CD133 allows elaborated discrimination and quantification of haematopoietic progenitor subsets in human haematopoietic stem cell transplants.

The success of haematopoietic stem cell (HSC) transplantation largely depends on numbers of transplanted HSCs, which reside in the CD34(+) populations of bone marrow (BM), peripheral blood stem cells (PBSC) and umbilical cord blood (UCB). More specifically HSCs reside in the CD38(low/-) subpopulation, which cannot be objectively discriminated from mature CD34(+)  CD38(+) progenitors. Thus, better marker combinations for the quantification of more primitive haematopoietic stem and progenitor cells in transplants are required. Recently, by combining CD34 and CD133 we could clearly distinguish CD133(+)  CD34(+) multipotent and lympho-myeloid from CD133(low)  CD34(+) erythro-myeloid progenitors in UCB samples. To qualify the assessment of CD133 for routine quality control of adult HSC sources, we analysed the developmental potentials of CD133(+) and CD133(low) subpopulations in BM and PBSC. Similar to UCB, CD133 expression objectively discriminated functionally distinct subpopulations in adult HSC sources. By implementing anti-CD45RA staining, which separates multipotent (CD133(+)  CD34(+)  CD45RA(-) ) from lympho-myeloid (CD133(+)  CD34(+)  CD45RA(+) ) progenitor fractions, UCB was found to contain 2-3 times higher multipotent progenitor frequencies than BM and PBSC. To test for the consistency of CD133 expression, we compared CD133(+)  CD34(+) contents of 128 UCB samples with maternal and obstetrical factors and obtained similar correlations to related studies focusing on CD34(+) cell contents. In conclusion, implementation of anti-CD133 staining into existing routine panels will improve the quality control analyses for HSC transplants.

Diagnostic value of full-dose FDG PET/CT for axillary lymph node staging in breast cancer patients.

PURPOSE: The aims of this study were (1) to evaluate FDG PET/CT and CT for the detection of axillary lymph node metastases in breast cancer (BC) patients and (2) to evaluate FDG PET/CT as a pre-test for the triage to sentinel lymph node biopsy (SLNB) versus axillary lymph node dissection (ALND). METHODS: The sensitivity, specificity, positive and negative predictive value (PPV, NPV), and accuracy of FDG PET/CT and CT for axillary lymph node metastases were determined in 61 patients (gold standard: histopathology). According to the equation "NPV = specificity (1-prevalence) / [specificity (1-prevalence) + (1-sensitivity) prevalence]" FDG PET/CT was evaluated as a triage tool for SLNB versus ALND. RESULTS: The sensitivity, specificity, PPV, NPV and accuracy of FDG PET/CT was 58, 92, 82, 77 and 79% and of CT 46, 89, 72, 71 and 72%, respectively. Patients with an up to approximately 60% risk for axillary lymph node metastases appear to be candidates for SLNB provided that the axilla is unremarkable on FDG PET/CT. CONCLUSION: FDG PET/CT cannot replace invasive approaches for axillary staging but may extend the indication for SLNB.

Breast cancer staging in a single session: whole-body PET/CT mammography.

UNLABELLED: Our objective was to compare the diagnostic accuracy of an all-in-one protocol of whole-body 18F-FDG PET/CT and integrated 18F-FDG PET/CT mammography with the diagnostic accuracy of a multimodality algorithm for initial breast cancer staging. METHODS: Forty women (mean age, 58.3 y; range, 30.8-78.4 y; SD, 12 y) with suspected breast cancer were included. For the primary tumor, we compared 18F-FDG PET/CT mammography versus MRI mammography; for axillary lymph node status, 18F-FDG PET/CT versus clinical investigation and ultrasound; and for distant metastases, 18F-FDG PET/CT versus a multimodality staging algorithm. Histopathology and clinical follow-up served as the standard of reference. The Fisher exact test evaluated the significance of differences (P < 0.05). Alterations in patient management caused by 18F-FDG PET/CT were documented. RESULTS: No significant differences were found in the detection rate of breast cancer lesions (18F-FDG PET/CT, 95%; MRI, 100%; P = 1). 18F-FDG PET/CT correctly classified lesion focality significantly more often than did MRI (18F-FDG PET/CT, 79%; MRI, 73%; P < 0.001). MRI correctly defined the T stage significantly more often than did 18F-FDG PET/CT (MRI, 77%; 18F-FDG PET/CT, 54%; P = 0.001). 18F-FDG PET/CT detected axillary lymph node metastases in 80% of cases; clinical investigation/ultrasound, in 70%. This difference was not statistically significant (P = 0.067). Distant metastases were detected with 18F-FDG PET/CT in 100% of cases, and the multimodality algorithm identified distant metastases in 70%. This difference was not statistically significant (P = 1). Three patients had extraaxillary lymph node metastases that were detected only by PET/CT (cervical, retroperitoneal, mediastinal/internal mammary group). 18F-FDG PET/CT changed patient management in 12.5% of cases. CONCLUSION: Our data suggest that a whole-body 18F-FDG PET/CT mammography protocol may be used for staging breast cancer in a single session. This initial assessment of the 18F-FDG PET/CT protocol indicates similar accuracy to MRI for the detection of breast cancer lesions. Although MRI seems to be more accurate when assessing the T stage of the tumor, 18F-FDG PET/CT seems able to more accurately define lesion focality. Although 18F-FDG PET/CT mammography was able to detect axillary lymph node metastases with a high sensitivity, this method cannot soon be expected to replace the combination of clinical examination, ultrasound, and sentinel lymph node biopsy for axillary assessment.