Immunologic Monitoring with Cytomegalovirus (CMV) ELISPOT for Prediction of Recurrent CMV Infection and Late-onset CMV Disease in Pediatric Allogenic Hematopoietic Stem Cell Transplant (HSCT) Recipients

The dynamics of recovery of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) and its impact on controlling clinically significant CMV infections following hematopoietic stem cell transplant (HSCT) are rarely reported in pediatric HSCT recipients. In this study, dynamics of recovery of CMV-specific CMI and its clinical significance in controlling CMV viremia and clinically significant CMV infections were assessed in pediatric allogeneic HSCT recipients. All subjects underwent CMV pp65- and IE1-specific enzyme-linked immune absorbent spot (ELISPOT) assays just before transplantation and then monthly until the detection of CMV-specific CMI with ≥ 5 spot-forming cells (SFC) / 2.0 × 105 cells. Clinically significant CMV infections were defined as CMV diseases, prolonged CMV infections, recurrent CMV infections or late onset CMV infections. Among 52 recipients, 88.5% of recipients recovered CMV-specific CMI with ≥ 5 SFC/ 2.0 × 105 cells at a median of 34 days (interquartile range [IQR]: 29–95 days) following HSCT, 55.8% at 30 days following HSCT, and 73.1% at 90 days following HSCT. The presence of CMV-specific CMI before HSCT was the significant factors for the reconstitution of CMV specific CMI after HSCT (adjusted odds ratio [aOR] = 13.33; 95% confidence interval [CI] = 1.21–142.86). After HSCT, 30 recipients experienced CMV viremia, of which 20 were clinically significant CMV infections. The full recovery of CMV-specific CMI with ≥ 50 SFC / 2.0 × 105 cells after HSCT was the protective factor for the development of clinically significant CMV infections (aOR = 0.13; 95% CI = 0.22–0.71). In the haploidentical HSCT recipients, 82.1% recovered CMV-specific CMI at a median of 65 days after HSCT (IQR: 34–118 days) with a tendency to recover their CMV-specific CMI later than did those from non-haploidentical donors (65 days vs. 30 days; P = 0.001). Clinically significant CMV infections tended to occur more frequently in the haploidentical HSCT recipients compared to those with matched donor HSCT (46.4% vs. 29.2%; P = 0.205). The full recovery of CMV-specific CMI with ≥ 50 SFC/2.0 × 105 cells after HSCT also lowered the risk of development of clinically significant CMV infections (aOR = 0.08; 95% CI = 0.01–0.90). However, transplantation from haploidentical donors was a significant risk factor hampering recovery of CMV-specific CMI (aOR = 0.08; 95% CI = 0.01–0.86) and full recovery of CMV-specific CMI (aOR = 0.05; 95% CI = 0.01–0.50). Pre-transplant CMV-specific CMI influenced the recovery of CMV-specific CMI, and the full recovery of CMV-specific CMI could be a surrogate marker for preventing clinically significant CMV infections in pediatric HSCT recipients. Immunologic monitoring using ELISPOT assay before and after HSCT helps in identifying patients with a high risk of CMV infection and in controlling CMV infection.

Download Full-text

Cytomegalovirus Management in Adult Hematopoietic Stem Cell Transplant Patients with Pre-Engraftment Viremia: A Single-Center, Retrospective, Descriptive Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.863 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S357-S357

Author(s):

Isabella Martin ◽

Robin Avery ◽

Douglas Gladstone ◽

Richard Ambinder ◽

Noah Tucker ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Conditioning Regimen ◽

Bone Marrow Toxicity ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Post Transplant ◽

Cmv Disease

Abstract Background Scant data exist regarding cytomegalovirus (CMV) viremia in hematopoietic stem cell transplant (HSCT) recipients during the pre-engraftment period. The goal of this study was to describe management of CMV in neutropenic adult HSCT patients at our institution, and to assess the possible impact of different quantitative CMV PCR tests (QPCRs). Methods Post-HSCT monitoring at this center includes weekly CMV QPCR from plasma. Three different QPCR assays were used sequentially during the study period (1/2010–12/2015): two with lower limits of quantification (LLOQ) of 300 and 100 copies/mL through 4/2013, and after that the FDA-approved assay with LLOQ of 137 IU/mL. Medical records of first-time HSCT patients were reviewed. Pre-/peri-engraftment CMV was defined as detectable CMV DNA with [ANC] < 1000 cells/mm3. Information collected included demographics, donor/recipient CMV serostatus, conditioning regimen, CMV QPCR and ANC results, dates of CMV treatment, CMV disease within 100 days, and death within 6 months of HSCT. Data were analyzed with STATA v14. Results Of 1151 total HSCT, 76 patients had a positive CMV QPCR when ANC < 1000 cells/mm3. CMV was first detected a median of 12 days (0–48) post-transplant, and was above LLOQ at a median of 28 days (0–49). 71/76 (93%) were treated at a median of 33 days post-transplant (range 4–105 days), most with valganciclovir (40) or ganciclovir (30); 1 received foscarnet initially. 5 patients with low-level viremia were monitored without treatment. At initiation of therapy, median CMV level was 1471 (range 159–22,900) copies or IU/mL and ANC was 1202 (range 28–9680) cells/mm3. Median treatment duration was 34 days (range 9–392). Only 2 patients had possible tissue-invasive CMV disease. Conclusion Ganciclovir and valganciclovir were used to treat most pre- and peri-engraftment CMV viremia, despite potential bone marrow toxicity. The LLOQ of different CMV QPCR tests did not affect the viral threshold for starting treatment. The time between first CMV DNA detection (median day +12) and initiation of treatment (median day +33) suggests clinicians waited for CMV DNA and/or ANC to rise before treating. With this deferred-treatment approach, the proportion of patients with tissue-invasive disease remained low. Disclosures All authors: No reported disclosures.

Download Full-text