Cytomegalovirus Infection in Allogeneic Hematopoietic Cell Transplantation Managed by the Preemptive Approach: Estimating the Impact on Healthcare Resource Utilization and Outcomes

Abstract

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.

Letermovir for primary and secondary cytomegalovirus prevention in allogeneic hematopoietic cell transplant recipients: Real‐world experience

“…We observed continued efficacy when extending primary letermovir prophylaxis beyond 14 weeks as only 1 of 29 patients reactivated CMV. Our institution reported rates of CMV viremia of 66.3% in a contemporary cohort of T‐cell–depleted HCT recipients.0 . Similarly, a 53%‐81% incidence of CMV viremia was reported in haploidentical allo‐HCT .…”

“…The conditioning regimens utilized and underlying hematologic malignancies were the same as the T‐cell–depleted group in this current observational study. The contemporary cohort also received routine CMV monitoring and preemptive management …”

“…Approximately 70% of ex vivo T‐cell–depleted HCT recipients require PET for CMV, often requiring an extended duration due to prolonged immunosuppression and resulting in substantial healthcare utilization. Up to 12.5% of T‐cell–depleted HCT with CMV viremia develop CMV disease by 1‐year post HCT, which has been associated with decreased overall survival . Additional studies are needed to quantify the impact of letermovir on the reduction of days of PET, readmissions, hospital length of stay, and overall long‐term survival in high‐risk patients.…”

“…Cord blood recipients were excluded from this analysis as preliminary results have been presented separately . Supportive care was provided by institutional standards of care (eg, acyclovir for herpes simplex virus and varicella zoster virus prevention) . Plasma CMV viral load (VL) was monitored by quantitative CMV PCR (COBAS® AmpliPrep/COBAS® TaqMan® CMV Test, Roche Diagnostics), starting on day + 5 and continued weekly until day + 100, then per immune recovery for unmodified allo‐HCT (non‐CD34‐selected) or every 1‐2 weeks for months 3‐6 for other transplant types.…”

Cytomegalovirus Reactivation in Hematopoietic Stem cell Transplantation managed by Preemptive Treatment with lower dose Valganciclovir

“…Risk factors for CMV reactivation identified such as CMV seropositive donor, type of coditioning regimen, use of T cell depletion, and graftversus-host disease (GVHD) [3]. Although this complication still remains an important cause of morbidity and mortality in patients undergoing HSCT, the availability of effective antiviral drugs and the implementation of preemptive threapy have led to dramatic improvements in patient outcomes [4]. For an effective preemptive treatment, quick and sensitive diagnostic methods that will detect CMV infection are needed.…”