)/L). Group 3 was associated with lower incidence of extensive chronic GVHD (p=0.013), better 3-yr OS (p=0.0030), and lower NRM rate (p<0.0001). In multivariate analyses, the PC at day +60 was identified as an independent prognostic factor (p=0.003) together with CD34+ cell dose (p<0.001), disease risk (p=0.004), and acute GVHD (p=0.033) in terms of NRM, and the PC (p=0.047) and CD34+ cell dose (p=0.026) in terms of incidence of infectious events. Measuring the platelet count at day +60 is a simple method for predicting the risk of chronic GVHD development and prognosis after allogeneic PBSCT.

Primary malignant melanoma of the lacrimal sac: A case report

Malignant melanoma of the lacrimal sac is very rare and primary malignant melanoma is extremely rare. It is usually diagnosed at an advanced stage after excision or biopsy of a tumor. We treated a patient with tearing and bloody discharge from the left eye. We performed a dacryocystectomy with the suspicion of a chronic dacryocystitis. However, the pathological findings and the immunohistochemical studies showed a malignant melanoma of the lacrimal sac. The patient underwent postoperative irradiation therapy. Follow up two months after surgery revealed no evidence of recurrence. Early diagnosis is very important for prognosis in patients with malignant melanoma of the lacrimal sac. Because this tumor often presents with symptoms similar to dacryocystitis and may masquerade as a chronic dacryocystitis, it can be difficult to make an early diagnosis.

Treatment outcomes of primary central nervous system lymphoma: Multi-center retrospective study / 대한내과학회지

BACKGROUND: A primary central nervous system lymphoma (PCNSL) is a rare neoplasm with a poor prognosis. The treatment of PCNSL involves a combination of chemotherapy, intrathecal chemotherapy and radiotherapy. This study retrospectively evaluated the treatment outcomes and prognostic factors of Korean patients with PCNSL. METHODS: Between 1995 and 2003, 58 patients diagnosed with PCNSL from the multi-center hospitals were enrolled in this study. Among 56 patients who had received treatment, 16 patients were treated with radiotherapy alone, while 40 patients were treated with combined chemotherapy (CHOP; 9 cases, high-dose methotrexate; 31 cases) and radiotherapy. RESULTS: The median age of the patients was 58 years (range, 19-76). A diffuse large B-cell lymphoma was diagnosed in 56 cases (96.6%), while a peripheral T-cell lymphoma was diagnosed in 2 cases. Of the 47 patients who could be assessed for their response after treatment, a CR and PR was observed in 32 (68%) and 11 patients (23%), respectively, giving an overall response rate of 91% (95% CI, 82~100%). The estimated 3-year overall survival rate for all the patients was 67+/-7.9% and the 3-year disease free survival rate was 53+/-8.3%. The overall survival of the high-dose methotrexate group was superior to that of the CHOP group (77+/-10% versus 47+/-19%, p=0.05). Leukoencephalopathy was observed as a late complication in 9 patients (21%). No significant prognostic factors affecting survival were found by univariate analysis. CONCLUSIONS: Approximately half of the patients could have long-term survival after treatment in this study. High-dose methotrexate containing chemotherapy followed by radiotherapy was found to be an effective treatment.

Impact of Day +11 Methotrexate on the Incidence of Graft-versus-host Disease after HLA-identical Allogeneic Peripheral Blood Stem Cell Transplantation

BACKGROUND: Cyclosporine (CSA) plus 4 doses of methotrexate (MTX) is the commonly used regimen for GVHD prophylaxis. It has been previously found that the omission of the day +11 dose of MTX was associated with an increased risk of acute GVHD in the allogeneic BMT setting. However, little is known about its impact in the PBSCT setting. METHODS: Of the 68 patients, 30 patients (44%) received 4 doses of MTX (the MTX4 group), while 38 patients (56%) received less than 4 doses (the MTX3 group) because of their severe mucositis, hepatic dysfunction or renal failure. RESULTS: The cumulative incidence of acute GVHD was 60% in the MTX4 and 86% in the MTX3 group (P=0.038), while that of grade III and IV acute GVHD was 7% in the MTX4 group and 39% in the MTX3 group (P=0.017). Of the 61 patients evaluated for chronic GVHD, the cumulative incidence of chronic GVHD was 54% in the MTX4 group and 97% in the MTX3 group (P=0.001), while that of extensive chronic GVHD was 26% in the MTX4 group and 63% in the MTX3 group (P=0.004). There were no differences in the overall survival and the incidence of relapse between the two groups. On multivariate analyses, MTX3 was a poor prognostic factor in terms of acute GVHD and extensive chronic GVHD. CONCLUSION: This study suggested that omitting day +11 MTX and the clinical situation of the MTX3 group seemed to be associated with an increased incidence of acute and chronic GVHD. Accordingly, administration of day +11 MTX accompanied by active treatment of mucositis may prevent GVHD in the allogeneic PBSCT setting, but we need to conduct a large scale prospective study.

