Transplantation of CD34+ peripheral blood cells selected using a fully automated immunomagnetic system in patients with high-risk breast cancer: results of a prospective randomized multicenter clinical trial

Abstract

Summary:Tumor contamination of autologous peripheral blood stem/progenitor cell grafts occurs in a substantial proportion of high-risk breast cancer patients, and the possibility that such contamination may contribute to relapse has focused attention on methods for removal of the contaminating cells prior to transplantation. One such approach is positive selection of CD34 + cells. A fully automated immunomagnetic cell selection system has recently been introduced to facilitate the positive selection process. A multicenter randomized clinical trial was designed to evaluate the capacity of CD34 + cells isolated using the fully automated system to support prompt hematopoietic reconstitution following high-dose chemotherapy in high-risk breast cancer patients, as well as to assess the safety and tolerability of the CD34 + cell transplants. In recipients of isolated CD34 + cells, the median time to an absolute neutrophil count у500/l was 10 days, a value identical to that observed in patients receiving unfractionated apheresis collections. In the isolated CD34 + cell recipients median time to a platelet count у20 000/l was 12 days, compared with 10 days in the unfractionated cell group. There were no statistically significant differences between the groups in median time to neutrophil or platelet engraftment. Infusion of autologous cells was well tolerated by the study groups. There were no intergroup differences in the incidence of infections, need for platelet transfusions, or duration of hospitalization. Isolated CD34+ cells were high in purity and sufficient in number for use in autologous transplantation. The fully automated immunomagnetic cell selection system affords an efficient and time-saving option for isolation of CD34 + cells to be used as autologous grafts in highrisk breast cancer patients, and the isolated CD34 + cells support undelayed hematopoietic reconstitution. Bone Marrow Transplantation (2000) 25, 1165-1174.

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

“…A number of randomized studies comparing the hematopoietic recovery in CD34-selected vs non-selected autologous transplant found no significant delay in recovery of neutrophils or platelets in the CD34-selected recipients. 12,24,25 Our study found a median ANC recovery time of 9 days, with median time to platelet transfusion independence of 12 days, which is in agreement with previous trials. The use of the CD34-selected PBPC did not have any deleterious effect on the outpatient transplant approach in our study.…”

“…At 1 year, no difference was found between the two arms; however, considering the small number of patients in disparate prognostic groups, a statistical difference may not be expected even with longer follow-up. 25 The 22% progression-free survival at 3 years reported in this study is a hopeful statistic. The disparate reports of progression-free survival in the high-dose setting make it impossible to assign importance to CD34 selection in the metastatic disease setting.…”

“…Only four patients in that study had bone disease. Yanovich and coworkers 25 randomized women with either stage II, III or IV breast cancer to either CD34-selected or unmanipulated PBPC following HDC. Twenty-four patients with stage IV disease were randomized to CD34 selection and 18 to an unfractionated cell group.…”

“…Other studies have looked at this in small groups of patients who received either CD34-selected PBPC or unmodified PBPC transplants. 24,25 In the study of Ahmed et al, 24 15 patients received CD34-selected stem cells and 30 patients received unmanipulated stem cells for stage IV breast cancer. They found no difference in the median overall and progression-free survivals.…”

Occult tumor cell contamination in patients with stage II/III breast cancer receiving sequential high-dose chemotherapy

“…Gene marking studies have provided limited arguments for the contribution of contaminating tumor cells to relapse in patients with acute myeloid leukemia, neuroblastoma or chronic myeloid leukemia; 13,14 these reports remain unconfirmed in the case of breast cancer 15,16 and the value of purging products for transplantation is unclear, both in breast cancer, [17][18][19] and in other malignancies, such as multiple myeloma. 20 Observation of tumor cell contamination of apheresis products has mostly been carried out in the setting of autologous stem cell transplantation for metastatic breast cancer, where the impact on outcome may be diluted by several important prognostic factors, such as tumor sites or chemoresistance. In the setting of autologous stem cell transplant as adjuvant treatment for poor risk breast cancer with significant axillary involvement, few studies 21 have reported the incidence of this phenomenon or examined its impact.…”