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The role of allogeneic stem-cell transplantation (allo-SCT) in treatment of myeloma patients is still controversial. Allo-SCT consolidates treatment by virtue of its graft-versus-myeloma (GvM) effect and results in a higher rate of molecular remission and lower risk of relapse. However, in our experience we observed extra-medullary relapse (EMR) which can be reversed by new post-transplantation strategies.  

The goal of our study is to evaluate the frequency, aspects and the prognosis of EMR  after a tandem auto-allogeneic bone marrow transplantation (allo-BMT) for MM.

Our study is retrospective about 25 patients with MM who underwent  allo-BMT between February 1998 and December 2013 in the 'Centre National de Greffe de Moelle Osseuse de Tunis'.  The median age at transplant were 42 years (range; 31-49). Conditioning regimen were oral or IV Bu 14-Cy (n=23), Fludarabine-TBI (n=2). All patients received cyclosporine with methotrexate as graft-versus-host disease (GVHD) prophylaxis; one patient received in addition mycophenolate mofetil. Responses were assessed using the IMWG criteria. EM relapse was defined as the presence of plasmocytoma evidenced by medical imaging techniques and secreting the same monoclonal component while the myelogram is normal and hematopoiesis was of donor type.

  After allogeneic –BMT, eight patients (32%) are alive after a median follow up of 36 months (range 2- 168 months). Nine patients (36%) died from toxicity mainly related to GVHD and its complications. Eleven patients (44%) relapsed (n=9) or progressed (n=2) after ABMT.   In eight patients (8/11; 72%), relapse was extra medullary with histological confirmation in 2 patients. Component monoclonal was IgG lambda (n=4), IgA lambda or kappa (n=2), IgG kappa (n=1) and light chains lambda (n=1). The median time between allogeneic- BMT and EM relapse was 29 months (range 3-132 months). The status of the disease before allograft was CR (n=4), PR (n=4). Six patients had a tumor mass adjacent to bone, 2 patients have soft tissue involvement or multiple organs involvement (pancreas, kidney and abdomen).  There were no evidences of medullary involvement at the time of relapse. Molecular and cytogenetic chimerism was performed in 5 patients and they were of donor type.   Seven patients were treated by chemotherapy (bortezomib or lenalidomid; n=4) and / or radiotherapy (n=6). Three patients from them (3/8; 37.5%) are alive after a median follow-up of 156 months (range; 132-168)  with partial (n=1) or complete remission (n=2).  

After allogeneic BMT, patients are at risk of TRM and extra medullary relapse. The effect GvM seems to be limited to the bone marrow. New treatments options (lenalidomide/bortezomib) in combination with radiotherapy seems controlling the disease.