Page 292 - Haematologica Vol. 109 - July 2024

LETTER TO THE EDITOR
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Figure 2. Levels and memory phenotypes of functional cytomegalovirus-specific T cells in the Triplex-vaccinated pediatric re- cipients. (A) Longitudinal levels of combined CD137+CD3+ CD4+ and CD137+CD3+ CD8+ T cells specific for pp65, IE1 and IE2 antigens (as specified at the top of each plot). The band shown was computed using the loess scatterplot smoother providing the mar- ginal geometric mean concentrations through time. A 95% confidence band is shown in gray, and individual measurement trajec- tories are shown for each participant up to 7 days before cytomegalovirus (CMV) reactivation, requiring antivirals (COH002 and COH011). Linear mixed models were used to evaluate the changes on log10-transformed concentration of CMV-specific T cells from day 28 through day 270. Both linear and quadratic terms of study days were included in the models on CMV-specific T cells. An autoregressive covariance matrix was used to account for the correlation in participant’s T-cell responses over time. Loga- rithmic spacing is used to aid visualization. Arrows indicate Triplex injections on days 28 and 56 post-transplant. (B) Box plots showing percentages on the arcsine scale of pp65-specific, CD137+CD8+ naïve, T central (TCM) and effector (TEM + TEMRA) mem- ory phenotype subset (as indicated at the top of each plot). The box spans the interquartile range, the central bar shows the median, and the whiskers extend to 1.5-times the interquartile range. Percentages of memory subsets from day 28 though day 270 were evaluated using linear mixed models and study day was included as a categorical predictor.
Authors
Corinna La Rosa,1 Yoonsuh Park,1 Dongyun Yang,1 Qiao Zhou,1 Teodora Kaltcheva,1 Nicole Karras,2 Jerry Cheng,2 Weili Sun,3 Don J. Diamond1# and Anna Pawlowska2#
1Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA; 2Department of Pediatrics, City of Hope National Medical Center, Duarte, CA and 3The Janssen Pharmaceutical Companies of Johnson & Johnson, Los Angeles, CA, USA
#AP and DJD contributed equally as senior authors.
Correspondence:
C. LA ROSA - clarosa@coh.org
https://doi.org/10.3324/haematol.2023.284256
feasibility and safety of vaccinating immunosuppressed pediatric patients with Triplex. The encouraging preliminary results suggest that in HCT pediatric patients receiving letermovir prophylaxis, Triplex safely expands large num- bers of long lasting functional CMV-specific T cells early post-transplant, which may prevent subsequent CMV reactivation requiring PET. The current key outcomes laid the groundwork for the planning of a multicenter, randomized placebo-controlled phase II trial. Though Triplex vaccination can overcome the letermovir-induced immune impairment,10 our long-term goal is to eliminate this daily oral medication for young patients who already have polypharmacy burdens. Novel successful strategies of vaccinating the immunocompetent HCT donor and pos- sibly also the recipient with Triplex may suffice to prevent CMV reactivation by promoting early post-HCT sustained, protective CMV-immune reconstitution.
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