Despite the small sample size, this study makes a significant contribution by suggesting that while negative feelings provoked by the failure to conceive should be acknowledged, people in this situation should also be enabled to consolidate their negative experiences of IVF constructively, helping them to move on with their lives.
4894 Introduction Diffuse large B-cell lymphoma (DLBL) is the commonest type of lymphoma worldwide. The condition is the same in Hong Kong and it accounts for about 30–40% of lymphoma cases. CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) was used for treatment of DLBL for many years. Rituximab, a chimeric anti-CD20 monoclonal antibody was used for the treatment of DLBL for about 10 years. Previous studies have shown the better efficacy of rituximab plus CHOP over CHOP alone, including the remission rate, overall and event-free survival. No previous study compared the efficacy of rituximab plus CHOP with CHOP alone in Hong Kong Chinese. We conducted a study to compare the outcomes of CHOP chemotherapy alone with rituximab plus CHOP in a local hospital in Hong Kong. Method It was a retrospective study from January 1999 to December 2009. Hong Kong Chinese patients with newly diagnosed diffuse large B-cell lymphoma were recruited in the study. They were divided into two groups. One group of patients was given CHOP chemotherapy and the other group was given rituximab plus CHOP. The remission rate, overall survival and event-free survival were compared in the two groups. Results 62 patients were recruited in the study. Twenty-nine patients with median age of 55 (range 23–77) were given CHOP chemotherapy alone. Thirty-two patients with a median age of 53 (range 20–75) were given rituximab plus CHOP. The baseline characteristics were similar in both groups. There were 41% of male patients in each group. IPI (international prognostic index) score as well as the proportion of patients at stage III and IV disease were similar in both groups. The complete remission rate was 38% in CHOP alone group and 78% in rituximab plus CHOP group (p=0.002, Fisher's exact test). The 3-year overall survival rate was 47% in CHOP group and 74% in rituximab plus CHOP group (p=0.043). The 3-year event-free survival was also better in the rituximab plus CHOP group (p=0.026). 19 events (including relapse, progression and death) were observed in the CHOP alone group and 8 events were observed in the rituximab plus chemotherapy group. The side effects profile was similar in both groups and the rate of infection is comparable in both arms. Conclusion This study has shown that the use of rituximab plus CHOP was better than CHOP alone in Hong Kong Chinese patients with newly diagnosed diffuse large B-cell lymphoma. The complete remission rate, overall survival and event-free survival were significantly higher in the rituximab plus chemotherapy group. Disclosures: No relevant conflicts of interest to declare.
803 Diffuse large B-cell lymphomas (DLBCL) is the most common form of lymphoma and these tumors demonstrate a striking molecular and clinical heterogeneity. Gene expression profiling has shown that these tumors can be divided into at least two groups, activated B cell-like (ABC) and germinal B cell-like (GCB), as well as a number of other cellular processes underlying survival and tumor biology. However, the molecular mechanisms which lead to the differential gene expression patterns are not well understood. Alternative splicing is a process through which individual exons that comprise genes that are assembled into different gene isoforms with potentially different function. Alternative splicing has been shown to be a ubiquitous mechanism of gene regulation in eukaryotes and a number of cancers. The role of alternative splicing in DLBCL is unknown. We hypothesized that alternative splicing might play an important role in DLBCL. We measured genome-wide expression of over 1 million exons in 106 primary DLBCL tumors using Affymetrix Exon 1.0 ST microarrays. The same cases were also profiled for gene expression using a conventional Affymetrix Gene microarray for comparison, and further sub-classified as the molecular subgroups of DLBCL and for independent assessment of gene expression associated with known biological processes. We identified those genes as alternatively spliced which had at least one exon that was significantly different (P<0.01) compared with the comparison group. Through examination of exon-level expression data, we found evidence for splicing events in over 10,000 genes that affect at least 10% of DLBCL cases. We identified over 200 genes that have differential exon usage between ABC and GCB DLBCL. The expression of selected alternatively spliced exons was confirmed by real-time PCR. We further examined the occurrence of alternative splicing in a number of cellular processes including each of the survival associated gene expression signatures. We found that alternative splicing regulates a significant number of genes underlying the survival-associated proliferation, stromal response and germinal center differentiation gene expression signatures (P<10−6 in all cases). In addition, a number of processes that are known to be important in oncogenesis appeared to be highly regulated by alternative splicing including transcription factor activity, DNA-repair and apoptosis (P<0.001). These data confirm that alternative splicing plays a significant role in regulating genes that are important mediators of DLBCL biology. We further investigated whether lineage-specific effects were responsible for some of the observed differences in splicing in the molecular subgroups of DLBCLs. We obtained normal resting B cells from healthy donors and stimulated them with IgM and CD40-ligand to generate activated B cells. We found that the gene-isoforms expressed highly in activated normal B cells were significantly enriched in ABC-DLBCLS (P<0.01), suggesting that lineage-derived differences in isoform splicing are preserved in their malignant counterparts. Our data indicate that alternative splicing provides an additional and significant component of regulation that encompasses nearly every biological process that is known to be important in DLBCL. Future studies that examine the role gene expression will need to recognize the specific isoforms that result in proteins with altered function. Disclosures: No relevant conflicts of interest to declare.
4366 Previous studies suggested that cytarabine was not required in the treatment of newly diagnosed acute promyelocytic leukaemia (APL). They suggested that omitting cytarabine in the treatment of APL could reduce treatment toxicity without increasing relapses and affecting survival. No previous study assessed the effect of cytarabine in the treatment of Chinese APL patients. We compared the outcome of APL patients with or without cytarabine in induction and consolidation therapy in Hong Kong Chinese in a local hospital. Method It was a retrospective study of newly diagnosed APL patients from Jan 1996 to Dec 2009. They were divided into two groups. One group was given ATRA (All-trans-retinoic acid) 45mg/m2/day combined with daunorubicin 60mg/m2/day for 3 days plus cytarabine 200mg/m2/day for 7 days as induction therapy. It was followed by two courses of consolidation with daunorubicin and cytarabine and then 2-year maintenance with low dose chemotherapy and intermittent ATRA. Another group was given the same treatment without cytarabine. The remission rate, relapse rate, overall survival and event-free survival were compared in the two groups of patients. Results Eighteen patients with median age of 41 (range 24–62) received cytarabine. 22% of them had initial WBC count >10,000/uL. Eight patients with median age of 42 (range 16–57) received no cytarabine. 25% of them had WBC count >10,000/uL. The complete remission rates were 100% in both groups. The two-year relapse rate was 5.5% (1/18) for cytarabine group and 62% (5/8) for no cytarabine group (p=0.004, Fisher's exact test). The two-year event-free survival was 82% for cytarabine group and 37% for no cytarabine group (p=0.0017). The two-year overall survival was 89% for cytarabine group and 75% for no cytarabine group (p=0.18). The adverse effects profile was similar in both groups. Conclusion The results support a role of cytarabine in addition to ATRA and daunorubicin in the treatment of newly diagnosed APL. The relapse rate was much lower in patients receiving cytarabine. The two-year event-free survival and two-year overall survival were also significantly better in the cytarabine group. Disclosures: No relevant conflicts of interest to declare.
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