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
Abstract: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 In… Show more
“…No patients had clinically significant EBV-associated complications, consistent with outcomes previously published with PTCy-based approaches [51]. CMV reactivation was controlled with pre-emptive therapy alone in all but 1 patient, which could in part be associated with the use of sirolimus [16,52]. Notably, post-BMT primary CMV infection was not uncommon; all cases occurred after weekly CMV monitoring had stopped, and 1 case progressed to CMV disease.…”
Section: Discussionsupporting
confidence: 81%
“…Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6, adenovirus, and BK virus were evaluated weekly in blood and, for BK virus, also urine by quantitative PCR. CMV monitoring and preemptive treatment were performed as previously published [16].…”
Allogeneic blood or marrow transplantation (BMT) is a potentially curative therapy for patients with primary immunodeficiency (PID). Safe and effective reduced-intensity conditioning (RIC) approaches that are associated with low toxicity, use alternative donors, and afford good immune reconstitution are needed to advance the field. Twenty PID patients, ranging in age from 4 to 58 years, were treated on a prospective clinical trial of a novel, radiation-free and serotherapy-free RIC, T-cell-replete BMT approach using pentostatin, low-dose cyclophosphamide, and busulfan for conditioning with post-transplantation cyclophosphamide-based graft-versus-host-disease (GVHD) prophylaxis. This was a high-risk cohort with a median hematopoietic cell transplantation comorbidity index of 3. With median follow-up of survivors of 1.9 years, 1-year overall survival was 90% and grade III to IV acute GVHD-free, graft-failure-free survival was 80% at day +180. Graft failure incidence was 10%. Split chimerism was frequently observed at early post-BMT timepoints, with a lower percentage of donor T cells, which gradually increased by day +60. The cumulative incidences of grade II to IV and grade III to IV acute GVHD (aGVHD) were 15% and 5%, respectively. All aGVHD was steroid responsive. No patients developed chronic GVHD. Few significant organ toxicities were observed. Evidence of phenotype reversal was observed for all engrafted patients, even those with significantly mixed chimerism (n = 2) or with unknown underlying genetic defect (n = 3). All 6 patients with pre-BMT malignancies or lymphoproliferative disorders remain in remission. Most patients have discontinued immunoglobulin replacement. All survivors are off immunosuppression for GVHD prophylaxis or treatment. This novel RIC BMT approach for patients with PID has yielded promising results, even for high-risk patients. Published by Elsevier Inc. on behalf of the American Society for Transplantation and Cellular Therapy.
“…No patients had clinically significant EBV-associated complications, consistent with outcomes previously published with PTCy-based approaches [51]. CMV reactivation was controlled with pre-emptive therapy alone in all but 1 patient, which could in part be associated with the use of sirolimus [16,52]. Notably, post-BMT primary CMV infection was not uncommon; all cases occurred after weekly CMV monitoring had stopped, and 1 case progressed to CMV disease.…”
Section: Discussionsupporting
confidence: 81%
“…Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6, adenovirus, and BK virus were evaluated weekly in blood and, for BK virus, also urine by quantitative PCR. CMV monitoring and preemptive treatment were performed as previously published [16].…”
Allogeneic blood or marrow transplantation (BMT) is a potentially curative therapy for patients with primary immunodeficiency (PID). Safe and effective reduced-intensity conditioning (RIC) approaches that are associated with low toxicity, use alternative donors, and afford good immune reconstitution are needed to advance the field. Twenty PID patients, ranging in age from 4 to 58 years, were treated on a prospective clinical trial of a novel, radiation-free and serotherapy-free RIC, T-cell-replete BMT approach using pentostatin, low-dose cyclophosphamide, and busulfan for conditioning with post-transplantation cyclophosphamide-based graft-versus-host-disease (GVHD) prophylaxis. This was a high-risk cohort with a median hematopoietic cell transplantation comorbidity index of 3. With median follow-up of survivors of 1.9 years, 1-year overall survival was 90% and grade III to IV acute GVHD-free, graft-failure-free survival was 80% at day +180. Graft failure incidence was 10%. Split chimerism was frequently observed at early post-BMT timepoints, with a lower percentage of donor T cells, which gradually increased by day +60. The cumulative incidences of grade II to IV and grade III to IV acute GVHD (aGVHD) were 15% and 5%, respectively. All aGVHD was steroid responsive. No patients developed chronic GVHD. Few significant organ toxicities were observed. Evidence of phenotype reversal was observed for all engrafted patients, even those with significantly mixed chimerism (n = 2) or with unknown underlying genetic defect (n = 3). All 6 patients with pre-BMT malignancies or lymphoproliferative disorders remain in remission. Most patients have discontinued immunoglobulin replacement. All survivors are off immunosuppression for GVHD prophylaxis or treatment. This novel RIC BMT approach for patients with PID has yielded promising results, even for high-risk patients. Published by Elsevier Inc. on behalf of the American Society for Transplantation and Cellular Therapy.
