Risk factors of clinically refractory cmv reactivation following allogeneic hsct: a single-center study in china

Risk factors of clinically refractory cmv reactivation following allogeneic hsct: a single-center study in china

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Access through your institution Buy or subscribe CMV reactivation remains the main cause of viral complications after allogeneic hematopoietic stem cell transplantation (aHSCT).1 In particular, CMV with gene mutations against antiviral drugs can lead to a high mortality rate.2 Nichols _et al._3 reported that increased viral load happened in 39% of patients because of the latent immunosuppression after preemptive therapy. Moreover, PBSC transplantation (PBSCT) showed a faster immune recovery compared with bone marrow transplantation4, 5 and could reduce the risk of persistent CMV antigenemia and disease.6 It appears that drug resistance should be suspected in patients who had viral load increases for more than 2 weeks of antiviral therapy and the category and degree of host immunosuppression have great impact on drug resistance. Thus, a retrospective study was analyzed to explore the clinical risk factors and outcome for CMV reactivation and CMV clinically refractory to antiviral chemotherapy. A total of 685 patients underwent aHSCT with a myeloablative conditioning regimen in the First Affiliated Hospital of Soochow University between January 2011 and 31 July 2014. The median time of follow-up was 16.7 months (range 1–46) through 30 April 2015. The characteristics of the patients are summarized in Table 1. GvHD prophylaxis consisted of cyclosporine and short term methotrexate, whereas patients with mismatched or unrelated donors also received mycophenolate mofetil as the part of GvHD prophylaxis. Meanwhile, 441 of all patients received antithymocyte globulin (ATG) as a component of GvHD prophylaxis. Degree and the treatment of acute GvHD (aGvHD) were executed according to the established categories and protocols.7, 8 This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access $259.00 per year only $21.58 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Meyers JD, Flournoy N, Thomas ED . Risk factors for cytomegalovirus infection after human marrow transplantation. _J Infect Dis_ 1986; 153: 478–488. Article  CAS  PubMed  Google Scholar  * Hantz S, Garnier-Geoffroy F, Mazeron MC, Garrigue I, Merville P, Mengelle C _et al_. Drug-resistant cytomegalovirus in transplant recipients: a French cohort study. _J Antimicrob Chemother_ 2010; 65: 2628–2640. Article  CAS  PubMed  Google Scholar  * Nichols WG, Corey L, Gooley T, Drew WL, Miner R, Huang M _et al_. Rising pp65antigenemia during preemptive anticytomegalovirus therapy after allogeneic hematopoietic stem cell transplantation: risk factors, correlation with DNA load, and outcomes. _Blood_ 2001; 97: 867–874. Article  CAS  PubMed  Google Scholar  * Ottinger HD, Beelen DW, Schaefer UW, Grosse-Wilde H . Improved immune reconstitution after allotransplantation of peripheral blood stem cells instead of bone marrow. _Blood_ 1996; 88: 2775–2779. CAS  PubMed  Google Scholar  * Trenschel R, Bernier M, Delforge A, Massy M, Lebeau De Hemricourt E, Maerevoet M _et al_. Myeloid and lymphoid recovery following bone marrow transplantation: a comparative study between related, unrelated bone marrow and allogeneic stem cell transplantation. _Leuk lymphoma_ 1998; 30: 325–352. Article  CAS  PubMed  Google Scholar  * Trenschel R, Ross S, Hüsing J, Ottinger H, Elmaagacli A, Roggendorf M _et al_. Reduced risk of persisting cytomegalovirus pp65 antigenemia and cytomegalovirus interstitial pneumonia following allogeneic PBSCT. _Bone Marrow Transplant_ 2000; 25: 665–672. Article  CAS  PubMed  Google Scholar  * Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J _et al_. 1994 consensus conference on acute gvhd grading. _Bone Marrow Transplant_ 1995; 15: 825. CAS  PubMed  Google Scholar  * Deeg HJ, Lin D, Leisenring W, Boeckh M, Anasetti C, Appelbaum FR _et al_. Cyclosporine or cyclosporine plus methylprednisolone for prophylaxis of graft-versus-host disease: a prospective, randomized trial. _Blood_ 1997; 89: 3880. CAS  PubMed  Google Scholar  * Feuchtinger T, Opherk K, Bethge WA, Topp MS, Schuster FR, Weissinger EM _et al_. Adoptive transfer of pp65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation. _Blood_ 2010; 116: 4360–4367. Article  CAS  PubMed  Google Scholar  * Boeckh M, Ljungman P . How we treat cytomegalovirus in hematopoietic cell transplant recipients. _Blood_ 2009; 113: 5711–5719. Article  CAS  PubMed  PubMed Central  Google Scholar  * Chevallier P, Hebia-Fellah I, Planche L, Guillaume T, Bressolette-Bodin C, Coste-Burel M _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_ 2010; 45: 1204–1211. Article  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS This work was funded by Jiangsu Provincial Special Program of Medical Science (BL2012005); Jiangsu Province’s Key Medical Center (ZX201102) and the Priority Academic; Program Development of the Jiangsu Higher Education Institutions (PAPD); National clinical key subject project; National Natural Science Foundation of China (Grant No.81370626). AUTHOR INFORMATION Author notes * X Bao and Q Zhu: Co-first author AUTHORS AND AFFILIATIONS * Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China X Bao, S Xue, Y Xu, X Ma, F Chen, X Hu, Z Zhu, S Chen, A Sun, D Wu & H Qiu * Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China X Bao, S Xue, Y Xu, X Ma, F Chen, X Hu, Z Zhu, S Chen, A Sun, D Wu & H Qiu * Suzhou Institute of Blood and Marrow Transplantation, Suzhou, China X Bao, S Xue, Y Xu, X Ma, F Chen, X Hu, Z Zhu, S Chen, A Sun, D Wu & H Qiu * Department of Hematology, 100th Hospital of People’s Liberation Army, Suzhou, China Q Zhu * Cyrus Tang Hematology Center, Soochow University, Suzhou, China Y Song Authors * X Bao View author publications You can also search for this author inPubMed Google Scholar * Q Zhu View author publications You can also search for this author inPubMed Google Scholar * S Xue View author publications You can also search for this author inPubMed Google Scholar * Y Xu View author publications You can also search for this author inPubMed Google Scholar * X Ma View author publications You can also search for this author inPubMed Google Scholar * F Chen View author publications You can also search for this author inPubMed Google Scholar * X Hu View author publications You can also search for this author inPubMed Google Scholar * Z Zhu View author publications You can also search for this author inPubMed Google Scholar * S Chen View author publications You can also search for this author inPubMed Google Scholar * A Sun View author publications You can also search for this author inPubMed Google Scholar * D Wu View author publications You can also search for this author inPubMed Google Scholar * Y Song View author publications You can also search for this author inPubMed Google Scholar * H Qiu View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to H Qiu. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Bao, X., Zhu, Q., Xue, S. _et al._ Risk factors of clinically refractory CMV reactivation following allogeneic HSCT: a single-center study in China. _Bone Marrow Transplant_ 51, 1625–1627 (2016). https://doi.org/10.1038/bmt.2016.231 Download citation * Published: 17 October 2016 * Issue Date: December 2016 * DOI: https://doi.org/10.1038/bmt.2016.231 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative

Access through your institution Buy or subscribe CMV reactivation remains the main cause of viral complications after allogeneic hematopoietic stem cell transplantation (aHSCT).1 In


particular, CMV with gene mutations against antiviral drugs can lead to a high mortality rate.2 Nichols _et al._3 reported that increased viral load happened in 39% of patients because of


the latent immunosuppression after preemptive therapy. Moreover, PBSC transplantation (PBSCT) showed a faster immune recovery compared with bone marrow transplantation4, 5 and could reduce


the risk of persistent CMV antigenemia and disease.6 It appears that drug resistance should be suspected in patients who had viral load increases for more than 2 weeks of antiviral therapy


and the category and degree of host immunosuppression have great impact on drug resistance. Thus, a retrospective study was analyzed to explore the clinical risk factors and outcome for CMV


reactivation and CMV clinically refractory to antiviral chemotherapy. A total of 685 patients underwent aHSCT with a myeloablative conditioning regimen in the First Affiliated Hospital of


Soochow University between January 2011 and 31 July 2014. The median time of follow-up was 16.7 months (range 1–46) through 30 April 2015. The characteristics of the patients are summarized


in Table 1. GvHD prophylaxis consisted of cyclosporine and short term methotrexate, whereas patients with mismatched or unrelated donors also received mycophenolate mofetil as the part of


GvHD prophylaxis. Meanwhile, 441 of all patients received antithymocyte globulin (ATG) as a component of GvHD prophylaxis. Degree and the treatment of acute GvHD (aGvHD) were executed


according to the established categories and protocols.7, 8 This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to


this journal Receive 12 print issues and online access $259.00 per year only $21.58 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy


now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer


support REFERENCES * Meyers JD, Flournoy N, Thomas ED . Risk factors for cytomegalovirus infection after human marrow transplantation. _J Infect Dis_ 1986; 153: 478–488. Article  CAS 


PubMed  Google Scholar  * Hantz S, Garnier-Geoffroy F, Mazeron MC, Garrigue I, Merville P, Mengelle C _et al_. Drug-resistant cytomegalovirus in transplant recipients: a French cohort study.


