Thomas Moss

Occult tumor contamination of hematopoietic stem-cell products does not affect clinical outcome of autologous transplantation in patients with metastatic breast cancer.

PURPOSE To determine whether occult tumor contamination of autologous bone marrow or peripheral-blood progenitor cells (PBPC) influences clinical outcome after high-dose chemotherapy in patients with stage IV breast cancer. PATIENTS AND METHODS We used an immunocytochemical assay capable of detecting one tumor cell in 5 x 10(5) hematopoietic cells to analyze bone marrow and/or PBPC collections obtained from 57 consecutive women with chemotherapy-sensitive metastatic breast cancer who received high-dose chemotherapy. The influence of occult tumor on time to progression, overall survival, and first site of recurrence (old or new) was studied. RESULTS Twenty-three of 57 (40%) patients received bone marrow (n=6) or peripheral-blood progenitor collections (n=17) that contained microscopic cancer. Median time to progression and overall survival were 9 and 22 months in patients who did not receive infused tumor cells, compared with 10 and 24 months, respectively, in those who received occult tumor (P=not significant [NS]). Worse survival, but not time to progression, was observed in six patients who received > or = 2/100,000 tumor cells. Regardless of whether occult tumor was infused, the majority of relapses occurred in prior, rather than new sites of disease. Three patients who received stem-cell products contaminated by microscopic breast cancer remain free from progression at 21+, 47+, and 52+ months. CONCLUSION Microscopic tumor was frequently detected by immunocytochemistry in hematopoietic stem-cell products, but did not predict for inferior treatment outcome in this cohort of patients with metastatic breast cancer. Quantitative information regarding infused tumor burden may have prognostic significance.

First international ISHAGE symposium on minimal residual cancer.

ABSTRACT This conference was held on June 23–25, 1996, at the Kunstlerhaus, Munich, Germany, and was sponsored by the International Society for Hematotherapy and Graft Engineering, as well as AMGEN...

PreSERVE-AMINovelty and Significance: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Intracoronary Administration of Autologous CD34+ Cells in Patients With Left Ventricular Dysfunction Post STEMI

Rationale: Despite direct immediate intervention and therapy, ST-segment–elevation myocardial infarction (STEMI) victims remain at risk for infarct expansion, heart failure, reinfarction, repeat revascularization, and death. Objective: To evaluate the safety and bioactivity of autologous CD34+ cell (CLBS10) intracoronary infusion in patients with left ventricular dysfunction post STEMI. Methods and Results: Patients who underwent successful stenting for STEMI and had left ventricular dysfunction (ejection fraction⩽48%) ≥4 days poststent were eligible for enrollment. Subjects (N=161) underwent mini bone marrow harvest and were randomized 1:1 to receive (1) autologous CD34+ cells (minimum 10 mol/L±20% cells; N=78) or (2) diluent alone (N=83), via intracoronary infusion. The primary safety end point was adverse events, serious adverse events, and major adverse cardiac event. The primary efficacy end point was change in resting myocardial perfusion over 6 months. No differences in myocardial perfusion or adverse events were observed between the control and treatment groups, although increased perfusion was observed within each group from baseline to 6 months (P<0.001). In secondary analyses, when adjusted for time of ischemia, a consistently favorable cell dose–dependent effect was observed in the change in left ventricular ejection fraction and infarct size, and the duration of time subjects was alive and out of hospital (P=0.05). At 1 year, 3.6% (N=3) and 0% deaths were observed in the control and treatment group, respectively. Conclusions: This PreSERVE-AMI (Phase 2, randomized, double-blind, placebo-controlled trial) represents the largest study of cell-based therapy for STEMI completed in the United States and provides evidence supporting safety and potential efficacy in patients with left ventricular dysfunction post STEMI who are at risk for death and major morbidity. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01495364.Rationale: Despite direct immediate intervention and therapy, ST-segment–elevation myocardial infarction (STEMI) victims remain at risk for infarct expansion, heart failure, reinfarction, repeat revascularization, and death. Objective: To evaluate the safety and bioactivity of autologous CD34+ cell (CLBS10) intracoronary infusion in patients with left ventricular dysfunction post STEMI. Methods and Results: Patients who underwent successful stenting for STEMI and had left ventricular dysfunction (ejection fraction≤48%) ≥4 days poststent were eligible for enrollment. Subjects (N=161) underwent mini bone marrow harvest and were randomized 1:1 to receive (1) autologous CD34+ cells (minimum 10 mol/L±20% cells; N=78) or (2) diluent alone (N=83), via intracoronary infusion. The primary safety end point was adverse events, serious adverse events, and major adverse cardiac event. The primary efficacy end point was change in resting myocardial perfusion over 6 months. No differences in myocardial perfusion or adverse events were observed between the control and treatment groups, although increased perfusion was observed within each group from baseline to 6 months ( P <0.001). In secondary analyses, when adjusted for time of ischemia, a consistently favorable cell dose–dependent effect was observed in the change in left ventricular ejection fraction and infarct size, and the duration of time subjects was alive and out of hospital ( P =0.05). At 1 year, 3.6% (N=3) and 0% deaths were observed in the control and treatment group, respectively. Conclusions: This PreSERVE-AMI (Phase 2, randomized, double-blind, placebo-controlled trial) represents the largest study of cell-based therapy for STEMI completed in the United States and provides evidence supporting safety and potential efficacy in patients with left ventricular dysfunction post STEMI who are at risk for death and major morbidity. Clinical Trial Registration: URL: . Unique identifier: [NCT01495364][1]. # Novelty and Significance {#article-title-42} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01495364&atom=%2Fcircresaha%2F120%2F2%2F324.atom

