Qualitative and quantitative analysis of human herpesviruses in chronic and acute B cell lymphocytic leukemia and in multiple myeloma

Hermouet, Sylvie; Sutton, C. A.; Rose, Timothy M.; Greenblatt, Rebecca J.; Corre, Isabelle; Garand, Richard; Neves, A.; Bataille, Régis; Casey, James W.

doi:10.1038/sj.leu.2402748

Cited by 55 publications

(48 citation statements)

References 43 publications

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“…It has been shown previously that primary AML marrow blasts can contain fairly large HCMV copy numbers in a significant proportion of affected patients. 32 Thus, HCMV infection of residual AML marrow blasts may similarly fade to a latent state as latent HCMV infections in other tissues after alloSCT. This in turn may lead to presentation of HCMVinduced peptides by AML blasts, which can serve as targets for specific cytotoxic donor cells.…”

Section: Discussionmentioning

confidence: 99%

Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients

Elmaagacli

Steckel

Koldehoff

et al. 2011

Blood

285

230

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The impact of early human cytomegalovirus (HCMV) replication on leukemic recurrence was evaluated in 266 consecutive adult (median age, 47 years; range, 18-73 years) acute myeloid leukemia patients, who underwent allogeneic stem cell transplantation (alloSCT) from 10 of 10 high-resolution human leukocyte Agidentical unrelated (n ‫؍‬ 148) or sibling (n ‫؍‬ 118) donors. A total of 63% of patients (n ‫؍‬ 167) were at risk for HCMV reactivation by patient and donor pretransplantation HCMV serostatus. In 77 patients, first HCMV replication as detected by pp65-antigenemia assay developed at a median of 46 days (range, 25-108 days) after alloSCT. Taking all relevant competing risk factors into account, the cumulative incidence of hematologic relapse at 10 years after alloSCT was 42% (95% confidence interval [CI], 35%-51%) in patients without opposed to 9% (95% CI, 4%-19%) in patients with early pp65-antigenemia (P < .0001). A substantial and independent reduction of the relapse risk associated with early HCMV replication was confirmed by multivariate analysis using time-dependent covariate functions for grades II to IV acute and chronic graft-versus-host disease, and pp65-antigenemia (hazard ratio ‫؍‬ 0.2; 95% CI, 0.1-0.4, P < .0001). This is the first report that demonstrates an independent and substantial reduction of the leukemic relapse risk after early replicative HCMV infection in a homogeneous population of adult acute myeloid leukemia patients.

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Section: Discussionmentioning

confidence: 99%

Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients

Elmaagacli

Steckel

Koldehoff

et al. 2011

Blood

285

230

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“…In this population, CMV antigenemia has been reported only in small series or case studies (7)(8)(9). Even among SCT and organ transplant recipients, largescale epidemiologic studies performed to determine the effects of underlying diseases (and associated treatment), sex, age, and ethnicity on antigenemia are scanty.…”

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confidence: 99%

Epidemiologic Analysis of Reactivated Cytomegalovirus Antigenemia in Patients with Cancer

