No abstract

The CTD (cyclophosphamide, thalidomide, and dexamethasone) regimen is known to be an effective primary therapy in patients with newly diagnosed multiple myeloma (MM). However, stem cell yields after CTD remain inconsistent. The aim of the present study is to identify the influence of the CTD regimen on the outcome of peripheral blood stem cell (PBSC) collection. Fifty-four patients received four cycles of CTD, and PBSCs were mobilized with cyclophosphamide and G-CSF or with G-CSF alone. Each patient from whom ≤4.0 × 10(6) CD34(+) cells/kg were collected received a second mobilization course. The median duration from the start of a CTD regimen to the first collection was 4.3 months. Forty-eight patients were mobilized with cyclophosphamide followed by G-CSF, and six patients were mobilized with G-CSF alone. The median day of apheresis was day 3 (range day 2-day 5). The overall response rate at mobilization was 96.3 %, including 11.1 % complete response, 22.2 % very good partial response, and 63.0 % partial response. The median number of harvested CD34(+) cells was 12.8 × 10(6) cells/kg. At the second mobilization, 88.9 % of patients reached the minimal stem cell collection target of ≥2.0 × 10(6) cells/kg, and 75.9 % of patients achieved the collection target of ≥4.0 × 10(6) cells/kg. CTD within four cycles is an effective primary therapy in patients with newly diagnosed MM and only minimally affects subsequent PBSC collection.

Drug metabolizing genes are involved in the detoxification of chemical carcinogens. Polymorphisms in drug-metabolizing genes affect the risk of some forms of cancer. We analyzed six polymorphisms to evaluate their association with risk for non-Hodgkin lymphoma (NHL), and to examine whether smoking modifies these associations in population-based study in Korea (713 cases and 1,700 controls). The GSTP1 rs1695 AG and the combined AG/GG genotypes were associated with decreased risk of NHL (odds ratio (OR) AG 5 0.67, 95% confidence interval (CI) 5 0.55-0.82; OR AG/GG 5 0.66, 95% CI 5 0.54-0.80) and DLBCL (OR AG 5 0.63, 95% CI 5 0.49-0.82; OR AG/GG 5 0.64, 95% CI 5 0.50-0.82). For T-cell lymphoma, only the combined AG/GG genotype was associated with decreased risk (OR AG/GG 5 0.65, 95% CI 5 0.44-0.96). The CYP1A1 rs1048943 AG genotype and the combined AG/GG genotypes were associated with increased risk of NHL (OR AG 5 1.28, 95% CI 5 1.07-1.54; OR AG/GG 5 1.26, 95% CI 5 1.06-1.51) and DLBCL (OR AG 5 1.32, 95% CI 5 1.04-1.66; OR AG/GG 5 1.30, 95% CI 5 1.03-1.63), but not T-cell lymphoma. Smoking does not modify the association between these polymorphisms and NHL risk. Our data provide evidence that the GSTP1 rs1695 and the CYP1A1 rs1048943 genotypes affect the risk of NHL in Korea. Am. J. Hematol. 84:821-825, 2009. V

1927 Backgrounds: CTD regimen has been known as an effective induction therapy in patients with newly diagnosed MM. But, there were inconsistent results for the autologous stem cell yield for transplantation. The aim of present study was to identify the influence of CTD therapy on outcome of peripheral blood stem cell (PBSC) collection. Methods: Forty-eight patients received 4 cycles of CTD therapy. Stem cells were mobilized with cyclophosphamide (3.0 g/m2) and G-CSF (10 ƒÝg/kg, daily) or G-CSF alone. Patients failing to collect ≤ 4.0 × 106 CD34+ cells /kg received a second mobilization courses. Results: The median age at diagnosis was 56 years (range, 39–69). Median duration from start of CTD therapy to first collection was 4.6 months (range, 3.3–8.7). Forty-four patients were mobilized with cyclophosphamide following with G-CSF and 4 patients with G-CSF alone. The median day of apheresis was 3 days (range, 2–7). The response rate for CTD regimen at mobilization was 10% (5/48) of CR, 25% (12/48) of VGPR and 63% (30/48) of PR. A median number of harvested CD34+ cells was 8.6 × 106 cells/kg. At the first mobilization, 83% (40/48) of patients had been reached the minimal PBSC collection target of ≥ 2.0 × 106 CD34+ cells/kg and 71% (34/48) of patients achieved the collection ≥ 4.0 × 106 CD34+ cells/kg. At the end of second mobilization, 90%(43/48) of patients had yields of at least ≥ 2.0 × 106 CD34+ cells/kg and 77% (37/48) of patients had yields of ≥ 4.0 × 106 CD34+ cells/kg. During mobilization period, three patients were developed grade 3/4 non-hematologic adverse events. Conclusion: CTD regimen is an effective induction therapy in patients with newly diagnosed MM showing high response rate and acceptable rate of autologuos stem cell yield without any detrimental effect for the following stem cell collection. Disclosures: No relevant conflicts of interest to declare.

Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) are key enzymes in folate metabolism, which is essential for DNA methylation and synthesis. It is known that polymorphisms in its genes have been associated with some forms of cancer including lymphoma. Previous studies have shown MTHFR 677TT was associated with decreased risk of non-Hodgkin’s lymphoma(NHL). However, recent two reports have shown MTHFR 677TT was associated with increased risk. To evaluate the association between the MTHFR C677T and MTR A2756G polymorphisms and risk of non-Hodgkin’s lymphoma, large-scale population-based case-control study was conducted in Chonnam University Hwasun Hospital between March 1997 and June 2005. Three hundreds sixty-five patients with histologically comfirmed lymphoma and 1,162 controls were evaluated. Genotyping was done using PCR-RFLP. The cases consisted of 203 diffuse large B-cell lymphomas(DLBCL), 77 T-cell lymphomas, 62 other B-cell lymphomas, and 23 unclassifiable lymphomas. The MTHFR 677CT and 677TT genotypes were inversely associated with NHL and DLBCL, respectively. Using subjects with the MTHFR 677CC as reference group, the odds ratio of MTHFR 677CT and 677TT were (0.70, 95% CI 0.54–0.90) and (0.46, 95% CI 0.32–0.68) for NHL. The association was more evident for DLBCL (OR 0.56, 95% CI 0.40–0.78 for 677CT; OR 0.40, 95% CI 0.24–0.65 for 677TT). Dose-response effect was evident for the MTHFR T-allele (p < 0.01). There was no significant association of MTR A2756G with NHL. These results suggest that the MTHFR polymorphism may play an important role in the pathogenesis of NHL, particularly DLBCL.