Clinicopathological characteristics of myelodysplastic syndromes with del(5q) in Taiwan.

BACKGROUND: Myelodysplastic syndromes (MDS) are a group of clonal haematopoietic stem cell disorders characterised by ineffective haematopoiesis and cytopenia. Studies have reported differences in MDS between Asian and Western countries, but data from Taiwan are scarce. MATERIALS AND METHODS: In this study we analysed the clinical and pathological features of 32 Taiwanese MDS patients with del(5q) (ie, del(5q) alone [Group A, n = 11], del(5q) with one additional cytogenetic abnormality other than monosomy 7 or del(7q) [Group B, del(5q)+1; n = 6], and del(5q) with ≥2 additional cytogenetic abnormalities [Group C, n = 15]). RESULTS: Progression-free survival (PFS) and overall survival (OS) were more favourable for Group A than for Groups B (p < 0.05) and C (p ≤ 0.001). Multivariate analysis showed that age >70 years, thrombocytopenia, and karyotype other than del(5q) alone were poor prognostic factors. Among the patients that had World Health Organization (WHO)-defined MDS with isolated del(5q), one patient (9%) had a typical marrow morphology of 5q minus syndrome with erythroid hypoplasia and four patients (36%) had hypolobated megakaryocytes. In addition, PFS and OS were significantly more favorable for the patients with del(5q) alone than for those with del(5q)+1 (p < 0.05). CONCLUSION: The bone marrow morphology, clinical features, and prognosis of Taiwanese MDS patients with del(5q) were different from those associated with MDS with isolated del(5q) as defined in the current WHO classification. Researchers should compare different geographic regions and racial populations to determine whether geographic and racial differences exist with respect to MDS with del(5q).

Adult T-cell leukaemia/lymphoma can mimic other lymphomas in a non-endemic area: dilemmas in diagnosis and treatment.

BACKGROUND: The diagnosis of Adult T-cell leukaemia/lymphoma (ATL) in non-endemic regions is challenging. AIM: This study analyses the clinicopathologic features and diagnostic processes of ATL patients in Taiwan. METHODS: ATL patients diagnosed and treated at Taipei Veterans General Hospital from 1998 through 2010 were retrospectively identified. The diagnosis of ATL was confirmed by in situ detection of human T-cell leukaemia virus type 1 (HTLV-1) when necessary. Patients' data were reviewed and analysed. RESULTS: Fourteen ATL patients were identified, among whom six (42.9%) had an antecedent diagnosis of other malignant lymphomas before the ATL diagnosis, including two diagnosed with Hodgkin disease (HD), one with peripheral T-cell lymphoma, two with chronic lymphocytic leukaemia and one with angioimmunoblastic T-cell lymphoma. Of the 14 patients, eight (57%) were subclassified as the acute type, three (21.4%) as the lymphoma type, and three (21.4%) as the chronic type ATL. Five of six (83.3%) patients with initial non-ATL misdiagnosis were diagnosed with non-acute type ATL. In particular, a patient with an antecedent diagnosis of HD presented with typical Reed-Sternberg (RS)-like cells harbouring Epstein-Barr virus genomes in affected lymph nodes. The patient progressed to acute type ATL 3 years after the initial diagnosis, and HTLV-1 genomes were identified in the previous RS-like cells. CONCLUSION: In non-endemic areas, such as Taiwan, ATL, particularly the non-acute type, may mimic other lymphomas and easily be misdiagnosed. HTLV-1 serology should be routinely screened in all malignant lymphoma patients. In situ detection of HTLV-1 is helpful in cases with diagnostic dilemmas.

Impact of Port-A-Cath device management in cancer patients with candidaemia.

This study investigated the impact of management of a totally implantable central venous access port device, Port-A-Cath (Smith Medical, St. Paul, MN, USA), on the outcome of 98 cancer patients with candidaemia. Port-A-Cath retention was found to be significantly associated with poorer outcome, independent of other significant adverse factors [breakthrough candidaemia, Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥ 21, and worse Eastern Cooperative Oncology Group (ECOG) performance score (3-4)]. However, retention of Port-A-Cath devices could be considered in patients who do not have definite catheter-related candidaemia, are not using total parenteral nutrition, do not have poor ECOG performance scores or APACHE II scores, and do not have septic shock.

