Comparison between Conventional Cytogenetics and Interphase Fluorescence in situ Hybridization (FISH) for Patients with Multiple Myeloma

BACKGROUND: For patients with multiple myeloma (MM), different strategies are used to detect chromosomal abnormalities (CA). There have been a few studies that have directly compared FISH with conventional cytogenetics (CC) for the detection of CA. In this study, we employed a combined approach of metaphase cytogenetics and interphase FISH to investigate the genetic basis for the great heterogeneity observed in the clinical behavior of 28 MM patients. METHODS: Cytogenetic analysis was performed via traditional metaphase karyotype analysis. The FISH studies were done using DNA probes to detect translocations involving the immunoglobulin heavy chain gene (IGH) at 14q32 and deletions of 17p13.1 and 13q14. RESULTS: CA were detected by CC in 16 patients (57.1%) and by FISH in 14 patients (50.0%) of the 28 patients we studied. 14q32 abnormalities and deletion abnormalities of 13q14 and 17p13.1 were detected by CC in five patients (17.9%), three patients (10.7%) and no patients (0%), respectively and these were detected by FISH in 12 (42.8%), four (14.3%) and five (17.8%), respectively, of the 28 patients we studied. The median follow-up timefor the patients was 23.85 months (range: 0.3~58.13 months). On the univariate and multivariate analyses, none of the abnormalities detected by cytogenetics and interphase FISH affected survival. CONCLUSION: On comparing the cytogenetics and interphase FISH results, we can suggest that both studies should be an essential part of the workup for the diagnosis of patients with MM. Also, both studies may complement each other to predict the prognosis.

Gemcitabine versus Gemcitabine Combined with Cisplatin Treatment Locally Advanced or Metastatic Pancreatic Cancer: A Retrospective Analysis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Gemcitabine is the most active agent to treat unresectable pancreatic cancer. The superiority of combining other drugs with cisplatin is still controversial; therefore, we performed a retrospective analysis of gemcitabine versus gemcitabine combined with cisplatin to determine the treatment outcomes for patients with locally advanced or metastatic pancreatic cancer. MATERIALS AND METHODS: From 2001 to 2007, we enrolled 60 patients who were treated with gemcitabine or gemcitabine combined with cisplatin for locally advanced or metastatic pancreatic cancer. Gemcitabine 1, 000 mg/m2 (G) was administrated at day 1 and day 8 every 3 weeks. Cisplatin 60 mg/m2 was added at day 1 every 3 weeks to the gemcitabine schedule (GP). RESULTS: Number of G: GP was 34: 26, locally advanced to metastatic ratio was 35% to 65% in group G and 46% to 54% in group GP. Median follow up duration was 29 months. The median number of chemotherapy cycles was 4 (range: 2~11) for the G group, and 4 (range: 1~11) for the GP group. The response rate of the G and GP groups was 17% and 11%, respectively. The progression free survival (PFS) was 4.5 months and 2.8 months, respectively, for the G and GP groups. The overall survival (OS) was 10.7 and 8.7 months respectively, for the G and GP groups, but there is no statistically significant difference of the PFS (p=0.2396) and OS (p=0.4643) between the 2 groups. The hematological toxicity profile was similar (the grade III neutropenia and thrombocytopenia was 4.4% and 3.1%, respectively, in G group, and 7.5% and 2.8%, respectively, in the GP group). But non-hematological toxicities such as skin rash, abnormal liver function and nausea/vomiting were observed in 3 patients of the GP group. On the prognostic factor analysis, no factors predicted a longer PFS and OS for both the G and GP groups. CONCLUSIONS: Gemcitabine single treatment might be more tolerable and it had the same efficacy compared to cisplatin combination treatment in this retrospective study.

A Phase II Study of Paclitaxel and Cisplatin as Salvage Therapy for Patients with Advanced or Metastatic Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the therapeutic activity and safety of paclitaxel and cisplatin combination chemotherapy in patients with advanced or metastatic gastric cancers that are unresponsive to primary chemotherapy. MATERIALS AND METHODS: Advanced or metastatic gastric cancer patients unresponsive to first line chemotherapy were entered into this trial. The treatment regimen consisted of paclitaxel, 175 mg/m(2) by 3-hour infusion on day 1, and cisplatin, 60 mg/m(2) by 1 hour infusion on day 1, with the treatment repeated every 3 weeks. RESULTS: 37 patients were entered in this study, with 32 fully evaluable for response. 4 (13%), 13 (40%) and 15 (47%) patients achieved a partial response, stable disease and progressed, respectively. The median time to progression was 4.0 months (95% CI: 2.0~6.0 months), and the median overall survival was 12.6 months (95% CI: 5.5~19.7 months), with a 1-year survival rate of 54%. Of a total of 135 cycles of chemotherapy, grades 3 and 4 hematological toxicities were neutropenia (14%) and anemia (3%). Grade > or =2 neuropathy was observed in 6 patients (17%). CONCLUSION: The combination of paclitaxel and cisplatin is an effective and tolerable salvage treatment modality for advanced gastric cancer.

