Monitoring Of Patients After Transplantation

Criteria for defining a complete response (CR) in patients with myeloma undergoing transplantation have evolved over time and may account in some cases for the differing CR rates observed in clinical trials. Early trials from the European Stem cell Transplant Registry (EBMTR) defined CR as the disappearance of immunoglobulin in serum and light chains in the urine using conventional electrophoresis or immunofixation, as well as the absence of myeloma cells in the marrow.1314 Using a more strict definition, investigators at Dana-Farber Cancer Institute (DFCI) and Fred Hutchinson Cancer Research Center (FHCRC) have required the absence of detectable monoclonal protein by immunofixation to define a CR. In an effort to establish uniform criteria for response, transplant registries have proposed criteria based upon immunofixation for defining CR, PR, relapse, and progressive disease in patients with multiple myeloma treated with high-dose therapy.15

Polymerase chain reaction (PCR) based techniques have also been used to evaluate MRD in patients with myeloma after high-dose therapy. PCR for MRD in multiple myeloma involves the amplification of the VH family of primers to identify the patient-specific immunoglobulin complementarity-determining region (CDRIII) sequences. Patient-specific primers can then be used to follow patients over time. Using the VH family primers alone, one myeloma cell in 103-104 normal cells can be detected. Increased sensitivity can be obtained using patient specific primers, to the degree that one myeloma cell in a background of 105-106 normal cells can be identified. Investigators are now using PCR to assess patients after transplantation and have reported in one study that molecular CR, defined as PCR negativity, occurs more frequently after allografting (7 of 14 patients) than after autografting (2 of 15 patients).16 Quantitative PCR using "Real-Time" technology can now also be used to follow patients with myeloma and provide a better estimate of the burden of disease.17

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