How to predict the outcome in mature T and NK cell lymphoma by currently used prognostic models?

To select an appropriate prognostic model in the treatment of mature T- and natural killer (NK) -cell lymphoma (peripheral T-cell lymphoma (PTCL) and NK-/T-cell lymphoma (NKTCL)) is crucial. This study investigated the usefulness of Ann Arbor staging classification International prognostic index (IPI), prognostic index for T-cell lymphoma (PIT) and International peripheral T-cell lymphoma Project score (IPTCLP). Between 2000 and 2009, 176 patients (122 males) with PTCL and NKTCL were diagnosed and treated from a single institute in Taiwan. The correlation between complete response (CR) rate, 3-year overall survival (OS), early mortality rate and four prognostic models was analyzed. Thirty-one patients received hematopoietic stem cell transplantation (HSCT) and were analyzed separately. Three-year OS rate was 34.7%, and anaplastic large-cell lymphoma harbored better outcome than others. IPI score had the lowest Akaike information criterion value (1081.197) and was the best score in predicting OS and early mortality (P=0.009). Ann Arbor stage classification can predict CR rate more precisely (P=0.006). OS was significantly better in patients who received HSCT, even in patients with unfavorable features compared with chemotherapy alone. All prognostic models were useful to evaluate the outcome of patients with PTCL and NKTCL but IPI score did best in predicting OS in PTCL and PIT score in NKTCL. This study also supported the role of HSCT in patients with high-risk or refractory PTCL or NKTCL.

Impact of bloodstream infections on outcome and the influence of prophylactic oral antibiotic regimens in allogeneic hematopoietic SCT recipients.

This study aimed to determine the impact of blood stream infections (BSIs) on outcome of allogeneic hematopoietic SCT (HSCT), and to examine the influence of old (non-levofloxacin-containing) and new (levofloxacin-based) prophylactic antibiotic protocols on the pattern of BSIs. We retrospectively enrolled 246 allogeneic HSCT recipients between January 1999 and June 2006, dividing patients into BSI (within 6 months post-HSCT, n=61) and non-BSI groups (n=185). We found that Gram-negative bacteria (GNB) predominated BSI pathogens (54%). Multivariate analyses showed that patients with a BSI, compared with those without, had a significantly greater 6-month mortality (hazard ratio, 1.75; 95% confidence interval, 1.09-2.82; P=0.021) and a significantly increased length of hospital (LOH) stay (70.8 vs 55.2 days, P=0.014). Moreover, recipients of old and new protocols did not have a significantly different 6-month mortality and time-to-occurrence of BSIs. However, there were significantly more resistant GNB to third-generation cephalosporins and carbapenem in recipients of levofloxacin-based prophylaxis. Our data suggest that BSIs occur substantially and impact negatively on the outcome and LOH stay after allogeneic HSCT despite antibiotic prophylaxis. Levofloxacin-based prophylaxis, albeit providing similar efficacy to non-levofloxacin-containing regimens, may be associated with increased antimicrobial resistance.

High incidence of oral squamous cell carcinoma independent of HPV infection after allogeneic hematopoietic SCT in Taiwan.

Hematopoietic SCT (HSCT) is a well-recognized therapeutic procedure to prolong life and cure patients with life-threatening hematological malignancies; however, the risk of developing secondary carcinoma may increase in long-term survivors. The objective of this study was to determine the incidence and risk factors for secondary squamous carcinoma after HSCT. Between 1984 and 2004, 170 allogeneic HSCT recipients aged >15 years, who had survived for >5 years were enrolled. Demographic data and the characteristics of secondary carcinoma were collected and analyzed for the determination of the incidence and risk of developing secondary carcinoma. Eight patients developed secondary carcinoma, including five oral squamous cell carcinomas, one esophageal, one gastric and one ovarian carcinoma, but no cutaneous carcinomas were detected at a median follow-up of 14.1 years (range, 5.1-23.3 years) after HSCT. The accrual 10-year cumulative incidence of secondary carcinoma was 2.89%. In univariate and multivariate analyses, chronic GVHD and age >40 years at the time of HSCT were both significant risk factors independently associated with the development of secondary carcinoma. Thus, the occurrence of secondary carcinoma is one of the late complications in patients undergoing HSCT. Oral squamous cell carcinoma was more common in our patients after HSCT, indicating the need for lifelong surveillance of the oral cavity. Moreover, because of the relatively long latency in developing secondary carcinoma, extended follow-up is required for a thorough understanding of the incidence and characteristics of secondary carcinoma after HSCT.

