Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

15
Bone Marrow Transplantation for Immune Therapy
Fabio Ciceri and Claudio Bordignon
15.1
Introduction
Allogeneic bone marrow transplantation (BMT), now otherwise defined as hematopoietic
cell transplantation (HCT), was initially considered for the treatment of malignancy
as a means to deliver supralethal doses of chemotherapy and total body radiation
[1±3]. Many malignancies exhibit a steep dose±response relationship to
chemo- or radiotherapy, with higher doses producing greater cytoreduction. BMT allows
escalation of doses of many agents beyond those producing severe bone marrow
toxicity. The marrow transplant was considered a supportive care modality to restore
hematopoiesis. It has become clear, however, that the high-dose therapy does
not eradicate the malignancy in many patients and that the therapeutic benefit of allogeneic
BMT is largely related to an associated immune-mediated graft-versus-malignancy
effect. In the last few years, the focus has shifted away from attempts at eradicating
malignant cells through high-dose chemoradiation therapy toward using
immunocompetent cells transplanted with the donor's stem cells, or arising from
them, to exert a potent graft-versus-tumor (GvT) effect. HCT is now definitely accepted
as an immunotherapeutic approach, rather than solely a vehicle to deliver
high-dose therapy [4].
15.2
Graft-versus-Host (GvH)Reactions
Cancer Immune Therapie: Current and Future Strategies
Edited by G. Stuhler and P. Walden
Copyright # 2002 Wiley-VCH Verlag GmbH & Co. KGaA
ISBNs: 3-527-30441-X (Hardback); 3-527-60079-5
(Electronic)
Two immunologic barriers must be crossed to establish successful HCT allografts.
The first consists of host-versus-graft (HvG) rejection and the second is made up of
GvH reactions. The immunosoppressive regimens used to overcome the HvG rejection
are administered before transplantation and are integrated into the high-dose
conditioning therapy. The regimens for overcoming GvH reactions deal with the
grafted donor immune cells and, accordingly, these treatments are delivered after
transplantation in order to prevent graft-versus-host disease (GvHD). This potentially
lethal complication of HCToccurs in 30±50% of patients undergoing HLA-matched-
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