“…Cytomegalovirus (CMV) viremia occurs in 40% to D 1 2 7 X X90% of CMV-D 1 2 8 X Xseropositive recipients (R + ) [1À3] and is associated with increased overall mortality after hematopoietic cell transplantation (HCT) [4]. Risk factors for CMV reactivation after HCT are well established and include T D 1 2 9 X Xcell depletion, allograft from D 1 3 0 X XHLA-mismatched or CMV-seronegative donor (D ¡ ), and graft-D 1 3 1 X Xversus-D 1 3 2 X Xhost disease (GVHD) [1,4]. Preemptive therapy (PET) has reduced the rates of CMV end-organ disease to less than 5% [5], the trade-off being increased use of CMV antivirals with their associated toxicities and potentially prolonged hospital length of stay (LOS).…”
We quantified cytomegalovirus (CMV) antiviral use and hospital length of stay (LOS) associated with CMV infection in a contemporary cohort of conventional (CONV) and CD34-selected (T D 1 0 8 X XcellÀD 1 0 9 X Xdepleted) hematopoietic cell transplantation (HCT) recipients managed by preemptive therapy (PET) in a single US center. Adults who received first allogeneic HCT at Memorial Sloan Kettering D 1 1 0 X XCancer Center from June 2010 through December 2014 were analyzed. Days on PET, number of readmissions, and readmission LOS by day 180 post-D 1 1 1 X XHCT were summarized. Estimated unit value (EUV) was defined as the expected number of PET days for a cohort of 100 HCT with characteristics as the analyzed cohort. Standardized incidence ratio D 1 1 2 X Xwas calculated as the ratio of observed outcomes of patients with CMV viremia over the outcomes of patients without CMV viremia. Of 318 patients, 88 received CONV and 230 CD34-selected HCT. Rates of CMV viremia were 26.3% for CONV and 41.9% for CD34selected (P = D 1 1 3 X X.003). Among D 1 1 4 X Xpatients with viremia 68.2% CONV and 97.9% CD34-selected received PET. EUV for PET was 852 days and 2D 1 1 5 X X821 days for CONV and CD34-selected, respectively. The standardized incidence ratios D 1 1 6 X Xfor number of readmission and readmission LOS were 1.7 D 1 1 7 X X(95% confidence interval [CI], D 1 1 8 X X1.4 to D 1 1 9 X X2.1D 1 2 0 X X) and 1.2 (95% CI, 1.1 to D 1 2 1 X X1.3), respectively, for CONV HCT and 1.7 (95% CI, 1.3 to D 1 2 2 X X2.1) and 1.6 (95% CI, 1.5 to D 1 2 3 X X1.7), respectively, for CD34selected HCT. Overall survival D 1 2 4 X Xwas similar between patients with and without CMV viremia by HCT type. CMV end-organ disease was associated with lower overall survival D 1 2 5 X Xonly in CD34-selected HCT (P = .0007). CMV infection managed by PET requires substantial antiviral useD 1 2 6 X X and is associated with longer readmission LOS more, particularly among CD34-selected HCT.
“…A summary of selected studies reporting CMV incidence can be found in Table 2. When compared to other graft sources, UCB transplants have been reported to have higher cumulative incidences of CMV infection and CMV disease 6, 26, 29 . The risk of CMV is also much higher in CMV seropositive recipients.…”
Section: Cytomegalovirus In Alternative Donor Transplantsmentioning
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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