A case of myeloid neoplasm associated with eosinophilia and KIAA1509-PDGFRß responsive to combination treatment with imatinib mesylate and prednisolone.

A 41-year-old woman presented with dyspnoea, persistent leucocytosis and eosinophilia for 8 months. High-resolution computed tomography scan and pathology of bronchoalveolar lavage confirmed the diagnosis of hypereosinophilic pneumonitis. The patient was treated with prednisolone (0·5-1 mg/kg/day) for more than 20 weeks under the impression of hypereosinophilic syndrome, but without improvement of leucocytosis and eosinophilia. The bone marrow aspiration smear disclosed hypercellular marrow with myeloid hyperplasia and eosinophilia. The fusion gene detection was positive for KIAA1509-PDGFRß. Myeloid neoplasm associated with eosinophilia and abnormality of PDGFRß was then diagnosed (Tefferi A, Vardiman JW, Leukemia, 22, 2008, 14). The tyrosine kinase inhibitor, imatinib mesylate (Glivec; 200 mg/day), was administered along with prednisolone (0·25-1 mg/kg/day). White blood cell (WBC) count decreased from 49,500/µL to 17,200/µL, and eosinophil count decreased from 1932/µL to 35/µL, which represent percentage dropped from 7·7%> to 0·2%. Withdrawal of prednisolone was done to avoid adverse events. However, absolute eosinophil count increased progressively despite the continue administration of imatinib and negative detection PDGFRß fusion gene. The patient then received combination therapy of imatinib and prednisolone again. WBC and absolute eosinophil were normalized subsequently. We had discontinued the prednisolone one more time, and rebound of eosinophilia was seen again. The phenomenon of rebounding of eosinophilia was observed in two subsequent withdrawals of prednisolone. Either steroid or imatinib mesylate alone failed to achieve complete haematological response. A synergistic effect of imatinib and steroid is postulated.

Efficacy and tolerability of bevacizumab plus capecitabine as first-line therapy in patients with advanced hepatocellular carcinoma.

BACKGROUND: Molecularly targeted agents with anti-angiogenic activity, including bevacizumab, have demonstrated clinical activity in patients with advanced/metastatic hepatocellular carcinoma (HCC). This multicentre phase II study involving patients from several Asian countries sought to evaluate the safety and efficacy of bevacizumab plus capecitabine in this population. METHODS: Histologically proven/clinically diagnosed advanced HCC patients received bevacizumab 7.5 mg kg(-1) on day 1 and capecitabine 800 mg m(-2) twice daily on days 1-14 every 3 weeks as first-line therapy. RESULTS: A total of 45 patients were enrolled; 44 (96%) had extrahepatic metastasis and/or major vessel invasion and 30 (67%) had hepatitis B. No grade 3/4 haematological toxicity occurred. Treatment-related grade 3/4 non-haematological toxicities included diarrhoea (n=2, 4%), nausea/vomiting (n=1, 2%), gastrointestinal bleeding (n=4, 9%) and hand-foot syndrome (n=4, 9%). The overall response rate (RECIST) was 9% and the disease control rate was 52%. Overall, median progression-free survival (PFS) and overall survival (OS) were 2.7 and 5.9 months, respectively. Median PFS and OS were 3.6 and 8.2 months, respectively, for Cancer of the Liver Italian Programme (CLIP) score < or =3 patients, and 1.4 and 3.3 months, respectively, for CLIP score 4 patients. CONCLUSION: The bevacizumab-capecitabine combination shows good tolerability and modest anti-tumour activity in patients with advanced HCC.

Haematopoietic stem cell transplantation in Taiwan: past, present, and future.

