Rituximab-induced late-onset neutropenia in newly diagnosed B-cell lymphoma correlates with Fc receptor FcγRIIIa 158(V/F) polymorphism.

Rituximab is a commonly utilized treatment agent for B-cell lymphoma. Late onset neutropenia (LON) has been identified as a complication associated with rituximab, primarily in conjunction with hematopoietic stem cell transplantation (HSCT). Scant data exists regarding rituximab-related LON outside the spectrum of HSCT, including newly-diagnosed lymphoma. We examined a large cohort of newly-diagnosed B-cell lymphoma patients treated with rituximab-based therapy. We identified patients with LON and analyzed the characteristics and outcomes. Furthermore, we utilized multiplex PCR for the detection of the FcgRIIIa 158 V/F polymorphism and correlated this with LON. Eighty consecutive B-cell lymphoma patients were examined. Nine of 80 (11.3%) patients developed LON. The clinical course of LON was generally self-limiting without adverse events. The onset of LON occurred at a mean of 66 days after the last course of treatment, while the mean duration of LON was 97 days. Moreover, the V/V and V/F polymorphisms were significantly associated with the occurrence of LON (P 5 0.046) yielding an odds ratio for the development of LON of1.47 (95% CI 1.21-1.78). We identified an incidence of LON following frontline rituximab-based treatment of 11.3%. The FcgRIIIa polymorphism was highly associated with development of LON.

The prognostic utility of haptoglobin genotypes in squamous cell carcinoma of the head and neck.

BACKGROUND: The aim of this study was to determine whether haptoglobin (Hp) genotypes are associated with prognosis in patients with squamous cell carcinoma of the head and neck (HNSCC). METHODS: We studied patients with HNSCC without distant metastasis at diagnosis. The Hp genotype of each patient was determined and the prognostic significance of the Hp genotype was further analyzed. Pearson's chi(2)-test or Fisher's exact test were used to analyze correlations between Hp genotype and clinical characteristics of HNSCC. Eighty patients with newly diagnosed HNSCC who were treated with curative modality were enrolled in this study. Kaplan-Meier plots and log-rank test were used to compare locoregional recurrence-free survival, distant-metastasis-free survival and overall survival of patients according to Hp genotype. Survival analysis was performed using Cox proportional hazard models. RESULTS: Eighty patients with newly diagnosed HNSCC were enrolled in this study. There was no significant difference in the distribution of Hp genotypes in HNSCC patients and healthy individuals (p=0.959). Matched-pair analysis showed that locoregional recurrence-free survival was poor (p=0.02) for HNSCC patients with Hp 2-2 or 2-0. There was no significant difference in distant metastasis-free survival and overall survival (p=0.422 and 0.509, respectively). Multivariate analysis showed that Hp 2-2 or 2-0 was associated with an increased risk of locoregional recurrence [Hazard ratio (HR) 5.9; 95% confidence interval (CI), 1.1-6.65; p=0.038]. The risk was still higher in patients with Hp 2-2 or 2-0 after further adjusting for age and treatment modality (HR 7.6; 95% CI, 1.2-46; p=0.028) in locoregional recurrence-free survival. CONCLUSIONS: The present data show that the Hp genotype is closely related to recurrence rate in patients with HNSCC. Patients with Hp 2-2 or 2-0 have greater locoregional recurrence and significantly increased HRs in multivariate analysis. The Hp genotype may be a prognostic factor in patients with HNSCC.

Detection of Hpdel in healthy individuals and cancer patients in Taiwan.

BACKGROUND: We investigated the genotypic distribution of Hp(del) in healthy subjects and cancer patients in Taiwan. METHODS: Blood samples were collected from 244 randomly selected healthy Taiwanese volunteers and 737 patients with various cancers. Samples were analyzed for the haptoglobin (Hp) gene, and the presence of the Hp(del) allele was determined from genomic DNA by an Hp(del)-specific polymerase chain reaction (PCR) method. The plasma concentration of Hp was also determined. RESULTS: The frequency of the Hp(del) allele was calculated to be 0.029, and was not different between the healthy subjects and patients with cancer. The prevalence of Hp deficiency caused by Hp(del) homozygosity was estimated to be approximately 0.85 in 1000. Fifty-seven subjects were reclassified from homozygous Hp(1) or Hp(2) to Hp(1)/Hp(del) or Hp(2)/Hp(del) genotypes. The Hp(del) allele is not associated with prevalence, severity or stage of any cancer. CONCLUSIONS: Congenital Hp deficiency caused by Hp(del) homozygosity is a condition present in Taiwan with a relatively high frequency. However, the Hp(del) variant does not play a role in cancer.

