Humoral immunity to viral and bacterial antigens in lymphoma patients 4–10 years after high-dose therapy with ABMT. Serological responses to revaccinations according to EBMT guidelines

Abstract

Summary:The aim of this study was to investigate the late effects of ABMT on the immune system with regard to protective humoral immunity against common antigens and responses to recall antigens (vaccines). The vaccines were given according to EBMT guidelines from 1995. The protocol included 35 patients with malignant lymphoma in CR 4-10 years after ABMT, and 35 controls. The results show that prior to ABMT the proportion of patients with protective immunity against poliomyelitis, tetanus and diphtheria was similar to that of controls. At study entry 4-10 years after ABMT, the proportion of patients with protective immunity against poliomyelitis and diphtheria was reduced, while all patients maintained protection against tetanus. A significant decrease in geometric mean antibody concentrations or titres was observed against all three antigens during this period. Serum levels of antibodies against different pneumococcal serotypes were lower in the patients than in the controls prior to vaccination. The responses to pneumococcal vaccination, which is considered to be a T cellindependent vaccine, were studied. Unlike controls, a minority of patients achieved protective levels of antibodies after a single vaccination. Despite persistent levels of protective antibodies in many patients post ABMT, secondary booster responses after one vaccination with T cell-dependent vaccines (tetanus, diphtheria and polio) were absent. In conclusion, this study shows that post ABMT, a full re-vaccination program was necessary to mount responses comparable to those observed after a single vaccination in controls. Bone Marrow Transplantation (2001) 28, 681-687.

Vaccination of stem cell transplant recipients: recommendations of the Infectious Diseases Working Party of the EBMT

“…In autologous SCT recipients, the response to a single dose of pneumococcal polysaccharide vaccine is poor regardless of the stem cell source 5,9 and remains decreased for several years after transplantation for lymphoma as compared to controls. 24 There is no advantage in vaccinating autologous SCT patients before stem cell harvest with pneumococcal polysaccharide-based vaccine. 25 Thus, vaccination responses to the polysaccharide vaccines are suboptimal in many autologous SCT recipients, especially lymphoma patients.…”

Increased Plasma-Immune Cytokines throughout the High-Dose Melphalan-Induced Lymphodepletion in Patients with Multiple Myeloma: A Window for Adoptive Immunotherapy

“…However, ASCT current procedures allow hematopoiesis reconstitution but do not support efficient immune reconstitution, leaving patients more susceptible to infections. HDM induces severe and persistent immunosuppression characterized by a delayed recovery of CD4 T cells that remain below normal counts for months to years after ASCT (2,3), a restricted T cell repertoire (4), and impaired T cell functions, including an increased susceptibility to apoptosis (5), a reduced proliferation intensity on stimulation with mitogens or defined Ags and a default in Th1 cytokine production that lasts at least 1 y post-ASCT in patients with MM (6,7). The B cell immune response is also altered after ASCT, because levels of plasma Abs after one recall vaccination are below those found in healthy donors (3).…”

Immunity for tumors and microbes after autotransplantation: if you build it, they will (not) come

“…13,22,[28][29][30][31] With the caveat that most of these studies included relatively small numbers of patients who were heterogeneous with respect to prior treatment, disease type and transplant therapy, several conclusions may be warranted: first, while immunizations with the pneumococcal polysaccharide vaccine at 12 and 24 months posttransplant are American Society for Blood and Marrow …”

“…Administration of the 23-valent pneumococcal vaccine to patients led to protective antibody levels in only 32-41% of patients depending on the serotype analyzed as compared to 80-94% of healthy controls. 22 When CD4 þ T cells do show recovery during the first year after high-dose therapy, it is mainly due to peripheral expansion of the limited number of mature memory cells (CD45RO þ CD4 þ ) which remain after chemotherapy or which may be reinfused with the stem cell graft; generation of CD45RA þ cells by thymic production appears to play a very minor role. 15 Furthermore, when these expanded CD45RO þ cells are stimulated in vitro by mitogens, susceptibility to apoptosis is significantly increased compared to normal donors.…”

“…However, even among patients who were in complete remission for 4-10 years after autologous transplants about one-third lacked protective immunity to diphtheria and poliovirus and nearly two-thirds lacked protection against S. pneumoniae. 22 Furthermore, single vaccinations to diphtheria and poliovirus elicited minimal responses (compared to healthy controls) although protective levels developed after a series of 3 vaccinations. Administration of the 23-valent pneumococcal vaccine to patients led to protective antibody levels in only 32-41% of patients depending on the serotype analyzed as compared to 80-94% of healthy controls.…”