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Title: | CliniMACS CD34-selected cells to support multiple cycles of high-dose therapy. | Authors: | Richardson G.;Seymour J.;Blakey D.;Haylock D.;Simmons P.;Wolf M.;Januszewicz E.;Westerman D.;Scarlett J.;Briggs P. ;Prince H.;Wall D.;Rischin D.;Toner G. | Institution: | (Prince, Wall, Rischin, Toner, Seymour, Blakey, Haylock, Simmons, Wolf, Januszewicz, Westerman) Blood and Marrow Transplant Service, Division of Haematology and Medical Oncology, Peter MacCallum Cancer Institute, Melbourne, Vic., Australia (Richardson, Scarlett, Briggs) Department of Medical Oncology and Clinical Haematology, Monash Medical Centre, Melbourne, Vic., Australia | Issue Date: | 3-Jun-2002 | Copyright year: | 2002 | Publisher: | Informa Healthcare (69-77 Paul Street, London EC2A 4LQ, United Kingdom) | Place of publication: | United Kingdom | Publication information: | Cytotherapy. 4 (2) (pp 147-155), 2002. Date of Publication: 2002. | Abstract: | Background: Traditionally, following high-dose therapy (HDT), unmanipulated autologous PBPC are infused. Alternatively, purified CD34+ cells can now be obtained by immunomagnetic separation using the CliniMACS device. Limited data currently exist examining hemopoietic recovery with such cells. Method(s): Ten patients with advanced breast cancer had PBPC mobilized with docetaxel (100 mg/m2) and G-CSF (10 mug/kg per day), harvested and processed using the CliniMACS CD34-selection device and equally divided into three aliquots for cryopreservation. Unmanipulated 'back-up' cells were also collected on a separate day of the same mobilization, divided into three and cryopreserved. Patients subsequently received three cycles of HDT with cyclophosphamide (4 g/m2), thiotepa (300 mg/m2) and paclitaxel (175 mg/m2). The intent was for patients to receive CD34-selected cells to support each of the three cycles of HDT (i.e., 1/3 for each cycle). If, however, hemopoietic recovery was delayed after Cycle 1, 1/3 of the unmanipulated cells were infused following Cycle 2 and the remaining CD34-selected cells (2/3) were used to support Cycle 3. Result(s): PBPC from 10 patients underwent CD34-selection with a resulting median purity of 93% (range: 76-98%) and yield of 62% (range: 16-93%). Of the 10 patients, only two were able to be supported with CD34-selected cells for all three cycles of HDT. The remaining eight patients required unmanipulated 'back-up' cells to support Cycle 2. Three patients also required infusion of 'back-up' unmanipulated cells because of persistent neutropenia (n = 1) or thrombocytopenia (n = 2) following cycles initially supported by CD34-selected cells. The median number of CD34-selected cells (x 106/kg) infused per cycle was 1.5 (0.7-2.6) (n = 20) and unselected cells was 1.7 (1.4-2.8) (n = 10). Comparing hemopoietic recovery between cycles of HDT supported by CD34-selected (n = 20) and unmanipulated cells (n = 10) there was a significant slowing with the CD34-selected cells; time to ANC > 1.0 = 13 days versus 10 days, platelets > 20 = 17 days versus 13 days, > 50 = 25 versus 17 days (all P values < 0.001). There was no correlation between the dose of CD34-selected cells infused and neutrophil/platelet recovery. Discussion(s): We have demonstrated that, although unmanipulated PBPC achieve rapid hemopoietic recovery (at modest CD34 doses of <= 2.8 x 106/kg), CliniMACS-selected CD34+ cells (in the doses utilized in this study of <= 2.6 x 106/kg) result in significantly prolonged recovery. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1080/146532402317381857 | PubMed URL: | 12006210 [http://www.ncbi.nlm.nih.gov/pubmed/?term=12006210] | ISSN: | 1465-3249 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/32853 | Type: | Article | Subjects: | *antineoplastic agent/dt [Drug Therapy] *CD34 antigen/ec [Endogenous Compound] ciprofloxacin/dt [Drug Therapy] cyclophosphamide/do [Drug Dose] cyclophosphamide/dt [Drug Therapy] docetaxel/do [Drug Dose] docetaxel/dt [Drug Therapy] mesna/do [Drug Dose] mesna/dt [Drug Therapy] paclitaxel/do [Drug Dose] paclitaxel/dt [Drug Therapy] ranitidine/dt [Drug Therapy] recombinant granulocyte colony stimulating factor/do [Drug Dose] recombinant granulocyte colony stimulating factor/sc [Subcutaneous Drug Administration] thiotepa/do [Drug Dose] thiotepa/dt [Drug Therapy] recombinant granulocyte colony stimulating factor/dt [Drug Therapy] adult article autotransplantation breast cancer/dt [Drug Therapy] breast cancer/su [Surgery] cancer resistance clinical article controlled study correlation analysis cryopreservation dose response drug megadose hematopoietic stem cell transplantation human infection/co [Complication] infection/dt [Drug Therapy] infection/pc [Prevention] leukocyte count neutropenia peripheral blood stem cell thrombocytopenia toxicity/si [Side Effect] aciclovir/dt [Drug Therapy] *antineoplastic agent/ae [Adverse Drug Reaction] *antineoplastic agent/do [Drug Dose] hematopoietic stem cell transplantation human infection / complication / drug therapy / prevention leukocyte count neutropenia peripheral blood stem cell thrombocytopenia autotransplantation article adult toxicity / side effect breast cancer / drug therapy / surgery cancer resistance clinical article controlled study correlation analysis cryopreservation dose response drug megadose |
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