Clinical Efficacy of Thalidomide Containing Regimens as a Primary Therapy in Patients with Multiple Myeloma

BACKGROUND: The aim of this study was to assess the efficacy and toxicity of thalidomide-containing regimens as the first-line therapy for patients with multiple myeloma. METHODS: A total of 60 patients were initially treated with thalidomide-containing regimens at three institutions. Thalidomide was given with two different regimens: the TD regimen (thalidomide and dexamethasone) and the TCD regimen (thalidomide, cyclophosphamide, and dexamethasone). Autologous peripheral blood stem cells (PBSC) were collected after mobilizing with G-CSF with or without cyclophosphamide. RESULTS: Of all the patients, 56 patients (TD regimen: 12 patients, TCD regimen: 44 patients) who received at least 4 cycles or more were evaluated for response and toxicity. The median age of the patients was 65.5 years (age range: 39~80 years). The overall response rate for the thalidomide-containing regimens was 85.5%. There were 3 (25%) complete responses and 6 (50%) partial responses for the TD regimen and there were 17 (38.6%) complete responses and 21 (47.7%) partial responses for the TCD regimen, respectively. The toxicity, according to the NCI-CTC (grade 3/4) included neutropenia in 7 patients (12.5%), thrombocytopenia in 4 patients (7.1%), infection in 6 patients (10.7%) and neuropathy in 10 patients (17.8%). In addition, there were 2 patients (3.6%) with thrombosis. Thirteen patients, who achieved more than a partial response to the thalidomide-containing regimen, proceeded to PBSC collection and the median number of CD34+ cells collected was 3.8 x 106/kg. CONCLUSION: Thalidomide-based combination chemotherapy is a safe, well tolerated and effective regimen for patients with newly diagnosed multiple myeloma, and it showed a high response rates, relatively low toxicity and sufficient collection of PBSCs.

A Multi-Center, Phase II Clinical Trial of Padexol(TM) (Paclitaxel) and Cisplatin for Patients Suffering with Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We conducted a multi-center, phase II trial to evaluate the efficacy and safety of using Padexol (a paclitaxel formulation) combined with cisplatin for the patients suffering with advanced gastric adenocarcinoma. MATERIALS AND METHODS: 39 patients (median age: 60 years; males: 90%) who were diagnosed with advanced gastric cancer were enrolled from 5 hospitals. Padexol 175 mg/m2 was administered as a 3-hr infusion, and this was followed by cisplatin 75 mg/m2 as an intravenous infusion on day 1, once every 3 weeks. RESULTS: Out of these 39 patients, 34 patients were assessable for treatment efficacy and 39 patients were assessable for the toxicity. Objective responses occurred in 13 patients (33%); 1 patient (3%) had a complete response and 12 patients (31%) had partial responses. 6 patients (15%) achieved a stable disease state. The median duration of response was 7.1 months, and the median time to progression and the overall survival were 4.8 months and 6.7 months, respectively. The major treatment-related adverse events were hematologic toxicity, including WHO grade 3 or 4 neutropenia in 13 patients (33%). However, febrile neutropenia occurred in only 1 patient and the non-hematologic toxicity was usually mild. CONCLUSION: The combination of Padexol and cisplatin was found to be active and it seems to be a relatively well-tolerated regimen for the treatment of advanced gastric cancer.

Biweekly Irinotecan and Cisplatin as Second-line Chemotherapy in Pretreated Patients with Advanced Gastric Cancer: A Multicenter Phase II Study

The current phase II study was conducted to evaluate the response rate and safety of a combination regimen of biweekly irinotecan plus cisplatin in pretreated patients with advanced gastric cancer. Patients with previously treated metastatic or recurrent gastric cancer received intravenous irinotecan 70 mg/m2 and cisplatin 30 mg/m2 on day 1 and 15 every 4-week cycle. Thirty-two patients were enrolled in the current study. Of these, 31 patients were assessable for efficacy and all for toxicity. No complete response and 5 partial responses were confirmed, giving an overall response rate of 15.6% (95% CI; 2.3-28.9%). The median time to progression and median overall survival for all patients was 113 days and 184 days, respectively. Grade 3/4 neutropenia occurred in 6 patients (18.8%), yet no febrile neutropenia was observed. In addition, grade 3 anorexia was observed in 4 patients (12.5%) and grade 3 diarrhea occurred in 2 patients (6.2%). The combination chemotherapy of biweekly irinotecan and cisplatin was found to be moderately effective and well tolerated in pretreated patients with advanced gastric cancer. Accordingly, this regimen can be regarded as an important second-line treatment option for advanced gastric cancer.

