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Role of Marrow Purging
AUTOLOGOUS BONE MARROW TRANSPLANTATION IN ACUTE
LEUKEMIA: THE ROLE OF MARROW PURGING
N.C. Gorin
Department of Hematology, Hôpital Saint Antoine, Paris, France
INTRODUCTION
Allogeneic bone marrow transplantation (BMT) has improved the prognosis
of acute leukemia in patients with HLA identical siblings. As an alternative,
in the past decade, several teams including ours, have developed autologous
bone marrow transplantation (ABMT) to allow high dose consolidation therapy
in an effort to offer a similar chance to most patients with no available donor.
Results of ABMT from various institutions and the European Registry indicate
that this goal may have been reached and, further, the possibility to extend
ABMT even to patients who are candidates for alio BMT is being considered.
Despite the clear demonstration in numerous animal models of the
efficacy of marrow purging in reducing leukemic cell contamination in marrow
collected in complete remission (CR) or in artificial marrow tumor cell
mixtures, resulting in cure of leukemia by ABMT in these models, the
important question of the efficacy of marrow purging in the human situation has
remained unanswered for several years. This situation has dramatically
changed in 1988 when for the first time the analysis of the European registry
demonstrated the value of marrow purging with mafosfamide in acute
myelocytic leukemia (AML) autografted in first remission (CR1) (1). Later,
this demonstration was confirmed by the 1989 (2) survey, and further extended
by the last EBMT analysis presented in May 1990 in the Hague. We will
summarize these data in a first part. In a second part, we wish to report on the
present status of our own trial in Hopital Saint Antoine Paris in 100 patients
with AML and ALL receiving marrow purged with mafosfamide at a level
individually adjusted, defined as the CFUGM LD 95 which spares 5 +_ 5 %
CFUGM. We found that the relapse rate was significantly related to the
residual amount of CFUGM progenitors in the marrow after purging. We
interpreted these data as indirect evidence that the outcome of patients
autografted is indeed dependent of the quality of the marrow infused (3).