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Human bone marrow depleted of CD33-positive cells mediates delayed but
durable reconstitution of hematopoiesis: clinical trial of MY9 monoclonal
antibody-purged autografts for the treatment of acute myeloid leukemia
MJ Robertson, RJ Soiffer, AS Freedman, SL Rabinowe, KC Anderson, TJ Ervin, C Murray, K Dear, JD Griffin and LM Nadler
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA
02115.
The CD33 antigen, identified by murine monoclonal antibody anti-MY9, is
expressed by clonogenic leukemic cells from almost all patients with acute
myeloid leukemia; it is also expressed by normal myeloid progenitor cells.
Twelve consecutive patients with de novo acute myeloid leukemia received
myeloablative therapy followed by infusion of autologous marrow previously
treated in vitro with anti-MY9 and complement. Anti-MY9 and complement
treatment eliminated virtually all committed myeloid progenitors
(colony-forming unit granulocyte- macrophage) from the autografts.
Nevertheless, in the absence of early relapse of leukemia, all patients
showed durable trilineage engraftment. The median interval post bone marrow
transplantation (BMT) required to achieve an absolute neutrophil count
greater than 500/microL was 43 days (range, 16 to 75), to achieve a
platelet count greater than 20,000/microL without transfusion was 92 days
(range, 35 to 679), and to achieve red blood cell transfusion independence
was 105 days (range, 37 to 670). At the time of BM harvest, 10 patients
were in second remission, one patient was in first remission, and one
patient was in third remission. Eight patients relapsed 3 to 18 months
after BMT. Four patients transplanted in second remission remain
disease-free 34+, 37+, 52+, and 57+ months after BMT. There was no
treatment-related mortality. Early engraftment was significantly delayed in
patients receiving CD33-purged autografts compared with concurrently
treated patients receiving CD9/CD10-purged autografts for acute
lymphoblastic leukemia or patients receiving CD6-purged allografts from
HLA- compatible sibling donors. In contrast, both groups of autograft
patients required a significantly longer time to achieve neutrophil counts
greater than 500/microL and greater than 1,000/microL than did patients
receiving normal allogeneic marrow. CD33(+)-committed myeloid progenitor
cells thus appear to play an important role in the early phase of
hematopoietic reconstitution after BMT. However, our results also show that
human marrow depleted of CD33+ cells can sustain durable engraftment after
myeloablative therapy, and provide further evidence that the CD33 antigen
is absent from the human pluripotent hematopoietic stem cell.
Volume 79,
Issue 9,
pp. 2229-2236,
05/01/1992
Copyright © 1992 by The American Society of Hematology
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