Haematologica 2003 - Supplements

tumor detectable following transplantation. Vaccine based
strategies aimed at inducing a tumor-specific immune response at
the time of minimal residual disease are attractive in this setting
but rely on adequate immune reconstitution. When this is
achieved depends on the underlying disease, conditioning, stem
cell source (marrow or PBSC) and whether any manipulation of
graft has been used (purging or CD 34+ selection).
The aim of this study was to assess the ability of patients with
plasma cell disorders to generate antibody and cellular responses
to tetanus toxoid (TT) vaccination (0.5ml). Immune responses
were measured pre and 1 month post-vaccination. Our cohort
consisted of 15 myeloma patients at least 15 months post-ASCT,
1 patient who was 3 months post ASCT, 3 patients in plateau
phase after conventional chemotherapy, 2 patients with
smouldering myeloma and 8 patients with MGUS. The responses
of these patients were compared with those of 15 healthy
volunteers. Anti-TT antibodies were measured by ELISA and
cellular responses by a lymphoproliferation assay and interferon γ
elispot.
Each autograft patient had received melphalan, 200mg/m2 as
conditioning, followed by an unmanipulated peripheral blood
stem cell transplant. The median time since transplantation was
31 months (range 15-81). Only one patient was vaccinated with
TT in the post-transplant period prior to this study.
RESULTS: Similar to the fifteen healthy volunteers, transplant
recipients who were at least 15 months post-ASCT, boosted their
TT-antibodies post-vaccination. This included three who initially
had non-protective levels (3) pre-vaccination in 5 /15 myeloma patients who were at
least 15 months post-transplant. Each of these 5 raised their SI
post-vaccination. Overall, in this transplant group the assay was
positive in 12/15 post-vaccination. Three of the fifteen were
found to be negative pre- and post-vaccination. The elispot assay
was positive in 1/15 of these patients prior to vaccination and in
6/15 post-vaccination. One patient had a positive elispot but a
negative lymphoproliferative response post-vaccination. The
lymphoproliferative assay was negative both pre and postvaccination
in the patient who was only 3 months post-ASCT.
This result is consistent with published data on the lack of
numerical CD4 T cell recovery at this stage post-transplantion.
In the plateau group, the lymphoproliferation assay was positive
in 1/3 patients pre-vaccination and positive in 3/3 postvaccination.
Elispot results are available for one of
this group and were positive both pre and post-vaccination.
Five of the 8 MGUS patients had a positive lymphoproliferation
assay pre-vaccination and all were positive post-vaccination.
These results present new information on functional immune
reconstitution post-ASCT in myeloma and help to determine the
timing for vaccine-based immunotherapy in this setting.
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