Frank S. Fan

Stevens-Johnson syndrome after treatment with STI571: a case report.

Summary.  Between seven and 21% of patients treated with the specific tyrosine kinase inhibitor STI571 have been reported to develop mild‐to‐moderate severity of adverse cutaneous reactions. We report a patient in the blast crisis phase of chronic myeloid leukaemia who developed a life‐threatening cutaneous reaction, Stevens–Johnson syndrome, following 1 week of STI571 therapy. This report may serve to remind the clinician about the possible severe cutaneous side‐effects of STI571 before instituting more extensive clinical application of this agent in the future.

Comparative genomic hybridization of esophageal squamous cell carcinoma

Esophageal carcinoma is a major cause of cancer‐related deaths among males in Taiwan. However, to date, the genetic alterations that accompany this lethal disease are not understood.

Fulminant hepatitis is significantly increased in hepatitis B carriers after allogeneic bone marrow transplantation.

BACKGROUND Bone marrow transplantation (BMT) is effective treatment for many hematologic disease, but performed in a population with a high endemic hepatitis B virus carrier rate, the incidence of liver function impairment and fulminant hepatitis (FH) is expected to be raised. METHODS Forty-three hepatitis B virus carriers received high-dose chemotherapy and BMT, 32 patients received an allogeneic graft, and 11 patients autologous marrow. Acute graft-versus-host disease prophylaxis consisted of methotrexate on day 1, 3, 6, and 11 and cyclosporine for 6 months. RESULTS After a median follow-up period of 68 months (range: 1-11.5 years), 26 (81.3%) allogeneic BMT patients developed impaired liver function (LF), 5 progressed to FH on day 93, 169, 170, 180, and 468, respectively, and died after an average of 13.8 days (range: 1-45 days). Whereas only 4 (36.4%) autologous BMT patients developed impaired LF, and none FH. Impaired LF (P=0.026, chi-square), and FH (odds ratio=12.86, P=0.009 for coefficient) were significantly related to an allogeneic marrow graft, and the timing of liver function impairment coincided with cyclosporine withdrawal. Hepatitis B surface antigen (HbsAg) disappeared from the serum in 4/14 (28.6%) patients receiving a marrow graft from an HbsAg+ donor. HbsAg was not detected in the serum after BMT in 2/11 (18.2%) autologous BMT patients. CONCLUSIONS Hepatitis B virus carriers receiving a marrow graft from an HbsAg+ donor have a significantly increased risk of FH.

Trisomy 21 in acute myeloid leukemia.

We report two cases of acute myeloid leukemia (AML), constitutionally normal, with trisomy 21. Trisomy 21 does not often occur as a sole numerical karyotypic abnormality in AML leukemia. The possible prognostic significance of the finding in acute leukemia is discussed.

Detection of reactivation and genetic mutations of the hepatitis B virus in patients with chronic hepatitis B infections receiving hematopoietic stem cell transplantation.

Background. This study elucidates the profiles for hepatitis B virus (HBV) reactivation and genetic mutation of the core promoter and precore regions for HBV-carriers receiving hematopoietic stem cell transplantation (HSCT). Methods. Sera from 20 HSCT patients diagnosed with hematological diseases, 13 donors and 36 healthy HBV-carriers, were collected regularly for analysis. The hepatic biochemistry profiles, serological HBV markers, and HBV-DNA titers were checked regularly, and primer-amplification of the HBV core promoter or precore region and sequencing were performed once the mutations were identified. Results. Deteriorated liver function was demonstrated for 13 of 20 post-HSCT patients, compared with none of the 36 controls (P <0.01). The HBV-DNA was detected more frequently for post-HSCT subjects than for controls (P =0.001). Incidence of the HBV precore nucleotide 1896 G-to-A mutation was significantly higher for HSCT patients (P =0.004), and a significant association was demonstrated for carriage of core promoter or precore mutations and the development of hepatitis (P =0.015). Different HBV genotypes were revealed in post-HSCT patients and the respective donors. Conclusions. Intensive chemotherapy and immunosuppression may cause HBV reactivation in HBV carriers receiving HSCT, and more frequent core promoter or precore mutations could be detected in HBV carriers receiving HSCT than healthy HBV carriers, with the chemotherapy/immunosuppression-induced immunocompromise possibly contributing to this effect. Donor HBV genotype did not interfere with that of the recipient after HSCT. Core promoter or precore region mutations were associated with a higher incidence of liver dysfunction than wild-type HBV carriers in the HSCT patients.

