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

Michael Robertson, Robert J. Soiffer, Arnold S. Freedman, Susan L. Rabinowe, Kenneth C. Anderson, Thomas J. Ervin, Christine Murray, Keith Dear, James D. Griffin, Lee M. Nadler, Jerome Ritz

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Abstract

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/μL was 43 days (range, 16 to 75), to achieve a platelet count greater than 20,000/μL 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/μL and greater than 1,000/μL 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.

Original languageEnglish (US)
Pages (from-to)2229-2236
Number of pages8
JournalBlood
Volume79
Issue number9
StatePublished - May 1 1992
Externally publishedYes

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Hematopoiesis
Autografts
Acute Myeloid Leukemia
Sialic Acid Binding Ig-like Lectin 3
Bone
Bone Marrow
Monoclonal Antibodies
Cells
Clinical Trials
Bone Marrow Transplantation
Macrophages
Therapeutics
Platelets
Stem cells
Allografts
Myeloid Progenitor Cells
Blood
Neutrophils
Erythrocyte Transfusion
Pluripotent Stem Cells

ASJC Scopus subject areas

  • Hematology

Cite this

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. / Robertson, Michael; Soiffer, Robert J.; Freedman, Arnold S.; Rabinowe, Susan L.; Anderson, Kenneth C.; Ervin, Thomas J.; Murray, Christine; Dear, Keith; Griffin, James D.; Nadler, Lee M.; Ritz, Jerome.

In: Blood, Vol. 79, No. 9, 01.05.1992, p. 2229-2236.

Research output: Contribution to journalArticle

Robertson, M, Soiffer, RJ, Freedman, AS, Rabinowe, SL, Anderson, KC, Ervin, TJ, Murray, C, Dear, K, Griffin, JD, Nadler, LM & Ritz, J 1992, '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', Blood, vol. 79, no. 9, pp. 2229-2236.
Robertson, Michael ; Soiffer, Robert J. ; Freedman, Arnold S. ; Rabinowe, Susan L. ; Anderson, Kenneth C. ; Ervin, Thomas J. ; Murray, Christine ; Dear, Keith ; Griffin, James D. ; Nadler, Lee M. ; Ritz, Jerome. / 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. In: Blood. 1992 ; Vol. 79, No. 9. pp. 2229-2236.
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abstract = "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/μL was 43 days (range, 16 to 75), to achieve a platelet count greater than 20,000/μL 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/μL and greater than 1,000/μL 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.",
author = "Michael Robertson and Soiffer, {Robert J.} and Freedman, {Arnold S.} and Rabinowe, {Susan L.} and Anderson, {Kenneth C.} and Ervin, {Thomas J.} and Christine Murray and Keith Dear and Griffin, {James D.} and Nadler, {Lee M.} and Jerome Ritz",
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N2 - 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/μL was 43 days (range, 16 to 75), to achieve a platelet count greater than 20,000/μL 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/μL and greater than 1,000/μL 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.

AB - 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/μL was 43 days (range, 16 to 75), to achieve a platelet count greater than 20,000/μL 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/μL and greater than 1,000/μL 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.

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