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Raymond Liang

Publications and source records attributed to Raymond Liang.

At least 37 records · Page 2Linked to original sources
PubMed2004

SOCS1 and SHP1 hypermethylation in multiple myeloma: implications for epigenetic activation of the Jak/STAT pathway.

SOCS1 and SHP1 negatively regulate the Janus kinase/signal transducer and activator of transcription (Jak/STAT) signaling pathway. The role of promoter hypermethylation leading to epigenetic inactivation of SOCS1 and SHP1 in myeloma was investigated. The methylation-specific polymerase chain reaction (MSP) was used to define SOCS1 and SHP1 methylation in 34 diagnostic myeloma samples. For SOCS1, MSP primers 3' to the translation start site were unreliable and gave positive results in normal controls. However, primers in the 5' promoter region were specific, although no myeloma samples showed methylation. For SHP1, 27 of 34 (79.4%) myeloma samples showed SHP1 hypermethylation. The biologic significance of SHP1 methylation was investigated in the U266 human myeloma line. U266 contained completely methylated SHP1. Furthermore, there was constitutive STAT3 phosphorylation. Treatment with 5-azacytidine led to progressive demethylation of SHP1 on days 2 to 5, with consequent increasing reexpression of SHP1 as shown by reverse transcription-polymerase chain reaction (RT-PCR). Concomitant with increasing SHP1, a parallel down-regulation of phosphorylated STAT3 occurred, so that by day 5 phosphorylated STAT3 was barely detectable. The overall survivals of patients with and without SHP1 methylation were similar. SHP1 methylation leading to epigenetic activation of the Jak/STAT pathway might have a tentative role in the pathogenesis of myeloma, which should be further confirmed by functional studies in primary myeloma samples.

Adult↗
PubMed2004

An indolent case of severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is a highly contagious and typically rapidly progressive form of atypical pneumonia, which spread from Asia to many parts of the world in early 2003. Clinical diagnosis of SARS requires the presence of unremitting fever and progressive pneumonia despite antibiotic therapy, particularly in the presence of lymphopenia and raised transaminase levels. We report the case of a woman who had undergone a successful allogeneic bone marrow transplant for acute myeloid leukemia. She presented initially with fever and a normal chest radiograph. Her indolent clinical course of SARS was punctuated by resolution of fever, but there was progressive radiologic deterioration and increasing serum antibody titer against SARS coronavirus. Treatment with oral prednisolone and ribavirin normalized her lymphopenia, altered transaminases, chest radiograph and high-resolution computed tomography appearances rapidly. Our experience should alert other clinicians in recognizing this atypical indolent presentation of SARS, to protect health care workers and the community at large and to ensure that these patients are properly treated.

Anti-Bacterial Agents↗
PubMed2004

Fludarabine, mitoxantrone and dexamethasone in the treatment of indolent B- and T-cell lymphoid malignancies in Chinese patients.

The treatment results of indolent lymphoid malignancies in Chinese are poorly reported. The efficacy of FND (fludarabine 25 mg/m2/d, x3; mitoxantrone 10 mg/m2/d, x1; dexamethasone 20 mg/d, x5; monthly cycles, x6) in 95 Chinese patients with indolent B-cell malignancies (at diagnosis: 55, relapse/refractory disease: 40) and nine Chinese patients with T-cell large granular lymphocyte leukaemia (T-LGL leukaemia) (at diagnosis: two, refractory disease: seven) was evaluated. For B-cell malignancies, the complete response (CR), partial response (PR) and overall response (OR) rates were 50.5%, 18% and 68.5% respectively. Better results were obtained for primary versus relapse/refractory disease (CR: 60% vs. 37.5%, P = 0.03; OR: 84% vs. 47.5%, P < 0.001; median progression-free survival (PFS): 44 months vs. 22 months; 2-year PFS: 66% vs. 47%, P = 0.039; overall survival (OS): not reached vs. 32%; 2-year OS: 92% vs. 58%, P < 0.001). Responsive patients (CR/PR) had a better median PFS (44 months vs. 5 months, P < 0.001) and OS (67 months vs. 13 months, P < 0.001) than unresponsive patients. For T-LGL leukaemia, the CR and molecular-remission rates were 56% and 67% (median follow-up: 23 months). FND is an active regimen for the treatment of indolent B- and T-cell malignancies in Chinese patients, with results comparable with Western patients with similar indolent lymphomas.

Adult↗
PubMed2004

FLT-3 aberrations in acute promyelocytic leukaemia: clinicopathological associations and prognostic impact.

