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Impact of Cytomegalovirus (CMV) Viral Load on Probability of Spontaneous Clearance and Response to Pre-Emptive Therapy in Allogeneic Stem Cell Transplant Recipients.

Impact of Cytomegalovirus (CMV) Viral Load on Probability of Spontaneous Clearance and Response to Pre-Emptive Therapy in Allogeneic Stem Cell Transplant Recipients.
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Camargo JF, Kimble E, Rosa R, Shimose LA, Bueno MX, Jeyakumar N, Morris MI, Abbo LM, Simkins J, Alencar MC, Benjamin C, Wieder E, Jimenez A, Beitinjaneh A, Goodman M, Byrnes JJ, Lekakis LJ, Pereira D, Komanduri KV,


Camargo JF, Kimble E, Rosa R, Shimose LA, Bueno MX, Jeyakumar N, Morris MI, Abbo LM, Simkins J, Alencar MC, Benjamin C, Wieder E, Jimenez A, Beitinjaneh A, Goodman M, Byrnes JJ, Lekakis LJ, Pereira D, Komanduri KV, (click to view)

Camargo JF, Kimble E, Rosa R, Shimose LA, Bueno MX, Jeyakumar N, Morris MI, Abbo LM, Simkins J, Alencar MC, Benjamin C, Wieder E, Jimenez A, Beitinjaneh A, Goodman M, Byrnes JJ, Lekakis LJ, Pereira D, Komanduri KV,

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Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 2017 12 04() pii 10.1016/j.bbmt.2017.11.038

Abstract

The optimal viral load threshold to initiate pre-emptive cytomegalovirus (CMV) therapy in hematopoietic cell transplant (HCT) recipients remains to be defined. In an effort to address this question we conducted a retrospective study of 174 allogeneic HCT recipients transplanted at a single center between August 2012 and April 2016. During this period, pre-emptive therapy started at the discretion of the treating clinician. 109 (63%) patients developed CMV viremia. Median time to reactivation was 17 (IQR, 7-30) days post-HCT. A peak viremia ≥150 IU/mL was strongly associated with a reduced probability of spontaneous clearance (RR, 95% CI: 0.16, 0.1-0.27), independent of established clinical risk factors including CMV donor serostatus, exposure to anti-thymocyte globulin and underlying lymphoid malignancy. The median time to clearance of viremia was significantly shorter in those who started therapy at CMV <350 IU/mL (19 days, 11-35) compared to those who started antiviral therapy at higher viremia thresholds (33 days, 21-42; p=0.02). The occurrence of treatment-associated cytopenias was frequent but similar in patients who started pre-emptive therapy at CMV <350 IU/mL and those who started at CMV >350 IU/mL (44 vs. 57%, p=0.42). Unresolved CMV viremia by treatment day 35 was associated with increased risk of therapeutic failure (32 vs 0%; p=0.001). Achieving eradication of CMV viremia by treatment day 35 was associated with a 74% reduction in one-year non-relapse mortality, NRM, (adjusted HR, 0.26; 95% CI, 0.1-0.8; p=0.02) whereas therapeutic failure was associated with a significant increase in the probability of one-year NRM (adjusted HR, 26; 95% CI, 8-87; p<0.0001). We conclude that among allogeneic HCT patients, a peak CMV viremia ≥150 IU/mL is associated with >80% reduction in the probability of spontaneous clearance independent of ATG administration, CMV donor serostatus, and lymphoid malignancy, and is a reasonable cutoff for pre-emptive therapy. Delaying initiation of therapy until CMV values ≥350 IU/mL is associated with more protracted CMV viremia, and unresolved viremia by treatment day 35 is associated with a significant increase in NRM.

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