Immuno-Pharmacologic Purging of Breast Cancer from Bone Marrow

Summary:The purpose of this study was to evaluate the frequency of detecting occult tumor cells in peripheral blood stem cell (PBSC) harvests and to determine the impact of infusing such cells on relapses after high-dose chemotherapy (HDC). Peripheral blood stem cell harvests from 223 patients with breast cancer were examined by an immunocytochemistry ( Nineteen patients who were infused with a mixture of ICC negative and untested PBSC harvests were excluded from analyses of relapse. The probabilities of relapse at 18 months for the 97 patients with stage II-III disease infused with ICC-negative and the 17 with ICC-positive PBSC were 0.19 and 0.13, respectively (P = 0.48). The probabilities of relapse at 18 months for patients achieving a CR or a CR in non-bone sites and improvement in bone lesions were 0.55 for the ICCnegative group (n = 30) and 0.45 for the ICC-positive group (n = 11) (P = 0.60). It was concluded that occult tumor cells were detected by ICC in PBSC harvests from a relatively small fraction of women with breast cancer, but were not associated with a significant increase in the probability of early relapse or progression when infused after HDC.

Section: Discussionmentioning

confidence: 99%

High-dose chemotherapy in patients with breast cancer: evaluation of infusing peripheral blood stem cells containing occult tumor cells

Weaver

Moss²,

Schwartzberg

et al. 1998

“…Different techniques of purging tumor cells have been The following ⌬ depletion values were obtained: ؉0.32 developed and are currently under investigation with the log (HTB 129, breast), ؉0.21 log (HTB 26, breast), focus on chemical or pharmacological [18][19][20] and immuno-؉0.04 log (HTB 26) for experiments with higher experimagnetic methods. 21,22 Since the CD34 antigen has not mental depletion, and −0.23 log (HTB 26), −0.9 log been detected in most solid tumors, 23 positive selection of (HTB 26, PBMNC from patient with multiple CD34 + cells from tumor contaminated peripheral blood myeloma), −0.82 log (HTB 131, breast) and −1.66 log mononuclear cell collections may represent an alternative (HTB 131) for lower depletion efficacy than calculated.…”

Section: Discussionmentioning

confidence: 99%

The efficiency of tumor cell purging using immunomagnetic CD34+ cell separation systems

Roots-Weiss

Papadimitriou

Serve

et al. 1997

Summary:over, plasma factors (eg paraprotein) may also have some impact. In summary, the Isolex 50 provides a high Immunomagnetic separation with anti-CD34 monopurity of CD34 ؉ cells and depletion of tumor cells was clonal antibodies and paramagnetic microbeads has efficient. However, calculated and experimental purging been used to enrich hematopoietic stem cells from efficiencies are not necessarily identical. human bone marrow (BM) or mobilized peripheral Keywords: immunomagnetic separation; CD34 + hematoblood mononuclear cells (PBMNC). The introduction of poietic cells; peripheral blood mononuclear cells; tumor this technique also constitutes a new principle of tumor cell purging; breast cancer cells; cloning assay cell purging. The efficiency in terms of purging tumor cells from PBMNC was evaluated in seven different experiments. Mobilized (chemotherapy and G-CSF) PBMNC were collected from patients with solid tumors Autologous reinfusion of peripheral blood mononuclear (n = 6) and multiple myeloma (n = 1) by leukapheresis cells (PBMNC) after high-dose chemotherapy constitutes using an automated MNC separation system and conan important alternative to autologous bone marrow transtaminated with 1% (n = 5) or 10% (n = 2) tumor cells plantation in patients with hematologic malignancies or from different epithelial cell lines being CD34-negative.solid tumors. 1-6 The cell mixture was sensitized with anti-CD34 (9C5)There are multiple advantages of PBMNC reinfusion vs antibodies and sheep anti-mouse IgG1 paramagnetic autologous bone marrow transplants. The collection promicrospheres and enriched for CD34 ؉ cells using an cedure with a central i.v. line is much easier abrogating any Isolex 50 magnetic separator. Purity of CD34 ؉ cells was need for general anesthesia for the donor. Hematological studied by flow cytometry (FACScan) and tumor cell reconstitution in the recipient is faster 4-7 which contributes depletion was evaluated by comparative human tumor to applicability of high-dose protocols. cloning assays (HTCA) containing methylcellulose and Although the rate of tumor cell contamination in agar. We achieved a median purity of CD34 ؉ cells of PBMNC has been reported to be significantly lower than 85.9% (range 69.8-92.9%) and a median yield of 48.1% in bone marrow transplants 8 the circulation of tumor cells (range 21.0-85.2%). From these data in each case the in the PBMNC transplant remains a major concern regardestimated log depletion of tumor cells was calculated ing the prognosis of patients. [9][10][11][12][13][14][15][16] Brenner et al 15 showed and compared with the experimentally achieved with genetic markers that residual tumor cells in autologous (HTCA) log depletion (log ⌬ depletion = log experibone marrow transplants can contribute to disease recurmental depletion − log calculated depletion). In our rence. Moreover, mobilization of hematopoietic stem cells experiments we achieved a median depletion of 2.75 log into peripheral blood by applying chemotherapy followed (range 1.55-3.69 log). When corr...

“…[11][12][13][14] Since the majority of breast cancers do not express CD34, positive selection of CD34 + cells provides a method for depletion of tumor cells without compromising the ability of PBPC to reconstitute normal hematopoiesis.…”

Section: Cd34mentioning

confidence: 99%

High-dose chemotherapy and CD34-selected peripheral blood progenitor cell transplantation for patients with breast cancer metastatic to bone and/or bone marrow

Hamm

Dansey

et al. 2001

Summary:Fifty women with breast cancer metastatic to bone or bone marrow involvement on light microscopy at the time of initial evaluation were treated with high-dose chemotherapy (HDC) and peripheral blood progenitor cell (PBPC) transplantation with CD34؉ cell selection using the Isolex 300i system. All patients received induction chemotherapy. PBPC were mobilized with chemotherapy and granulocyte colony-stimulating factor. The median CD34+ progenitor purity was 94.7% (range 72-98.7%) and recovery 38.4% (range 21-60%). Fortyeight hours after HDC with cyclophosphamide, cisplatin and carmustine, PBPC were reinfused. Median time to neutrophil count Ͼ0.5 ؋ 10 9 /l was 9 (range 9-12) days and to platelet transfusion independence 11 (4-30) days. These data demonstrate that selected CD34 ؉ PBPCs allow rapid hematologic reconstitution after HDC. During follow-up, 23% of patients developed herpes zoster. Two patients developed cytomegalovirus infections. Three patients developed fungal infections. The development of these infections was not associated with steroid use but appeared more frequently in patients with diabetes mellitus. Seventy-four per cent of patients received steroids for pulmonary toxicity. Treatmentrelated mortality was 4%. Progression-free survival and overall survival at 35 months was 22.4% and 40.5%, with a median of 11.4 months and 15.4 months, respectively. Bone Marrow Transplantation (2001) 28, 1023-1029. Keywords: CD34; immunomagnetic separation; peripheral blood progenitor cell transplantation; metastatic breast cancer High-dose chemotherapy (HDC) and autologous hematopoietic cell transplant has been shown in both phase I and phase II studies and from registry data to achieve longer disease-free and overall survivals in women with metastatic