CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia

Green, Margaret L.; Leisenring, Wendy; Xie, Hu; Walter, Roland B.; Mielcarek, Marco; Sandmaier, Brenda M.; Riddell, Stanley R.; Boeckh, Michael

doi:10.1182/blood-2013-02-487074

Cited by 266 publications

(280 citation statements)

References 27 publications

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“…Previous 34 as well as recently published data show that CMV reactivation confers a protective effect against early (100-day) 35 or even later relapses 36 in patients who received an allo-HCT for AML. Even though we did not include incidence and time of CMV reactivation as a variable in our analysis, we observed a favorable effect of recipient CMV seropositivity at the time of transplantation, resulting in a lower CIR.…”

Section: Discussionmentioning

confidence: 87%

Comparing i.v. BU dose intensity between two regimens (FB2 vs FB4) for allogeneic HCT for AML in CR1: a report from the Acute Leukemia Working Party of EBMT

Kharfan‐Dabaja

Labopin

Bazarbachi

et al. 2014

Bone Marrow Transplant

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This retrospective analysis compared two regimens of fludarabine combined with i.v. BU 6.4 mg/kg (FB2) or BU 12.8 mg/kg (FB4) for allografting of AML in first CR. A total of 437 patients (median age: 50 years) were administered FB2 (n = 225, 51%) or FB4 (n = 212, 49%). Median follow-up time was 28 months. Use of FB2 resulted in a longer time to neutrophil engraftment (17 vs 15 days, P o 0.0001) but no difference in incidence of grade II-IV acute (P = 0.54) or chronic GVHD (P = 0.51). In patients o 50 years of age, FB2 was associated with a higher 2-year cumulative incidence of relapse (33 ± 6% vs 20 ± 4%, P = 0.04), but there was no difference in 2-year leukemia-free survival (LFS) (P = 0.45), OS (P = 0.53) or non-relapse mortality (P = 0.17). In recipients ⩾ 50 years of age, FB2 resulted in better 2-year LFS (63 ± 4% vs 42 ± 7%, P = 0.02) and OS (68 ± 4% vs 45 ± 7%, P = 0.006); a lower 2-year non-relapse mortality, albeit not statistically significant (15 ± 3% vs 29 ± 6%, P = 0.06), was observed with FB2. FB2 is an effective and welltolerated regimen in patients ⩾ 50 years of age and does not compromise survival when used in patients o 50 years undergoing allogeneic transplantation for AML in first CR.

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Section: Discussionmentioning

confidence: 87%

Comparing i.v. BU dose intensity between two regimens (FB2 vs FB4) for allogeneic HCT for AML in CR1: a report from the Acute Leukemia Working Party of EBMT

Kharfan‐Dabaja

Labopin

Bazarbachi

et al. 2014

Bone Marrow Transplant

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“…[1][2][3] This was demonstrated in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). 4 Other studies have demonstrated both early and late protective effects, but all have been on matched related or unrelated donors.…”

mentioning

confidence: 99%

Cytomegalovirus viremia, disease, and impact on relapse in T-cell replete peripheral blood haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide

Goldsmith¹,

Slade²,

DiPersio³

et al. 2016

Haematologica

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“…In addition to the absence of a predictable link between KIR genotype and phenotype, one must also consider potential viral imprinting of both the donor and recipient NK cell repertoires. Given that adaptive NK cell responses to CMV can be transferred from an allogeneic donor to the recipient (21), it was speculated that high frequencies of educated and differentiated NK cells in the donor or the emergence of such NK cell populations in the recipient may contribute to the reduced risk for relapse associated with CMV reactivation in myeloid malignancies (22)(23)(24). This hypothesis was recently supported by the observed link among CMV reactivation, expansion of CD56 dim CD57 + NKG2C + NK cells, and reduced leukemia relapse in patients receiving reduced-intensity conditioning (RIC) (25).…”

mentioning

confidence: 99%

Naive Donor NK Cell Repertoires Associated with Less Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation

Björklund

Clancy

Goodridge

et al. 2016

The Journal of Immunology

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Acute and latent human CMV cause profound changes in the NK cell repertoire, with expansion and differentiation of educated NK cells expressing self-specific inhibitory killer cell Ig-like receptors. In this study, we addressed whether such CMV-induced imprints on the donor NK cell repertoire influenced the outcome of allogeneic stem cell transplantation. Hierarchical clustering of high-resolution immunophenotyping data covering key NK cell parameters, including frequencies of CD56bright, NKG2A+, NKG2C+, and CD57+ NK cell subsets, as well as the size of the educated NK cell subset, was linked to clinical outcomes. Clusters defining naive (NKG2A+CD57−NKG2C−) NK cell repertoires in the donor were associated with decreased risk for relapse in recipients with acute myeloid leukemia and myelodysplastic syndrome (hazard ratio [HR], 0.09; 95% confidence interval [CI]: 0.03–0.27; p < 0.001). Furthermore, recipients with naive repertoires at 9–12 mo after hematopoietic stem cell transplantation had increased disease-free survival (HR, 7.2; 95% CI: 1.6–33; p = 0.01) and increased overall survival (HR, 9.3; 95% CI: 1.1–77, p = 0.04). Conversely, patients with a relative increase in differentiated NK cells at 9–12 mo displayed a higher rate of late relapses (HR, 8.41; 95% CI: 6.7–11; p = 0.02), reduced disease-free survival (HR, 0.12; 95% CI: 0.12–0.74; p = 0.02), and reduced overall survival (HR, 0.07; 95% CI: 0.01–0.69; p = 0.02). Thus, our data suggest that naive donor NK cell repertoires are associated with protection against leukemia relapse after allogeneic HSCT.

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CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia

Abstract: Key Points CMV reactivation after HCT is associated with a reduced risk of early relapse in patients with AML but not other disease groups. The benefit, however, is offset by an increased risk of nonrelapse mortality.

Cited by 266 publications

References 27 publications

Comparing i.v. BU dose intensity between two regimens (FB2 vs FB4) for allogeneic HCT for AML in CR1: a report from the Acute Leukemia Working Party of EBMT

Comparing i.v. BU dose intensity between two regimens (FB2 vs FB4) for allogeneic HCT for AML in CR1: a report from the Acute Leukemia Working Party of EBMT

Cytomegalovirus viremia, disease, and impact on relapse in T-cell replete peripheral blood haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide

Naive Donor NK Cell Repertoires Associated with Less Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation

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