More on Donor-Derived T-Cell Leukemia after Bone Marrow Transplantation
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《新英格兰医药杂志》
To the Editor: In the case reported by Tamaki and Matsuoka (April 20 issue),1 there is no definite evidence of human T-cell lymphotropic virus type I (HTLV-I) infection in the hematopoietic stem-cell donor, and there seems to be no clonality marker such as monoclonal proviral integration in the donor. We therefore cannot conclude that adult T-cell leukemia–lymphoma (ATL) in the recipient was instigated by undetected HTLV-I in the asymptomatic donor. The possibility of an acquired infection of donor T cells by HTLV-I in the recipient has not been excluded. We propose that the profound immunosuppression attributable to pretransplantation conditioning and prophylaxis against post-transplantation graft-versus-host disease could have accelerated the development of ATL.2 Even if the donor was a healthy carrier of HTLV-I, proviral integration occurs in only about 0.1 to 1.0 percent of peripheral-blood mononuclear cells. However, although it is "T-cell lymphotropic," HTLV-I can infect extrahematopoietic cell types in vitro.3,4,5 Viral-genome sequencing could have shown the source of the HTLV-I.
Daniele Focosi, M.D.
Mario Petrini, M.D.
Ospedale Santa Chiara
56100 Pisa, Italy
focosi@icgeb.org
References
Tamaki H, Matsuoka M. Donor-derived T-cell leukemia after bone marrow transplantation. N Engl J Med 2006;354:1758-1759.
Bangham CRM. The immune control and cell-to-cell spread of human T-lymphotropic virus type 1. J Gen Virol 2003;84:3177-3189.
LeVasseur RJ, Southern SO, Southern PJ. Mammary epithelial cells support and transfer productive human T-cell lymphotropic virus infections. J Hum Virol 1998;1:214-223.
Liu B, Li Z, Mahesh SP, Kurup SK, Giam CZ, Nussenblatt RB. HTLV-1 infection of human retinal pigment epithelial cells and inhibition of viral infection by an antibody to ICAM-1. Invest Ophthalmol Vis Sci 2006;47:1510-1515.
Manel N, Battini JL, Taylor N, Sitbon M. HTLV-1 tropism and envelope receptor. Oncogene 2005;24:6016-6025.
The authors reply: We believe that the brothers described in our report were infected with the same strain of HTLV-I because mother-to-child transmission through breast-feeding is a primary route of infection.1 Furthermore, HTLV-I has little variation in sequence.2 Indeed, we detected no difference in 5'–long-terminal-repeat and env sequences of HTLV-I provirus between the peripheral-blood leukocytes from the brothers and donor-derived ATL cells. Sequencing the HTLV-I genome is a useless way to determine the origin of the donor ATL clone.
This clone was undetectable in the donor with the use of tumor-specific polymerase chain reaction (PCR), but it was detectable in the recipient three weeks after transplantation. This period was too short for HTLV-I–infected cells to expand clonally after HTLV-I infection in the recipient. In addition, the DNA methylation pattern of HTLV-I provirus in donor-derived ATL cells was similar to that in asymptomatic carriers. These findings suggest that the clone existed in the donor as a minor population below the sensitivity of PCR, although we cannot completely exclude the possibility of a new infection in the recipient after transplantation.
Hiroya 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, Japan
References
Kinoshita K, Amagasaki T, Hino S, et al. Milk-borne transmission of HTLV-I from carrier mothers to their children. Jpn J Cancer Res 1987;78:674-680.
Van Dooren S, Pybus OG, Salemi M, et al. The low evolutionary rate of human T-cell lymphotropic virus type-1 confirmed by analysis of vertical transmission chains. Mol Biol Evol 2004;21:603-611.
Daniele Focosi, M.D.
Mario Petrini, M.D.
Ospedale Santa Chiara
56100 Pisa, Italy
focosi@icgeb.org
References
Tamaki H, Matsuoka M. Donor-derived T-cell leukemia after bone marrow transplantation. N Engl J Med 2006;354:1758-1759.
Bangham CRM. The immune control and cell-to-cell spread of human T-lymphotropic virus type 1. J Gen Virol 2003;84:3177-3189.
LeVasseur RJ, Southern SO, Southern PJ. Mammary epithelial cells support and transfer productive human T-cell lymphotropic virus infections. J Hum Virol 1998;1:214-223.
Liu B, Li Z, Mahesh SP, Kurup SK, Giam CZ, Nussenblatt RB. HTLV-1 infection of human retinal pigment epithelial cells and inhibition of viral infection by an antibody to ICAM-1. Invest Ophthalmol Vis Sci 2006;47:1510-1515.
Manel N, Battini JL, Taylor N, Sitbon M. HTLV-1 tropism and envelope receptor. Oncogene 2005;24:6016-6025.
The authors reply: We believe that the brothers described in our report were infected with the same strain of HTLV-I because mother-to-child transmission through breast-feeding is a primary route of infection.1 Furthermore, HTLV-I has little variation in sequence.2 Indeed, we detected no difference in 5'–long-terminal-repeat and env sequences of HTLV-I provirus between the peripheral-blood leukocytes from the brothers and donor-derived ATL cells. Sequencing the HTLV-I genome is a useless way to determine the origin of the donor ATL clone.
This clone was undetectable in the donor with the use of tumor-specific polymerase chain reaction (PCR), but it was detectable in the recipient three weeks after transplantation. This period was too short for HTLV-I–infected cells to expand clonally after HTLV-I infection in the recipient. In addition, the DNA methylation pattern of HTLV-I provirus in donor-derived ATL cells was similar to that in asymptomatic carriers. These findings suggest that the clone existed in the donor as a minor population below the sensitivity of PCR, although we cannot completely exclude the possibility of a new infection in the recipient after transplantation.
Hiroya 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, Japan
References
Kinoshita K, Amagasaki T, Hino S, et al. Milk-borne transmission of HTLV-I from carrier mothers to their children. Jpn J Cancer Res 1987;78:674-680.
Van Dooren S, Pybus OG, Salemi M, et al. The low evolutionary rate of human T-cell lymphotropic virus type-1 confirmed by analysis of vertical transmission chains. Mol Biol Evol 2004;21:603-611.