High dose Chemotherapy and Autologous Stem Cell Transplantation for Poor Risk and Recurrent Non-Hodgkin's Lymphoma: A Single-Center Experience of 50 Patients

BACKGROUND: The long-term survival of patients with non-Hodgkin's lymphoma after conventional chemotherapy is about 35%, with the remaining 65% of patients tending to be refractory or experience relapse. As such, primary refractory patients responding to salvage chemotherapy, and sensitive relapsed patients and primary high- risk patients are recommended to receive high-dose chemotherapy (HDC) and autologous peripheral blood stem cell transplantation (PBSCT). We evaluated the role of HDC and autologous PBSCT in patients with primary refractory, primary high risk, and sensitive relapsed non-Hodgkin's lymphoma. METHODS: We performed a retrospective analysis of the data from 50 patients with non-Hodgkin's lymphoma who were treated with HDC and autologous PBSCT in the Catholic Hematopoietic Stem Cell Transplantation Center between 1997 and 2002. RESULTS: Of the 50 patients, the conditioning regimen was BEAM in 20, CMT (cyclophosphamide, melphalan and thiotepa) in 19, fludarabine- and total body irradiation (TBI) -based regimen in 8, and cyclophosphamide and TBI in 2. There were 3 (6%) deaths due to treatment-related toxicity within the first 50 days after transplantation. Twenty-five patients remain alive at a median follow-up duration of 40.5 months (range 9~61). Among the patients with partial response before transplantation, 76% showed further response after transplantation. In half of these responders, the disease state was changed into complete response (CR) after transplantation. 2-year overall survival was 52% and 2-year progression free survival was 36.8%. Median overall survival was 34 months (range 8~60), and median progression-free survival was 8 months (range 1~14). Median overall survival was 14 months (range 9~19) in the primary high-risk group (n=13), 7 months (range 4~10) in the resistance relapse group (n=5), and 6 months (range 0~14) in the primary refractory group (n=10). Overall survival in the sensitive relapse group (n=22) did not reach the median; the mean overall survival in this group was 33 months. The disease status before transplantation was the only significant prognostic factor in determining overall survival (p=0.032) and progression- free survival (p=0.001). CONCLUSION: HDC and autologous PBSCT appears to produce high response rate. Primary high-risk group and sensitive relapse group had good prognosis, while refractory and resistance relapse group had poor prognosis. And the pre-transplantation disease status was the only significant prognostic factor in multivariate analysis.

Total Plasma Exchange in a Patient with HD-MTX-induced Acute Renal Failure: A Case Report / 대한혈액학회지

A 16-year-old male patient was diagnosed as chondroid osteosarcoma of the left humeral shaft. He showed normal serum creatinine level and no complications following the first course of high-dose methotrexate (HD-MTX) chemotherapy with a total dose of 12g/m2. After the 2nd HD-MTX chemotherapy with the same dosage as in the 1st course, plasma MTX levels soared up to 72micromol/L and serum creatinine level increased to 1.39mg/dL. We failed to lower the plasma MTX levels and to recover the renal function by high-dose leucovorin rescue and plasmapheresis. Plasma MTX level was successfully lowered after three consecutive total plasma exchanges and the withdrawal of aceclofenac which was suspected as an aggravating agent. No rebound in plasma MTX level was observed. We report that total plasma exchanges were effective in a patient with renal failure and delayed MTX excretion which occurred after HD-MTX chemotherapy.

BEAM conditioning regimen and autologous peripheral stem cell transplantation in patients with malignant lymphoma / 대한내과학회지