FLT-3 aberrations that occur as an internal tandem duplication (ITD) or a mutation at the activation-loop position 835, D835, are common in acute promyelocytic leukaemia (APL). We investigated the clinicopathological associations and prognostic impact of FLT-3 aberrations in a cohort of APL patients. FLT-3 exons 11 and 12 were amplified by polymerase chain reaction (PCR), and the ITD was recognized as an increase in the size of the PCR product. FLT-3 exon 17 was amplified, and D835 mutation was identified by loss of an EcoRV site, followed by DNA sequencing. Of 82 patients studied, FLT-3 aberrations were detected in 35 cases (43%) at diagnosis (ITD: 16; D835 mutation: 18; ITD + D835 mutation: 1). FLT-3 ITD, but not D835 mutations, was significantly associated with higher presentation white blood cell count (WBC) and microgranular morphology. Early/induction deaths were related to male sex and high presentation WBC. There was a trend for FLT-3 ITD to be associated with non-remission (P = 0.06). For disease-free survival, high WBC was the only significant adverse factor. Male sex, high WBC and FLT-3 ITD were significant adverse factors for overall survival. These findings have important implications on the possible use of FLT-3 inhibitors in the treatment of APL.

Adolescent↗
PubMed2003

Primary nasal natural killer cell lymphoma: long-term treatment outcome and relationship with the International Prognostic Index.

Nasal natural killer (NK) cell lymphoma is rare, so that its optimal therapy, long-term outcome, and prognostic factors are unclear. Data on 52 men and 15 women with well-characterized nasal NK cell lymphomas were analyzed retrospectively to define the impact of primary therapy on remission and long-term outcome and the validity of the International Prognostic Index (IPI). Most (84%) had stage I/II disease with an IPI score of 1 or less (52%). Seven patients received radiotherapy only; 47 patients received anthracycline-containing chemotherapy plus consolidation radiotherapy; and 12 patients received nonanthracycline-containing chemotherapy plus radiotherapy. The overall complete remission (CR) rate was 64.2%; the 20-year overall survival (OS) and disease-free survival (DFS) rates were 37.1% and 33.5%, respectively. Front-line radiotherapy was apparently better than chemotherapy for CR (100% versus 59%, P =.04) and OS (83.3% versus 32.0%, P =.03). Relapses occurred in 4 radiotherapy-treated (all local) and 14 chemotherapy-treated patients (9 local, 4 systemic). Among these, 5 late relapses (4 local, 1 systemic) occurred at 170 months (range, 92-348 months) from CR. The IPI score was of prognostic significance for the whole group (IPI or= 2 for 20-year OS: 57.4% versus 27.6%, P = 0.012), as well as for patients treated with chemotherapy/radiotherapy (IPI or= 2 for CR: 76.7% versus 35.7%, P =.017; and 10-year OS: 63.8% versus 26.8%, P =.003).

Adolescent↗
PubMed2003

Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy.

BACKGROUND & AIMS: Hepatitis B virus reactivation is a serious cause of morbidity and mortality in hepatitis B surface antigen-positive patients treated with chemotherapy. We compared the efficacy of early and deferred preemptive lamivudine therapy in reducing the incidence of hepatitis due to hepatitis B virus reactivation in hepatitis B surface antigen-positive lymphoma patients treated with chemotherapy. METHODS: Thirty consecutive hepatitis B surface antigen-positive lymphoma patients undergoing intensive chemotherapy were randomized (1:1) to receive lamivudine 100 mg daily 1 week before chemotherapy (group 1) or to have this treatment deferred until there was serological evidence of hepatitis B virus reactivation on the basis of serial 2-week-interval serum hepatitis B virus DNA monitoring by a Digene Hybrid Capture II assay (group 2). RESULTS: Eight (53%) patients in group 2 and none in group 1 had hepatitis B virus virological reactivation after chemotherapy (P = 0.002). Seven patients in group 2 still had hepatitis (5 anicteric hepatitis, 1 icteric hepatitis, and 1 hepatic failure). Survival free from hepatitis due to hepatitis B virus reactivation in group 1 patients was significantly longer than that in group 2 (P = 0.002 on the log-rank test). The median onset of hepatitis B virus reactivation in these patients was 16 weeks (range, 4-36 weeks) after the initiation of chemotherapy. Three (13%) of the 23 patients treated with lamivudine had hepatitis B virus-related hepatitis after lamivudine withdrawal. CONCLUSIONS: Lamivudine should be considered preemptively before or at the initiation of chemotherapy for all hepatitis B surface antigen-positive lymphoma patients undergoing intense chemotherapy.

Adult↗
PubMed2003

Hepatitis B reactivation in patients positive for hepatitis B surface antigen undergoing autologous hematopoietic cell transplantation.

