T-cell receptor excision circles: a novel prognostic parameter for the outcome of transplantation in multiple myeloma patients Mirija Svaldi, 1,2 Andrea Judith Lanthaler, 1 Martin Dugas, 3 Peter Lohse, 2 Norbert Pescosta, 1 Christian Straka 4 and Manfred Mitterer 1 1 Department of Hematology and Bone Marrow Transplantation Centre, Regional Hospital, Bozen, Italy, 2 Department of Clinical Chemistry – Grosshadern, 3 Department of Medical Informatics, Biometrics and Epidemiology (IBE), 4 Medizinische Klinik-Innenstadt, University of Munich, Munich, Germany Received 20 January 2003; accepted for publication 2 April 2003 Summary. This study investigated whether T-cell receptor excision circles (TRECs) are a prognostic marker for the outcome of myeloma patients undergoing a tandem autol- ogous peripheral blood stem cell transplantation (PBSCT). Twenty-five patients were enrolled. Samples were obtained at study enrolment, after conventional therapy, between first and second transplantation and 3, 6, 12 and 24 months after the second PBSCT. TRECs were quantified using real-time polymerase chain reaction. A high variation in TREC levels was found at diagnosis (median TREC level 136/10 5 peripheral blood mononuclear cells (PBMCs); range 1–1729), suggesting individual differences in thymic output of naive T cells. Patients with more than 136 TRECs/ 10 5 P BMCs at diagnosis had a statistically significant better overall survival (P ¼ 0®05) and event-free survival (P ¼ 0®045), whereas low TREC levels correlated with a higher incidence of infectious complications. Median TREC values were lowest after the first PBSCT (52/10 5 PBMCs) and reached the baseline 12 months after the second transplantation. Patients with high TREC levels after the second PBSCT had a significantly higher probability of being in complete or partial remission 30 months after the second PBSCT. TREC levels were not correlated with b 2 -micro- globulin and C-reactive protein levels at diagnosis. These data suggest that TRECs could be a relevant prognostic factor for patients who receive high-dose chemotherapy and autologous PBSCT. Keywords: multiple myeloma, autologous transplantation, survival, infections, T-cell receptor excision circles (TRECs). High-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (PBSCT) is the treatment of choice for multiple myeloma (MM) patients (Attal et al, 1996; Barlogie et al, 1997). The prospective, randomized French study (Attal et al, 1996) has shown that high-dose therapy combined with autologous stem cell support improves the response rate and the event-free and overall survival of myeloma patients. Prognostic factors of transplantation outcome have gained in importance in recent years. Beta 2 -microglobulin (B 2 M) and C-reactive protein (CRP) levels (Bataille et al, 1992), as well as cytogenetic aberrations such as mono- somy or deletion of chromosome 13 (Barlogie et al, 1999), are established parameters for a more accurate prognostic evaluation. Tricot et al (2002) demonstrated that factors associated with an event-free survival (EFS) ‡ 5 years were the absence of chromosome 11 and 13 abnormalities, £ 12 months of preceding standard-dose therapy and a B 2 M level £ 2®5 mg/l at the time of first ABMT. Twenty-five per cent of all myeloma patients enrolled in the study had favourable prognostic factors, and 35% of them had a 7-year EFS, compared with 10–15% of patients with one or two unfavourable variables. The authors concluded that complete remission of 7 years duration without disease progression is consistent with cure in MM patients. T-cell response can be used as an additional prognostic factor in myeloma. Brown et al (1997) showed a good correlation between the presence of T-cell receptor beta (TCR-b) gene rearrangements and idiotype-reactive T cells Correspondence: Dr Mirija Svaldi, Department of Hematology and Bone Marrow Transplantation Centre, Regional Hospital, Regional Hospital Bozen, Lorenz-Bo ¨hlerstr. 5, 39100 Bozen, Italy. E-mail: mirija.svaldi@asbz.it British Journal of Haematology, 2003, 122, 795–801 Ó 2003 Blackwell Publishing Ltd 795