Summary:Isolated extramedullary relapse of acute lymphoblastic leukaemia (ALL) with sparing of the marrow after allogeneic bone marrow transplantation (BMT) is a rare occurrence, and the mechanisms underlying the selective involvement of extramedullary sites remain undefined. These might be due to relapse in sanctuary sites where the leukaemic cells are resistant to chemotherapy, or a stronger putative graft-versus-leukaemia (GVL) effect in the marrow as compared with peripheral tissues. We report two ALL patients with repeated episodes of extramedullary relapse after BMT in whom both mechanisms might be operating. In the first patient, the marrow was in morphologic and molecular remission before isolated leukaemic relapse in the central nervous system (CNS) occurred. Subsequent secondary infiltration of leukaemic cells into the marrow was only evident molecularly but not morphologically, implying that the relapse had arisen in a sanctuary CNS site. In the second patient, a first relapse in the marrow, which was induced into morphologic and molecular remission by chemotherapy and donor lymphocyte infusion, was followed by extramedullary relapses without any subsequent involvement of the marrow. This suggested that factors, likely to be due to a GVL effect, were stronger in the marrow than in peripheral tissues. Keywords: extramedullary relapse; leukaemia; allogeneic bone marrow transplantation For adult acute lymphoblastic leukaemia (ALL), bone marrow transplantation (BMT) from an HLA-identical donor offers the best chance of cure. 1 This is attributed partly to high-dose chemotherapy and radiotherapy (RT), and partly to an immunological graft-versus-leukaemia (GVL) effect, 2 evident in the lower relapse rates associated with significant graft-versus-host disease (GVHD), and in the effectiveness of donor lymphocyte infusion (DLI) in inducing remission in post-BMT relapses. Extramedullary disease in lymphoid tissue and sanctuary sites, such as the central nervous sys- 4 However, isolated extramedullary relapse after BMT in the absence of marrow involvement has occasionally been reported. The underlying mechanisms leading to selective sparing of the marrow in these cases remain undefined. We describe two patients with extramedullary relapse of ALL after allogeneic BMT from HLA-identical siblings. Despite recurrent extramedullary disease, both patients retained morphological remission and full donor chimerism in the marrow. The possible underlying mechanisms of isolated extramedullary relapses as revealed by investigations in these two cases are discussed.
Materials and methods
Case reportsPatient 1 was a 37-year-old woman presenting with Philadelphia (Ph) chromosome-positive common ALL. A short complete remission (CR) of 3 months was obtained with combination induction chemotherapy. 5 The disease relapsed in the bone marrow (BM) and CNS, and she underwent allogeneic BMT with the leukaemia not in remission from an HLA-identical brother donor. Etoposide (60 mg/kg), cyclophosphamide (CY) (100 mg/kg), and total body ...