Bone marrow transplantation from unrelated donors for patients with adult T-cell leukaemia/lymphoma

Abstract

Adult T-cell leukaemia/lymphoma (ATLL) is a highly aggressive haematological malignancy. More than 40 cases of ATLL treated by allogeneic bone marrow transplantation (BMT) from sibling donors have been reported, while there have been only a few cases of unrelated BMT for treatment of this disease. We began performing allogeneic BMT from unrelated donors in 1999 to improve the outcome of ATLL patients with no suitable sibling donors. Eight ATLL patients underwent unrelated BMT; five received the conventional conditioning regimen consisting of cyclophosphamide and total body irradiation, while three received a reduced-intensity preparative regimen. Two patients died due to encephalopathy of unknown aetiology on days 10 and 35, and one patient died due to progression of ATLL 25 months after BMT. Five patients are currently alive and disease-free at a median of 20 months after BMT. Proviral human T-lymphotropic virus type-I (HTLV-I) DNA load in peripheral blood mononuclear cells (PBMCs) was assessed in four cases before and after BMT. HTLV-I proviral DNA load was reduced significantly after transplantation. Unrelated BMT is feasible for treatment of ATLL. Further studies in a larger number of cases are required to determine the optimal conditioning regimen and stem cell source.

IRF-4 and c-Rel expression in antiviral-resistant adult T-cell leukemia/lymphoma

“…Recently, a number of ATLL patients have been reported to be in continuous remission after allogeneic stem cell transplantation. 6,7 Our studies and those of other investigators demonstrate that specific molecular signatures are associated with sensitivity or resistance to antiviral therapy that may useful in deciding on initial therapy for ATLL patients. In the presence of poor prognostic molecular features, early allogeneic stem cell transplantation should probably be considered when feasible for ATLL patients and perhaps for those who have responded to antiviral therapy and have persistent molecular evidence of the disease and a suitable stem cell donor.…”

“…4,5 Allogeneic bone marrow transplantation, including reduced-intensity regimens, has been successful in a number of ATLL patients, though severe immunodeficiency resulting from the underlying disease and the preparatory regimens poses a significant problem. 6,7 IL-2 receptor-directed therapies (anti-Tac) have proven to be useful in some ATLL patients, 8,9 but these are also expensive and unlikely to be feasible in many areas in which HTLV-1 is endemic.…”

Treatment of Patients with Adult T Cell Leukemia/Lymphoma with Cord Blood Transplantation: A Japanese Nationwide Retrospective Survey

“…b b m t . o r g (OS) of approximately 30% [8][9][10][11][12][13][14][15][16]. However, patients with ATLL typically lack a suitable HLA-identical sibling donor because both the recipients and donors are typically elderly and because the aggressive ATLL tumor burden reduces the available time to find a suitable unrelated donor within the Japan Marrow Donor Program.…”

Transplantation of allogeneic hematopoietic stem cells for adult T-cell leukemia: a nationwide retrospective study

“…[20][21][22][23] Over the past decade, improved access to alternative stem cell sources and the development of less toxic conditioning regimens have led to a rapid increase in the number of cases of ATL treated with allogeneic HSCT, albeit without consistent efficacy. [24][25][26][27][28][29][30] Therefore, we conducted a nationwide retrospective cohort study to identify pretransplantation factors that affect survival after allografting for ATL, with special emphasis on the effect of graft source: we compared the outcomes of human leukocyte antigen (HLA)-mismatched related bone marrow or peripheral blood transplantation, unrelated bone marrow transplantation, and unrelated cord blood transplantation with those of HLA-matched related bone marrow or peripheral blood transplantation as treatment for ATL. We also evaluated the effect of donor HTLV-I serostatus on outcomes among patients who received transplants from related donors.…”