Han

2007

J Clin Microbiol

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The epidemiologic features of reactivated cytomegalovirus (CMV) antigenemia were studied among 4,382 cancer patients who were cared for and tested at the University of Texas M. D. Anderson Cancer Center from 2001 to 2004. The effects of stem cell transplant (SCT) status, underlying disease, age, sex, ethnicity, and antibody status (prior to CMV exposure) on the incidence of CMV antigenemia were determined; and the CMV burdens were quantified. Antigenemia occurred in 9.3% of patients with non-SCT (n ‫؍‬ 2511), 12.0% with autologous SCT (n ‫؍‬ 582), and 39.1% with allogeneic SCT (n ‫؍‬ 1289). Non-SCT patients with lymphoid tumors had a significantly higher rate of antigenemia than those with myeloid tumors (13.6% versus 3.9%) (P < 0.001); however, after allogeneic SCT, the underlying diseases had little effect, except for multiple myeloma (56.8%) (P ‫؍‬ 0.014). Among the allogeneic SCT recipients, higher CMV antigenemia rates were also associated with female sex, older age, and positivity for pre-SCT CMV antibody. Depending on the underlying disease and its associated initial CMV risk, allogeneic SCT increased the risk by 2.6-to 29.6-fold (overall, 4.0-fold). With or without SCT, Asians had the highest CMV antigenemia rates and burdens, followed by blacks, Hispanics, and whites, and these partially correlated with antibody prevalence. Among the 808 patients with antigenemia, the circulating peak CMV burden was significantly higher among non-SCT patients (geometric mean, 18.7 positive cells per 10 6 leukocytes) than among allogeneic SCT patients (geometric mean, 7.7 positive cells per 10 6 leukocytes) or autologous SCT patients (geometric mean, 7.0 positive cells per 10 6 leukocytes) who underwent monitoring for CMV. Together, these results allow stratification of CMV risks and suggest a substantial CMV reactivation among non-SCT cancer patients and, thus, the need for better diagnosis and control.Human cytomegalovirus (CMV), a ␤-herpesvirus, causes a variety of infections, such as congenital infections in neonates, infectious mononucleosis in healthy individuals, and reactivation in immunocompromised patients (18). CMV reactivation is a common and severe problem in organ and stem cell transplant (SCT) recipients and in those infected with human immunodeficiency virus (HIV), particularly before the era of effective antiretroviral therapy. Among SCT recipients, the rate of CMV reactivation in the bloodstream (antigenemia or viremia) has been reported to be from 30% to 70% (2, 11, 13). Routine monitoring of CMV antigenemia by testing for the CMV pp65 antigen (or other means) has played a crucial role in detecting the virus and guiding effective antiviral therapy in SCT recipients (4, 16).The incidence of CMV antigenemia among patients who have severe underlying diseases, such as leukemia, lymphoma, or solid tumors, but who are not transplant recipients or HIV infected is largely unknown. In this population, CMV antigenemia has been reported only in small series or case studies (7-9). Even among SCT and organ transpla...

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“…reported that HHV8 DNA was present in bone marrow dendritic cells of multiple myeloma (MM) patients, but subsequent studies had inconsistent findings (Olsen et al, 1998;Beksac et al, 2001;Patel et al, 2001;Hermouet et al, 2003). Several studies found that HHV8 antibodies did not associate with MM (MacKenzie et al, 1997;Masood et al, 1997;Parravicini et al, 1997;Bouscary et al, 1998;Perna et al, 1998;Santarelli et al, 1998;Ablashi et al, 2000), although one study found an association (Gao et al, 1998).…”

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confidence: 99%

Joint Nordic prospective study on human herpesvirus 8 and multiple myeloma risk

et al. 2005

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An association between human herpesvirus 8 (HHV8) and multiple myeloma (MM) has been reported, though most studies have not confirmed such association. To follow-up on a previous prospective seroepidemiological study, where HHV8 tended to associate with MM risk, we linked five large serum banks in the Nordic countries with the Nordic cancer registries and 329 prospectively occurring cases of MM were identified, together with 1631 control subjects matched by age and gender. The HHV8 seroprevalences among cases and controls were similar (12 and 15%, respectively) and HHV8 seropositivity did not associate with the risk of MM, neither when considering positivity for lytic antibodies (relative risk (RR) ¼ 0.8, 95% confidence interval (CI) ¼ 0.5 -1.1) nor for latent antibodies (RR ¼ 0.6, 95% CI ¼ 0.1 -2.7). Similar risks were seen when analysis was restricted to case -control sets with at least 2 years lag before diagnosis (RR ¼ 0.8, 95% CI ¼ 0.5 -1.2 and RR ¼ 0.9, 95% CI ¼ 0.1 -4.2). In conclusion, the data indicate that HHV8 infection is not associated with MM.

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Qualitative and quantitative analysis of human herpesviruses in chronic and acute B cell lymphocytic leukemia and in multiple myeloma

Cited by 55 publications

References 43 publications

Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients

Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients

Epidemiologic Analysis of Reactivated Cytomegalovirus Antigenemia in Patients with Cancer

Joint Nordic prospective study on human herpesvirus 8 and multiple myeloma risk

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