Variable Number of Tandem Repeats (VNTR) Disparity between Donor and Recipient has a Potential to Predict the Outcomes of HLA-identical Allogeneic Stem Cell Transplantation

BACKGROUND: Detection of variable number of tandem repeats (VNTR) between recipient and donor has been adopted to monitor the degree of chimerism after allogeneic stem cell transplantation (SCT). In allogeneic SCT, besides MHC-disparity, the disparity of various polymorphous proteins encoded by several genes may play a critical role in the pathogenesis of graft-versus-host disease (GVHD). However, the biologic effect of VNTR disparity has been scarcely studied. METHODS: We analyzed 84 patients receiving SCT from HLA-identical sibling (n=68) or unrelated donors (n=16). Enrolled diseases included AML 48, ALL 8, CML 15, NHL 10, and high-risk MDS 3. The PCR was performed to amplify 3 VNTR regions (D1S80, D1S111, and D17S5). RESULTS: We observed strong correlation between the D1S80 disparity and transplant outcomes in terms of OS (P=0.0179) or non-relapse mortality (NRM) (P=0.0305), but not for D1S111 or D17S5 disparity. The D1S80-fully matched pair showed a better OS (72% vs 38%) and lower NRM (17% vs 50%) compared to partially matched or mismatched pairs. In multivariate analyses, D1S80-fully matched pair was found to be independent favorable prognostic factor for OS (P=0.03) or NRM (P=0.05). In addition, the D1S80 disparity was significantly associated with the myeloid engraftment speed (P=0.01) or the occurrence of gut chronic GVHD (P=0.05). CONCLUSION: Our data suggest that disparities in D1S80-located on chromosome1-seemed to be associated with increased incidence of gut chronic GVHD and NRMs, thus suggesting the existence of unknown genes of minor histocompatibility antigens targeting gut or cytokine/cytokine receptor on chromosome 1.

Phase II Study of Cyclophosphamide, Epirubicin, Vincristine, Prednisone, and Etoposide (CEOP-E) for Aggressive Non-Hodgkin 's Lymphoma

The main objectives of the current study were to evaluate the efficacy and safety of a CEOP-E regimen for patients with aggressive non-Hodgkin's lymphoma (NHL). Fifty-one consecutive patients with newly diagnosed aggressive NHL were enrolled in the study. Median age of patients was 57 (range, 18-75) yr old, and male to female ratio was 1.32:1. Diffuse large B cell lymphoma (68.8%) was the most common histological subtype. Thirty patients (58.8%) had Ann Arbor stage III or IV diseases at diagnosis. One course of chemotherapy consisted of an intravenous combination of cyclophosphamide 750 mg/m2, epirubicin 50 mg/m2, vincristine 2 mg, etoposide 80 mg/m 2 on day 1 and oral administration of 100 mg prednisone on days 1 to 5 (CEOP-E). A complete response or unconfirmed complete response was achieved in 31 (63.3%) out of 49 evaluated patients. With a median follow-up of 16.3 months, 26 events including relapse and death were observed. The estimated 2-yr survival rate for all patients and disease free survival rate for patients achieving complete re-sponse was 58.9% and 57.1%, respectively. Episodes of febrile neutropenia occurred in 5 (10.2%) patients. Transient episodes of ECG abnormality (1st degree AV block) were observed in 2 patients. Accordingly, the CEOP-E regimen produced comparable results to those of other regimens, including CHOP, in terms of the response rate and overall survival. The current regimen seemed to minimize the cardiac toxicity due to an accumulated dose of anthracycline in the treatment of aggressive NHL.

Allogeneic Peripheral Blood Stem Cell Transplantation in Hematological Malignancies: Stem Cell Mobilization with GM-CSF alone or a combination of GM-CSF and G-CSF from Normal Healthy Donors / 대한혈액학회지

BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) has been used in normal heathy donors to mobilize hematopoietic progenitors. Recently, it was reported that an addition of granulocyte-macrophage-CSF (GM-CSF) mobilized more primitive CD34+ subsets than did G- CSF alone. We investigated the result of the allogeneic peripheral blood stem cell transplantation (PBSCT) with stem cells mobilized with GM-CSF alone or a combination of GM-CSF and G-CSF from normal healthy donors in hematological malignancies. METHODS: Twenty-nine patients with hematologic malignancies had allogeneic PBSCT from normal sibling donors. Nine healthy donors were mobilized with GM-CSF (Leucogen (R)) alone and 20 with a combination of GM-CSF and G-CSF (Leucostim (R)). After 5~8 days of cytokine treatment, PBSCs were collected by large volume leukapheresis and analyzed. RESULTS: Stem cells were collected from the HLA matched normal healthy sibling donors. The mean harvested cell content was 8.74+/-3.22X10(8) MNCs/kg, 15.65+/-16.02X10(6) CD34+ cells/kg of the patients. There were significant differences in the harvested MNC count between mobilization group with GM-CSF alone and group with a bination of GM-CSF and G-CSF. Observed side effects of cytokine mobilization were myalgia (76%), headache (41%), febrile sense (24%) and skin rash (10%). These complications disappeared within 48 hours after discontinuation of cytokines. The median interval to achieve a WBC count>500/uL was 15.00+/-4.23 days, and 14.00+/-33.01 days to a platelet count>20,000/uL. The actual incidence of acute GVHD was 36.4%, 22.7%, and 4.5% for skin, GIT, and liver, respectively. Immunosuppressant responsive chronic GVHD developed in 63.1% (12/19) of assessable patients including 6 cases who had donor lymphocyte infusions. CONCLUSION: In this study, GM-CSF based cytokine mobilization was able to collect sufficient numbers of stem cells and allow rapid engraftment in the allogeneic PBSCT. Mobilization protocol with a combination of GM-CSF and G-CSF seemed to be superior to GM-CSF alone. Acute GVHD in patients with allogeneic PBSCT didn't appear to be more severe than in patients undergoing allogeneic BMT.

The Frequency and Clinical Significance of Multidrug Resistance-1 (MDR-1) Gene Expression in Acute Myeloid Leukemia / 대한혈액학회지

BACKGROUND: The expression of the multidrug resistance-1 (MDR-1) gene which encodes p-glycoprotein, is recognized as a biological mechanism possibly contributing to treatment failure in patients with acute myeloid leukemia (AML). Recent studies indicate its association with poor risk factors such as cytogenetic pattern and surface phenotype of blasts. We analyzed the role of MDR-1 gene expression in 36 chemo-naive AML patients. METHODS: In 36 patients, clinical data were reviewed and compared to MDR-1 gene expression, immunophenotyping results on CD7 & CD34, cytogenetic pattern and other suggestive prognostic factors. RESULTS: Median follow-up period was 150 days. The MDR-1 gene expression was observed in 19 out of 36 patients (52.8%). Significant correlation between MDR-1 gene and CD7 & CD34 expression was found. Sixteen out of 17 (94.1%) MDR-1 negative patients harbored favorable cytogenetic patterns, where as 11 out of 19 (57.9%) MDR-1 positive patients had favorable cytogenetic patterns. MDR-1 gene expression was not correlated to disease free survival (DFS), nor overall survival (OS) statistically although it has shown significant correlation to complete remission (CR) rate (P =0.001). CONCLUSION: We found that lack of MDR-1 gene expression was exclusively associated to favorable cytogenetic patterns in our study. In order to clarify the relationship between the role of MDR-1 gene and clinical outcome or other prognostic features, including cytogenetic pattern, further larger studies would be necessary.

Long-term Observation of 87 Cases with Chronic Idiopathic Thrombocytopenic Purpura in Adult / 대한혈액학회지

BACKGROUND: Information about the natural history of chronic idiopathic thrombocytopenic purpura (ITP) is still vague and far from complete due to a lack of studies. The purpose of the present study is to define ultimate outcome of adults with chronic ITP by long-term observation of patients. Method : We retrospectively analyzed eighyty-seven ITP patients diagnosed at the Department of Internal Medicine, Kyungpook National University Hospital and Taegu-Hyosung Catholic University Hospital and Taegu-Fatima Hospital between March 1986 and March 1998. RESULTS: Median age was 36 years (range 15 to 74) at the time of diagnosis and median follow-up duration was 46 months (7 to 133). Female to male ratio was 4 : 1. Twenty-four patients who were asymptomatic with stable disease or a platelet count over 50,000/microliter were managed on a wait and see basis. A total of 63 patients received an initial treatment with prednisone (1 mg/kg/day for 1 month). Refractory or relapsed cases underwent splenectomy and/or other therapeutic modalities. An initial complete or partial response to prednisone was observed in 79%. A sustained complete remis- sion (CR) lasting more than 6 months was attained in 11%. Thirty-two refractory or relapsed patients underwent splenectomy. Twenty-two patients (69%) had a CR, with twenty-one (66%) achieving a sustained CR. 5 other cases obtained a partial remission (PR). Long-lasting responses were observed in 3 other case (12 %) following alternative treatment. Five deaths were recorded, but only one was due to thrombocytopenia and the remaining four deaths were unrelated to ITP. Two patients had laboratory features and a clinical history consistent with an autoimmune disease. CONCLUSION: The majority of patients who undergo splenectomy can have a CR for many years. The therapeutic modalities tried as supplements or alternatives to splenectomy all produced some transient remissions but few prolonged recoveries. But the long-term prognosis of chronic ITP is benign even in refractory cases and the development of overt autoimmune diseases is relatively uncommon.