Hepatitis due to reactivation of hepatitis B virus is an important cause of liver-related morbidity and mortality in hepatitis B surface antigen (HBsAg) positive patients undergoing autologous hematopoeitic cell transplantation. With the recent introduction of sensitive serum HBV DNA quantitation assay, the diagnosis of hepatitis B reactivation can now be made more reliably. As these hepatitis are driven by the host immune response to a surge of hepatitis B viral load, the availability of effective nucleoside analogues which can inhibit hepatitis B viral replication has opened up new approaches to this previously untreatable condition. Up till now, two such nucleoside analogues, lamivudine and adefovir dipivoxil, have been approved for the treatment of chronic hepatitis B infection. However, further studies are needed to determine which nucleoside analogues should be chosen in this transplant setting. Due to the high dose chemotherapy generally needed in autologous hematopoeitic cell transplantation, there is a high risk of post-transplant hepatitis B reactivation. Hence, all HBsAg positive patients undergoing autologous hematopoeitic cell transplantation should preferably be treated pre-emptively with nucleoside analogous. An alternative approach is to defer treatment with nucleoside analogous until there is evidence of hepatitis B virological reactivation. However, the latter approach would need the patient's hepatitis B viral load be monitored at a very close interval and might not be cost-effective.

Antiviral Agents↗
PubMed2002

High hepatitis B virus (HBV) DNA viral load as the most important risk factor for HBV reactivation in patients positive for HBV surface antigen undergoing autologous hematopoietic cell transplantation.

The risk factors for hepatitis due to hepatitis B virus (HBV) reactivation in patients positive for hepatitis B surface antigen (HBsAg) treated with autologous hematopoietic cell transplantation (HCT) are unknown. We evaluated 137 consecutive patients (23 positive for HBsAg, 37 positive for hepatitis B surface antibody, and 77 negative for HBV) who underwent HCT. Serial serum ALT were measured before transplant and after transplant at 1 to 4 weekly intervals for the first year and then at 2 to 12 weekly intervals thereafter. Before HCT, basic core promoter (T(1762)/A(1764)) and precore (A(1896)) HBV variants were determined in HBsAg-positive and HBV DNA-positive (by polymerase chain reaction assay) patients by direct sequencing and serum HBV DNA quantitation using the Digene Hybrid Capture II assay. Cox proportional hazards analysis was used to assess the association between pretransplantation HBV virologic and host factors and occurrence of hepatitis due to HBV reactivation. After HCT, hepatitis due to HBV reactivation was more common in HBsAg-positive patients than in HBsAg-negative patients (hazard ratio, 33.3; 95% confidence interval [CI], 7.35-142.86; P <.0001). HBsAg-positive patients with detectable serum HBV DNA before HCT (on Digene assay) had a significantly higher risk of hepatitis due to HBV reactivation than HBsAg-positive patients with no detectable serum HBV DNA (adjusted hazard ratio, 9.35; 95% CI, 1.65-52.6; P =.012). Thus, we found that hepatitis due to HBV reactivation is common in HBsAg-positive patients undergoing autologous HCT. A high HBV DNA level (>10(5) copies/mL) was the most important risk factor for HBV reactivation, and its lowering by administration of nucleoside analogues before transplantation should be considered.

Adolescent↗
PubMed2002

Peripheral T-cell lymphoma.

Peripheral (post-thymic) T-cell lymphoma consists of a wide spectrum of disorders with marked differences in biology and behavior. Proper classification is pivotal for evaluating treatment results, and most studies performed a decade ago lump together different disease entities and cannot be interpreted. With improved use of immunophenotyping and molecular methods for these disorders, their exact nature is better defined in the Revised European-American Lymphoma and subsequent World Health Organization (WHO) classifications. The WHO classification of post- thymic T/natural killer (NK)-cell lymphoma consists of 15 entities, including about 30% that are unclassified cases. A wide range in incidence exists between different populations, but it is likely to be lower than previously estimated. Certain entities, like nasal/nasal-type T/NK-cell lymphoma and human T-cell leukemia/lymphoma virus 1, are much more prevalent in certain racial groups and show exquisite viral association. In these entities as a group, prognosis and treatment seem inferior to those of their B-cell counterparts, but treatment must be tailored to the exact pathologic diagnosis and prognostic index. Aggressive combination chemotherapy appears to be curative for certain entities (eg, anaplastic lymphoma kinase-positive), whereas purine analogues may be useful for low-grade entities. The role of autologous and allogeneic stem cell transplantation is still poorly defined. Specific antibody-based therapy is also on the horizon.

Humans↗
PubMed2002

Real-time quantitative analysis of polyoma BK viremia and viruria in renal allograft recipients.

