Prognostic Significance of Magnetic Resonance Imaging (MRI) of Bone Marrow (BM) in Patients with Multiple Myeloma (MM) Undergoing Treatment with High-Dose Melphalan (HDM) and Autologous Stem Cell Transplantation (ASCT).

Purpose: We have previously reported that diffuse pattern of bone marrow involvement as determined by MRI imaging of the spine, in newly diagnosed patients with MM is associated with features of advanced disease and with shorter survival compared to patients with normal, focal or variegated pattern of BM involvment. Purpose of the study was to determine the prognostic value of spinal bone MRI in the outcome of MM patients undergoing treatment with HDM and ASCT.

Materials and methods: Between October 1995 and June 2006, 63 MM patients for whom a MRI of the spine before first line therapy was available, received treatment with HDM (200mg/m² iv) and ASCT, in our Department. Four patterns of BM involvement in MRI were identified:

• normal pattern which required no evidence of abnormal signal,

• focal pattern, which consists of localized areas of abnormal marrow (on T1-weighted images, focal lesions are darker than yellow marrow and slightly darker or isointense to red marrow; on T2-weighted images they are brighter than both red and yellow marrow),

• diffuse pattern of abnormal marrow, where the normal bone marrow is completely replaced by the abnormal process and the intervertebral discs appear brighter or are isointense to the diseased marrow, and

• variegated pattern, which consists of innumerable small foci of disease on a background of intact marrow.

MRI pattern of BM involvement and multiple clinical and laboratory parameters were evaluated for their possible correlation with progression free survival (PFS) after HDM.

Results: Patients’ median age was 55years (range: 23 to 74 years), 60% of patients had ISS 2 or 3 before initial treatment, 54% of patients were transplanted during remission and 46% of patients had active myeloma at the time of HDM (primary refractory: 34%, resistant relapse: 12%). Nine patients (14%) had a normal MRI pattern, 33 (53%) had focal, 4 (6%) variegated and 17 (27%) diffuse MRI pattern of BM involvement. The median PFS for all patients was 20 months. Significant adverse prognostic factors for PFS included elevated creatinine and LDH serum levels, and ISS stage 3 at diagnosis. Furthermore the pattern of BM involvement by MRI correlated strongly with PFS: median PFS of 72 months for normal pattern, 20 months for focal pattern, 16 months for variegated and 9 months for diffuse pattern (p=0.016). Patients with both ISS stage 3 and diffuse MRI pattern had a median PFS of only 6 months.

Conclusion: MRI of the spine before treatment provides prognostic information for the outcome of MM patients with myeloma after HDM and ASCT. Diffuse marrow replacement on MRI of the spine identifies patients with advanced MM who have a poor prognosis even after intensive therapy. Such patients are candidates for innovative treatments.