Allogeneic transplantation for multiple myeloma: late relapse may occur as localised lytic lesion/plasmacytoma despite ongoing molecular remission

Abstract

Summary:Allogeneic SCT for myeloma may be curative for young patients, but its role remains controversial because of a reported high TRM in some series. Since 1991, we have performed 25 allografts for myeloma using fully matched sibling donors. Of the 18 evaluable patients, 13 achieved CR at a median time of 2.5 months post-transplant. The five patients who were not in CR when assessed at 3 months received a short course of a-interferon and four subsequently achieved CR with this approach at a median of 82 days. One patient who failed to respond to IFN went on to achieve CR after four doses of DLI therapy, thus giving an overall CR rate of 72%. Seven patients have relapsed at a median of 4.7 years post-transplant (range 1.38-7.7 years) including two patients who had received IFN therapy. In five of these cases, relapse has been as a localised area of bone disease or isolated plasmacytoma with no evidence of marrow involvement by trephine biopsy or molecular analysis. All patients with localised relapse were treated with local radiotherapy 7DLI and four are currently disease free despite two patients having had further treatment for a second localised lesion. Six patients died of TRM (24%) and the OS at 8 years is currently 69% with an EFS of 26%. These results suggest that allogeneic SCT for myeloma can be carried out with an acceptable TRM and a high CR rate. However, late relapses as localised disease may be a frequent finding and may represent foci of myeloma not eradicated by the conditioning. The use of pretransplant MRI scanning and top-up radiotherapy to involved areas may be useful in preventing this type of relapse. Allogeneic transplantation for multiple myeloma has been shown to result in a high CR rate and is thought to be curative for a proportion of individuals. 1 However, conventional allografts for myeloma have remained controversial owing to the high reported TRM rates which has led to superior survival being demonstrated for patients undergoing autologous transplants compared to allografts. 2 Although recent data suggest that there has been a major improvement in survival of conventional myeloma allografts since 1994 owing to a significant reduction in transplant-related mortality, 3 many centres are instead exploring the use of nonmyeloablative allogeneic transplants for patients with myeloma. In principle, this should be associated with a low transplant-related mortality, relying on the potent graft-versus-myeloma effect to elicit a cure. However, the relapse risk of this approach is still unknown. Indeed, relapse remains a major concern even after conventional allografts for myeloma, where it is estimated to be 45% at 5 years 1 and with no apparent plateau in the relapse rate being seen on the most recent EBMT registry analysis. 3 In our series of 25 patients receiving conventional myeloablative-matched sibling allografts for myeloma, we have observed seven cases of relapsed disease. In five of these cases relapse occurred late, as an isolated osteolytic lesion or solitary plasmacytoma witho...

Peripheral Dose Heterogeneity Due to the Thread Effect in Total Marrow Irradiation With Helical Tomotherapy

“…In support of this, Endo et al reported localized relapse of ALL in bone marrow of the extremities (femur and humerus), although relapse from the sternum or iliac bone marrow were also common(18). Bryne et al reported a relapse of multiple myeloma from the humerus where TBI was used as a part of conditioning regimen(19). In addition, little is known about the biology of hematopoiesis in the extremities.…”

“…Although it is well known that relapse of leukemia or multiple myeloma from extremities is rare, several groups reported localized relapse of acute lymphoblastic leukemia (ALL) in bone marrow of extremities(18) or the relapse of multiple myeloma from humerus where TBI was used as a part of conditioning regimen(19). On the other hand, chronic skeletal system complications including avascular bone necrosis and clinically evident osteoporosis have been observed after compensator-based intensity-modulated total body irradiation of 12 Gy(20).…”

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

“…3 Previous reports on the incidence of EM relapse are of MM patients who received an allogeneic MA SCT. Byrne et al 4 published a series of 18 MA-transplanted patients with a follow-up of 5.3 years of whom 7 relapsed. One patient (14%) with a systemic relapse also had an EM localisation (skin).…”

The outcome of unrelated donor stem cell transplantation for patients with multiple myeloma

“…In this group, we found an overall relapse rate of 55%, which, at the time of analysis was not different between recipients of myeloablative or RIC, perhaps because of the high number of patients treated with CAMPATH in both groups. However, follow‐up is short and it is known that myeloma patients may relapse many years after allogeneic SCT (Byrne et al , 2003).…”