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Quantitation of circulating tumor cells (CTCs) constitutes an emerging tool for the diagnosis and staging of cancer, assessment of response to therapy, and evaluation of residual disease after surgery. Unfortunately, no existing technology has the sensitivity to measure the low numbers of tumor cells (< 1 CTC per ml of whole blood) that characterize minimal levels of disease. We present a method, intravital flow cytometry, that noninvasively counts rare CTCs in vivo as they flow through the peripheral vasculature. The method involves i.v. injection of a tumor-specific fluorescent ligand followed by multiphoton fluorescence imaging of superficial blood vessels to quantitate the flowing CTCs. Studies in mice with metastatic tumors demonstrate that CTCs can be quantitated weeks before metastatic disease is detected by other means. Analysis of whole blood samples from cancer patients further establishes that human CTCs can be selectively labeled and quantitated when present at [approximately equal to] 2 CTCs per ml, opening opportunities for earlier assessment of metastatic disease. folate conjugates | in vivo imaging | multiphoton microscopy | metastasis | cancer diagnosis

Curing acute lymphoblastic leukemia (ALL) may not mean total eradication of all abnormal cells. Using extremely sensitive assays, researchers periodically assessed numbers of leukemic cells in the bone marrow of 24 ALL patients in first remission. Seven patients relapsed. Seventeen remained in remission over a 2- to 35-month period. Relapse was associated with a rise in the number of abnormal cells. However, no threshold could be found, and 15 of the 17 patients in continued remission have leukemic marrow cells. Based on the known relapse rate, only 1 of these 15 patients will relapse.

There are blood tests using the polymerase chain reaction (PCR) that can detect the presence of cancerous cells even when they are present in small quantities. This condition is called minimal residual disease. The test will allow doctors to eliminate cancer cells completely in many patients with chronic myeloid leukemia.

The ability to cure patients with leukemia after they go into remission and then relapse depends on a number of factors. Leukemia is caused by abnormal and continued growth of cancerous white blood cells. Chemotherapy can reduce the number of cancer cells to a low level, and the patient is said to be in remission. However, residual cancer may still exist in the bone marrow. The polymerase chain reaction (PCR) can be used to detect these cells but sophisticated techniques are required to detect very low levels. And it is not clear that patients with residual disease will benefit from additional treatment.

New data suggest that the bone marrow of children in long-term remission from acute lymphoblastic leukemia (ALL) may contain leukemic cells. The development of highly sensitive assays has made detection of low numbers of cells possible. However, the implications are unclear. Research will have to determine whether these are cancerous cells kept in check by the immune system, precancerous cells lacking some other genetic abnormality that triggers cancer, or that the marker gene the assay uses is an innocent gene shared by the cell's formerly cancerous parent line. Meanwhile, patients considered cured should not worry.