Long-term remission of APL with a second allogeneic BMT after CNS relapse following HLA-identical allogeneic BMT

Abstract

Summary:Second allogeneic bone marrow transplantation (BMT) for AML relapsing after an initial BMT has a poor prognosis, with a probability of a 2-y disease-free survival below 30 per cent, caused both by treatment-related mortality (TRM) and high relapse rate. While TRM is most likely due to heavy pretreatment, AML relapse after BMT may be due to resistant disease or to a poor graftversus-leukaemia (GvL) effect of the transplant. The degree of GvL may depend on individual donor/recipient immunoreactivity. In most published cases of second allogeneic BMT, both transplants were performed from the same donor. Here, we describe a patient who was first transplanted for acute promyelocytic leukaemia (APL) (AML FAB M3v) from his HLA-identical brother and received intensive immunotherapy including donor lymphocytes and IL2. He remained free from GvHD 4I1, but developed CNS relapse. After a second BMT from another HLA-identical brother, he spontaneously developed GvHD III1, and has now been disease free for nearly 3 years. In this patient, long-term remission of AML relapsing after BMT was achieved by combining remission induction using an individual chemotherapy protocol with a second BMT from an alternative matched related donor and transient GvHD III1, which probably conferred a GVL effect. Bone Marrow Transplantation (2003) 32, 843-846. doi:10.1038/sj.bmt.1704225 Keywords: AML; APL; CNS-relapse; GvL Published data on second allogeneic transplants after leukaemia relapse indicate high treatment related mortalities (TRM) and relapse rates. [1][2][3][4] . In the most recently published series, a 2-year disease-free survival of 21% was found. 1 Munoz et al 3 reported five of 21 pediatric patients event-free at 5 years, with eight of 21 relapsing, and another eight of 21 dying from TRM. All except two had the same donor in both transplants. Bosi et al found an event-free survival of 26% at 5 years, with a TRM of 46%. 2 Late relapse, full conditioning, and remission before BMT were identified as good prognostic factors. 2 Other studies found even higher incidences of fatal complications. 4 The high rate of TRM can be attributed to heavy pretreatment in most patients. For leukaemia relapse, the main reasons may be resistant disease and an insufficient graft-versus-leukaemia (GvL) effect. Since the degree of GvL depends on the individual donor/recipient immunoreactivity, it is of interest to study cases of sequential bone marrow transplantations (BMTs) using different donors.Acute promyelocytic leukaemia (APL) or acute myelogeneous leukaemia, FAB M3, is caused by the chromosomal translocation t(15;17) leading to a fusion protein consisting of the growth suppressor protein PML and the retinoic acid receptor-a(RARa). 5,6 By inhibition of terminal differentiation in promyelocytes this protein leads to unlimited blast proliferation. The subtype FAB M3v, characterized by the microgranular morphology of the blasts, is associated with a high incidence of hyperleukocytosis and severe coagulopathy at presentation, and the prognosis ...

Isolated central nervous system recurrence of acute promyelocytic leukemia in children

“…These included 20 articles and 81 abstracts. From these we identified 19 published peer‐reviewed manuscripts and 1 abstract for further detailed analysis 2, 5, 7, 9–25. These reports contained 431 de novo pediatric APL patients, of whom 81.2% (350/431) attained a complete remission and 81 (23.1%) sustained a relapse (documented by standard morphologic criteria and/or molecular studies).…”

“…For these reports, we had to assume that there were no CNS relapses. Another issue is the fact that several treatment regimens detected in our review included CNS prophylaxis 10, 14, 15, 20. However, this involved only 13% (47 patients) of the children who attained remission.…”

Treatment of splenic marginal zone lymphoma of the CNS with high-dose therapy and allogeneic stem cell transplantation

“…Another group described donor-derived lymphocytes in the cerebrospinal fluid after transplantation [20]. Furthermore, the successful treatment by allogeneic BSCT of patients with isolated CNS relapse of acute leukemia has been published [21]. In a prior publication we reported the successful therapy of CNS-relapse of high-grade NHL with alloSCT, immunomodulation and irradiation [22].…”

Combined immunoradiotherapy induces long-term remission of CNS relapse of peripheral, diffuse, large-cell lymphoma after allogeneic stem cell transplantation: Case study

“…In addition, donor-derived lymphocytes have been detected in the cerebrospinal fluid after transplantation (Hibi et al, 1997). Furthermore, the successful treatment by allogeneic BSCT of patients with isolated CNS relapse of acute leukemia has been published (Classen et al, 2003). Usually, multimodal therapy is not suffi cient to cure an intracerebral relapse of lymphoma (van Besien et al, 1998).…”