Tamoxifen and colchicine-modulated vinblastine followed by 5-fluorouracil in advanced renal cell carcinoma: a phase II study

OBJECTIVES Chemotherapy resistance of renal cell carcinoma (RCC) has been attributed in large part to multidrug resistance (MDR). Reported MDR-modulated chemotherapy for RCC, however, has resulted in only marginal response benefits. In this study, the MDR-modulated effect of paired tamoxifen and colchicine on vinblastine and the possible additive effect of 5-fluorouracil (5-FU) were investigated in the treatment of advanced RCC. METHODS Chemotherapy was administered every 4 weeks with biweekly vinblastine (4 mg/m(2)/day, intravenously on days 1 and 15) modulated by oral tamoxifen (100 mg/day) and colchicine (1 mg/day) from days -1 to 2 and from days 13 to 16. 5-FU (800 mg/m(2)/day from days 2 to 5) was administered after vinblastine administration as a continuous infusion. RESULTS Of 17 eligible patients with advanced RCC available for evaluation, 1 achieved a complete response (CR) and 3 a partial response (PR), with an overall response (CR plus PR) rate of 23.5%. The median overall survival time of all patients was 10 months (95% confidence interval [CI] 3.5 to 16.5); that of our patients with poor, intermediate, and favorable risks as stratified by Motzers model was 6 (95% CI 1.7 to 10.3), 10 (95% CI 7.9 to 12.2), and 26 (95% CI 24.4 to 27.6) months, respectively. These results are encouraging in view of the poor efficacy of chemotherapy in RCC observed previously. Additionally, the treatment toxicity was limited: toxicity of grade 3 or greater occurred in only 1 patient with leukopenia, and no treatment-related mortality was found. CONCLUSIONS The encouraging response rates and overall survival with limited toxicity warrant further investigation of this combination therapy as an integrated part of immunochemotherapy for RCC.

Prognostic-factors-based risk-stratification model for invasive urothelial carcinoma of the urinary bladder in Taiwan

Objectives. To develop a prognostic-factors-based predictive model for invasive urothelial carcinoma of the urinary bladder derived from statistical comparison of clinical characteristics.Methods. The medical records for patients with invasive urinary bladder urothelial carcinoma were reviewed. Clinical data for age, sex, serum lactate dehydrogenase, creatinine, albumin, alkaline phosphatase, alanine aminotransferase, total bilirubin and hemoglobin levels, white blood cell and platelet counts, positive urine cytology, Eastern Cooperative Oncology Group performance status score, tumor size, histologic grading, T stage, presence of lymph node metastases, squamous differentiation, hydronephrosis, prostatic involvement, Charlson comorbidity index, surgical procedures, and adjuvant chemotherapy status were recorded. Univariate and multivariate analyses were performed to test independent factors for prediction of survival and disease recurrence.Results. After univariate and multivariate analyses, six independent prognostic factors were found: T stage, grading, prostatic involvement, Eastern Cooperative Oncology Group performance status score, and pretreatment serum creatinine and albumin levels. A scoring system was developed on the basis the relative risk associated with the proposed prognostic factors and patients were stratified into three groups according to their scores, with statistically significant prognostic differences revealed for each of the between-group comparisons. Independent factors affecting recurrence-free survival and best predicted disease recurrence were pretreatment serum creatinine, T stage, and surgical procedure.Conclusions. This prognostic-factors-based risk-stratification model for invasive urothelial carcinoma of the urinary bladder may help clinicians predict outcome and select the most appropriate therapeutic modalities. The incidence of recurrent disease is significantly higher for patients with poor renal function before treatment or advanced T stage and those undergoing transurethral tumor resection instead of radical cystectomy.