In Taiwan, haematopoietic stem cell transplantation (HSCT) has been used to treat patients with haematological diseases since 1983. Thereafter till 2007, there were 2537 patients who had undergone HSCT in more than 15 hospitals. Their diseases included acute myeloid leukaemia in 27.8% of cases, non-Hodgkin's lymphoma 23.3%, acute lymphoblastic leukaemia 12.8%, chronic myeloid leukaemia 11.9%, severe aplastic anaemia 8.7%, and multiple myeloma 4.1%. Most of the cases received myeloablative conditioning regimens. More than 15% of cases received non-myeloablative regimens, and the mean age of these cases was at least 10 years older than those who received myeloablative regimens. The types of graft included peripheral blood (60.4%) and bone marrow (32.0%). A total of 35% of patients received autologous grafts. Of 1557 allogeneic HSCT patients, 338 (21.7%) received grafts from unrelated donors. Cord blood transplantation has been successfully performed in paediatric patients with thalassaemia major and with a large body size, and adult patients. The incidence of acute graft-versus-host disease was relatively low in Taiwan. On the contrary, a relatively higher proportion of hepatitis B carrier in the recipients had led to a higher incidence of reactivation hepatitis, which was markedly decreased following lamivudine prophylaxis. In conclusion, HSCT has become a routine therapy for major medical centres in Taiwan. Our unique experiences in the past decades also contributed to the progress of HSCT. With the establishment of professional association and patient supportive groups, we hope we can fully improve our daily practice and clinical as well as basic research in HSCT.

Hepatitis B infection in haematopoietic stem cell transplantation: still unresolved.

Impact of hepatitis B virus (HBV) infection on haematopoietic stem cell transplantation (HSCT) was reported earlier since late 1980s. It was shown that changing patterns of HBV serological markers was accompanied by variable severity of hepatitis after transplantation. Recipient's hepatitis B virus surface antigen (HBsAg) positivity was not considered an absolute contra-indication to allogeneic HSCT. However, HBsAg positivity was an important risk factor of reactivation hepatitis after transplantation, especially in allogeneic setting. Managing HBV reactivation in HSCT recipients was not successful till the availability of lamivudine since mid-1990s. For HBsAg-positive recipients, prophylactic lamivudine has been shown to significantly reduce reactivation hepatitis. As for HBsAg-negative recipients, there have been a small number of patients who develop so-called reverse seroconversion, that is, appearance of HBsAg after transplantation. In addition to chronic graft-versus-host disease, the risk was also high in allogeneic HSCT recipients who received fludarabine-antithymocyte globulin-containing conditioning regimens. The HBV is harboured earlier in the recipients before transplantation rather than transmitted via transfusion. At present, the optimal duration of lamivudine prophylaxis is not well-defined, and there are several fatal cases associated with early withdrawal and resistant HBV mutants. In conclusion, in HBV-endemic areas, the war between HBV and HSCT recipients continued even though several anti-HBV agents and molecular detection techniques are available. It deserves additional effort to overcome and also presents a chance to elucidate underlying mechanisms of HBV immunity, which are not easily studied in non-HSCT setting.

Candidemia in cancer patients: impact of early removal of non-tunneled central venous catheters on outcome.

OBJECTIVE: To explore the impact of retention of non-tunneled central venous catheters (CVCs) on survival in candidemic cancer patients, where CVCs are commonly used and essential. A second object was to determine whether early CVC removal would benefit a subset of cancer patients. METHODS: We retrospectively evaluated 92 cancer patients who had a single, non-tunneled CVC in place. Patients were grouped according to CVC retention or removal; the later group was subdivided into early (CVC removed

Current status of hematopoietic stem cell transplantation in Taiwan.

In Taiwan, hematopoietic SCT (HSCT) has been used to treat patients with hematological diseases since 1983. Since then, more than 2200 patients have undergone HSCT in 15 large hospitals. The disease entities included acute leukemia in 37% of cases, non-Hodgkin's lymphoma in 26%, CML in 10%, multiple myeloma in 7% and severe aplastic anemia in 6%. The conditioning regimens used were mainly myeloablative (84% of cases). Non-myeloablative regimens were fludarabine-based. The average age of allogeneic recipients was at least 10 years older than those in the era before their application. The grafts of all patients were derived from peripheral blood in 85% of cases, BM in 13% and cord blood (CB) in 2%. Forty percent of HSCT patients received autologous grafts, whereas more than 25% of allogeneic HSCT patients received grafts from unrelated donors, and overall, there were more than 200 Taiwan HSCT recipients. Currently, CB has been used successfully in pediatric patients with thalassemia major and also in adult patients with hematological malignancy. After transplantation, there was a relatively lower prevalence of acute GVHD. However, a relatively higher proportion of hepatitis B carriers in the recipients had led to a higher incidence of viral reactivation and clinical hepatitis, which was dramatically decreased following lamivudine prophylaxis. In conclusion, HSCT has been successfully adapted to routine clinical care in Taiwan. Several important findings contributing to the progress of HSCT in the past two decades have also been noticed on this island.

