Prophylactic Foscarnet for Human Herpesvirus 6: Effect on Hematopoietic Engraftment after Reduced-Intensity Conditioning Umbilical Cord Blood Transplantation

Najla El Jurdi; John Rogosheske; Todd DeFor; Nelli Bejanyan; Mukta Arora; Veronika Bachanova; Brian Betts; Fiona He; Shernan Holtan; Murali Janakiram; Samantha Larson; Joseph Maakaron; Armin Rashidi; Erica Warlick; John E. Wagner; Jo Anne H. Young; Daniel Weisdorf; Claudio G. Brunstein

doi:10.1016/j.bbmt.2020.10.008

Prophylactic Foscarnet for Human Herpesvirus 6: Effect on Hematopoietic Engraftment after Reduced-Intensity Conditioning Umbilical Cord Blood Transplantation

Najla El Jurdi, John Rogosheske, Todd DeFor, Nelli Bejanyan, Mukta Arora, Veronika Bachanova, Brian Betts, Fiona He, Shernan Holtan, Murali Janakiram, Samantha Larson, Joseph Maakaron, Armin Rashidi, Erica Warlick, John E. Wagner, Jo Anne H. Young, Daniel Weisdorf, Claudio G. Brunstein

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

The high incidence of human herpesvirus-6 (HHV-6) reactivation, potentially interfering with engraftment after umbilical cord blood (UCB) hematopoietic cell transplantation (HCT), remains a major challenge. To potentially address this problem, we evaluated the effect of prophylactic foscarnet administered twice daily beginning on day +7 and continuing through engraftment in 25 patients. To determine the impact of foscarnet on HHV-6, engraftment, and other transplantation outcomes, we compared results in 61 identically treated patients with hematologic malignancies. Treatment and control groups underwent reduced-intensity conditioning UCB HCT with a conditioning regimen of fludarabine, cyclophosphamide, and total body irradiation 200 cGy with or without antithymocyte globulin (ATG), using sirolimus plus mycophenolate mofetil immune suppression. The treatment and control groups were similar in terms of age, disease risk, use of ATG, Hematopoietic Cell Transplantation Comorbidity Index, and graft CD34 cell dose; however, foscarnet-treated patients were less likely to receive a double UCB graft and to be treated more recently (2016 to 2018). The cumulative incidence of HHV-6 reactivation by day +100 was 63% for all patients (95% confidence interval [CI], 51% to 75%) and was not significantly different between the 2 groups. HHV-6 reactivation occurred at a median of 34 days in the foscarnet group and 25.5 days in the control group. The incidence of neutrophil engraftment at day 42 was higher in the foscarnet group compared with the control group (96%; [95% CI, 83% to 100%] versus 75% [95% CI, 64% to 85%]; P< .01). The cumulative incidence of platelet engraftment by 6 months was 92% (95% CI, 69% to 100%) for the foscarnet group versus 75% (95% CI, 60% to 90%) for the control group (P= .08), and multivariate analysis identified the use of foscarnet as an independent predictor of better platelet engraftment. No patients died as a result of graft failure in recipients of foscarnet, whereas 5 patients died from graft failure in the control group. Six-month overall survival (OS) and nonrelapse mortality (NRM) were better in the foscarnet group (96% versus 72% [P= .02] and 4% versus 18% [P= .07], respectively). Even though foscarnet prophylaxis did not prevent HHV-6 viremia, we observed a delay in time to HHV-6 reactivation, a trend toward differences in engraftment, NRM, and OS compared with historical controls.

Original language	English (US)
Pages (from-to)	84.e1-84.e5
Journal	Biology of Blood and Marrow Transplantation
Volume	27
Issue number	1
DOIs	https://doi.org/10.1016/j.bbmt.2020.10.008
State	Published - Jan 2021

Bibliographical note

Funding Information:
Financial disclosure: See Acknowledgments on page XXX. Please edit acknowledgments to read as such: Acknowledgments This research was supported by NIH grant P30 CA77598 utilizing the Biostatistics and Bioinformatics Core of the Masonic Cancer Center, University of Minnesota and the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR002494. This work was supported in part by grants from the National Cancer Institute P01 CA65493 (C.G.B, J.E.W, T.E.D).We would like to acknowledge Michael Franklin, MS, for assistance in editing this manuscript.

