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Donor limitations: The key limiting factor in the use of BMT is the lack of donors.
Because only 25 to 30% of patients have an HLA-identical sibling, alternative donors are
often required. Two possibilities exist: (1) Marrow can be procured from unrelated living
donors; marrow donation is a simple, safe procedure. National and international registries
of prospective volunteer donors are being expanded to increase the likelihood of finding
an exact HLA match for any given recipient. (2) Related donors who are not HLA-identical
have been used with increasing frequency. Results with either procedure suggest long-term
disease-free survival probabilities of 30 to 50% in patients with acute and chronic
leukemia or aplastic anemia; ie, in most situations the results are somewhat inferior to
those with marrow from HLA-identical siblings. Another option for BMT is autologous
transplantation (removal of a patient's own marrow when a complete remission has been
induced, followed by ablative treatment of the patient with the hope of destruction of any
residual tumor and rescue with the patient's own bone marrow). Since an autograft is used,
no immunosuppression is necessary other than the short-term high-dose chemotherapy used
for tumor eradication and bone marrow ablation; posttransplant problems with GVHD are
minimal. Indications for autologous BMT are relapsed, chemotherapy-sensitive lymphoma, in
which a 30 to 40% success rate has been achieved, and acute leukemia in remission, in
which 20 to 50% success rates have been observed. Success rates are inferior with more
advanced disease and with responsive solid cancers (eg, breast or germ cell tumors). Two
major obstacles remain for successful application of autologous BMT: the possibility of
contamination of the marrow inoculum with tumor cells, and the absence of graft-vs.-tumor
activity (in contrast with that seen in allogeneic BMT), both of which contribute to the
observed higher rates of tumor recurrence. Thus, developing schemes for ex vivo marrow
purging and for recipient immune modulation posttransplant is an active area of research. |
