Abstract
Occurrence of CMV, EBV and human herpes virus 6 (HHV6) infections and immune reconstitution were compared in 15 adult patients receiving a cord blood transplantation (CBT) and 40 patients who received an allogeneic transplantation from a matched unrelated donor (MUD). Herpes virus DNA quantifications in the blood (459 samples) were performed before and then monthly up to 9 months after transplant and the main lymphocytes populations were counted at 3, 6 and 9 months. Incidence of HHV6 infection was significantly higher in the CBT group (80 vs 42.5%; P<0.0001), with higher viral load (P<0.0001). In multivariate analysis, the use of a CBT and a myeloablative conditioning regimen were found to increase the risk of HHV6 infection (odds ratio (OR)=5.4, P=0.02 and OR=3.5, P=0.04, respectively). Incidences of CMV were similar between the two groups whereas MUD increased the risk of EBV infection, in univariate analysis only. HHV6 reactivation translated toward delayed neutrophils and plts engraftment in the two groups. MUD and CBT do not share the same immune reconstitution patterns, notably for B and CD8 lymphocytes and NK cells. There is a strong and specific relationship between HHV6 infection and the use of cord blood cells.
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References
Laughlin MJ, Eapen M, Rubinstein P, Wagner JE, Zhang MJ, Champlin RE et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 2004; 351: 2265–2275.
Rocha V, Labopin M, Sanz G, Arcese W, Schwerdfeger R, Bosi A et al. Transplants of umbilical cord blood or bone marrow from unrelated donors in adults with acute leukemia. N Engl J Med 2004; 351: 2276–2285.
Parody R, Martino R, Rovira M, Vazquez L, Vazquez MJ, de la Camara R et al. Severe infections after unrelated donor allogeneic hematopoietic stem cell transplantation in adults: comparison of cord blood transplantation with peripheral blood and bone marrow transplantation. Biol Blood Marrow Transplant 2006; 12: 734–748.
Takahashi S, Ooi J, Tomonari A, Konuma T, Tsukada N, Oiwa-Monna M et al. Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell transplants from related donors in adult patients with hematologic malignancies after myeloablative conditioning regimen. Blood 2007; 109: 1322–1330.
Brunstein CG, Barker JN, Weisdorf DJ, DeFor TE, Miller JS, Blazar BR et al. Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease. Blood 2007; 110: 3064–3070.
Hamza NS, Lisgaris M, Yadavalli G, Nadeau L, Fox R, Fu P et al. Kinetics of myeloid and lymphocyte recovery and infectious complications after unrelated umbilical cord blood versus HLA-matched unrelated donor allogeneic transplantation in adults. Brit J Haematol 2004; 124: 488–498.
Saavedra S, Sanz GF, Jarque I, Moscardo F, Jimenez C, Lorenzo I et al. Early infections in adult patients undergoing unrelated donor cord blood transplantation. Bone Marrow Transplantation 2002; 30: 937–943.
Narimatsu H, Matsumura T, Kami M, Miyakoshi S, Kusumi E, Takagi S et al. Bloodstream infection after cord blood transplantation using reduced-intensity stem cell transplantation for adult patients. Biol Blood Marrow Transplant 2005; 11: 429–436.
Sashihara J, Tanaka-Taya K, Tanaka S, Amo K, Miyagawa H, Hosoi G et al. High incidence of human herpes virus 6 infection with a high viral load in cord blood stem cell transplant recipients. Blood 2002; 100: 2005–2011.
Tomonari A, Takahashi S, Ooi J, Iseki T, Takasugi K, Uchiyama M et al. Human herpesvirus 6 variant B infection in adult patients after unrelated cord blood transplantation. Int J Hematol 2005; 81: 352–355.
Yamane A, Mori T, Suzuki S, Mihara A, Yamazaki R, Aisa Y et al. Risk factors for developing human herpesvirus 6 (HHV-6) reactivation after allogeneic hematopoietic stem cell transplantation and its association with central nervous system disorders. Biol Blood Marrow Transplant 2007; 13: 100–106.
Gautheret-Dejean A, Manichanh C, Thien-Ah-Koon F, Fillet AM, Mangeney N, Vidaud M et al. Development of a real-time polymerase chain reaction assay for the diagnosis of human herpesvirus 6 infection and application to bone marrow transplant patients. J Virol Methods 2002; 100: 27–35.
Bressollette-Bodin C, Coste-Burel M, Besse B, Andre-Garnier E, Ferre V, Imbert-Marcille BM . Cellular normalization of viral DNA loads on whole blood improves the clinical management of cytomegalovirus or Epstein-Barr virus infections in the setting of pre-emptive therapy. J Med Virol 2009; 81: 90–98.
Andre-Garnier E, Robillard N, Costa-Mattioli M, Besse B, Billaudel S, Imbert-Marcille BM . A one-step RT-PCR and a flow-cytometry method as two specific tools for direct evaluation of human herpesvirus 6 replication. J Virol Methods 2003; 108: 213–222.
Clark DA, Nacheva EP, Leong HN, Brazma D, Li YT, Tsao EH et al. Transmission of integrated human herpesvirus 6 through stem cell transplantation: implications for laboratory diagnosis. J Infect Dis 2006; 193: 912–916.
Kamble RT, Clark DA, Leong HN, Heslop HE, Brenner MK, Carrum G . Transmission of integrated human herpesvirus-6 in allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2007; 40: 563–566.
Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA matched sibling donors. Transplantation 1974; 18: 295–304.
Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sala GE et al. Chronic graft-versus-host syndrome in man: a long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980; 69: 204–217.
