Retroviral gene transfer in autologous bone marrow transplantation for adult acute leukemia

Kenneth Cornetta, Edward F. Srour, Ann Moore, Amy Davidson, E. Randolph Broun, Robert A Hromas, Robert C. Moen, Richard A. Morgan, Lorraine Rubin, W. French Anderson, Ronald Hoffman, Guido Tricot

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

To evaluate whether marrow contributes to relapse after autologous bone marrow transplantation (AuBMT) for acute leukemia, transplanted marrow was marked with the G1N retroviral vector (Genetic Therapy Inc.) containing the neomycin phosphotransferase gene (neo). Between April 1992 and August 1993, 4 patients were transplanted for acute myeloid leukemia (AML) in second complete remission (CR) and 1 patient for acute lymphoid leukemia in first CR. An average of 12.4% (range 5-19%) of transplanted marrow mononuclear cells were exposed to G1N vector for 4 hr. In the vector-treated portion of the marrow, 4.9% of GM-CFU and 3.6% of erythroid burst-forming units (BFU-E) were resistant to G418 in vitro. In the 5 patients, the polymerase chain reaction (PCR) detected the neo sequence on only two occasions after AuBMT. Of 4 patients surviving 1 year after transplantation, only 1 had evidence of gene marked cells by PCR. Two AML patients have relapsed, one of whom had evidence of neo sequences in the bone marrow at day 100 but not at relapse 11 months after AuBMT. The second patient relapsed 18 months after AuBMT but never had PCR evidence of neo sequences before or after relapse. Our results indicate vector-transduced autologous bone marrow from heavily pretreated adults with acute leukemia mark with low efficiency, although vector sequences have been detected in bone marrow and peripheral blood up to 1 year after transplant. Of the 2 relapsed patients, no evidence of vector-marked leukemic blasts have been detected.

Original languageEnglish (US)
Pages (from-to)1323-1329
Number of pages7
JournalHuman Gene Therapy
Volume7
Issue number11
DOIs
StatePublished - Jul 10 1996
Externally publishedYes

Fingerprint

Autologous Transplantation
Bone Marrow Transplantation
Leukemia
Bone Marrow
Genes
Erythroid Precursor Cells
Acute Myeloid Leukemia
Recurrence
Polymerase Chain Reaction
Kanamycin Kinase
Granulocyte-Macrophage Progenitor Cells
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Genetic Therapy
Transplantation
Transplants

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Cornetta, K., Srour, E. F., Moore, A., Davidson, A., Broun, E. R., Hromas, R. A., ... Tricot, G. (1996). Retroviral gene transfer in autologous bone marrow transplantation for adult acute leukemia. Human Gene Therapy, 7(11), 1323-1329. https://doi.org/10.1089/hum.1996.7.11-1323

Retroviral gene transfer in autologous bone marrow transplantation for adult acute leukemia. / Cornetta, Kenneth; Srour, Edward F.; Moore, Ann; Davidson, Amy; Broun, E. Randolph; Hromas, Robert A; Moen, Robert C.; Morgan, Richard A.; Rubin, Lorraine; Anderson, W. French; Hoffman, Ronald; Tricot, Guido.

In: Human Gene Therapy, Vol. 7, No. 11, 10.07.1996, p. 1323-1329.

