Impact of early CMV reactivation in cord blood stem cell recipients in the current era

Ramanathan, Muthalagu; Teira, Pierre; Battiwalla, Minoo; Barrett, John; Ahn, Kwang Woo; Chen, M; Green, J; Laughlin, Mary J.; Lazarus, Hillard M.; Marks, David I.; Saad, Ayman; Seftel, Matthew D.; Saber, Wael; Savani, Bipin N.; Waller, Edmund K.; Wingard, John R.; Auletta, Jeffery J.; Lindemans, Caroline A.; Boeckh, Michael; Riches, Marcie L.

doi:10.1038/bmt.2016.89

Cited by 35 publications

(28 citation statements)

References 34 publications

(40 reference statements)

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“…immunomodulation of donor-derived antiviral immunity by PTCy that depend on donor/graft serostatus. Furthermore, our finding that UCB was associated with high rates of CMV infection and prolonged treatment duration are consistent with a prior study [18]. Unique to our study is how post-HCT events, particularly steroid use, modify the known pre-HCT predictive factors.…”

Section: Discussionsupporting

confidence: 91%

Cytomegalovirus Infection Incidence and Risk Factors Across Diverse Hematopoietic Cell Transplantation Platforms Using a Standardized Monitoring and Treatment Approach: A Comprehensive Evaluation from a Single Institution

Melendez-Munoz

Marchalik

Jerussi

et al. 2019

Biology of Blood and Marrow Transplantation

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Human cytomegalovirus (CMV) infection and disease remains a significant cause of morbidity and mortality for hematopoietic cell transplantation (HCT) recipients. Disruption of or weak reconstitution of virus-specific cellular immune function, such as with certain HCT approaches, poses significant risk for CMV-related complications. The incidence of and risk factors for CMV infection and the nature of CMV disease were evaluated retrospectively among 356 consecutive HCT recipients transplanted at the National Institutes of Health using all graft sources, including bone marrow, peripheral blood stem cell (PBSC), and umbilical cord blood (UCB), and a range of in vivo and ex vivo approaches for graft-versus-host disease (GVHD) prophylaxis. The cumulative incidence of CMV infection was higher for CMV-seropositive recipients at 33%, regardless of donor CMV serostatus. Patients transplanted with CMV-seropositive donors had a significantly shorter duration of antiviral therapy. Among graft sources UCB was associated with the highest cumulative incidence of CMV infection at 65% and significantly longer treatment duration at a median of 36 days, whereas PBSC HCT was associated with the lowest incidence at 26% and the shortest CMV treatment duration at a median of 21 days. There were significant differences in the cumulative incidence of CMV infection by T cell manipulation strategy when systemic steroids were included as a risk-modifying event. Over one-third of CMV infections occurred in the setting of systemic steroid administration. CMV disease occurred in 5% of HCT recipients, with 70% of cases in the setting of treatment for GVHD. Although factors related to serostatus, graft source, and GVHD prophylaxis were associated with varied CMV infection incidence, unplanned post-HCT corticosteroid therapy contributed greatly to the incidence of both CMV infection and disease across HCT approaches, highlighting this post-HCT intervention as a key time to potentially tailor the approach to monitoring, preemptive therapy, and even prophylaxis.

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Section: Discussionsupporting

confidence: 91%

Cytomegalovirus Infection Incidence and Risk Factors Across Diverse Hematopoietic Cell Transplantation Platforms Using a Standardized Monitoring and Treatment Approach: A Comprehensive Evaluation from a Single Institution

Melendez-Munoz

Marchalik

Jerussi

et al. 2019

Biology of Blood and Marrow Transplantation

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“…The majority of UCB recipients were CMV seropositive (71%) and all UCB recipients received ATG 9 . Similarly, a CIBMTR review of 1011 CMV‐seropositive UCB recipients with acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) reported CMV reactivation in 40% of patients, with similar reactivation rates in both AML and ALL groups 31 …”