Tanaka N, Kimura H, Hoshino Y, Kato K, Yoshikawa T, Asano Y et al. Monitoring four herpesviruses in unrelated cord blood transplantation. Bone Marrow Transplantation 2000; 26: 1193–1197.
Brunstein CG, Weisdorf DJ, DeFor T, Barker JN, Tolar J, van Burik JA et al. Marked increased risk of Epstein-Barr virus-related complications with the addition of antithymocyte globulin to a non myeloablative conditioning prior to unrelated umbilical cord blood transplantation. Blood 2006; 108: 2874–2880.
Walker CM, van Burik JA, DeFor TE, Weisdorf DJ . Cytomegalovirus infection after allogeneic transplantation: comparison of cord blood with peripheral blood and marrow graft sources. Biol Blood Marrow Transplant 2007; 13: 1106–1115.
De Bolle L, Naesens L, De Clercq E . Update on human herpesvirus 6 biology, clinical features and therapy. Clin Microbiol Rev 2005; 18: 217–245.
Hall CB, Caserta MT, Schnabel K, Shelley LM, Marino AS, Carnahan JA et al. Chromosomal integration of human herpesvirus 6 is the major mode of congenital human herpesvirus 6 infection. Pediatrics 2008; 122: 513–520.
Ljungman P, Singh N . Human hepesvirus-6 infection in solid organ and stem cell transplant recipients. J Clin Virol 2006; 37: S87–S91.
Boutolleau D, Fernandez C, Andre E, Imbert-Marcille BM, Milpied N, Agut H et al. Human herpesvirus (HHV)-6 and HHV-7: two closely related viruses with different infection profiles in stem cell transplantation recipients. J Infec Dis 2003; 187: 179–186.
Maeda Y, Teshima T, Yamada M, Shinagawa K, Nakao S, Ohno Y et al. Monitoring of human herpes-viruses after allogeneic peripheral blood stem cell transplantation and bone marow transplantation. Brit J Haematol 1999; 105: 295–302.
Ljungman P, Wang FZ, Clark DA, Emery VC, Remberger M, Ringden O et al. High levels of human herpesvirus 6 DNA in peripheral blood leucocytes are correlated to platelet engraftment and disease in allogeneic stem cell transplant patients. Brit J Haematol 2000; 111: 774–781.
Behzad-Behbahani A, Pouransari R, Tabei SZ, Rahiminejad MS, Robati M, Yaghobi R et al. Risk of viral transmission via bone marrow progenitor cells versus umbilical cord blood hematopoeitic stem cells in bone marrow transplantation. Transplant Proc 2005; 37: 3211–3212.
Brown J, Boussiotis VA . Umbilical cord blood transplantation: basic biology and clinical challenges to immune reconstituion. Clin Immunol 2008; 127: 286–297.
Szabolcs P, Niedzwiecki D . Immune reconstitution in children after unrelated cord blood transplantation. Cytotherapy 2007; 9: 111–122.
DesJardin JA, Cho E, Supran S, Gibbons L, Werner BG, Snydman DR . Association of human herpesvirus 6 reactivation with severe cytomegalovirus-assciated disease in orthotopic liver transplant recipients. Clin Infect Dis 2001; 33: 1358–1362.
Crough T, Khanna R . Immunobiology of human cytomegalovirus: from bench to bedside. Clin Microbiol Rev 2009; 22: 76–98.
Lusso P . HHV6 and the immune system: mechanisms of immunomodulation and viral escape. J Clin Virol 2006; 37: S4–S10.
Thulke S, Radonic A, Nitsche A, Siegert W . Quantitative expression analysis of HHV6 cell receptor CD46 on cells of human cord blood, peripheral blood and G-CSF mobilized leukapheresis cells. Virol J 2006; 3: 77–80.
Robin M, Marque-Juilet S, Scieux C, Peffault de la Tour R, Ferry C, Rocha V et al. Disseminated adenovirus infections after allogeneic hematopoietic stem cell transplantation: incidence, risk factors and outcome. Haematologica 2007; 92: 1254–1257.
Beziat V, Nguyen S, Lapusan S, Hervier B, Dhedin N, Bories D et al. Fully functional NK cells after unrelated cord blood transplantation. Leukemia 2009; 23: 721–728.
Imbert-Marcille BM, Tang XW, Lepelletier D, Besse B, Moreau P, Billaudel S et al. Human herpesvirus 6 infection after autologous or allogeneic stem cell transplantation: a single-center prospective longitudinal study of 92 patients. Clin Infect Dis 2000; 31: 881–886.
Smith A, Santoro G, Di Lullo L . Selective suppression of IL12 production by human herpesvirus 6. Blood 2003; 102: 2877–2884.
Yoshikawa T . Human herpesvirus 6 infection in haematopoietic stem cell transplants patients. Brit J Haematol 2004; 124: 421–432.
Tanaka-Taya K, Sashihara J, Kurahashi H, Amo K, Miyagawa H, Kondo K et al. Human herpesvirus 6 (HHV-6) is transmitted from parent to child in an integrated form and characterization of cases with chromosomally integrated HHV-6 DNA. J Med Virol 2004; 73: 465–473.
Leong HN, Tuke PW, Tedder RS, Khanom AB, Eglin RP, Atkinson CE et al. The prevalence of chromosomally integrated human herpesvirus 6 genomes in the blood of UK blood donors. J Med Virol 2007; 79: 45–51.
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Chevallier, P., Hebia-Fellah, I., Planche, L. et al. Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source. Bone Marrow Transplant 45, 1204–1211 (2010). https://doi.org/10.1038/bmt.2009.326
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DOI: https://doi.org/10.1038/bmt.2009.326
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