Isolation and transplantation of highly purified autologous peripheral CD34 + progenitor cells: Purging efficacy, hematopoietic reconstitution following high dose chemotherapy in patients with breast cancer: Results of a feasibility study in Japan
High-dose chemotherapy with autologous stem cell support may have some therapeutic impact on certain groups of the patients with advanced breast cancer(BRCA). Since stem cell contamination by tumor cells might contribute to relapse, development of a tumor cell purging technique would improve the clinical outcome. The present study was undertaken to evaluate the purging efficacy of autologous mobilized CD34+peripheral stem cells in patients with breast cancer (BRCA) in an advanced stage or relapse.
CD34+cells were selected from autologous peripheral blood stem cells (PBSC) using a clinical scale of magnetic-activated cell sorting system (CliniMACS), followed by high-dose chemotherapy with transplantation of CD34+ selected cells. Amplification of cytokeratin 19 (CK19) and 20 (CK20) gene in leukapheresis products were measured to evaluate the performance of tumor cell elimination.
Seven patients were entered into this study. After leukopheresis, 1 patient was dropped form this study due to poor mobilization. Among 6 patient, a total of 8 CD34+ selection was performed. The median purity and recovery rate of the CD34+ cells post selection was 85.1% (range 62.5-98.1%) and 74.2% (range 50.2-90.2%), respectively. After isolation of CD34+cells, the elimination rate in the logarithmic transformation of CK19 was 2.77 log, and that of CK20 were 2.43 log and 2.53 log. In 4 patients, high-dose chemotherapy was performed, followed by the transplantation of the isolated CD34+cells. Rapid neutrophil recovery, as well as platelet recovery was seen with a median time to reach 0.5 x 109/l neutrophils of 9 days(range 8-9), and 20 x 109/l platelets of 12 days (range 10-13). There was no treatment related death and no serious adverse events directly associated with the selection procedure or infusion of selected cells.
The present study demonstrated that the CliniMACS system is a highly effective positive selection method and that a high purging efficacy could be obtained without compromising the hematopoietic reconstitution capacity of the graft in BRCA patients undergoing high-dose chemotherapy.
[Show abstract][Hide abstract] ABSTRACT: Thirty patients with malignant pheochromocytoma (PHEO) or paraganglioma (PGL) were treated with high-dose 131I-MIBG. Patients were 11-62 (mean 39) years old: 19 patients males and 11 females. Nineteen patients had PGL, three of which were multifocal. Six PGLs were nonsecretory. Eleven patients had PHEO. All 30 patients had prior surgery. Fourteen patients were refractory to prior radiation or chemotherapy before 131I-MIBG. Peripheral blood stem cells (PBSCs) were collected and cryopreserved. 131I-MIBG was synthesized on-site, by exchange-labeling 131I with 127I-MIBG in a solid-phase Cu2+-catalyzed exchange reaction. 131I-MIBG was infused over 2 h via a peripheral IV. Doses ranged from 557 mCi to 1185 mCi (7.4 mCi/kg to 18.75 mCi/kg). Median dose was 833 mCi (12.55 mCi/kg). Marrow hypoplasia commenced 3 weeks after 131I-MIBG therapy. After the first 131I-MIBG therapy, 19 patients required platelet transfusions; 19 received GCSF; 12 received epoeitin or RBCs. Four patients received a PBSC infusion. High-dose 131I-MIBG resulted in the following overall tumor responses in 30 patients: 4 sustained complete remissions (CRs); 15 sustained partial remissions (PRs); 1 sustained stable disease (SD); 5 progressive disease (PD); 5 initial PRs or SD but relapsed to PD. Twenty-three of the 30 patients remain alive; deaths were from PD (5), myelodysplasia (1), and unrelated cause (1). Overall predicted survival at 5 years is 75% (Kaplan Meier estimate). For patients with metastatic PHEO or PGL, who have good *I-MIBG uptake on diagnostic scanning, high-dose 131I-MIBG therapy was effective in producing a sustained CR, PR, or SD in 67% of patients, with tolerable toxicity.
Annals of the New York Academy of Sciences 09/2006; 1073(1):465-90. DOI:10.1196/annals.1353.050 · 4.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: CD34(+)-selection of hematopoietic grafts for patients undergoing autologous hematopoietic stem cell transplantation (HSCT) is frequently used to obtain a tumor-free graft. The majority of published experience is with peripheral blood stem cell (PBSC) products; only scant information has been published on bone marrow (BM) grafts. We reviewed our experience using CD34(+) selection of BM grafts in children undergoing autologous BM transplantation. After obtaining institutional approval, we performed a retrospective review of the medical records of patients who underwent autologous stem cell collection at St. Jude. From January 1, 1999, to December 31, 2003, 373 patients underwent autologous HSCT; 131 received marrow grafts, 237 received PBSC grafts, and 5 received a combination. Seventeen patients underwent BM harvests for CD34(+) selection of their stem cell grafts. Sixteen patients received 19 CD34 purified grafts processed on the Isolex 300i Magnetic Cell Selection System device. Four patients were not included in the engraftment analysis as 1 did not receive the collected product, 1 received a tandem product, and 2 received products that were composed of 2 or 3 combined purified products. Following selection, marrow grafts contained a median of 1.4 x 10(6) CD34(+) cells/kg (range: 0.09-8.3 x 10(6)/kg) and a median of 0.014 x10(8) total nucleated cell cells/kg (range: 0.001-0.09 x 10(8)/kg). The median CD34% recovery was 30.9% (range: 9.3%-57.1%), with the median CD34 purity being 95.5% (range: 62.2%-98.8%). All patients engrafted. The median time to absolute neutrophil count > or = 500/mm(3) was 19 days (range: 12-35 days), and to platelet recovery was 28 days (range 18-37 days). No patient died from transplant-related complications. Our study demonstrates that CD34(+)-selection of marrow grafts is feasible, and these grafts are able to successfully reconstitute hematopoiesis in patients undergoing autologous BMT.
Biology of Blood and Marrow Transplantation 05/2007; 13(5):608-14. DOI:10.1016/j.bbmt.2007.01.074 · 3.40 Impact Factor
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