Funding Information:
Financial disclosure: This research was supported by National Institutes of Health Grant P30 CA77598 to the Biostatistics and Bioinformatics Core of the Masonic Cancer Center, University of Minnesota and National Cancer Institute Grant P01 CA65493 (to C.G.B, J.E.W, and T.E.D). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Keywords

Foscarnet
Graft failure
HHV-6
Hematopoietic cell transplantation
Toxicity

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El Jurdi, N., Rogosheske, J., DeFor, T., Bejanyan, N., Arora, M., Bachanova, V., Betts, B., He, F., Holtan, S., Janakiram, M., Larson, S., Maakaron, J., Rashidi, A., Warlick, E., Wagner, J. E., Young, J. A. H., Weisdorf, D., & Brunstein, C. G. (2021). Prophylactic Foscarnet for Human Herpesvirus 6: Effect on Hematopoietic Engraftment after Reduced-Intensity Conditioning Umbilical Cord Blood Transplantation. Biology of Blood and Marrow Transplantation, 27(1), 84.e1-84.e5. https://doi.org/10.1016/j.bbmt.2020.10.008

Prophylactic Foscarnet for Human Herpesvirus 6 : Effect on Hematopoietic Engraftment after Reduced-Intensity Conditioning Umbilical Cord Blood Transplantation. / El Jurdi, Najla; Rogosheske, John; DeFor, Todd; Bejanyan, Nelli; Arora, Mukta ; Bachanova, Veronika ; Betts, Brian ; He, Fiona ; Holtan, Shernan ; Janakiram, Murali; Larson, Samantha; Maakaron, Joseph ; Rashidi, Armin ; Warlick, Erica ; Wagner, John E.; Young, Jo Anne H.; Weisdorf, Daniel ; Brunstein, Claudio G.

In: Biology of Blood and Marrow Transplantation, Vol. 27, No. 1, 01.2021, p. 84.e1-84.e5.

Research output: Contribution to journal › Article › peer-review

El Jurdi, N, Rogosheske, J, DeFor, T, Bejanyan, N, Arora, M , Bachanova, V , Betts, B , He, F , Holtan, S , Janakiram, M, Larson, S, Maakaron, J , Rashidi, A , Warlick, E , Wagner, JE , Young, JAH , Weisdorf, D & Brunstein, CG 2021, 'Prophylactic Foscarnet for Human Herpesvirus 6: Effect on Hematopoietic Engraftment after Reduced-Intensity Conditioning Umbilical Cord Blood Transplantation', Biology of Blood and Marrow Transplantation, vol. 27, no. 1, pp. 84.e1-84.e5. https://doi.org/10.1016/j.bbmt.2020.10.008

El Jurdi, Najla ; Rogosheske, John ; DeFor, Todd ; Bejanyan, Nelli ; Arora, Mukta ; Bachanova, Veronika ; Betts, Brian ; He, Fiona ; Holtan, Shernan ; Janakiram, Murali ; Larson, Samantha ; Maakaron, Joseph ; Rashidi, Armin ; Warlick, Erica ; Wagner, John E. ; Young, Jo Anne H. ; Weisdorf, Daniel ; Brunstein, Claudio G. / Prophylactic Foscarnet for Human Herpesvirus 6 : Effect on Hematopoietic Engraftment after Reduced-Intensity Conditioning Umbilical Cord Blood Transplantation. In: Biology of Blood and Marrow Transplantation. 2021 ; Vol. 27, No. 1. pp. 84.e1-84.e5.

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title = "Prophylactic Foscarnet for Human Herpesvirus 6: Effect on Hematopoietic Engraftment after Reduced-Intensity Conditioning Umbilical Cord Blood Transplantation",

