The clinical efficacy of FOLFOX combined with bevacizumab/cetuximab in the first line treatment of advanced colorectal cancer with wild-type KRAS / 肿瘤

Objective: To compare the efficacy and main side effects of bevacizumab vs cetuximab plus FOLFOX regimen as the first-line treatment in advanced colorectal cancer patients with wild-type KRAS gene, and to evaluate the survival. Methods: Between January 2008 and February 2014, 72 patients were pathologically diagnosed of stage IV colorectal cancer with wild-type KRAS gene in People's Liberation Army General Hospital. Of 72 patients, 28 received FOLFOX regimen, 17 received bevacizumab combined with FOLFOX regimen, and 27 received cetuximab combined with FOLFOX regimen. After three cycles of chemotherapy, the short-term response was evaluated; the side effects were observed. All the patients were followed-up, and the progression-free survival (PFS) was calculated. Results: In FOLFOX regimen group, the objective response rate (ORR), disease control rate (DCR) and median PFS were 14.3%, 75.0% and 8.0 months, respectively; in bevacizumab combined with FOLFOX regimen group, these outcome measurements were 64.7%, 94.1% and 10.0 months, respectively; and in cetuximab combined with FOLFOX regimen group, these outcome measurements were 59.3%, 92.6% and 9.2 months, respectively. The ORR of FOLFOX regimen group was significantly lower than those in bevacizumab/cetuximab combined with FOLFOX regimen groups (χ2 = 12.101, P= 0.000 5; χ2 = 12.014, P = 0.000 5). There were no significant differences in DCR and median PFS among the three groups (P > 0.05). Conclusion: Bevacizumab/cetuximab combined with FOLFOX regimen can improve the ORR, DCR and median PFS in advanced colorectal cancer patients with wild-type KRAS. These two combined regimens have a quite similar efficacy, less adverse reactions and good tolerance.

Seventeen cases of nonmyeloablative stem cell transplantation using a conditioning regimen containing fludarabine / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the efficiency and toxicity of non-myeloablative stem cell transplantation (NAST) for hematological disease.</p><p><b>METHODS</b>Seventeen patients, including 3 acute myeloid leukemia, 6 chronic myelogenous leukemia, 4 severe aplastic anemia, 2 non-Hodgkin's lymphoma, 1 multiple myeloma and 1 myelodysplastic syndromes received NAST from HLA-identical sibling donors. Peripheral blood stem cells were mobilized by G-CSF 300 microg/12 hours x 5 d. (2.15 -10.01) x 10(6) CD(34)(+) cells/kg were transplanted. A non-myeloablative conditioning regimen included fludarabine 30 mg.m(-2).d(-1) x 6 d;busulfan 4 mg.kg(-1).d(-1) x 2 d or cyclophosphamide 50 mg.kg(-1).d(-1) x 2 d and antilymphocytic globulin 12 approximately 15 mg.kg(-1).d(-1) x 4 d. Cyclosporin A was used to prevent graft versus host disease (GVHD) alone and no G-CSF was administered after NAST.</p><p><b>RESULT</b>Hematopoiesis reconstitution resumed on day 8 to day 19 (average of day 13). Severe mucositis was absent. Hepatic venoocclusive disease did not occur. Infectious complications were rare. Acute and chronic GVHD each occurred in 5 patients. Idiopathic pneumonia was developed in 5 patients. In the follow-up duration of 120 to 425 days, 16 of the 17 cases had a stable mixed or complete chimerical states. Fourteen of 17 patients are alive.</p><p><b>CONCLUSION</b>NAST is an effective therapy in the treatment of hematological diseases with less complications, less blood transfusion and lower cost.</p>

The supportive effect of primary bone marrow stromal cell layers on retroviral-mediated transduction of human hematopoietic stem/progenitor cells / 中国实验血液学杂志

To elucidate the effect of established primary bone marrow stromal layers on the gene transduction of human hematopoietic stem/progenitor cells (HSC/HPC), mononuclear cells (MNC) from adult bone marrow were isolated by centrifugation on Ficoll-Hypaque gradients and plated in stromal culture medium. The cells were incubated until passage 4 to establish primary stromal layers. The HSC/HPC prestimulated by cytokines were transduced by retroviral supernatant containing mdr1 gene in presence of irradiated stroma-contact support. Transduced cells were plated in a colony-forming unit assay with and without vincristine (VCR) to assess the efficiency of transduction. Individual colonies were also analyzed by polymerase chain reaction (PCR) for the presence of provirus. The results showed that the mixed adherent cell layers were formed when adult bone marrow stromal cells were incubated for four to six weeks, mainly being composed of fibroblasts. In the presence of stroma-contact support, the average of gene transduction efficiency in marrow-derived progenitors increased 2.1 to 3.3 folds measured by colony-forming assay and/or PCR, significantly higher than those without support of stroma. It is concluded that the presence of bone marrow stroma support in combination with cytokine facilitates augmenting the extent of retroviral-mediated gene transduction.

Aldehyde-dehydrogenase gene-transduced hematopoietic cell line K562 overcomes the cytoxicity of cyclophosphamide in vitro / 中国实验血液学杂志

The identification of genes inducing resistance to anticancer chemotherapeutic agents and their introduction into hematopoietic cells represents a promising approach to overcome bone marrow toxicity, the limiting factor for most high-dose chemotherapy regimens. Because resistance to cyclophosphamide has been correlated with increased levels of expression of the aldehyde-dehydrogenase (ALDH1) gene in tumor cells lines in vitro, this study tested whether ALDH1 overexpression could directly induce cyclophosphamide resistance. Results showed that a retroviral vector was used to transduce full-length human ALDH1 cDNA into human hematopoietic cell line K562 that was then tested for resistance to 4-hydroxycyclophosphamide (4-HC), an active analogue of cyclophosphamide. Overexpression of the ALDH1 gene resulted in a significant increases in cyclophosphamide resistance in transduced K562 cells (50% inhibition concentration, IC50 = 10 micro mol/L). These findings indicate that ALDH1 overexpression is sufficient to induce cyclophosphamide resistance in vitro and provide a basis for testing the efficacy of ALDH1 gene transduction to protect bone marrow cells from high-dose cyclophosphamide in vivo.