Correspondence
Donor-Derived T-Cell Leukemia after Bone Marrow Transplantation
N Engl J Med 2006; 354:1758-1759April 20, 2006
- Article
To the Editor:
Asymptomatic carriers of human T-cell lymphotropic virus type I (HTLV-I) are considered acceptable as donors in allogeneic stem-cell transplantation for patients with adult T-cell leukemia–lymphoma (ATL).1 However, the infusion of HTLV-I–infected cells from HTLV-I–seropositive donors could lead to the development of donor-derived ATL under immunosuppressive conditions after stem-cell transplantation. Here we describe a patient in whom ATL derived from donor cells developed four months after transplantation of stem cells from a sibling with HTLV-I.
A 44-year-old Japanese man with lymphoma-type ATL underwent transplantation of bone marrow from his HLA-identical brother in February 2004. The conditioning regimen included intravenous cyclophosphamide (120 mg per kilogram of body weight) and total-body irradiation (12 Gy). Cyclosporine and a short course of methotrexate were given as prophylaxis against graft-versus-host disease (GVHD). On day 26, low-dose prednisone was instituted because of GVHD-associated fever. With stable hematopoietic engraftment, complete donor chimerism was confirmed in a T-cell fraction on day 20 (Figure 1Figure 1
Analysis of T Cells at Engraftment (Day 20) and at the Onset of ATL (Day 133).). On day 133, the patient's white-cell count increased to 49.1×109 per liter with 89 percent ATL cells, although the original tumor had completely disappeared. Southern blot analysis revealed monoclonal integration of HTLV-I provirus in the ATL cells. Although we discontinued immunosuppressive therapy and administered chemotherapeutic agents, the patient died of the tumor in August 2004 (day 177).A test for the status of donor–recipient chimerism in a T-cell–enriched fraction at the onset of ATL after transplantation showed a donor pattern (Figure 1). In September 2004, hematologic and blood chemical values of the donor were almost normal, although the white-cell count included 1 percent atypical lymphocytes. Southern blot analysis showed no monoclonal integration of the HTLV-I provirus in the peripheral-blood mononuclear cells of the donor. These findings suggest that the donor was still an asymptomatic carrier without substantial clonal proliferation of HTLV-I–infected cells.
Suppression of the host immune system increases the occurrence of virus-associated lymphoid cancers.2 ATL develops in approximately 5 percent of HTLV-I carriers after an incubation period of several decades.3 However, ATL has been reported to develop at a younger age in renal-transplant recipients with HTLV-I infection during immunosuppressive therapy4 and sooner after the transmission of HTLV-I infection through blood transfusion in patients under immunosuppressive conditions.5 Thus, the immunosuppressive status in recipients of stem-cell transplants also potentially contributes to the development of ATL in donor-derived T cells that are infected with HTLV-I.
5 ReferencesHiroya Tamaki, M.D., Ph.D.
Osaka Minami Medical Center, Osaka 586-8521, Japan
tamaki@ommc-hp.jp Masao Matsuoka, M.D., Ph.D.
Kyoto University Institute for Virus Research, Kyoto 606-8507, Japan1
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H Tamaki, Y Taniguchi, A Kikuchi, T Yamagami, T Soma, M Matsuoka. (2007) 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 21:7, 1594-1596
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