Pulmonary function changes in long-term survivors of chronic myelogenous leukemia after allogeneic bone marrow transplantation: a Taiwan experience.

Pulmonary function in 42 patients with chronic myelogenous leukemia (CML) was tested before and after HLA-matched (39 related, 3 unrelated) allogeneic bone marrow transplantation (BMT) between 1985 and 1999. Pulmonary function tests (PFTs) including ventilatory capacity, lung volumes, and diffusion capacity for carbon monoxide (DLCO) were performed before and 3, 6, 12, and 24 months after BMT, and every 12 months thereafter. Possible pre- and post-BMT risk factors were evaluated for their influence on pulmonary function. Patients were divided into two groups according to their survival duration for more than 12 months or not. Pretransplant PFTs were essentially normal except for mild reduction in DLCO values in the short-term survival group. Overall pulmonary function changes revealed persistent and significant decrease of forced vital capacity (FVC) and DLCO values after BMT. The DLCO values reached abnormal levels (<80%) and showed a trend of incomplete recovery. Decrease of forced expiratory volume in the first second (FEV1) and vital capacity were also noted but the FEV1/FVC ratio remained within normal limits after BMT. Transient fall of total lung capacity after BMT was noted. However, its values did not reach abnormal levels such as to cause restrictive ventilatory impairment. Possible risk factors including gender, smoking, bronchiolitis obliterans, acute and chronic graft-versus-host disease (GVHD) were found to have significant influences on posttransplant pulmonary function changes by multiple regression analysis. Most patients except those who developed bronchiolitis obliterans were clinically asymptomatic. Development of bronchiolitis obliterans was the most important factor to cause both clinical symptoms and impaired pulmonary function. In summary, pulmonary function changes before and after HLA-matched allogeneic BMT in long-term survivors of CML only showed modest dysfunction. The primary negative presentation with the development of oxygenation defect had no clinical significance in most patients. The influences on the impairment of pulmonary function were multifactorial.

Molecular analysis of mucosa-associated lymphoid tissue (MALT) lymphoma of ocular adnexa

Lymphomas of mucosa-associated lymphoid tissue (MALT) are a distinct subgroup of extranodal B-cell non-Hodgkins lymphomas. Most studies have failed to demonstrate the clonal rearrangement of BCL-1, BCL-2 or c-MYC genes for MALT lymphomas. Further, alteration of the p53 gene is rarely demonstrated in low-grade MALT lymphomas, but can be detected in high-grade disease. Lymphomas of the ocular adnexa represent approximately eight percent of all extranodal lymphomas, most of which are MALT lymphomas, but few studies had explored the alterations of BCL-1, BCL-2, c-MYC and p53 genes specifically for ocular MALT lymphomas. We investigated the changes to BCL-1, BCL-2, c-MYC and p53 genes in these lymphomas for Taiwanese patients. Clonal rearrangement for immunoglobulin heavy-chain (IgH), BCL-1, BCL-2, c-MYC and p53 genes was examined for 16 cases of ocular MALT lymphoma. Restriction-length polymorphism and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) of the DNA, corresponding to exons 5 through 9, followed by DNA sequencing, were utilized to analyze the possible mutations of the p53 gene for these tumors. Thirteen of the cases revealed rearranged IgH genes using Southern blotting or PCR. No rearrangement of BCL-1, BCL-2, c-MYC or p53 genes was discovered, with point mutation of the p53 gene in one case. As for other types of MALT lymphomas, BCL-1, BCL-2 and c-MYC genes are not implicated in the pathogenesis of the ocular sub-group. Although alteration of the p53 gene is rare for low-grade ocular MALT lymphoma, its role in disease progression merits further research.

Low incidence of BCL-6 gene alterations for diffuse large B-cell lymphomas in Taiwan Chinese

In Western populations, rearrangement of the BCL‐6 gene can be identified in 20–40% of patients with diffuse large B‐cell lymphoma (DLBCL). Analysis of the BCL‐6 gene has revealed the presence of point mutations or small deletions in 70% of DLBCL tumors; however, few studies have investigated BCL‐6 gene alteration in patients with non‐Hodgkins lymphoma (NHL) of Chinese descent.