abstract = "The high incidence of human herpesvirus-6 (HHV-6) reactivation, potentially interfering with engraftment after umbilical cord blood (UCB) hematopoietic cell transplantation (HCT), remains a major challenge. To potentially address this problem, we evaluated the effect of prophylactic foscarnet administered twice daily beginning on day +7 and continuing through engraftment in 25 patients. To determine the impact of foscarnet on HHV-6, engraftment, and other transplantation outcomes, we compared results in 61 identically treated patients with hematologic malignancies. Treatment and control groups underwent reduced-intensity conditioning UCB HCT with a conditioning regimen of fludarabine, cyclophosphamide, and total body irradiation 200 cGy with or without antithymocyte globulin (ATG), using sirolimus plus mycophenolate mofetil immune suppression. The treatment and control groups were similar in terms of age, disease risk, use of ATG, Hematopoietic Cell Transplantation Comorbidity Index, and graft CD34 cell dose; however, foscarnet-treated patients were less likely to receive a double UCB graft and to be treated more recently (2016 to 2018). The cumulative incidence of HHV-6 reactivation by day +100 was 63% for all patients (95% confidence interval [CI], 51% to 75%) and was not significantly different between the 2 groups. HHV-6 reactivation occurred at a median of 34 days in the foscarnet group and 25.5 days in the control group. The incidence of neutrophil engraftment at day 42 was higher in the foscarnet group compared with the control group (96%; [95% CI, 83% to 100%] versus 75% [95% CI, 64% to 85%]; P< .01). The cumulative incidence of platelet engraftment by 6 months was 92% (95% CI, 69% to 100%) for the foscarnet group versus 75% (95% CI, 60% to 90%) for the control group (P= .08), and multivariate analysis identified the use of foscarnet as an independent predictor of better platelet engraftment. No patients died as a result of graft failure in recipients of foscarnet, whereas 5 patients died from graft failure in the control group. Six-month overall survival (OS) and nonrelapse mortality (NRM) were better in the foscarnet group (96% versus 72% [P= .02] and 4% versus 18% [P= .07], respectively). Even though foscarnet prophylaxis did not prevent HHV-6 viremia, we observed a delay in time to HHV-6 reactivation, a trend toward differences in engraftment, NRM, and OS compared with historical controls.",

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author = "{El Jurdi}, Najla and John Rogosheske and Todd DeFor and Nelli Bejanyan and Mukta Arora and Veronika Bachanova and Brian Betts and Fiona He and Shernan Holtan and Murali Janakiram and Samantha Larson and Joseph Maakaron and Armin Rashidi and Erica Warlick and Wagner, {John E.} and Young, {Jo Anne H.} and Daniel Weisdorf and Brunstein, {Claudio G.}",

note = "Funding Information: Financial disclosure: See Acknowledgments on page XXX. Please edit acknowledgments to read as such: Acknowledgments This research was supported by NIH grant P30 CA77598 utilizing the Biostatistics and Bioinformatics Core of the Masonic Cancer Center, University of Minnesota and the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR002494. This work was supported in part by grants from the National Cancer Institute P01 CA65493 (C.G.B, J.E.W, T.E.D).We would like to acknowledge Michael Franklin, MS, for assistance in editing this manuscript. Funding Information: Financial disclosure: This research was supported by National Institutes of Health Grant P30 CA77598 to the Biostatistics and Bioinformatics Core of the Masonic Cancer Center, University of Minnesota and National Cancer Institute Grant P01 CA65493 (to C.G.B, J.E.W, and T.E.D). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. ",

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language = "English (US)",

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T1 - Prophylactic Foscarnet for Human Herpesvirus 6

T2 - Effect on Hematopoietic Engraftment after Reduced-Intensity Conditioning Umbilical Cord Blood Transplantation

AU - El Jurdi, Najla

AU - Rogosheske, John

AU - DeFor, Todd

AU - Bejanyan, Nelli

AU - Arora, Mukta

AU - Bachanova, Veronika

AU - Betts, Brian

AU - He, Fiona

AU - Holtan, Shernan

AU - Janakiram, Murali

AU - Larson, Samantha

AU - Maakaron, Joseph

AU - Rashidi, Armin

AU - Warlick, Erica

AU - Wagner, John E.

AU - Young, Jo Anne H.

AU - Weisdorf, Daniel

AU - Brunstein, Claudio G.

N1 - Funding Information: Financial disclosure: See Acknowledgments on page XXX. Please edit acknowledgments to read as such: Acknowledgments This research was supported by NIH grant P30 CA77598 utilizing the Biostatistics and Bioinformatics Core of the Masonic Cancer Center, University of Minnesota and the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR002494. This work was supported in part by grants from the National Cancer Institute P01 CA65493 (C.G.B, J.E.W, T.E.D).We would like to acknowledge Michael Franklin, MS, for assistance in editing this manuscript. Funding Information: Financial disclosure: This research was supported by National Institutes of Health Grant P30 CA77598 to the Biostatistics and Bioinformatics Core of the Masonic Cancer Center, University of Minnesota and National Cancer Institute Grant P01 CA65493 (to C.G.B, J.E.W, and T.E.D). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

