Longitudinal analysis of antibody response to immunization in paediatric survivors after allogeneic haematopoietic stem cell transplantation

Abstract

The long-term antibody responses to re-immunization in recipients of allogeneic haematopoietic stem cell transplantation (allo-HSCT) have not been well studied. We prospectively and longitudinally evaluated the antibody responses to eight vaccine antigens (diphtheria, tetanus, pertussis, measles, mumps, rubella, hepatitis B, and poliovirus) and assessed the factors associated with negative titres in 210 allo-HSCT recipients at St. Jude Children's Research Hospital. Antibody responses lasting for more than 5 years after immunization were observed in most patients for tetanus (95.7%), rubella (92.3%), poliovirus (97.9%), and, in diphtheria-tetanus-acellular pertussis (DTaP) recipients, diphtheria (100%). However, responses to pertussis (25.0%), measles (66.7%), mumps (61.5%), hepatitis B (72.9%), and diphtheria in tetanus-diphtheria (Td) recipients (48.6%) were less favourable, with either only transient antibody responses or persistently negative titres. Factors associated with vaccine failure were older age at immunization; lower CD3, CD4 or CD19 counts; higher IgM concentrations; positive recipient cytomegalovirus serology; negative titres before immunization; acute or chronic graft-versus-host disease; and radiation during preconditioning. These response patterns and clinical factors can be used to formulate re-immunization and monitoring strategies. Patients at risk for vaccine failure should have long-term follow-up; those with loss of antibody response or no seroconversion should receive booster immunizations.

Fig 1

Longitudinal changes in the percentage of patients with protective/positive antibodies for diphtheria, tetanus, and pertussis after immunization (A) and for diphtheria among DTaP and Td recipients (B). Error bars represent standard errors of proportion estimates.

Fig 2

Longitudinal changes in the percentage of patients with protective/positive antibodies for measles, mumps, and rubella (A); hepatitis B (B); and poliovirus types 1, 2, and 3 (C) after immunization. Error bars represent standard errors of proportion estimates.

Fig 3

Response patterns of patients for whom 3 or more measurements were available after immunization. Patients who maintained or acquired protective/positive antibodies (filled in black), had persistently negative titres (not filled), and lost protective/positive antibodies during follow-up (filled in grey).