Serologic response and safety of COVID-19 vaccination in HSCT or CAR T-cell recipients: a systematic review and meta-analysis

Abstract

Background Patients receiving hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T cell (CAR T-cell) therapy are immunocompromised and at high risk of viral infection, including SAR2-CoV-2 infection. However, the effectiveness and safety of COVID-19 vaccines in these recipients is not well characterized. The present meta-analysis evaluated the serologic response and safety of COVID-19 vaccines in these population. Methods Literature databases (MEDLINE, EMBASE, Web of Science, MedRvix and BioRvix) were searched for original studies with serologic response post COVID-19 vaccination in HSCT or CAR T-cell recipients published until July 14, 2022. The analysis included 27 observational studies with a total of 2899 patients receiving allogeneic HSCT (2506), autologous HSCT (286) or CAR T-cell therapy (107), and 683 healthy participants with serologic response data. Random effects models were used to pool the rate of serologic response to COVID-19 vaccination in HSCT or CAR T-cell recipients and odds ratio comparing with healthy controls. Results The pooled seropositivity rates in HSCT and CAR T-cell recipients were 0.624 [0.506–0.729] for one dose, 0.745 [0.712–0.776] for two doses. The rates were significantly lower than those in healthy controls (nearly 100%). In subgroup analysis, CAR T-cell recipients exhibited an even lower seroconversion rate (one dose: 0.204 [0.094–0.386]; two doses: 0.277 [0.190–0.386]) than HSCT counterparts (one dose: 0.779 [0.666–0.862]; two doses: 0.793 [0.762–0.821]). The rates were comparable between autologous and allogeneic HSCT recipients. Other possible impact factors related to seropositivity were time interval between therapy and vaccination, use of immunosuppressive drugs and immune cell counts. Most vaccine-related adverse effects were mild and resolvable, comparable to general population. Conclusions This analysis revealed a diminished response to COVID-19 vaccines in HSCT or CAR T-cell recipients. Our findings may inform regular COVID-19 vaccination at appropriate intervals after HSCT or CAR T-cell therapy.

A Third Dose COVID-19 Vaccination in Allogeneic Hematopoietic Stem Cell Transplantation Patients

“…Some patients had an extremely low antibody titer, which was associated with low serum IgG, low lymphocyte count, or with or without immunosuppressants and steroids [3]. Several studies reported seroconversion rates of 75-86% in allogeneic HSCT patients [5,[9][10][11], and a recent meta-analysis study also revealed a diminished response in HSCT patients [6]. Regarding the third vaccination, Kimura et al reported that 89% of allogeneic HSCT patients obtained seroconversion after the third dose of vaccine [12].…”

“…Several reports revealed that some immunocompromised hosts, such as patients taking immunosuppressive agents or with hematological disease, had difficulty obtaining immunogenicity and that antibody titers against the S1 spike protein decreased early [4,5]. A recent systematic review and meta-analysis has shown that immune response to COVID-19 vaccines is impaired in HSCT patients, with a seropositive proportion after the second dose of about 79% [6]. Although a booster shot (third dose of vaccine) is widely accepted, research into the booster shot in HSCT patients remains unsatisfactory.…”

Humoral response and safety of the BNT162b2 and mRNA-1273 COVID-19 vaccines in allogeneic hematopoietic stem cell transplant recipients: An observational study

“…In addition to a short time interval between allo-HSCT and vaccination [ 11 , 16 , 17 ], various factors, such as conditioning regimen (e.g., reduced intensity conditioning) [ 16 ], donor type (e.g., haploidentical donors) [ 10 , 16 , 17 ], immunosuppressant intake [ 11 , 12 , [17] , [18] , [19] ], GVHD presence [ 16 ], hypogammaglobulinemia [ 15 , 19 ], and lymphocytopenia [ 10 , 11 , 15 , 17 , 19 , 20 ] have been proposed as the potential predictors of impaired humoral response. Our study indicates that immunosuppressive agent use, hypogammaglobulinemia, lymphocytopenia, and low B-cell fraction (<3%) is associated with impaired humoral response, which is in line with some previous reports.…”

A Third Dose COVID-19 Vaccination in Allogeneic Hematopoietic Stem Cell Transplantation Patients

“…3 Several studies reported seroconversion rates of 75-86% in allogeneic HSCT patients, 5 9 10 11 and a recent meta-analysis study also revealed a diminished response in HSCT patients. 6 Regarding the third vaccination, Kimura et al reported that 89% of allogeneic HSCT patients obtained seroconversion after the third dose of vaccine. 12 They pointed out that chronic kidney disease, haploidentical donor status, and median lymphocyte counts at the third dose were significantly associated with suboptimal antibody response.…”

“…4,5 A recent systematic review and meta-analysis has shown that immune response to COVID-19 vaccines is impaired in HSCT patients, with a seropositive proportion after the second dose of about 79%. 6 Although a booster shot (third dose of vaccine) is widely accepted, research into the booster shot in HSCT patients remains unsatisfactory.…”