Section: Cytomegalovirus In Alternative Donor Transplantsmentioning

confidence: 99%

Incidence of viral and fungal complications after utilization of alternative donor sources in hematopoietic cell transplantation

et al. 2020

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Allogeneic hematopoietic cell transplantation (HCT) remains the only curable option for adult patients with hematologic malignancies. According to guidelines published by the American Society for Transplantation and Cellular Therapy, allogeneic HCT should be offered to all intermediate‐ and high‐risk patients with acute leukemia. While matched‐related donor (MRD) grafts continue to be the preferred stem cell source for allogeneic HCT, studies comparing MRD grafts to matched‐unrelated donor (MUD) grafts showed comparable outcomes in patients with acute leukemia. Unfortunately, for those without a suitable matched‐related graft, the probability of finding a suitable matched‐unrelated donor varies significantly depending on racial and ethnic background. With allogeneic HCT procedures increasing year after year due to the increased availability of suitable donors, each of these alternative donor sources merits special clinical considerations, specifically with regard to infections. Infections remain a significant cause of morbidity and mortality after allogeneic transplant, especially in those receiving alternative donor grafts. Due to the high‐risk nature associated with these donor grafts, it is important to understand the true risk of developing infectious complications. While there are a multitude of infections that have been described in patients post‐allogeneic HCT, this review seeks to focus on the incidence of cytomegalovirus (CMV) and invasive fungal infections (IFI) in adult patients receiving alternative donor source transplantation for hematologic malignancies.

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“…Cytomegalovirus (CMV) is an immunomodulatory herpesvirus that significantly contributes to morbidity after hematopoietic cell transplantation (HCT) . Despite preventative efforts, CMV disease (end organ damage) occurs in 3.5%‐10% of HCT recipients, with a mortality rate of 30%‐90% .…”

Section: Introductionmentioning

confidence: 99%

Mixed vs full donor engraftment early after hematopoietic cell transplant: Impact on incidence and control of cytomegalovirus infection

Green

Shanley

Brunstein

et al. 2019

Transplant Infectious Dis

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Recovery of cytomegalovirus (CMV)‐specific immunity after hematopoietic cell transplantation (HCT) is essential in controlling CMV infection. We hypothesize that mixed donor engraftment as measured by chimerism at day 30 in CMV D(+) HCTs and full chimerism in CMV D(−) HCTs will be predictive of CMV reactivation. Prospectively collected data for 407 CMV R+ HCT recipients transplanted from 2006 to 2014 at the University of Minnesota were retrospectively analyzed. Full and mixed donor engraftment were defined as ≥95% or <95% donor cells at day 30, respectively. Source of engraftment determination included preferentially peripheral blood CD3 fraction, then myeloid cell fraction (CD15+), then bone marrow. In 407 CMV R+ subjects, 77% (n = 313) were CMV D(−) cells from umbilical cord blood (n = 209), peripheral blood (n = 58) or marrow (n = 46). Fifty three per cent received reduced intensity conditioning (RIC). At day +30, full donor engraftment was seen in 82% of myeloablative and 55% of RIC transplants. The cumulative incidence of CMV infection 1‐year after transplant was not different in patients with full (54%, n = 276) or mixed (53%, n = 131) donor engraftment. Control of CMV did not significantly differ among the two groups. In multiple regression analysis, there was no significant association between donor engraftment (mixed or full) and incidence or control of CMV.

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Impact of early CMV reactivation in cord blood stem cell recipients in the current era

Cited by 35 publications

References 34 publications

Cytomegalovirus Infection Incidence and Risk Factors Across Diverse Hematopoietic Cell Transplantation Platforms Using a Standardized Monitoring and Treatment Approach: A Comprehensive Evaluation from a Single Institution

Cytomegalovirus Infection Incidence and Risk Factors Across Diverse Hematopoietic Cell Transplantation Platforms Using a Standardized Monitoring and Treatment Approach: A Comprehensive Evaluation from a Single Institution

Incidence of viral and fungal complications after utilization of alternative donor sources in hematopoietic cell transplantation

Mixed vs full donor engraftment early after hematopoietic cell transplant: Impact on incidence and control of cytomegalovirus infection

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