BACKGROUND: The long-term survival in patients with non-Hodgkin's lymphoma (NHL) after conventional chemotherapy is about 35% and the rest of the patients tend to have relapse. So, in relapsed or refractory NHL, the outcome of patients undergoing high-dose chemotherapy and autologous peripheral stem cell transplantation (APBSCT) was evaluated, and the main prognostic factors were determined. METHODS: 17 patients with relapsed or resistant NHL (5 complete response group, 7 partial response group, 4 primary refractory group, 1 resistant relapse) underwent BEAM (carmustine, etoposide, cytarabine, melphalan) chemotherapy and APBSCT between July 1997 and February 1999. RESULTS: The median follow-up duration was 17 months (range: 4-47). The response rate was 58.3% (complete response 33.3%, partial response 25.0%) in 12 patients in whom complete response group was not included. The 2-year, 3-year overall response rate were 41.2%, 27.5%, respectively. And 2-year progression free survival was 35.3%. The disease status before high-dose chemotherapy was the only significant prognostic factor in determining overall survival (univariate p=.024, multivariate p=.059) and progression free survival (univariate p=.013, multivariate p=.026). Patients with complete response to salvage regimen had better overall survival (p=.021) and progression free survival (p=.008) than patients with refractory response. WBC (> or = 1,000/uL) was recovered at the median 11 days (range; 8-24), and platelet (> or = 50,000/uL) was recovered at the median 18 days (range; 9-44). There was no treatment-related death and no grade 3 and 4 toxicity. Neutropenic infection was in 4 patients (1 Herpes zoster, 1 typhlitis, 1 perianal infection, 1 otitis externa). CONCLUSION: The pre-transplant disease status was the main prognostic factor. Patients with complete response to salvage regimen had the significant benefit in survival from high-dose chemotherapy and APBSCT, but patients with refractory or resistant relapsed NHL did not have any significant benefit.

Results of IVAM chemotherapy in relapsed or refractory non-Hodgkin's Lymphoma / 대한내과학회지

BACKGROUND: Patients with non-Hodgkin's lymphoma who do not respond to first-line chemotherapy or those who relapse after obtaining a complete response have a poor prognosis and are rarely cured with usual salvage chemotherapy. We investigated the treatment responses, toxicities, prognostic factors and mobilization efficacy of peripheral blood stem cells (PBSC) used as salvage chemotherapy. METHODS: 55 patients with refractory (36) or relapsed (19) NHL were treated from Novembr 1997 to October 1999 with IVAM (ifosfamide, etoposide, cytarabine, methotrexate) regimen. Each patients was scheduled to receive one to three cycles of chemotherapy. When the leukocyte count reached 5x109/L after chemotherapy, PBSC collection was performed. The treatment was repeated every 4 weeks. RESULTS: The median age was 48 years (range, 19-76). Median 2.1 cycles of chemotherapy were administered. 15 patients (27.3%) achieved complete response and 29 (52.7%) partial response, with an overall response rate of 80.0%. Myelosuppression was the major toxicity, with 98.2% of grade 3, 4 neutropenia and thrombocytopenia, but there was no serious hemorragic event. Neutropenic fever occurred in 25.5% of the patients with one treatment-related death due to sepsis. Non-hematologic toxicity was modest. PBSC was collected in 36 patients for high dose chemotherapy and autologous stem cell transplantation. The median number of mononuclear cells collected was 9.9x108/kg and the median number of CD34(+) cells collected was 11.9x106/kg. After a median follow-up of 13 months (range, 3-26), median progression free survival were 12 months and median overall survival has not been reached yet. 1-year overall survival and progression free survival were 61.9% and 46.1%, respectively. In univariate analyses, unfavorable prognosis was associated with poor performance status (p=0.001), high LDH (p=0.041), stage III,IV (p=0.04), extralymphatic lesion (p=0.027), B sx (p=0.034), bone marrow involvement (p=0.039) and performing high dose chemotherapy (p=0.005). Multivariate analysis showed that performance status(p=0.0042), B sx(p=0.049) was a significant independent risk factors for death. CONCLUSION: These results suggest that IVAM is an effective salvage chemotherapy for refractory or relapsed NHL and allow effective PBSC collection for high dose chemotherapy and autologous PBSCT.

The Effect of retinoic acid on the expression of cell adhesion molecules and binding to peritoneal mesothelium in gastric cancer cells

