Extramedullary vs medullary relapse after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) in multiple myeloma (MM) and its correlation to clinical outcome

Abstract

Summary:Risk-adapted treatment of multiple myeloma (MM) includes autologous (auto-) and allogeneic (allo-) hematopoietic stem cell transplantation (HSCT). Case reports on extramedullary (EM) compared to bone marrow (BM) relapse after HSCT suggest a dismal prognosis. We compared the outcome of 78 MM patients relapsing after auto-(group A: n ¼ 53) or allo-(group B: n ¼ 25) HSCT, stratified into BM (64 patients) vs EM (14 patients) relapse. The relapse-specific groups were also compared with respect to risk factors, including age, b2-microglobulin, pretreatment, cytogenetics and stage. EM relapse sites were lungs (5), soft tissue (4), pericardium (2), bone (1), skin (1) and CNS (1). As of May 2004, the overall (OS) and progression-free (PFS) survival after HSCT in patients relapsing from EM sites was not significantly different from BM relapse patients, both after auto-and allo-HSCT. Although MM patients relapsing from EM sites after allo-HSCT used to be regarded as having few therapeutic options, we observed encouraging responses to donor lymphocyte infusions (DLI). Treatment responses to DLIs were observed in 5/9 (56%) BM relapse patients, and in 3/4 (75%) EM relapse patients. These observations suggest that EM relapse after HSCT is common and needs an individualized diagnostic and therapeutic approach in MM during clinical follow-up after HSCT.

Extramedullary relapses after allogeneic non-myeloablative stem cell transplantation in multiple myeloma patients do not negatively affect treatment outcome

“…5,6 Reasons for this discrepancy are not clear but may be due to the allogeneic transplant itself or the immunosuppressive regimen used after transplant. Another explanation might be that the GVM is more effective in the bone marrow than at EM sites, thereby predisposing allogeneic SCT patients to this type of relapse.…”

“…In a prognostic worse cohort of 25 MAtransplanted patients, the EM relapse rate was 32%. 6 This suggests that the most important factor is not the induction therapy before allogeneic SCT but the status of the disease at the time of transplantation. Allogeneic transplantation in progressive patients may enhance the risk of EM relapse.…”

“…Others have reported an effect by DLI treatment alone in three out of four patients with EM relapse, indicating that GVM can be effective in EM relapses. 6 The biological behaviour of (a subclone of) plasma cells already present before the allogeneic transplant might influence the type of relapse after transplant. In accordance with Zeiser et al, 6 we demonstrated that the presence of deletion of chromosome 13 at diagnosis, which is an established poor prognostic factor, is also a risk factor for the occurrence of EM relapse.…”

“…This low EM relapse rate is in accordance with Terpos et al 5 who reported one EM relapse in 16 allogeneic MA-transplanted patients. Zeiser et al 6 published a series of 37 MM patients with a MA allogeneic SCT of whom 25 relapsed during a follow-up of 28 months. This was a poor prognostic group with several unfavourable risk factors such as advanced age, more prior lines of therapy and more advanced disease as compared to the patients undergoing an autologous SCT being described in the same publication.…”

Isolated orbital relapse of multiple myeloma in a patient with severe chronic GVHD after allogeneic hematopoietic SCT

“…7,8 Furthermore, malignant plasma cells may have survived in the fatty tissue of the orbit, potentially providing a sanctuary for persistence of malignant cells. Our observation adds an alternative, not yet described aspect: as the isolated extramedullary relapse included a subconjunctival infiltrate and occurred at a site exposed to intense topical immunosuppressive treatment including CYA in addition to a multiagent systemic immunosuppression despite active cGVHD, the topical immunosuppression might have been a contributing factor for orbital relapse of multiple myeloma in the present case.…”