Humoral Responses and Chronic GVHD Exacerbation after COVID-19 Vaccination Post Allogeneic Stem Cell Transplantation

Abstract

The COVID-19 pandemic threatens patients with a compromised immune and endothelial system, including patients who underwent allogeneic stem cell transplantation (alloSCT). Thus, there is an unmet need for optimizing vaccination management in this high-risk cohort. Here, we monitored antibodies against SARS-CoV-2 spike protein (anti-S1) in 167 vaccinated alloSCT patients. Humoral immune responses were detectable in 81% of patients after two vaccinations with either mRNA-, vector-based, or heterologous regimens. Age, B-cell counts, time interval from vaccination, and the type of vaccine determined antibody titres in patients without systemic immunosuppression (sIS). Similar to a healthy control cohort, mRNA vaccine-based regimens induced higher titres than vector-based vaccines. Patients on two or more immunosuppressants rarely developed immunity. In contrast, 62% and 45% of patients without or on only one immunosuppressant, respectively, showed a strong humoral vaccination response (titre > 100). Exacerbation of cGVHD upon vaccination was observed in 6% of all patients and in 22% of patients receiving immunosuppression for cGVHD. cGVHD exacerbation and low antibody titres were both associated with higher angiopoietin-2 (ANG2) serum levels. In conclusion, mRNA-based vaccines elicit strong humoral responses in alloSCT patients in the absence of double sIS. Biomarkers such as ANG2 might help with weighing cGVHD risk versus beneficial responses.

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

“…Siemens SARS-CoV-2 IgG (Siemens sCOVG); ≥ 1.0 U/ml 5. Wantai SARS-CoV-2 IgG ELISA (Wantai S IgG) ≥ 0.75 AU/ml Amandine Le Bourgeois [ 46 ] France/2021 2 117 (117) Allo-HSCT No AML, MDS, MF, MDS/MF, CML, BPDCN, NHL, HL, ALL, MM, NNAA, porphyria 57 (20–75) 40.0% BNT162b2 35 (18–77) days Elecsys anti–SARS-CoV-2-S (Roche Elecsys, Rotkreuz, Switzerland); ≥ 0.8 U/mL Amandine Le Bourgeois-2 [ 44 ] France/2021 3 80 (80) Allo-HSCT 25 (25) Healthy controls myeloid, lymphoid, others 57 (20–75) 43.8% BNT162b2 94.5 (55–220) days Elecsys anti–SARS-CoV-2-S (Roche Elecsys, Rotkreuz, Switzerland); ≥ 0.8 U/mL Anne-Claire Mamez [ 43 ] Switzerland/2021 2 63 (63) Allo-HSCT No Acute leukemia, MDS/MPS, lymphoid diseases, hemoglobinopathie 54 (18–78) 38.0% BNT162b2; mRNA-1273 38 (13–98) days Semi-quantitative Elecsys ® Anti-SARSCoV-2 immunoassay (Roche); ≥ 0.8 U/mL Binod Dhakal [ 47 ] US/2021 1, 2 71 (71) Allo-HSCT; 45 (45) Auto-HSCT; 14 (14) CAR T No lymphoma, myeloma, some were not reported 25–77 not reported BNT162b2; mRNA-1273; Ad26.COV2.S ≥ 2 weeks Enzyme immunoassay testing antibodies to the S1 domain of the SARS-CoV-2 spike protein (EUROIMMUN) Caroline Pabst [ 24 ...…”

Predictors of Covid-19 Vaccination Response After In-Vivo T-Cell–Depleted Stem Cell Transplantation

“… 6 As summarized in Table 4 , responses are consistently worse in those vaccinated within the first six months to one year after transplantation. 8 , 9 , 14 , 16 , 18 , 22 , 23 , 24 , 25 , 30 , 66 Low lymphocyte counts, 8 , 23 , 29 , 66 low B cell 22 , 24 , 25 , 28 or NK cell counts, low CD4 counts 28 , low CD/CD8 ratio 24 , or low immunoglobulin levels 12 , 28 , 29 are all associated with poor response. Worse responses are found in those with GVHD, 9 , 10 , 23 , 30 those receiving immunosuppressants (particularly ibrutinib and ruxolitinib) 8 , 11 , 12 , 17 , 21 , 22 , 26 , 30 , 66 and those under active treatment for their underlying disease.…”

“… 8 , 9 , 14 , 16 , 18 , 22 , 23 , 24 , 25 , 30 , 66 Low lymphocyte counts, 8 , 23 , 29 , 66 low B cell 22 , 24 , 25 , 28 or NK cell counts, low CD4 counts 28 , low CD/CD8 ratio 24 , or low immunoglobulin levels 12 , 28 , 29 are all associated with poor response. Worse responses are found in those with GVHD, 9 , 10 , 23 , 30 those receiving immunosuppressants (particularly ibrutinib and ruxolitinib) 8 , 11 , 12 , 17 , 21 , 22 , 26 , 30 , 66 and those under active treatment for their underlying disease. 8 , 66 Other less frequently mentioned or examined predictors include recent exposure to rituximab, 10 , 23 reduced intensity conditioning 26 , receiving ATG in conditioning, 16 , 18 older recipient age, 10 , 16 , 18 , 22 , male gender.…”

“…Worse responses are found in those with GVHD, 9 , 10 , 23 , 30 those receiving immunosuppressants (particularly ibrutinib and ruxolitinib) 8 , 11 , 12 , 17 , 21 , 22 , 26 , 30 , 66 and those under active treatment for their underlying disease. 8 , 66 Other less frequently mentioned or examined predictors include recent exposure to rituximab, 10 , 23 reduced intensity conditioning 26 , receiving ATG in conditioning, 16 , 18 older recipient age, 10 , 16 , 18 , 22 , male gender. 15 , 24 Having had a prior episode of COVID-19 may be a predictor of better response.…”

“…Recent reports on covid-19 vaccination in allogeneic transplant recipients have shown encouraging results. 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 But nearly all published data pertain to patients undergoing stem cell transplantation from adult donors. Conditioning regimens or graft versus host disease (GVHD) prophylaxis are usually not detailed.…”