Prediction of Cytomegalovirus Reactivation by Recipient Cytomegalovirus-IgG Titer before Allogeneic Hematopoietic Stem Cell Transplantation

Kawamura, Satoshi; Nakasone, Hideki; Takeshita, Junko; Kimura, Shun‐ichi; Nakamura, Yuhei; Kawamura, Masakatsu; Yoshino, Nozomu; Misaki, Yukiko; Yoshimura, Kazuki; Matsumi, Shimpei; Gomyo, Ayumi; Akahoshi, Yu; Kusuda, Machiko; Kameda, Kazuaki; Tanihara, Aki; Tamaki, Masaharu; Kako, Shinichi; Kanda, Yoshinobu

doi:10.1016/j.jtct.2021.04.024

Cited by 6 publications

(5 citation statements)

References 27 publications

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“…Recent investigations by Arcuri et al (2020) and Kawamura et al (2021) evidenced that the quantitative anti-CMV IgG value pre-allo-HSCT is associated with the risk for CMV reactivation after TX. In both studies, a higher anti-CMV IgG titer correlated with a higher risk of CMV reactivation [ 18 , 25 ]. In line with these previous findings, we observed that patients with anti-CMV IgG values pre-TX ≥ 250 AU/ml (group A) were at significant higher risk of CMV reactivation, including clinically relevant infections, compared to patients with lower IgG values (IgG 6-249 AU/ml, group B).…”

Section: Discussionmentioning

confidence: 99%

“…The detection of anti-CMV IgG is an important qualitative biomarker for the definition of latent CMV infection in recipients and donors, whereas the relevance of anti-CMV IgG as quantitative value has been poorly considered. The few available data suggest that the quantitative determination of specific anti-CMV IgG could represent an early parameter of CMV risk assessment in candidates for allo-HSCT [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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CMV-IgG pre-allogeneic hematopoietic stem cell transplantation and the risk for CMV reactivation and mortality

Eberhardt

Jung

Knops

et al. 2023

Bone Marrow Transplant

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Cytomegalovirus (CMV) represents one of the most common infectious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Currently, a common diagnostic test used to stratify the risk for CMV infection in allo-HSCT recipients is the qualitative CMV serology of donor and recipient. A positive serostatus of the recipient is the most important risk factor for CMV reactivation and associated with reduced overall survival post-transplantation (TX). Direct and indirect effects of CMV are involved in the poorer survival outcome. The present study investigated if the quantitative interpretation of anti-CMV IgG before allo-HSCT might serve as a novel parameter for the identification of patients at risk for CMV reactivation and worse outcome post-TX. For this purpose, a cohort of 440 allo-HSCT recipients over a period of 10 years was retrospectively analyzed. Our findings indicated that patients with high CMV IgG pre-allo-HSCT had a higher risk to develop CMV reactivation, including clinically relevant infections, and a worse prognosis 36 months post-allo-HSCT as compared to recipients with low CMV IgG values. In the letermovir (LMV) era, this group of patients might benefit from a closer CMV monitoring, and hence, earlier intervention if needed, especially after discontinuation of prophylaxis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CMV-IgG pre-allogeneic hematopoietic stem cell transplantation and the risk for CMV reactivation and mortality

Eberhardt

Jung

Knops

et al. 2023

Bone Marrow Transplant

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“…Considering the increasing number of HCTs successfully performed all over the world, larger prospective studies and algorithm propositions, such as ours, are necessary to optimize clinical outcomes and resource utilization. In addition, recent data suggest that the higher the CMV serology titer of an allogeneic HCT CMV R+, the higher the probability of posttransplant CMV reactivation [ 13 , 14 ]. Clearly, the importance and clinical impact of CMV serology in allo-HCTRs requires a second fresh look.…”

Section: Discussionmentioning

confidence: 99%

Revisiting Cytomegalovirus Serology in Allogeneic Hematopoietic Cell Transplant Recipients