PY - 2021/1

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N2 - The high incidence of human herpesvirus-6 (HHV-6) reactivation, potentially interfering with engraftment after umbilical cord blood (UCB) hematopoietic cell transplantation (HCT), remains a major challenge. To potentially address this problem, we evaluated the effect of prophylactic foscarnet administered twice daily beginning on day +7 and continuing through engraftment in 25 patients. To determine the impact of foscarnet on HHV-6, engraftment, and other transplantation outcomes, we compared results in 61 identically treated patients with hematologic malignancies. Treatment and control groups underwent reduced-intensity conditioning UCB HCT with a conditioning regimen of fludarabine, cyclophosphamide, and total body irradiation 200 cGy with or without antithymocyte globulin (ATG), using sirolimus plus mycophenolate mofetil immune suppression. The treatment and control groups were similar in terms of age, disease risk, use of ATG, Hematopoietic Cell Transplantation Comorbidity Index, and graft CD34 cell dose; however, foscarnet-treated patients were less likely to receive a double UCB graft and to be treated more recently (2016 to 2018). The cumulative incidence of HHV-6 reactivation by day +100 was 63% for all patients (95% confidence interval [CI], 51% to 75%) and was not significantly different between the 2 groups. HHV-6 reactivation occurred at a median of 34 days in the foscarnet group and 25.5 days in the control group. The incidence of neutrophil engraftment at day 42 was higher in the foscarnet group compared with the control group (96%; [95% CI, 83% to 100%] versus 75% [95% CI, 64% to 85%]; P< .01). The cumulative incidence of platelet engraftment by 6 months was 92% (95% CI, 69% to 100%) for the foscarnet group versus 75% (95% CI, 60% to 90%) for the control group (P= .08), and multivariate analysis identified the use of foscarnet as an independent predictor of better platelet engraftment. No patients died as a result of graft failure in recipients of foscarnet, whereas 5 patients died from graft failure in the control group. Six-month overall survival (OS) and nonrelapse mortality (NRM) were better in the foscarnet group (96% versus 72% [P= .02] and 4% versus 18% [P= .07], respectively). Even though foscarnet prophylaxis did not prevent HHV-6 viremia, we observed a delay in time to HHV-6 reactivation, a trend toward differences in engraftment, NRM, and OS compared with historical controls.

AB - The high incidence of human herpesvirus-6 (HHV-6) reactivation, potentially interfering with engraftment after umbilical cord blood (UCB) hematopoietic cell transplantation (HCT), remains a major challenge. To potentially address this problem, we evaluated the effect of prophylactic foscarnet administered twice daily beginning on day +7 and continuing through engraftment in 25 patients. To determine the impact of foscarnet on HHV-6, engraftment, and other transplantation outcomes, we compared results in 61 identically treated patients with hematologic malignancies. Treatment and control groups underwent reduced-intensity conditioning UCB HCT with a conditioning regimen of fludarabine, cyclophosphamide, and total body irradiation 200 cGy with or without antithymocyte globulin (ATG), using sirolimus plus mycophenolate mofetil immune suppression. The treatment and control groups were similar in terms of age, disease risk, use of ATG, Hematopoietic Cell Transplantation Comorbidity Index, and graft CD34 cell dose; however, foscarnet-treated patients were less likely to receive a double UCB graft and to be treated more recently (2016 to 2018). The cumulative incidence of HHV-6 reactivation by day +100 was 63% for all patients (95% confidence interval [CI], 51% to 75%) and was not significantly different between the 2 groups. HHV-6 reactivation occurred at a median of 34 days in the foscarnet group and 25.5 days in the control group. The incidence of neutrophil engraftment at day 42 was higher in the foscarnet group compared with the control group (96%; [95% CI, 83% to 100%] versus 75% [95% CI, 64% to 85%]; P< .01). The cumulative incidence of platelet engraftment by 6 months was 92% (95% CI, 69% to 100%) for the foscarnet group versus 75% (95% CI, 60% to 90%) for the control group (P= .08), and multivariate analysis identified the use of foscarnet as an independent predictor of better platelet engraftment. No patients died as a result of graft failure in recipients of foscarnet, whereas 5 patients died from graft failure in the control group. Six-month overall survival (OS) and nonrelapse mortality (NRM) were better in the foscarnet group (96% versus 72% [P= .02] and 4% versus 18% [P= .07], respectively). Even though foscarnet prophylaxis did not prevent HHV-6 viremia, we observed a delay in time to HHV-6 reactivation, a trend toward differences in engraftment, NRM, and OS compared with historical controls.

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Prophylactic Foscarnet for Human Herpesvirus 6: Effect on Hematopoietic Engraftment after Reduced-Intensity Conditioning Umbilical Cord Blood Transplantation

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Bibliographical note

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