Relatively favorable outcomes of post-transplant pulmonary function in patients with chronic myeloid leukemia receiving non-myeloablative allogeneic hematopoietic stem cell transplantation.

Pulmonary function tests were performed in 20 patients with chronic myeloid leukemia before and after human leukocyte antigen-matched allogeneic sibling hematopoietic stem cell transplantation (HSCT) to identify any conditioning treatment effects on post-transplant function from January 1995 to December 2002. Of 20 patients, eight received non-myeloablative conditioning treatment and 12 received conventional myeloablative conditioning treatment. Pulmonary function tests including forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and diffusion capacity for carbon monoxide (DLCO) were performed pretransplant, 6 and 12 months post-transplant. Possible pre-HSCT and post-HSCT risk factors were evaluated for association with pulmonary function. The results showed that myeloablative conditioning treatment had greater negative impact on FEV1, FVC, and DLCO than non-myeloablative conditioning therapy. We conclude that non-myeloablative allogeneic HSCT may apply a better transplant choice in patients who need special concern with post-transplant pulmonary function changes.

Hematopoietic stem cell transplantation for severe aplastic anemia--experience of an institute in Taiwan.

Hematopoietic stem cell transplantation (HSCT) is an accepted treatment strategy for patients with severe aplastic anemia (SAA). We report our experience in a general hospital in Taiwan. From March 1985 to July 2001, 79 consecutive SAA patients, 46 male and 33 female, with a median age of 22 (4-43) years, received 80 courses of transplantation. Cyclophosphamide and total body radiation were used for the conditioning regimen, and cyclosporine-A and methotrexate for graft-versus-host disease (GVHD) prevention. Patients were followed for a median of 39 months (from 8 days to 194 months). Myeloid and platelet engraftment occurred in a median of 15 (8-27) days and 18 (8-77) days, respectively. Three patients had primary and three patients secondary graft failure. Five patients (6.8%) had grade II-IV acute GVHD in 73 evaluable patients. Chronic GVHD occurred in 23 (34.8%) patients, with extensive stage in six. Only two patients had CMV disease. The projected 3- and 5-year overall survival rates estimated by the Kaplan-Meier method were 76.08 and 74.13%, respectively. Age at transplant, non-sibling donor, mononuclear cell dose, grade II-IV acute GVHD, interval from diagnosis to transplant, and red blood cell and platelet transfusion before transplant were poor prognostic factors for overall survival by univariate analysis. Grade II-IV acute GVHD was the only prognostic factor affecting overall survival after multivariate Cox regression analysis (P=0.040). In conclusion, SAA patients receiving HSCT have good long-term survival. The low incidence of acute GVHD in our patients may be related to ethnicity.

Myelodysplastic syndrome complicated by autoimmune hemolytic anemia: remission of refractory anemia following mycophenolate mofetil.

Autoimmune hemolytic anemia (AIHA) rarely occurs in myelodysplastic syndrome (MDS). A 36-year-old Asian female was diagnosed with MDS (refractory cytopenia with multilineage dysplasia, RCMD) and complicated by AIHA 7 months later. Secondary myelofibrosis developed at the same time. Steroid therapy was ineffective and cyclosporin A (CsA) was discontinued due to its neurotoxicity with the development of leukoencephalopathy. However, the patient achieved a good hematological response after the use of mycophenolate mofetil (MMF, CellCept) with a dose of 1 g/day and prednisolone (15 mg/day). Prednisolone was tapered off over the next 3 weeks. The patient did not require any blood support 4 weeks after the use of MMF and has been hematologically stable for 4 months. To our knowledge, this is the first report of using MMF in treating MDS complicated by AIHA. MMF might be considered as a salvage therapy for patients with refractory anemia complicated by AIHA.

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-Hodgkin's 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.

Relapse of Graves' disease after successful allogeneic bone marrow transplantation.

