Association between the kinetics of cytomegalovirus reactivation in terms of the area under the curve of cytomegalovirus antigenemia and non‐relapse mortality after allogeneic hematopoietic stem cell transplantation

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

doi:10.1111/tid.13715

Cited by 3 publications

(1 citation statement)

References 31 publications

(63 reference statements)

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“…P values were not corrected for multiple comparisons in exploratory analyses. Third, although the clearance speed of CMVR after pre-emptive therapy might affect the risk of relapse as well as NRM, 59 the kinetics of CMVR are not available in our database.…”

Section: Discussionmentioning

confidence: 99%

CMV reactivation after allogeneic HCT is associated with a reduced risk of relapse in acute lymphoblastic leukemia

et al. 2023

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Cytomegalovirus reactivation (CMVR) after allogeneic hematopoietic cell transplantation (HCT) is a frequent complication related to survival outcomes, but the impact of CMVR on relapse is still unclear, especially in acute lymphoblastic leukemia (ALL). In this nationwide retrospective study, we included patients with acute myeloid leukemia (AML) and ALL in first or second complete remission who underwent their first HCT using pre-emptive strategy for CMVR. Because ninety percent of cases with CMVR had occurred by day 64 and ninety percent of cases with grades II to IV acute GVHD had occurred by day 58, a landmark point was set at day 65. In the landmark analyses, 3793 patients with AML and 2213 patients with ALL who survived without relapse for at least 65 days were analyzed. In the multivariate analyses, CMVR was associated with a lower incidence of relapse in both AML (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.69-0.95; P = 0.009) and ALL (HR, 0.81; 95% CI, 0.66-0.99; P = 0.045). These findings were confirmed when we treated CMVR as a time-dependent covariate. Moreover, our study suggested that the protective effect of CMVR on relapse was independent of acute GVHD. A post-hoc subgroup analysis that combined AML and ALL showed that CMVR had a mild anti-leukemia effect without effect modification in contrast to the impact of CMVR on NRM. Our findings may provide important implications for the strategy used for CMV prophylaxis after HCT.

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Section: Discussionmentioning

confidence: 99%

CMV reactivation after allogeneic HCT is associated with a reduced risk of relapse in acute lymphoblastic leukemia

et al. 2023

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Risk factors and outcomes of definite or clinical idiopathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation

Tamaki

Nakasone

Nakamura

et al. 2022

Leukemia & Lymphoma

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Cytomegalovirus viral load at initiation of pre‐emptive antiviral therapy impacts cytomegalovirus dynamics in pediatric allogeneic hematopoietic cell transplantation recipients

Gutierrez,

Stanek,

Ardura

et al. 2024

Transplant Infectious Dis

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BackgroundCytomegalovirus (CMV) contributes to morbidity and mortality in allogeneic hematopoietic cell transplantation (allo‐HCT) recipients. Pre‐emptive antiviral therapy (PET) reduces the incidence of CMV end‐organ disease (EOD), though relevant viral thresholds to initiate PET remain undefined. We evaluated the impact of viral loads (VLs) at PET initiation on virologic and clinical outcomes following pediatric allo‐HCT.MethodsSingle‐center retrospective cohort analysis of children who underwent their first allo‐HCT from January 2014 to December 2020. Weekly quantitative plasma CMV polymerase chain reaction was performed until Day +100 and PET was initiated once VL exceeded a pre‐defined threshold per institutional guidelines. Patients were followed for 1‐year post‐HCT to evaluate virologic and clinical outcomes including end‐organ disease (EOD), overall survival (OS), and non‐relapse mortality (NRM).ResultsAmong 146 allo‐HCT recipients, CMV DNAemia occurred in 40 patients (27%) at a median of 15 days post‐HCT (interquartile range 6–28.5). Ten percent (n = 4) had spontaneous resolution of DNAemia, while 90% (n = 36) required PET. PET initiated when CMV VL was ≥ 1000 IU/mL (n = 21) vs when VL < 1000 IU/mL (n = 15) resulted in higher peak CMV VL (12,670 vs. 1284 IU/mL, p = 0.0001) and longer time to CMV DNAemia resolution (36 vs. 24 days, p = 0.035). There were no differences in EOD, OS, or NRM at 12 months post‐HCT based on VL at PET initiation.ConclusionsInitiating PET when CMV VL was ≥1000 IU/mL resulted in significantly higher peak VL and prolonged DNAemia, with no differences in EOD, OS, or NRM at 12 months post pediatric HCT. image

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Association between the kinetics of cytomegalovirus reactivation in terms of the area under the curve of cytomegalovirus antigenemia and non‐relapse mortality after allogeneic hematopoietic stem cell transplantation

Cited by 3 publications

References 31 publications

CMV reactivation after allogeneic HCT is associated with a reduced risk of relapse in acute lymphoblastic leukemia

CMV reactivation after allogeneic HCT is associated with a reduced risk of relapse in acute lymphoblastic leukemia

Risk factors and outcomes of definite or clinical idiopathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation

Cytomegalovirus viral load at initiation of pre‐emptive antiviral therapy impacts cytomegalovirus dynamics in pediatric allogeneic hematopoietic cell transplantation recipients

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