_J Antimicrob Chemother_ 2010; 65: 2628–2640. Article  CAS  PubMed  Google Scholar  * Nichols WG, Corey L, Gooley T, Drew WL, Miner R, Huang M _et al_. Rising pp65antigenemia during


preemptive anticytomegalovirus therapy after allogeneic hematopoietic stem cell transplantation: risk factors, correlation with DNA load, and outcomes. _Blood_ 2001; 97: 867–874. Article 


CAS  PubMed  Google Scholar  * Ottinger HD, Beelen DW, Schaefer UW, Grosse-Wilde H . Improved immune reconstitution after allotransplantation of peripheral blood stem cells instead of bone


marrow. _Blood_ 1996; 88: 2775–2779. CAS  PubMed  Google Scholar  * Trenschel R, Bernier M, Delforge A, Massy M, Lebeau De Hemricourt E, Maerevoet M _et al_. Myeloid and lymphoid recovery


following bone marrow transplantation: a comparative study between related, unrelated bone marrow and allogeneic stem cell transplantation. _Leuk lymphoma_ 1998; 30: 325–352. Article  CAS 


PubMed  Google Scholar  * Trenschel R, Ross S, Hüsing J, Ottinger H, Elmaagacli A, Roggendorf M _et al_. Reduced risk of persisting cytomegalovirus pp65 antigenemia and cytomegalovirus


interstitial pneumonia following allogeneic PBSCT. _Bone Marrow Transplant_ 2000; 25: 665–672. Article  CAS  PubMed  Google Scholar  * Przepiorka D, Weisdorf D, Martin P, Klingemann HG,


Beatty P, Hows J _et al_. 1994 consensus conference on acute gvhd grading. _Bone Marrow Transplant_ 1995; 15: 825. CAS  PubMed  Google Scholar  * Deeg HJ, Lin D, Leisenring W, Boeckh M,


Anasetti C, Appelbaum FR _et al_. Cyclosporine or cyclosporine plus methylprednisolone for prophylaxis of graft-versus-host disease: a prospective, randomized trial. _Blood_ 1997; 89: 3880.


CAS  PubMed  Google Scholar  * Feuchtinger T, Opherk K, Bethge WA, Topp MS, Schuster FR, Weissinger EM _et al_. Adoptive transfer of pp65-specific T cells for the treatment of


chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation. _Blood_ 2010; 116: 4360–4367. Article  CAS  PubMed  Google


Scholar  * Boeckh M, Ljungman P . How we treat cytomegalovirus in hematopoietic cell transplant recipients. _Blood_ 2009; 113: 5711–5719. Article  CAS  PubMed  PubMed Central  Google Scholar


  * Chevallier P, Hebia-Fellah I, Planche L, Guillaume T, Bressolette-Bodin C, Coste-Burel M _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_ 2010; 45: 1204–1211. Article  CAS  PubMed  Google Scholar 


Download references ACKNOWLEDGEMENTS This work was funded by Jiangsu Provincial Special Program of Medical Science (BL2012005); Jiangsu Province’s Key Medical Center (ZX201102) and the


Priority Academic; Program Development of the Jiangsu Higher Education Institutions (PAPD); National clinical key subject project; National Natural Science Foundation of China (Grant


No.81370626). AUTHOR INFORMATION Author notes * X Bao and Q Zhu: Co-first author AUTHORS AND AFFILIATIONS * Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow


University, Suzhou, China X Bao, S Xue, Y Xu, X Ma, F Chen, X Hu, Z Zhu, S Chen, A Sun, D Wu & H Qiu * Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China X


Bao, S Xue, Y Xu, X Ma, F Chen, X Hu, Z Zhu, S Chen, A Sun, D Wu & H Qiu * Suzhou Institute of Blood and Marrow Transplantation, Suzhou, China X Bao, S Xue, Y Xu, X Ma, F Chen, X Hu, Z


Zhu, S Chen, A Sun, D Wu & H Qiu * Department of Hematology, 100th Hospital of People’s Liberation Army, Suzhou, China Q Zhu * Cyrus Tang Hematology Center, Soochow University, Suzhou,


China Y Song Authors * X Bao View author publications You can also search for this author inPubMed Google Scholar * Q Zhu View author publications You can also search for this author


inPubMed Google Scholar * S Xue View author publications You can also search for this author inPubMed Google Scholar * Y Xu View author publications You can also search for this author


inPubMed Google Scholar * X Ma View author publications You can also search for this author inPubMed Google Scholar * F Chen View author publications You can also search for this author


inPubMed Google Scholar * X Hu View author publications You can also search for this author inPubMed Google Scholar * Z Zhu View author publications You can also search for this author


inPubMed Google Scholar * S Chen View author publications You can also search for this author inPubMed Google Scholar * A Sun View author publications You can also search for this author


inPubMed Google Scholar * D Wu View author publications You can also search for this author inPubMed Google Scholar * Y Song View author publications You can also search for this author


inPubMed Google Scholar * H Qiu View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to H Qiu. ETHICS DECLARATIONS


COMPETING INTERESTS The authors declare no conflict of interest. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Bao, X., Zhu, Q., Xue, S. _et al._ Risk


factors of clinically refractory CMV reactivation following allogeneic HSCT: a single-center study in China. _Bone Marrow Transplant_ 51, 1625–1627 (2016).


https://doi.org/10.1038/bmt.2016.231 Download citation * Published: 17 October 2016 * Issue Date: December 2016 * DOI: https://doi.org/10.1038/bmt.2016.231 SHARE THIS ARTICLE Anyone you


share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the


Springer Nature SharedIt content-sharing initiative