| BackgroundHematopoietic stem cell transplantation changed revolutionarily the conventional chemo-radio therapeutic mode of hematologic malignancies. In the past two decades, with the wide-spread application of G-CSF and the improved techniques of harvesting and selecting of blood stem cells, autologous peripheral blood stem cell (PBSC) transplantation has substituted traditional autologous bone marrow stem cell transplantation. And PBSC has been widely used in the transplantation therapy of many hematologic malignancies as the main source of hematopoietic stem cells. Yet there are still many controversial questions about transplantation, such as factors affecting mobilization and harvesting, the appropriate numbers of stem cells to transplant, complications and death associated with transplantation, relapse rate and long term survival and so on. Since different centers report inconsistent results, we need accumulate more experience to find our own answer.ObjectivesTo explore the therapeutic effects of ASCT in treating hematologic malignancies, and to investigate the efficacy of mobilization and harvesting of peripheral blood stem cells, reconstition of hematopoiesis, toxicity and tolerance of preparative regimens and clinical outcomes of auto-PBSCT.MethodsDuring the 10 years between 1996 and 2005, 94 patients underwent auto-PBSCT who were diagnosed as hematologic malignancies including acute and chronic leukemia, iymphoma (Hodgkin's and non-Hodgkin's) and multiple myeloma. Their clinical information and follow-up conditions were collected, and retrospective statistics analysis methods were used to explore the regularity.ResultsFor patients that underwent auto-PBSCT, most could be harvested enough stem cells after 1 mobilization which is comprised of chemotherapy and G-CSF. After consecutive harvesting for 1～3 days, (5.27±3.76)×10~8/kg MNC and (8.08+7.46)×10~6/kg CD34~+ could be obtained. (4.61±4.13)×10~6/kg CD34~+ were reinfused and reconstituted hemopoiesis effectively. The median time for ANC＞500/ul was at d+10, and the median time for PLT＞20000/ul free of transfusion was at d+13. Time for ANC and PLT recovery correlates negatively with the number of CD34~+ stem cells reinfused (r=-0.324 and -0.338, p=0.002 and 0.002). And this relation was not restricted by the time G-CSF was prescribed. But when more than 2×10~6/kg CD34~+ cells were reinfused, the speed of hemopoiesis recovery did not correlate with the number of CD34~+ cells reinfused any longer (r=-0.176 and -0.185, p=0.097 and 0.099).Complications during transplantation included symptoms of digestive,fever,mucositis, bleeding inclination, hypohepatia and so on. They were tolerated well. Most of the pathogens responsible for infections were gram negative bacilli. Interstitial pneumonitis, hemorrhagic cystitis and graft failure were rare. No veno-occlusion disease occurred.Totally 88.3% (n=83) patients received follow-up after transplantation. The median time of follow-up was 17.5 months. During follow-up, 51.8% maintained stable or CR, 44.6% relapsed, and 22.9% died. The main cause of death was the progression or relapses of original diseases. 70.3% of the relapses occurred in the 1st year after transplantation. 16.9% patients were transplanted with in vitro manipulated CD34~+ stem cells. But no significant effects were found on relapse.The overall survival (OS) rate at 1st year was 85.6%, at 3rd year was 72.9%, and at 5th year was 65.2%. The median survival time for multiple myeloma (MM) was 40 months, and for acute leukemia (AL) 73 months. The OS rate for MM patients at 1st year was 90%, at 3rd year was 67.5%; The OS rate for AL patients at 1st year was 85.7%, at 3rd year was 65.3%, and at 8th year was 43.6%; For lymphoma patients the OS rate at 1st year was 84.6%, at 3rd year was 78.6%, at 5th year was 71.4%. No significant difference was found among the 3 groups.The total disease free survival (DFS) at 1st year was 62.2%, at 3rd year was 51.6%, and at 5th year was 38.8%. The median disease-free survival time for MM was 23 months, for acute leukemia 43 months and for lymphoma 52 months. The DFS rate for MM patients at 1st year was 63.6%, at 3rd year was 31.8%; for AL patients the DFS rate at 1st year was 63%, at 3rd year was 52.5%, and at 5th year was 39.4%; For lymphoma patients at 1st year was 62.4%, at 3rd year was 52.9%, at 5th year was 45.3%. No significant difference was found among the three groups.CD4~+ T cells number and NK cells number in 6 months after transplantation were correlated with clinical outcome with statistical significance. The higher numbers of CD4~+ cells or NK was, the better outcome would probably be. Whether TBI was included in preparative regimen correlate with clinical outcome also, Group of not including TBI seemed to have a better outcome.Conclusion1. Chemotherapy with G-CSF could effectively mobilize efficent peripheral blood stem cells in patients with heamotologic malignancy for auto-PBSCT. Time for ANC and PLT recovery correlated negatively with the number of CD34~+ cells transplanted. Suggest to transfuse at least 2×10~6/kg to accelerate reconstitution of hemopoiesis.2. Complications during transplantation period included symptoms of digestive,fever,mucositis,bleeding inclination,hypohepatia and so on. But they were well tolerated. Pathogens of infections usually were gram negative bacilli. Virus and fungus infection also can occur and be worthy of paying attention to.3. The median overall survival time after Auto-PBSCT for MM was 40 months, for AL was 73 months. The median DFS time for MM was 23 months, for AL was 43 months, and for lymphoma was 52 months. The OS and DFS rate for these 3 groups at 1st year separately were: MM 90% and 63.6%, AL 85.7% and 63%, lymphoma 84.6% and 62.4%. No significant difference was found among the three groups.4. CD4~+ T cells numbers in 6 months following transplantation correlated with clinical outcome with statistical significance. The Higher numbers of CD4~+ cells were, the better outcomes would probably be. And a better recovery of NK cells after transplantation may have good effect on OS and DFS. 5. Selection of CD34+ stem cells in vitro may not affect relapse rate. Source of relapse probably is the residual tumor cells in patients' body.6. Sustained treatment probably has no benefit to avoid relapse.7. Including TBI in preparative regime seemed to have a worse outcome. |
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