Summary:The study purpose was to determine if G-CSF plus doseintensive cyclophosphamide 5.25 g/m 2 , etoposide 1.05 g/m 2 and cisplatin 105 mg/m 2 (DICEP) results in superior autologous blood stem cell mobilization (BSCM) than less intensive chemotherapy. From January 1993 until May 1997, 152 consecutive patients with non-Hodgkin's lymphoma (n = 55), breast cancer (n = 47), Hodgkin's disease (n = 14), multiple myeloma (n = 9), AML (n = 9), or other cancers (n = 18) initially underwent BSCM by one of three methods: Group 1: G-CSF alone ؋ 4 days (n = 30). Group 2: disease-oriented chemotherapy, dosed to avoid blood transfusions, followed by G-CSF starting day 7 or 8, and apheresis day 13 or 14 (n = 82). Group 3: DICEP days 1-3, G-CSF starting day 14, and apheresis planned day 19, 20 or 21 (n = 40). A multivariate analysis was performed to determine which factors independently predicted BSCM. The median peripheral blood CD34 + (PB CD34 + ) cell count the morning of apheresis linearly correlated with the number of CD34 + cells removed per litre of apheresis that day. The median PB CD34 + cell count and median CD34 + cells ؋ 10 6 removed per litre of apheresis were highest for Group 3, intermediate for Group 2, and lowest for Group 1. By multivariate analysis, mobilization group (3 Ͼ 2 Ͼ 1), disease other than AML, no prior melphalan or mitomycin-C, and less than two prior chemotherapy regimens predicted better BSCM. Out of 15 Group 3 patients who had infiltrated marrows, 11 had no detectable cancer in marrow and apheresis products after DICEP. These data suggest that DICEP results in superior BSCM than less intensive chemotherapy regimens. increasing for a variety of cancers, not all patients mobilize sufficient autologous blood stem cells (ABSC) to receive this therapy safely. 1 An additional concern, albeit still of controversial significance, is tumor contamination of the autograft. Current in vitro purging techniques unfortunately result in significant ABSC loss from the autograft, and only treat the graft, not the patient. 1,2 Tumor cytoreduction in the patient is as important as in the autograft since survival following HDCT and ASCT correlates with tumor bulk. 3 We began using dose-intensive cyclophosphamide, etoposide and cisplatin (DICEP) chemotherapy in 1995 to treat multiple myeloma and poor prognosis (primary refractory, bulky and/or marrow-positive relapsed) lymphoma patients prior to ABSC collection. Initially, we used DICEP for antitumor therapy, but quickly found it mobilized stem cells as well. DICEP is a well studied, intensive, but non-myeloablative regimen with acceptable treatment-related morbidity and mortality rates. [4][5][6] It is very closely related to a common 'high-dose' regimen used with ASCT for Hodgkin's and non-Hodgkin's lymphoma called CBV (cyclophosphamide 6 g/m 2 , BCNU 300 mg/m 2 and etoposide 750 mg/m 2 ). 3,7 DICEP plus G-CSF has previously been reported to mobilize blood stem cells. [8][9][10] Demirer and colleagues found C 4 g/m 2 , E 600 mg/m 2 and P 105 mg/m 2 to be superio...
Summary:CD90 or Thy-1 is an antigen co-expressed with CD34 ؉ on putative immature hematopoietic stem cells. Peak mobilization of CD34 ؉ 90 ؉ cells into the blood occurs a few days earlier than peak mobilization of total CD34 ؉ cells. Because it is not known which cell type best correlates with engraftment, the optimal timing of apheresis remains unclear. The purpose of the study was to determine if the CD34 ؉ 90 ؉ cell dose predicts engraftment of autologous blood stem cells independent of the total CD34 ؉ cell dose/kg, the dose of other CD34 ؉ cell subsets (CD34 ؉ 33 ؊ , CD34 ؉ 38 ؊ , CD34 ؉ 41 ؉ ), or various clinical factors. Data were analyzed on 125 consecutive patients ranging in age from 19 to 66 years (median 46) who underwent autologous blood stem cell transplantation (ABSCT) for breast cancer (54), lymphoma (59), or other malignancies (12). By univariate analysis, neutrophil (у0.5 ؋ 10 9 /l) and platelet (у20 ؋ 10 9 /l or у100 ؋ 10 9 /l) engraftment correlated better with the total CD34 ؉ cell dose than with the CD34 ؉ 90 ؉ cell subset. Using Cox proportional hazards models, factors independently associated with both neutrophil engraftment (у0.5 ؋ 10 9 /l) and platelet engraftment (у20 ؋ 10 9 /l and у100 ؋ 10 9 /l) were higher total CD34 ؉ dose/kg and high-dose regimen (melphalan-containing slower than other regimens). In conclusion, the total CD34 ؉ dose/kg was a better predictor of hematopoietic engraftment following ABSCT than the dose of any CD34 ؉ subset, including CD34 ؉ 90 ؉ cells. Apheresis should continue to be timed according to peak CD34 ؉ levels. Bone Marrow Transplantation (2000) 25, 435-440. Keywords: hematopoietic stem cell transplantation; hematopoietic stem cells A prerequisite for safely treating patients with high-dose chemotherapy and autologous blood stem cell transplantation (ABSCT) is the ability to accurately predict hematopoietic recovery. At present, the marker most commonly utilized for this purpose is the total CD34 ϩ cell dose/kg. [1][2][3] Within the CD34 ϩ cell population, however,
We previously reported a 50% (95% CI = 33-76%) 5 year event-free survival (EFS) rate for 23 patients with Hodgkin's disease (HD) who received salvage therapy with single agent high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT). Predictors of poor outcome included bulky disease and initial remission <1 year. Since 1995, similar poor prognosis patients have been treated with double high-dose therapy consisting of dose-intensive cyclophosphamide 5.25 g/m2, etoposide 1.05 g/m2, cisplatin 105 mg/m2 (DICEP) for tumor cytoreduction and stem cell mobilization followed by HDM/ASCT. The purpose of the present study is to determine if the use of DICEP is associated with improved event-free (EFS) and overall survival (OAS) for patients treated with HDM/ASCT. From February 1981 to June 1999, 46 consecutive patients received HDM/ASCT for relapsed (n = 35) or refractory (n = 11) HD. DICEP re-induction and blood stem cell mobilization was used for 21 patients. Factors considered for univariate and multivariate analyses included age at transplant, number of failed chemotherapy regimens, prior radiotherapy, length of initial remission, relapsed or refractory disease status, extranodal relapse, B symptoms at relapse, bulk, post-ASCT radiotherapy, and DICEP re-induction therapy. Cox proportional hazards models were constructed for both event and death. DICEP and HDM were well tolerated with no early treatment-related mortality or toxicity requiring life-sustaining measures. For all 46 patients, the projected 5 year EFS was 52% (95% CI = 38-72%) and OAS was 57% (95% CI = 40-82). Factors independently associated with relapse in multivariate analysis included bulk >5 cm (RR = 6.38, P = 0.002), prior radiotherapy (RR = 3.59, P = 0.027), and not using DICEP (RR = 5.29, P = 0.005). Factors independently associated with death included bulk >5 cm (RR = 5.13, P = 0.009), > or =3 prior chemotherapy regimens (RR = 4.72, P = 0.019), and not using DICEP (RR = 7.49, P = 0.015). This study demonstrates that DICEP re-induction prior to HDM/ASCT is feasible. The preliminary data are sufficiently encouraging to warrant a multicenter phase II or a phase III trial evaluating DICEP followed by HDM/ASCT as salvage therapy for HD.
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