Portillo,

Masouridi-Levrat,

Royston

et al. 2023

Clinical Infectious Diseases

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Background Allogeneic hematopoietic cell transplant recipients (allo-HCTR) with positive CMV serology may have false positive results due to blood product transfusions associated passive immunity. Methods This is a single-center cohort study including consecutive adult allo-HCTR (01.01.2018-31.12.2022) with negative baseline (at hematologic malignancy diagnosis) and indeterminate or low-positive (CMV-IgG-titer: ≥ 0.6-<50 U/mL) pretransplant CMV-serology with negative pretransplant plasma CMV DNAemia. The CMV serology status of those patients was reclassified from R + to R- (CMVR- reclassification group). We compared those patients to allo-HCTR with negative (CMV-IgG-titer < 0.6 U/mL) pretransplant CMV IgG serology (CMVR- group). We describe the number and type of patients, whose pretransplant CMV serology status was reclassified from indeterminate/positive to negative. Moreover, we reviewed all plasma CMV DNAemia tests performed during the first 6 months posttransplant in both groups, to assess the safety of this approach. Results Amongst 246 (84.5%) of 291 transplanted patients identified as CMVR + pretransplant, 60/246 (24.4%) were reclassified from CMV serology indeterminate (N:10) or low-positive (N:50) to R-. Only 1/60 (1.67%) patient in the CMVR- reclassification group vs 3/44(6.8%; p = 0.30) in the CMVR- group developed CMV-DNAemia during the 6-month posttransplant follow-up period. There were no significant differences in the number of CMV-DNAemia tests performed, CMV-DNAemia range and time posttransplant between the two groups. Conclusion One out of four allo-HCT CMVR + may be falsely flagged as R+, with significant impact on donor selection and prophylaxis administration. A 2-step approach including CMV-serology testing at hematologic malignancy diagnosis in allo-HCTR candidates and careful review of pretransplant CMV IgG-titers may help correctly classify CMV-serology status.

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“…Well-known CMV reactivation risk factors during allo-HSCT include CMV-positive recipient serostatus, acute GVHD grade ≥2 and its duration, and unrelated or mismatched donors [ 27 , 29 , 36 – 38 ]. In addition, the use of ATG [ 39 ], a higher titer of CMV-IgG in recipients before allo-HSCT [ 40 ], and the titer of the human leukocyte antigen allele type [ 41 ] have also been associated with CMV reactivation. ATG use or dose may increase CMV reactivation in patients with aplastic anemia and renal transplantation [ 42 – 45 ].…”

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus reactivation under pre-emptive therapy following allogeneic hematopoietic stem cell transplant: Pattern, survival, and risk factors in the Republic of Korea

Kang,

Jeon,

et al. 2023

PLoS ONE

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Introduction Pre-emptive therapy for cytomegalovirus (CMV) reactivation has been used in allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is unclear if this strategy has poorer clinical outcomes in CMV-endemic areas and if more aggressive prophylaxis is required. Methods We retrospectively analyzed the patterns and survival after CMV reactivation in patients undergoing pre-emptive therapy following allo-HSCT and assessed high-risk patients who could benefit from aggressive CMV prophylaxis in endemic areas. Results Of the 292 patients who underwent allo-HSCT, 70.5% (donor+ or recipient+) were CMV seropositive. CMV reactivation occurred in 139 patients (47.6%), with a median of 31.5 days from day 0 of allo-HSCT. The overall survival of patients with CMV reactivation who received pre-emptive therapy did not differ from those without reactivation. Of the 139 patients with CMV reactivation, 78 (56.1%) underwent ≥2 rounds of pre-emptive therapy. In multivariate analysis, the risk of CMV reactivation was higher in patients with multiple myeloma, with CMV seropositivity of the recipient and donor, administered with a higher dose of anti-thymocyte globulin (ATG), and with acute graft-versus-host disease (aGVHD) ≥ grade 2. Conclusion Although half of the patients with allo-HSCT were administered with pre-emptive therapy for CMV, CMV reactivation did not affect their survival, indicating the advantages of pre-emptive therapy, even in CMV-endemic areas. The cost-effectiveness of more aggressive CMV prophylaxis should be re-evaluated in patients at a high risk for CMV reactivation.

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Prediction of Cytomegalovirus Reactivation by Recipient Cytomegalovirus-IgG Titer before Allogeneic Hematopoietic Stem Cell Transplantation

Cited by 6 publications

References 27 publications

CMV-IgG pre-allogeneic hematopoietic stem cell transplantation and the risk for CMV reactivation and mortality

CMV-IgG pre-allogeneic hematopoietic stem cell transplantation and the risk for CMV reactivation and mortality

Revisiting Cytomegalovirus Serology in Allogeneic Hematopoietic Cell Transplant Recipients

Cytomegalovirus reactivation under pre-emptive therapy following allogeneic hematopoietic stem cell transplant: Pattern, survival, and risk factors in the Republic of Korea

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