Umbilical cord blood transplantation (CBT) is an alternative allogeneic haematopoietic stem cell transplantation (HSCT) strategy for patients with haematological diseases who do not have a matched related or unrelated donor and who need urgent transplantation. The value of CBT using myeloablative preparative regimens has already been confirmed among paediatric and adult patients (Laughlin et al, 2004;Rocha et al, 2004;Takahashi et al, 2004). However, conventional myeloablative preparative regimens are associated with significant morbidity and mortality, particularly in older patients or in those who have experienced extensive prior therapy or organ dysfunction associated with transplantation-related mortality. Various reduced-intensity preparative regimens that have been applied to such patients by several groups, including the authors of the present study, have proven feasible (Barker et al, 2003(Barker et al, , 2005Chao et al, 2004;Jacobsohn et al, 2004;Miyakoshi et al, 2004Miyakoshi et al, , 2007Yuji et al, 2005;Misawa et al, 2006;Ballen et al, 2007;Brunstein et al, 2007;Komatsu et al, 2007;Uchida et al, 2008).
We evaluated the usefulness of prognostic markers in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) ± rituximab (R-CHOP) in Japan. We studied 730 patients with DLBCL; 451 received CHOP and 279 R-CHOP. We analyzed biopsy samples immunohistochemically for markers of germinal center B cells (CD10, Bcl-6), postgerminal center B cells (Multiple myeloma-1), and apoptosis (Bcl-2). The median follow-up period for surviving patients was 56.4 months for the CHOP group and 25.2 months for the R-CHOP group. DLBCL were categorized as germinal center B (GCB) subtype (352/730; 48.2%) or non-GCB subtype (378/730; 51.8%). In the CHOP group, the high expression of CD10 (P = 0.022) or Bcl-6 (P = 0.021), or GCB subtype (P = 0.05) was associated with better overall survival, whereas the high expression of Bcl-2 (P = 0.001) or MUM1 (P = 0.011), or non-GCB subtype (P = 0.05) was associated with worse overall survival. In the R-CHOP group, however, these biomarkers except Bcl-6 were not significant prognostic factors. The patients with non-GCB subtype showed improved survival in the R-CHOP group (P = 0.756). The International Prognostic Index was a useful clinical marker of survival in the CHOP group (P < 0.001) and also in the R-CHOP group ( P < 0.001). Results of improved survival with rituximab addition indicate that the relevance of previously recognized prognostic factors should be re-evaluated.
Summary:initially reported by Stiff et al 1 in 1983. Makino et al 2 modified this method and evaluated its clinical use for peripheral blood stem cell transplantation (PBSCT) in 1991. A simplified method for cryopreservation at −80؇C of peripheral blood stem cells (PBSC) has been increasThey reported that rates of CFU-GM remained at more than 70% during 18 months of cryopreservation and that rapid ingly used for autologous PBSC transplantation in Japan. Although this method, using 6% hydroxyethyl and sustained trilineage engraftment was obtained in 10 patients who received marrow-ablative chemotherapy and starch (HES) and 5% dimethyl sulfoxide (DMSO) as a cryoprotectant without rate-controlled freezing, has sevautotransplantation of PBSC cryopreserved by this method. While this simplified method has several advantages eral advantages over the conventional method using 10% DMSO with rate-controlled freezing, little is such as being a quick and inexpensive procedure and less clumping of the thawed cells compared with the convenknown about effects of long-term cryopreservation for years and thawing process on hematopoietic progenitional method using rate-controlled freezing with 10% DMSO and storage in liquid nitrogen, 2 little is known about tors. We examined the recovery rates of BFU-E and CFU-GM in sample tubes cryopreserved by the simplithe influence of long-term cryopreservation for years and of the thawing process on frozen-thawed hematopoietic fied method under various conditions as follows: (1) long-term storage for 1-5 years; (2) DMSO exposure stem cells. In order to assess the clinical efficacy of this simplified for 1 h after rapid thawing; and (3) thawing at a lower temperature other than 37؇C. In our study, we found method, we investigated effects of long-term cryopreservation (1-5 years), exposure of frozen-thawed cells to that the recovery rates of BFU-E and CFU-GM were not affected by the length of cryopreservation period; DMSO, and slow thawing at room temperature on hematopoietic activity of PBSC when they were cryopreserved by they remained at more than 70% on average for 16-61 months. In our hands, a 1-h exposure to DMSO after this method. rapid thawing was not toxic for hematopoietic progenitors. Furthermore, there was no significant difference in the recovery rates of BFU-E and CFU-GM between Materials and methods thawing at 37؇C and 20؇C. These observations indicate that PBSC cryopreserved for at least 5 years by the simPreparation of peripheral blood mononuclear cells plified method can be used clinically without losing hematopoietic activity, and suggest that hematopoietic Peripheral blood mononuclear cells (PBMNC) were collected by apheresis from patients with hematologic maligactivity of the thawed PBSC may be unaffected when PBSC are infused slowly within 60 min or even when nancies in remission during hematologic recovery from consolidation chemotherapy with or without G-CSF. Aph-PBSC are thawed gradually at room temperature.
Summary:with acute myelogenous leukemia (AML). 1,2 However, most will relapse despite consolidation and maintenance chemotherapy. Therefore, post-remission therapy is one of The safety and efficacy of myeloablative therapy followed by autologous peripheral blood stem cell transthe most important issues in the treatment of AML. An increasing number of AML patients have been treated with plantation (ABSCT) for acute myelogenous leukemia (AML) were evaluated in 60 patients. Peripheral blood intensified consolidation chemotherapy, autologous bone marrow transplantation (BMT), or allogeneic BMT. ditioning regimen and graft-versus-leukemia (GVL) effects. 5 Nevertheless, in addition to the requirement of was used for pretransplant conditioning in 13 patients. For the remaining 47 patients, granulocyte colony-HLA-identical marrow donors, transplant-related morbidity and mortality remain the major obstacles to improving stimulating factor (G-CSF) was administered concurrently with the BEA regimen during conditioning.clinical results of allogeneic BMT. In autologous BMT, regimen-related toxicities are fewer, although a GVL effect Unpurged, cryopreserved PBSC containing a median number of 5.4 × 10 8 MNC/kg or 12 × 10 4 CFU-GM/kg cannot be obtained. One randomized study has demonstrated that patients treated with autologous BMT have were reinfused at transplantation. The median number of days to granulocytes exceeding 500/l and last platesuperior disease-free survivals (DFS) to those receiving intensive chemotherapy alone.3 let transfusion were 15 (8-44) and 24 (0-Ͼ180), respectively. The 3-year probabilities of disease-free survival Recently, autologous peripheral blood stem cell transplantation (ABSCT) has begun to replace autologous BMT (DFS) and relapse were 78.6 and 21.4% for patients transplanted in first remission, 29.6 and 64.4% for those because of rapid engraftment and low transplant-related mortality. 6-11 However, high relapse rates have been in second or third remission, and 11.1 and 77.8% for those in relapse, respectively. There were no transplantreported after ABSCT for AML. from all patients or responsible family members.
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