BACKGROUND: Peritoneal metastasis is one of the maj or types of the stomach cancer recurrence and the role of the adhesion molecules is thought to be very much important in this event. Retinoic acid (RA) has been known to induce the growth inhibition and differentiation of various malignancies, and apoptpsis and the change of expression of adhesion molecules have been reported to be involved in the action of RA. METHODS: We studied the adhesion abilities of SNU- 1, SNU-5, and SNU-6 cells to the peritoneal endothelial cells as well as the expression of the adhesion molecules (CD44, ICAM- 1) in Western blot analysis. And also we studied the expression of apoptosis and the change of expression patterns of the various isoforms of CD44 and the change of the adhsion abilities of the cell line cells after RA treatment. RESULTS: CD44 was expressed in SNU-5 and - 16, together with an isoform in SNU- 16. ICAM- 1 was not expressed in any of the cell line cells tested. After the treatment of RA in the concentration range of 1 - 5X10 - 5 M to three stomach cancer cell lines, growth inhibition, apoptosis and the change of expression of the CD44 were noted. After RA treatment , the expression of CD44H was weakly increased in SNU- 1, and was markedly increased in SNU-5. In SNU- 16, the expression of CD44H was decreased while that of CD44E were markedly increased. The adhesibility of cells to peritoneal cells was increased in relation with the increase of the CD44H expression, which shows the fact that the adhesibility of tumor cells to peritoneal mesothelial cells is mediated by CD44H recognizing hyaluronic acid. CONCLUSION: RA induces growth inhibition of stomach cancer cell line cells and increase the adhesiblity of stomach cancer cell line cells to peritoneal mesothelium. It is believed that RA decreases the metastatic ability of stomach cancer cells by upregulating the CD44H expression.

A Case of Triple-Alkylating Regimen and Peripheral Blood Stem Cell Transplantation for a Patient with Relapsed Ovarian Carcinoma / 대한암학회지

Despite an aggressive surgical debulking followed by front-line chemotherapy, most patients with advanced ovarian carcinoma die of drug-resistant disease. Drug resistance can be overcome in a subset of patients with hematologic malignancies and lymphoma with high-dose therapy (HDT) and hematopoietic stem cell transplantation, suggesting that this therapy may also be value in ovarian carcinoma. We report the successful outcome of HDT and peripheral blood stem cell transplantation (PBSCT) in a 41-year-old nulliparous woman who initially was diagnosed with advanced ovarian carcicnoma with FIGO stage IIIc. Her disease relapsed after 19 months from initial therapy of definitive surgery and intra- and post-operative chemotherapy. Subsequently, she received optimal debulking surgery and salvage chemotherapy followed by HDT with triple- alkylating regimen, composed of cyclophosphamide (100 mg/kg), thiotepa (500 mg/m2), and melphalan (100 mg/m2). Her pretranplant characteristics were platinum-sensitive and complete response state. She showed rapid hematologic recovery and mild regimen-related toxicity (Bear man's toxicity criteria), stomatitis (grade I), cardiac toxicitiy (grade II). She has been followed up for 36 months after the inital therapy and is doing well without relapse.

Potentials of Fractionated Infusions of Low-dose Peripheral Blood Stem Cells (PBSCs) to Overcome the Hematologic Toxocities after Combination Chemotherapy / 대한암학회지

PURPOSE: We tried to evaluate the clinical usefullness of fractionated low-dose infusions of peripheral blood stem cells (PBSCs) as a supportive care. MATERIALS AND METHODS: Four patients were entered onto this study who were diagnosed to have gastric lymphoma (n=1) and advanced ovarian carcinomas (n=3). To overcome the hematologic toxicities, G-CSF-mobilized PBSCs were collected early in disease course. Harvested products were cryopreserved in aliquotes and then infused after each cycle. Planned therapeutic schedules should be performed without changes of dose and interval regardless of hematologic toxicities. RESULTS: 20 cycles of chemotherapies were performed and data of infused cell doses were as follows: median number of PBSCs infusions, 4.5 (3~5); median MNCs, CFU-GM colony counts per infusion of low-dose PBSCs, 1.7 108/kg (1.0~2.4), 3.2 104/kg (2.1~11.8). Among 20 cycles, delayed recovery of thrombocytopenia was shown on 10 cycles. Leukopenia (III/IV) and thrombocytopenia (III/IV) were shown on 8/6 cycles and 8/2 cycles. In spite of myelosuppression, they were successfully treated with planned dose-intensity. Especially incomplete platelet recovery was successfully rescuced by using fractionated infusions of low-dose PBSCs. CONCLUSION: These data warrant further clinical trials to evaluate the potentials of fractionated low-dose infusions of PBSCs collected early in disease course for overcoming accumulated hematologic toxicities, especially thrombocytopenia complicated by repeated chemotherapies.