As shown in many reports, allogeneic BMT can help cure autoimmune diseases. Conversely, we present a 24-year-old woman with Graves' disease, which was diagnosed just before BMT for CML. The Graves' disease remitted immediately after BMT but relapsed 18 months later. Since the donor was free from thyroid diseases and the patient showed a rapid shift to complete donor chimerism after BMT, the autoimmune problem seemed neither to arise directly from the donor nor simply from the recipient's residual lymphocytes. On the contrary, it was most likely compounded by chronic GVHD as suggested by the accompanying GVHD symptoms and the absolute donor karyotype in bone marrow cells. A Graves' disease-susceptible HLA allele was also shared between recipient and donor, possibly enhancing the chances of this condition developing. Thus, allogeneic BMT may facilitate relapses in autoimmune diseases as well as alleviating them.

Immunophenotypic and genotypic characteristics of chronic myelogenous leukemia in blast crisis.

BACKGROUND: Chronic myelogenous leukemia (CML) may transform into blast crisis (BC) if not properly treated. Among patients with transformation, 20% to 30% will develop BC with lymphoid-associated antigens (Ly-BC), and the remaining cases with myeloid-associated antigens (My-BC) or with both (Mix-BC). In this study, we investigated the lineage of blast cells in CML-BC using immunophenotypic and genetic analyses and analyzed the prognostic significance of genotypic change in CML-BC. METHODS: Twenty-one patients with CML-BC diagnosed at the Taipei Veterans General Hospital from 1982 to 1992 were included. Immunophenotyping was done by using the avidin-biotin immunoperoxidase technique. Genetic analyses were carried out by using Southern Blot hybridization. The prognostic influence of genotypic change was analyzed. RESULTS: Thirteen patients (61.9%) expressed myeloid-associated antigens, one patient (4.8%) expressed megakaryoblast-associated antigens, four patients (19%) expressed B lymphoid-associated antigens and three patients (14.3%) expressed both myeloid and B lymphoid antigens. Clonal rearrangement of the immunoglobulin heavy chain (IgH) gene was found in six cases. Among them, four expressed B lymphoid markers only and two expressed both myeloid and B lymphoid markers. Patients with clonal IgH gene rearrangement tended to have a better response to chemotherapy (50% vs 8.3%, p = 0.08) and significantly longer survival (median survival, 5 months vs 3 months, p < 0.05) than did those with a germline configuration. CONCLUSIONS: Clonal rearrangement of the IgH gene was found mostly in cases of Ly-BC and Mix-BC. We found that CML-BC with clonal rearrangement of the IgH gene had a more favorable prognosis than in cases with a germline configuration.

Paraneoplastic syndromes in patients with hepatocellular carcinoma in Taiwan.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignancy in Taiwan. Some patients may manifest paraneoplastic syndromes during the clinical course of the disease. In this study, the authors evaluated the clinical significance of these paraneoplastic syndromes, compared the prevalence of these syndromes between cases of hepatitis B virus (HBV)-related and hepatitis C virus (HCV)-related HCC, and estimated significant predictors associated with the syndromes. METHODS: Clinical data on 1197 HCC patients, including age, gender, Child-Pugh score, survival time, laboratory data (including liver biochemistry, hepatitis markers, and serum alpha-fetoprotein [AFP]), and tumor features (including tumor size, portal vein thrombosis, and histologic pictures), were retrospectively reviewed. RESULTS: A total of 232 of 1197 patients (19.4%) had paraneoplastic syndromes. HCC patients with paraneoplastic syndromes had significantly higher serum AFP; higher rates of initial main portal vein thrombosis, metastasis, and bilobal tumor involvement; larger tumor volume; and shorter survival than those without these syndromes. Patients with HBV-related HCC had a significantly higher prevalence of paraneoplastic syndromes than patients with HCV-related HCC (20.1% vs. 11.2%, P = 0.005). In a stepwise multivariate logistic regression analysis, AFP >50,000 ng/mL and tumor volume >30% were significant predictive variables associated with the presence of paraneoplastic syndromes in HCC patients. CONCLUSIONS: HCC patients with paraneoplastic syndromes usually had higher levels of serum AFP and larger tumor volumes than those without. Patients with HBV-related HCC had a significantly higher prevalence of paraneoplastic syndromes than those with HCV-related HCC.