Rituximab-induced Interstitial Pneumonitis in a Young Patient: A Case Report and Review of the Literature

Side effects of rituximab are mild in most cases, but there have been a few cases of severe pulmonary toxicity reported in elderly patients. Here we report a case of interstitial pneumonitis following rituximab treatment in a young patient. A 35-year-old woman with diffuse large B-cell lymphoma was admitted complaining of dry cough and dyspnea without fever after the 3 treatments with rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. Her chest CT with high-resolution CT scanning confirmed the presence of bilateral diffuse ground-glass opacities. The analysis of arterial blood gases indicated hypoxemia. The pulmonary function testing showed a restrictive pattern. There were no other findings suggesting an infection. The findings were compatible with a rituximab-induced interstitial pneumonitis. After the patient was treated with prednisolone, the symptoms resolved. Cases with rituximab-induced interstitial pneumonitis develop principally in elderly patients. However, the condition also can occur in young patients.

Oxaliplatin with Biweekly Low Dose Leucovorin and Bolus and Continuous Infusion of 5-fluorouracil (Modified FOLFOX 4) as a Salvage Therapy for Patients with Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To determine the activity and the toxicity associated with a low dose regimen of leucovorin (LV) plus 5-fluorouracil (5-FU) combined with oxaliplatin every two weeks (modified FOLFOX 4) as a salvage therapy for advanced gastric cancer patients. MATERIALS AND METHODS: Between December 2003 and December 2004, 33 patients were enrolled in this study. The patients were treated with oxaliplatin 85 mg/m2 as a 2-hour infusion on the first day plus LV 20 mg/m2 over 10 minutes. Subsequently, the patients were given a 5-FU bolus 400 mg/m2 followed by a 22-hour continuous infusion of 600 mg/m2 on days 1~2. The treatment was repeated at 2 week intervals. RESULTS: The median age of the patients was 50 years (range: 31~74), 82% (27/33) had the Eastern Cooperative Oncology Group performance status was 0 and 1. Of the 30 patients who could be evaluated for their tumor response, 8 achieved a partial response, with an overall response rate of 26.7% (95% confidence interval (CI): 20.5~32.7%). Fifteen patients (50%) showed stable disease and 7 patients (23.3%) progressed during the course of treatment. The median time from the start of chemotherapy to progression was 3.5 months (95% CI: 2.6~4.4 months) and the median overall survival time was 7.9 months (95% CI: 5.9~9.9 months). The major grade 3/4 hematological toxicity encountered included neutropenia (45.4%) and thrombocytopenia (3.0%). Neutropenic fever occurred during only 2 of the 178 cycles. The most common non-hematological toxicity encountered was grade 1/2 nausea/vomiting, which occurred in 18.2% of patients, diarrhea in 12.1% and neuropathy in 15.2%. There were no treatment related deaths. CONCLUSIONS: The modified FOLFOX 4 regimen appears to be a safe and effective salvage therapy for advanced gastric cancer patients.

Hematologic Recovery and Clinical Outcomes according to Cell Dose after HLA-matched Sibling Allogeneic Bone Marrow Transplantation

BACKGROUND: There has been changed in estimation of the stem cell content of the graft for several decades. However, there is not always correlating the transplanted cell dose with hematologic recovery, and there are few reports in human leukocyte antigen (HLA)-matched sibling allogeneic bone marrow transplantation (AlloBMT) in Korea. The purpose of this study is to report the influence of number of transplanted cell dose on hematologic recovery and the clinical outcomes in HLA-matched sibling AlloBMT. METHODS: Between June 1999 and March 2004, 31 AlloBMT from HLA-matched sibling donor was done in patients with hematologic malignancy. All patients were conditioned with busulfan and cyclophosphamide. Short course methotrexate and cyclosporine regimen was used for prophylaxis of graft-versus-host disease. We analyzed hematologic recovery time and clinical outcomes according to transplanted cell dose. RESULTS: There were 16 male and 15 female patients, with a median age of 34 years (range, 16~48). Underlying diseases were 17 acute myeloid leukemia, 4 acute lymphoblastic leukemia, 3 myelodysplastic syndrome (high-risk), and 7 chronic myelogenous leukemia. The median number of total nucleated cell (TNC), mononuclear cell (MNC) and CD34+ cell infused was 3.95x10(8)/kg (range, 1.67~7.30x10(8)/kg), 0.65x10(8)/kg (range, 0.11~2.50x10(8)/kg), and 2.32x106/kg (range, 0.35~7.45x106/kg), respectively. The median days of neutrophil and platelet engraftment (ANC>500/microliter and platelet > 20,000/L without transfusion) were 15 (range, 10~19), 16 (range, 7~37), respectively. Relationship between the rate of neutrophil engraftment and the number of infused TNC was only statistically significant (P=0.038, R2=0.328). This study showed survival benefit with the increment of CD34+ cell dose without significance statistically (P=0.082). CONCLUSION: Although the dose of the number of transplanted MNC and CD34+ cells had no influence on granulocyte or platelet recovery, the number of TNC had only a beneficial effect on neutrophil recovery. The transplanted dose of CD34+ cells, rather than those of TNC and MNC may be related with better survival.