Polyoma BK virus (BKV) remains dormant in the urinary tract and circulating leucocytes and becomes reactivated during immunosuppression. BK viruria is prevalent in renal allograft recipients and BK viremia may be related to nephropathy and allograft rejection. How BK viruria and viremia are related in renal allograft patients is undefined. In this study, BKV copies in paired urine and serum samples of renal allograft recipients were measured by a real time quantitative polymerase chain reaction (Q-PCR) to test the hypothesis that their quantitative relationship might help to delineate viral reactivation patterns in these tissues. Urine and plasma samples from 44 renal allograft recipients with stable graft function were collected during outpatient follow-up and the genome copies of BKV were determined by Q-PCR. All patients showed quantifiable viremia and two groups of patients were identified: one group of patients (n=35) showed low viral load (median: 270/ml, range: 108-1000/ml) and the other group (n=9) with high viral load (median: 5x10(4)/ml, range: 2x10(4)-6x10(4)/ml). The corresponding median levels of viruria were 2000 and 900 ml. BK viremia and viruria were not related quantitatively. BK viremia/viruria were also not related to age, immunosuppression, time and source of renal grafts and serum creatinine levels. The absence of a quantitative relationship between BK viremia and viruria may reflect independent BKV reactivation in different tissues during immunosuppression.

Adolescent↗
PubMed2002

Resolution of chronic hepatitis B and anti-HBs seroconversion in humans by adoptive transfer of immunity to hepatitis B core antigen.

BACKGROUND & AIMS: Impaired T-cell reactivity is believed to be the dominant cause of chronic hepatitis B virus (HBV) infection. We characterized HBV-specific T-cell responses in chronic hepatitis B surface antigen carriers who received bone marrow from HLA-identical donors with natural immunity to HBV and seroconverted to antibody to hepatitis B surface antigen. METHODS: T-cell reactivity to HBV antigens and peptides was assessed in a proliferation assay, the frequency of HBV core- and surface-specific T cells was quantified directly by ELISPOT assays, and T-cell subsets were analyzed by flow cytometry. RESULTS: CD4+ T-cell reactivity to HBV core was common in bone marrow donors and the corresponding recipients after hepatitis B surface antigen clearance, whereas none reacted to surface, pre-S1, or pre-S2 antigens. Furthermore, CD4+ T cells from donor/recipient pairs recognized similar epitopes on hepatitis B core antigen; using polymerase chain reaction for the Y chromosome, the recipients' CD4+ T lymphocytes were confirmed to be of donor origin. The frequency of core-specific CD4+ and CD8+ T cells was several-fold higher than those specific for surface antigen. CONCLUSIONS: This study provides the first evidence in humans that transfer of hepatitis B core antigen-reactive T cells is associated with resolution of chronic HBV infection. Therapeutic immunization with HBV core gene or protein deserves further investigation in patients with chronic hepatitis B.

Adolescent↗
PubMed2002

Preemptive use of lamivudine reduces hepatitis B exacerbation after allogeneic hematopoietic cell transplantation.

Exacerbation of hepatitis B virus (HBV) is a serious cause of morbidity and mortality in hepatitis B surface antigen (HBsAg)-positive patients undergoing transplantation. Our aim was to evaluate the effectiveness of lamivudine to prevent hepatitis due to exacerbation of HBV in HBsAg-positive patients treated with allogeneic hematopoietic cell transplantation. We studied 20 consecutive HBsAg-positive recipients of allogeneic hematopoietic cell transplantation who received lamivudine 100 mg daily starting one week before transplantation until week 52 after transplantation (group 1). Serial serum alanine aminotransferase and HBV DNA levels were measured before and after transplantation at 4- to 8-week intervals for the first year and then 4- to 12-week intervals. Their virologic and clinical outcomes were compared with 20 case-matched recipients who did not receive any antiviral therapy to HBV (anti-HBV) before and after hematopoietic cell transplantation (group 2). After transplantation, 9 patients (45%) in group 2 and one patient (5%) in group 1 had hepatitis due to exacerbation of HBV (P <.008), with 3 hepatic failures in group 2 and none in group 1. The one-year actuarial probability of survival without hepatitis due to exacerbation of HBV was higher in group 1 than group 2 (94.1% vs. 54.3%, P =.002). By multivariate Cox analysis, preemptive use of lamivudine effectively reduced hepatitis due to exacerbation of HBV (adjusted hazards ratio, 0.09; P =.021). In conclusion, preemptive lamivudine reduced HBV exacerbation. The use of lamivudine with other immunosuppressive regimens to prevent exacerbation of HBV should be further explored.

Adolescent↗