Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and B M from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 X I O 5 mononuclear cells. lmmunostained tumor cells were detected in 9.8% (1 3/133) PBSC specimens from 9/48 (1 8.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < ,005). IGH-DOSE chemotherapy followed by autologousH marrow infusion appears to be an effective treatment for some patients with locally advanced or metastatic breast cancer.I4 However, using sensitive immunocytochemical techniques, tumor cells can be observed in histologically normal bone marrow (BM) in 20% to 45% of patients with operable disease and in 20% to 70% of patients with metastatic breast cancer.'-* As a result, many patients who have multiple bone or BM metastases have not been considered eligible for autologous BM transplantation (BMT).Recently, peripheral blood stem collections (PBSC) have been used as an alternative to BM for hematopoietic support in patients with breast cancer or hematologic malignancies who have BM Several studies examining patients with neuroblastoma and lymphoma"-I3 suggest that PBSC collections are less likely to contain tumor cells than BM and thus may provide a less contaminated source of hematopoietic stem cell support after high-dose chemotherapy.The incidence and quantity of tumor cell contamination of PBSC collections in breast cancer patients has not been widely inve~tigated.'~,'' We prospectively examined the incidence of tumor cell contamination in paired samples of PBSC and BM collections from 48 advanced-stage breast cancer patients using a highly sensitive immunocytochemical technique. To determine whether these tumor cells were capable of clonogenic growth in vitro, tumor cell-specific clonogenic assays were performed on 58 BM or PBSC collections. MATERIALS AND METHODS Patient population andparticipating centers.Patients with histologically documented locally advanced or metastatic adenocarcinoma of the breast who were enrolled on high-dose chemotherapy programs at the participating treating institutions were eligible for this study. This protocol was approved by the Institutional Review Board for Human Investigation and each patient gave written in-The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/1 O5 mononuclear cells (range 0.33 to 2.0/105) compared with 22.9/105 mononuclear cells in BM (range 1 to 3,000/105, P < .0001). In culture experiments, clonogenic tumor colonies grew in 21 /26 immunocytochemically po...

Immunocytologic analysis of bone marrow aspirates is more sensitive than conventional analysis in detecting tumor cells and provides prognostic information. The relations among marrow metastases, age at diagnosis, and clinical outcome illustrate the biologic heterogeneity of neuroblastoma.

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Diabetes is a major global health issue and the number of individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) increases annually across multiple populations. Research to develop a cure must overcome multiple immune dysfunctions and the shortage of pancreatic islet β cells, but these challenges have proven intractable despite intensive research effort more than the past decades. Stem Cell Educator (SCE) therapy—which uses only autologous blood immune cells that are externally exposed to cord blood stem cells adhering to the SCE device, has previously been proven safe and effective in Chinese and Spanish subjects for the improvement of T1D, T2D, and other autoimmune diseases. Here, 4‐year follow‐up studies demonstrated the long‐term safety and clinical efficacy of SCE therapy for the treatment of T1D and T2D. Mechanistic studies found that the nature of platelets was modulated in diabetic subjects after receiving SCE therapy. Platelets and their released mitochondria display immune tolerance‐associated markers that can modulate the proliferation and function of immune cells. Notably, platelets also expressed embryonic stem cell‐ and pancreatic islet β‐cell‐associated markers that are encoded by mitochondrial DNA. Using freshly‐isolated human pancreatic islets, ex vivo studies established that platelet‐releasing mitochondria can migrate to pancreatic islets and be taken up by islet β cells, leading to the proliferation and enhancement of islet β‐cell functions. These findings reveal new mechanisms underlying SCE therapy and open up new avenues to improve the treatment of diabetes in clinics. Stem Cells Translational Medicine 2017;6:1684–1697

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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.

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Tumor surveillance tests are used to detect relapse and to guide the clinician in making therapeutic changes. Identification of relapse early in the course of disease may improve long-term survival. For patients with neuroblastoma, current conventional surveillance methods include radiologic testing, bone marrow analysis, physical examination, and measurement of urinary catecholamine metabolites. Immunocytologic analysis of blood for the detection of circulating tumor cells is a highly specific and sensitive method, which may prove useful in monitoring patients with neuroblastoma. In our study, circulating tumor cells were detected in seven of 10 patients with known disseminated disease at diagnosis and in six of 13 patients during therapy. In some patients, as few as two tumor cells were identified among 100,000 normal hematopoietic cells. The presence or absence of circulating neuroblasts in the 13 patients evaluated during therapy was significantly correlated with tumor relapse (P = .002). We conclude that immunocytologic analysis of blood is a sensitive method for the detection of circulating neuroblasts. We recommend that this technique be used in conjunction with other conventional methods for improved tumor detection and subsequent monitoring of neuroblastoma patients.