undertaken with monoclonal antibodies, with cytotoxic agents active in vitro, 
or by physicochemical means. In animal and pre-clinical human studies all of 
these methods reduce contamination with malignant cells -if these are 
deliberately added to the marrow, but none have been shown to reduce the 
risk of relapse in naturally occurring disease. Marrow for ABMT is harvested 
in remission when - by definition - no malignant cells are detectable. It is 
therefore impossible to undertake any form of quality control to determine if 
residual malignant cells have genuinely been eliminated. Moreover, there is 
no evidence that malignant cells with the ability to reestablish the malignancy 
after ABMT are physically, phenotypically, or biochemically identical to the 
cells of the "mature” tumor. At present, therefore, the justification for and 
practicality of bone marrow purging largely remain matters of faith. This is 
cause for considerable concern. The techniques of purging almost invariably 
damage normal progenitor cells, so that the engraftment of purged marrow is 
generally substantially slower than the engraftment of untreated marrow. 
Morbidity and mortality from the complications of hemopoietic and immune 
system failure are correspondingly increased. 
2.4 Biology of Autologous Reconstitution 
Little is known in man of the fundamental biology of autologous marrow graft 
recovery. It is unknown whether the cryopreserved marrow contains viable 
stem cells which subsequently reconstitute the patient, or whether the 
autograft simply provides temporary replenishment of committed progenitor 
cells whilst surviving host stem cells gradually repopulate the individual. If 
hauvested marrow does contain stem cells, nothing is known of the in vivo 
signals which modify their entry into cell cycle or which modulate proliferation 
versus lineage commitment. This lack of knowledge hampers efforts to 
improve the speed and effectiveness with which autologous marrow 
reconstitutes the patient. Even though large volumes of marrow may be taken, 
patients may still suffer prolonged marrow hypoplasia and immune 
dysfunction. If ABMT cures patients by virtue of the more intensive chemo- 
radiotherapy it permits, then multiple ABMT might cure a higher proportion 
of patients. This approach cannot readily be contemplated until techniques 
which improve marrow regeneration are available, as the procedure related 
morbidity and mortality would otherwise be unacceptably high. 
3.0 RATIONALE FOR CURRENT PROPOSAL 
The most recent protocols for the therapy for AML have used dramatically different 
approaches to eliminate residual marrow disease after patients achieved a CR. In 
AML-80, one year of intensive post remission chemotherapy resulted in multiple 
episodes of marrow hypoplasia. The alternative approach of relatively continuous 
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