Evaluation of efficacy and safety of fentanyl-TTS in adult patients with cancer-related pain / 대한내과학회지

The transdermal administration of narcotics is one of the alternative ways of providing adequate pain relief for the patients with chronic cancer pain. A Phase 4 trial was conducted to evaluate the efficacy and safety of Fentanyl-TTS in adult patients with cancer-related pain in Korea. METHODS: Patients with histologically confirmed malignancy, who have pain related to the cancer and/or therapy, pain necessitating the use of opoid analgesics, age of 18 yr or older, ability to communicate effectively with study personnel, and signed on informed consent were included. The patients were titrated with a short-acting narcotic to control their cancer pain before they are converted to a fentanyl-transdermal therapeutic system(TTS). Short acting parenteral morphine and MS contin were used as rescue medications. All patients were evaluated initially and were followed up with a pain visual analogue scale(VAS), quality of life(QOL)-VAS. Patients were asked to keep the daily record for 21 days about pain VAS, QOL-VAS, amount of rescue morphine used, and side effects. RESULTS: Twenth two patients were enrolled from January 1996 to October 1997. The dose of fentanyl-TTS required, ranged between 25 and 75 ug/hr (25 microgram/hr in 13, 50 microgram/hr in 4, and 75 microgram/hr in 2). The mean dose of morphine required before the use of the fentanyl-TTS was 135.3 mg (20-285 mg/day), but it was decreased after the use of the fentanyl-TTS. Pain VAS and QOL-VAS were in adquate level during the fentanyl- TTS treatment. Patients favored continuous use of fentanyl after the study was finished. Side effect of fentanyl-TTS was minimal. CONCLUSION: Transdermal fentanyl seems to be a convenient and effective analgesic for the control of cancer related pain in Korean. A controlled trial comparing fentanyl-TTS to morphine needs to be followed.

Two Cases of Tuberculous Splenic Abscess Occured in Immunocompetent Patients / 감염

Tuberculous splenic abscess is extremely rare in non- immunocompromised host. Although it has been increased since 1991, particularly in the HIV positive patients, it remains rare in the healthy patients. Only three cases have been reported in Korea. We report two cases of tuberculous splenic abscess presented as FUO in the previously healthy. One was improved by medical therapy and the other by splenectomy. It is important to include tuberculous splenic abscess in differential diagnosis of FUO, especially in case of splenic abscess that do not respond to empirical antibiotic therapy.

A Case of SIADH Related to Drug-indeced Generalized Maculopapular Rash / 대한내분비학회지

Syndrome of inappropriate antidiutetic hormone(SIADH) secretion is the most common cause of hyponatremia in clinical medicine. Before diagnosis of the SIADH is made, other causes for a decreased diluting capacity and nonosmotic stimuli for AVP release need to be rule out. Disorders associated with SIADH can be divided into 4 major etiologic groups: malignancies, pulmonary diseases, central nervous disorders, and drugs. A 45-year-old woman was admitted due to maculopapular skin eruption and fever after taking medications for fever and myalgia. Generalized tonic clonic seizure was developed nine days later, and laboratory results showed marked hyponatremia. During the evaluation, treatment, and subsequent follow-up, the diagnosis of SIADH was confirmed, but the definitive cause was obscure. With fluid restriction, sodium replacement and demeclocycline therapy, she recovered completely 6 months later. We suggest that the SIADH might be related to drug-induced generalized maculopapular rash via menmgitis-like reaction in CSF as one of systemic adverse side effects to drugs rather than direct effect of related drugs.

A Case of Traumatic Nonfuctional Adrenal Pseudocyst / 대한내분비학회지

The adrenal glands are rarely injured by blunt trauma, because they are well protected by the ribs, paraspinal muscles, and the overlying abdominal contents. Although most of adrenal cysts are clinically silent, the number of incidentally detected adrenal cysts have increased due to advanced and widespread application of various sensitive imaging methods. Recently, we have encountered a case of a 62-year-old man who have developed a left adrenal pseudoeyst one and a half months after the blunt trauma from a pedestrian traffic accident. The pseudocyst was non-functional and measured about 5 * 4 cm in size with the same fluid density of a gall bladder in abdominal computerized tomography(CT). Turbid cystic fluid was aspirated by CT-guided method, and the aspirate was composed of degenerated old blood cells without any malignant cells. Since the cyst was developed following trauma and its microscopic content showed blood cells, impending rupture was anticipated. Hence, a laparoscopic adrenalectomy was performed.