Haptoglobin genotypes in nasopharyngeal carcinoma.

AIM: Haptoglobin polymorphisms are associated with different cancers; however, the occurrence of nasopharyngeal carcinoma (NPC) in relation to haptoglobin polymorphisms has not been reported. In this study, the distribution of haptoglobin genotypes among patients with NPC was investigated and the prognostic significance of haptoglobin genotypes was further analyzed. MATERIAL AND METHODS: Haptoglobin genotypes were analyzed using polymerase chain reaction and electrophoresis. The genotypes were determined in the sera of 49 NPC patients and in 134 controls. RESULTS: The haptoglobin genotypes of patients with NPC were as follows: Hp 1-1, 2%; Hp 2-1, 39%; Hp 2-2, 59%. The frequency of the Hp 2-2 genotype was much higher in NPC patients than in control individuals (p=0.044). Furthermore, NPC patients with the Hp 2-2 genotype had advanced T stages (p=0.001) and larger primary tumor volumes (p=0.035) than those with Hp 2-1 or 1-1. CONCLUSION: An increased frequency of the Hp 2-2 genotype was associated with NPC. The Hp 2 allele was also overexpressed in NPC patients. NPC patients with the Hp 2-2 genotype had advanced T stage and a larger primary tumor volume. Hp 2-2 may be a negative prognostic factor in NPC.

Differentially expressed serum haptoglobin alpha chain isoforms with potential application for diagnosis of head and neck cancer.

BACKGROUND: The discovery of molecular biomarkers is crucial to the diagnosis of head and neck squamous cell cancer (HNSCC). METHODS: Proteins from pre-surgery serum samples of patients with HNSCC and healthy individuals were analyzed by 2-dimensional gel electrophoresis (2-DE) using a 17 cm-long immobilized pH gradient gel strip (large gel). The differentially expressed protein spots were detected by statistical analysis. Because 2 haptoglobin (Hp) alpha chains were found to be differentially expressed, the genotypic distribution of Hp alpha chains in patients and healthy individuals was assayed by polymerase chain reaction. The protein expression levels of Hp alpha chains in individuals carrying different Hp alleles were analyzed by 2-DE with a small gel. RESULTS: Two isoforms of haptoglobin alpha2 chain (Hp alpha2) in patients' sera were found from 2-DE analysis to be up-regulated, while the isoforms of haptoglobin alpha1 chain (Hp alpha1) were significantly down-regulated. Apolipoprotein AII and 2 isoforms of apolipoprotein CII were also differentially expressed in the sera of patients with HNSCC. The Hp alpha2 chain was significantly up-regulated in the patients carrying at least one haptoglobin 2 allele, according to the spot intensities from scanned images of small-gel 2-DE. CONCLUSIONS: The expression pattern of seven differentially expressed polypeptides and the up-regulation of Hp alpha2 in individuals with the Hp 2 allele are potential biomarkers.

hSNF5 /INI1 mutation analysis in acute myeloid leukemia.

Previous studies indicated that region 11.2 of the long arm of chromosome 22 (22q11.2) might be a locus encoding a tumor suppressor gene, since its deletion is a recurrent genetic characteristic of aggressive pediatric cancer. This region is found in the human immunodeficiency virus integrase interactor 1 (hSNF5/INI1) gene. To investigate whether the hSNF5/INI1 gene is involved in leukemogenesis, mutation analysis of the hSNF5/INI1 gene was performed in the present study using 5 hematopoietic cell lines, acute myeloid leukemia (AML) specimen and normal control. We found two single nucleotide polymorphisms at the hSNF5/INI1 gene in exon 4 and exon 9. The results of this study suggest that the hSNF5/INI1 gene does not play an important role in the leukemogenesis of AML.