In multiple myeloma, stringent CR utilising in situ nucleic acid hybridisation provides a cheap, robust alternative for patient stratification post autograft

• Published in: Bone marrow transplantation (Basingstoke) Vol. 43; no. S1; p. S197
• Main Authors: Lund, K, Marron, G, Parker, A.N, McQuaker, I.G, Jackson, R, Moffat, D, Clark, A
• Format: Journal Article
• Language: English
• Published: Nature Publishing Group 01.03.2009
• Subjects: Autografts; Care and treatment; Health aspects; Multiple myeloma; Nucleic acid hybridization; Patient outcomes; Prognosis; Australia; United Kingdom
• ISSN: 0268-3369

The most useful means of assessing response to therapy in myeloma is controversial. Multiparameter flow cytometry (MFC) and PCR based techniques can accurately predict survival post autograft. However, the additional impact of such sensitive tests of MRD on practical decision making in the clinical setting is still unproven. In addition, these techniques are expensive, time-consuming and not accessible in many centres. We have found that in situ hybridization (ISH) defined "stringent Complete Remission" (sCR) is simple to calculate and provides excellent prognostic information, comparable to more complex tests. Requiring only two informative probes, ISH clearly identifies plasma cell populations and allows accurate assessment of light chain restriction, in contrast to immunocytochemistry where background staining hampers interpretation. We validated this technique in 110 patients who underwent autologous stem cell transplant between 1998 and 2004. Informative biopsies were available in 105 patients (>95%). ISH was used to measure light chain restriction of residual plasma cells on trephine biopsy (> 4: 1 or 1: 2 Kappa: Lambda ratio was defined as abnormal). CR by standard EBMT criteria was associated with improved progression-free survival (p=0.011). This was more marked for ISH negative patients compared to ISH positive patients (p=0.001). Those in CR with negative ISH results (sCR) had the best outcome with median event-free survival of 81 months compared to 30 months in those that did not attain sCR (p=0.008). Of interest MRD negative/paraprotein positive patients show a trend towards a longer progression free interval than their MRD positive/paraprotein negative counterparts. A similar result is seen in relation to overall survival (sCR vs others = median survival not yet reached vs 86 months (p=0.026)). We do develop informative MFC panels at diagnosis but, since there is no data supporting alteration of therapy post transplant at present and pending further clarification of the clinical utility of these more expensive tests, we currently use ISH based sCR as a pragmatic way to stratify patients to enable therapeutic decisions to be made and inform patients of their likely prognosis.