Extramedullary relapse after allogeneic bone marrow transplantation for haematological malignancy

Abstract

Summary:We describe the risk factors for and the natural history and response to treatment of extramedullary (EM) relapse in 183 patients who underwent allogeneic bone marrow transplantation (alloBMT) for a variety of haematological malignancies at our institution over a 7. year period. Fifty-one patients relapsed; 15 had EM relapse either alone or in association with marrow involvement. A retrospective analysis found that the presence of chronic GVHD and a longer interval between transplant and relapse were independently associated with an increased risk of EM compared to marrow-only relapse. EM relapse was also associated with a longer post-relapse survival. Patients with EM relapse appeared to respond to cytotoxic therapy but not to DLI. EM relapse after alloBMT may be more common than previously thought and have a better prognosis than marrow-only relapse. While patients developing chronic GVHD after alloBMT have a lower overall relapse risk than those who do not, they may be more prone to delayed relapse at EM sites. Bone Marrow Transplantation (2000) 26, 1011-1015. Keywords: allogeneic bone marrow transplantation; extramedullary relapse; graft-versus-host disease; donor lymphocyte infusion Allogeneic bone marrow transplantation (alloBMT) is potentially curative therapy for haematological malignancies including acute leukaemia, myelodysplastic syndrome (MDS), and chronic myeloid leukaemia (CML). 1-3 However, 30-50% of patients transplanted for acute myeloid leukaemia (AML) beyond first remission eventually relapse -usually within 12 months. 4 The post-transplant relapse rate for advanced acute lymphoblastic leukaemia (ALL) is higher, and accelerated phase CML carries a relapse risk of up to 60%. 2,3 Disease relapse is usually in the bone marrow, but some patients develop extramedullary (EM) relapse either alone, or in association with marrow relapse. EM relapse after alloBMT has been thought to be rare and the prognosis relatively poor. A survey conducted by the European Group Little is known about predisposing factors, natural history and response to treatment of EM as compared to marrow relapse. We addressed these issues in a retrospective analysis of a cohort of patients with relapsed haematological malignancy following alloBMT. In this analysis, hepatosplenomegaly and lymphadenopathy were not considered manifestations of extramedullary disease. Leptomeningeal disease was not considered extramedullary unless positive cerebrospinal fluid cytology was accompanied by a structural lesion on radiological imaging.

Preemptive alloimmune intervention in high-risk pediatric acute lymphoblastic leukemia patients guided by minimal residual disease level before stem cell transplantation

“…In addition, several of the relapses presented at unusual extramedullary sites, a phenomenon described before in conjunction with DLI. [35][36][37][38][39] Together, these observations are compatible with the notion that immune intervention may have influenced the timing and presentation of leukemia recurrence. Strong indications for the presence of immunological pressure on leukemic AML cells by the emergence of HLA loss variants have been recently reported.…”

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

“…In addition, a large study of extramedullary relapse of haematological malignancies following allogeneic transplantation included three cases of isolated soft-tissue plasmacytoma occurring between 30 and 51 months post-transplant in patients with multiple myeloma. 8 This study suggested that extramedullary relapse was relatively resistant to graft-versus-tumour effects with poor responses to DLI. These data are in keeping with a report by Zomas et al 6 who described a patient treated with DLI for frank marrow relapse post allogeneic transplant in whom there was complete response of the systemic disease but the patient subsequently went on to develop subcutaneous plasmacytomas.…”

“…A review of the literature suggests that similar localised or extramedullary relapse has been observed by several other authors after allogeneic transplantation for myeloma and may, in fact, be a frequent finding. [4][5][6][7][8][9] Patients and methods A total of 25 patients who received allogeneic transplants from matched-sibling donors for multiple myeloma (n ¼ 23) or plasma cell leukaemia (n ¼ 2) in a single centre from 1991 to 2000 were studied. Patient characteristics are shown in Table 1.…”

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

“…This is not only reported for MM, but also for acute leukaemias. 15,16 These EM relapses are believed to indicate transformation of the disease, associated with a more aggressive behaviour, therapy resistance and short survival. However, reports regarding this subject in MM are lacking data on the efficacy of the relapse treatment or are case reports.…”