Abstract
To increase the availability of alternative stem-cell donors for patients with adult T-cell leukemia (ATL), we examined the feasibility of HLA-incompatible family transplantation, especially from a grown-up child (donor) to a parent (recipient). Since January 2004, seven patients with advanced-phase ATL (three males and four females, median age 59 years), for whom a timely HLA-compatible donor was unavailable, were enrolled. All patients received allografts from their HLA-incompatible sons with reduced-intensity conditioning stem cell transplantation (RIST). Combined graft-versus-host disease (GVHD) prophylaxis involved cyclosporine A or tacrolimus, mycophenolate mofetil or corticosteroid, and short-term methotrexate. All patients achieved prompt engraftment, and there was no 100-day relapse-related mortality. Only one patient had grade-IV acute-GVHD, but this was resolved. The median follow-up period was 251 days (range 112–1,018 days), and the estimated 1-year overall and 1-year progression-free survival rates were 57.1 and 28.6%, respectively. Four patients died, with causes of death being relapse (n = 2), transplantation-associated microangiopathy (n = 1), and septicemia (n = 1). Three are currently alive: two are in complete remission and one has stable disease. Despite a high rate of relapse, RIST using an allograft from an HLA-incompatible grown-up child donor may be feasible for patients with advanced-phase ATL, and may prolong survival.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Utsunomiya A, Miyazaki Y, Takatsuka Y, et al. Improved outcome of adult T-cell leukemia/lymphoma with allogeneic stem cell transplantation. Bone Marrow Transplant. 2001;27:15–20.
Kami M, Hamaki T, Miyoshi S, et al. Allogeneic hematopoietic stem cell transplantation for the treatment of adult T-cell leukemia/lymphoma. Br J Haematol. 2003;120:304–9.
Okamura J, Utsunomiya A, Tanosaki R, et al. Allogeneic stem-cell transplantation with reduced intensity conditioning as a novel immunotherapy and antiviral therapy for adult T-cell leukemia/lymphoma. Blood. 2005;105:4143–5.
Fukushima T, Miyazaki Y, Honda S, et al. Allogeneic hematopoietic stem cell transplantation provides sustained long-term survival for patients with adult T-cell leukemia/lymphoma. Leukemia. 2005;19:829–34.
Kolb HJ, Schmid C, Barrett AJ, Schendel DJ. Graft-versus-leukemia responses in allogeneic chimeras. Blood. 2004;103:767–76.
Yoshihara T, Okada K, Kobayashi M, et al. Outcome of non-T-cell-depleted HLA-haploidentical hematopoietic stem cell transplantation from family donors in children and adolescents. Int J Hematol. 2007;85:246–55.
Ogawa H, Ikegame K, Yoshihara S, et al. Unmanipulated HLA 2–3 antigen-mismatched (haploidentical) stem cell transplantation using nonmyeloablative conditioning. Biol Blood and Marrow Transplant. 2006;12:1073–84.
Fujiwara H, Kawada H, Matsushita K, et al. Case of a patient with progressive adult T-cell leukemia/lymphoma treated successfully by reduced-intensity conditioning stem cell transplantation from an HLA-incompatible related donor. Int J Hematol. 2005;82:357–61.
Shapira M, Tsirigotis P, Resnick I, Or R, Abdul Hai A, Slavin S. Allogeneic hematopoietic stem cell transplantation in the elderly. Crit Rev Oncol/Hematol. 2007;doi:10.1016/j.critrevonc.2007.01.004.
Matsushita K, Arima N, Otsubo H, et al. Granulocyte-colony stimulating factor-induced proliferation of primary adult T-cell leukemia cells. Br J Haematol. 1997;96:715–23.
Przepiorka D, Weisdorf D, Martin P, et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825–8.
Sullivan KM, Agura E, Anasetti C, et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol. 1991;28:250–9.
Ruggeri L, Capanni M, Casucci M, et al. Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation. Blood. 1999;94:333–9.
Harashima N, Kurihara K, Utsunomiya A, et al. Graft-versus-tax response in adult T-cell leukemia patients after hematopoietic stem cell transplantation. Cancer Res. 2004;64:391–9.
Tamaki H, Taniguchi Y, Kikuchi A, Yamagami T, Soma T, Matsuoka M. Development of adult T-cell leukemia in donor-derived human T-cell leukemia virus type I-infected T cells after allogeneic bone marrow transplantation. Leukemia. 2007;21:1594–6.
Rizzeri D, Koh L, Long G, et al. Partially matched, nonmyeloablative allogeneic transplantation: clinical outcomes and immune reconstitution. J Clin Oncol. 2007;25:690–7.
Ogawa H, Ikegame K, Kawakami M, Taniguchi Y, Oka Y, Kawase I. Allogeneic bone marrow transplantation with non-T-cell-depleted marrow from two HLA-antigen-mismatched related donors. Haematologica. 2004;89:373–5.
Ogawa H, Ikegame K, Kawakami M, et al. Powerful graft-versus-leukemia effect exerted by HLA-haploidentical grafts engrafted with a reduced-intensity regimen for relapse following myeloablative HLA-matched transplantation. Transplantation. 2004;3:488–9.
Acknowledgment
This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Fujiwara, H., Ozaki, A., Yoshimitsu, M. et al. Allogeneic stem cell transplantation for refractory adult T-cell leukemia using a non-T-cell-depleted HLA-incompatible family donor graft, with reference to the grown-up child donor to parent recipient setting: report of a pilot study. Int J Hematol 87, 319–326 (2008). https://doi.org/10.1007/s12185-008-0042-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12185-008-0042-2