PreSERVE-AMINovelty and Significance

Rationale: Despite direct immediate intervention and therapy, ST-segment–elevation myocardial infarction (STEMI) victims remain at risk for infarct expansion, heart failure, reinfarction, repeat revascularization, and death. Objective: To evaluate the safety and bioactivity of autologous CD34+ cell (CLBS10) intracoronary infusion in patients with left ventricular dysfunction post STEMI. Methods and Results: Patients who underwent successful stenting for STEMI and had left ventricular dysfunction (ejection fraction⩽48%) ≥4 days poststent were eligible for enrollment. Subjects (N=161) underwent mini bone marrow harvest and were randomized 1:1 to receive (1) autologous CD34+ cells (minimum 10 mol/L±20% cells; N=78) or (2) diluent alone (N=83), via intracoronary infusion. The primary safety end point was adverse events, serious adverse events, and major adverse cardiac event. The primary efficacy end point was change in resting myocardial perfusion over 6 months. No differences in myocardial perfusion or adverse events were observed between the control and treatment groups, although increased perfusion was observed within each group from baseline to 6 months (P<0.001). In secondary analyses, when adjusted for time of ischemia, a consistently favorable cell dose–dependent effect was observed in the change in left ventricular ejection fraction and infarct size, and the duration of time subjects was alive and out of hospital (P=0.05). At 1 year, 3.6% (N=3) and 0% deaths were observed in the control and treatment group, respectively. Conclusions: This PreSERVE-AMI (Phase 2, randomized, double-blind, placebo-controlled trial) represents the largest study of cell-based therapy for STEMI completed in the United States and provides evidence supporting safety and potential efficacy in patients with left ventricular dysfunction post STEMI who are at risk for death and major morbidity. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01495364.Rationale: Despite direct immediate intervention and therapy, ST-segment–elevation myocardial infarction (STEMI) victims remain at risk for infarct expansion, heart failure, reinfarction, repeat revascularization, and death. Objective: To evaluate the safety and bioactivity of autologous CD34+ cell (CLBS10) intracoronary infusion in patients with left ventricular dysfunction post STEMI. Methods and Results: Patients who underwent successful stenting for STEMI and had left ventricular dysfunction (ejection fraction≤48%) ≥4 days poststent were eligible for enrollment. Subjects (N=161) underwent mini bone marrow harvest and were randomized 1:1 to receive (1) autologous CD34+ cells (minimum 10 mol/L±20% cells; N=78) or (2) diluent alone (N=83), via intracoronary infusion. The primary safety end point was adverse events, serious adverse events, and major adverse cardiac event. The primary efficacy end point was change in resting myocardial perfusion over 6 months. No differences in myocardial perfusion or adverse events were observed between the control and treatment groups, although increased perfusion was observed within each group from baseline to 6 months ( P <0.001). In secondary analyses, when adjusted for time of ischemia, a consistently favorable cell dose–dependent effect was observed in the change in left ventricular ejection fraction and infarct size, and the duration of time subjects was alive and out of hospital ( P =0.05). At 1 year, 3.6% (N=3) and 0% deaths were observed in the control and treatment group, respectively. Conclusions: This PreSERVE-AMI (Phase 2, randomized, double-blind, placebo-controlled trial) represents the largest study of cell-based therapy for STEMI completed in the United States and provides evidence supporting safety and potential efficacy in patients with left ventricular dysfunction post STEMI who are at risk for death and major morbidity. Clinical Trial Registration: URL: . Unique identifier: [NCT01495364][1]. # Novelty and Significance {#article-title-42} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01495364&atom=%2Fcircresaha%2F120%2F2%2F324.atom

ONE YEAR FOLLOW-UP RESULTS FROM PRESERVE-AMI: A RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED CLINICAL TRIAL OF INTRACORONARY INFUSION OF AUTOLOGOUS CD34+ CELLS IN PATIENTS WITH LEFT VENTRICULAR DYSFUNCTION POST STEMI

ST segment Elevation Myocardial Infarction (STEMI) affects 160,000 annually in the US. Guidelines direct immediate revascularization and adjunctive medical therapies. Yet STEMI victims remain at risk for infarct expansion, heart failure, reinfarction, repeat revascularization and death. In pre-

Meeting Report: First International ISHAGE Symposium on Minimal Residual Cancer

ABSTRACT This conference was held on June 23–25, 1996, at the Kunstlerhaus, Munich, Germany, and was sponsored by the International Society for Hematotherapy and Graft Engineering, as well as AMGEN...