Research output: Contribution to journalArticle

Cornetta, K, Srour, EF, Moore, A, Davidson, A, Broun, ER, Hromas, RA, Moen, RC, Morgan, RA, Rubin, L, Anderson, WF, Hoffman, R & Tricot, G 1996, 'Retroviral gene transfer in autologous bone marrow transplantation for adult acute leukemia', Human Gene Therapy, vol. 7, no. 11, pp. 1323-1329. https://doi.org/10.1089/hum.1996.7.11-1323
Cornetta, Kenneth ; Srour, Edward F. ; Moore, Ann ; Davidson, Amy ; Broun, E. Randolph ; Hromas, Robert A ; Moen, Robert C. ; Morgan, Richard A. ; Rubin, Lorraine ; Anderson, W. French ; Hoffman, Ronald ; Tricot, Guido. / Retroviral gene transfer in autologous bone marrow transplantation for adult acute leukemia. In: Human Gene Therapy. 1996 ; Vol. 7, No. 11. pp. 1323-1329.
@article{f688f9174ed1421c93d27dbcd161844c,
title = "Retroviral gene transfer in autologous bone marrow transplantation for adult acute leukemia",
abstract = "To evaluate whether marrow contributes to relapse after autologous bone marrow transplantation (AuBMT) for acute leukemia, transplanted marrow was marked with the G1N retroviral vector (Genetic Therapy Inc.) containing the neomycin phosphotransferase gene (neo). Between April 1992 and August 1993, 4 patients were transplanted for acute myeloid leukemia (AML) in second complete remission (CR) and 1 patient for acute lymphoid leukemia in first CR. An average of 12.4{\%} (range 5-19{\%}) of transplanted marrow mononuclear cells were exposed to G1N vector for 4 hr. In the vector-treated portion of the marrow, 4.9{\%} of GM-CFU and 3.6{\%} of erythroid burst-forming units (BFU-E) were resistant to G418 in vitro. In the 5 patients, the polymerase chain reaction (PCR) detected the neo sequence on only two occasions after AuBMT. Of 4 patients surviving 1 year after transplantation, only 1 had evidence of gene marked cells by PCR. Two AML patients have relapsed, one of whom had evidence of neo sequences in the bone marrow at day 100 but not at relapse 11 months after AuBMT. The second patient relapsed 18 months after AuBMT but never had PCR evidence of neo sequences before or after relapse. Our results indicate vector-transduced autologous bone marrow from heavily pretreated adults with acute leukemia mark with low efficiency, although vector sequences have been detected in bone marrow and peripheral blood up to 1 year after transplant. Of the 2 relapsed patients, no evidence of vector-marked leukemic blasts have been detected.",
author = "Kenneth Cornetta and Srour, {Edward F.} and Ann Moore and Amy Davidson and Broun, {E. Randolph} and Hromas, {Robert A} and Moen, {Robert C.} and Morgan, {Richard A.} and Lorraine Rubin and Anderson, {W. French} and Ronald Hoffman and Guido Tricot",
year = "1996",
month = "7",
day = "10",
doi = "10.1089/hum.1996.7.11-1323",
language = "English (US)",
volume = "7",
pages = "1323--1329",
journal = "Human Gene Therapy",
issn = "1043-0342",
publisher = "Mary Ann Liebert Inc.",
number = "11",

}

TY - JOUR

T1 - Retroviral gene transfer in autologous bone marrow transplantation for adult acute leukemia

AU - Cornetta, Kenneth

AU - Srour, Edward F.

AU - Moore, Ann

AU - Davidson, Amy

AU - Broun, E. Randolph

AU - Hromas, Robert A

AU - Moen, Robert C.

AU - Morgan, Richard A.

AU - Rubin, Lorraine

AU - Anderson, W. French

AU - Hoffman, Ronald

AU - Tricot, Guido

PY - 1996/7/10

Y1 - 1996/7/10

N2 - To evaluate whether marrow contributes to relapse after autologous bone marrow transplantation (AuBMT) for acute leukemia, transplanted marrow was marked with the G1N retroviral vector (Genetic Therapy Inc.) containing the neomycin phosphotransferase gene (neo). Between April 1992 and August 1993, 4 patients were transplanted for acute myeloid leukemia (AML) in second complete remission (CR) and 1 patient for acute lymphoid leukemia in first CR. An average of 12.4% (range 5-19%) of transplanted marrow mononuclear cells were exposed to G1N vector for 4 hr. In the vector-treated portion of the marrow, 4.9% of GM-CFU and 3.6% of erythroid burst-forming units (BFU-E) were resistant to G418 in vitro. In the 5 patients, the polymerase chain reaction (PCR) detected the neo sequence on only two occasions after AuBMT. Of 4 patients surviving 1 year after transplantation, only 1 had evidence of gene marked cells by PCR. Two AML patients have relapsed, one of whom had evidence of neo sequences in the bone marrow at day 100 but not at relapse 11 months after AuBMT. The second patient relapsed 18 months after AuBMT but never had PCR evidence of neo sequences before or after relapse. Our results indicate vector-transduced autologous bone marrow from heavily pretreated adults with acute leukemia mark with low efficiency, although vector sequences have been detected in bone marrow and peripheral blood up to 1 year after transplant. Of the 2 relapsed patients, no evidence of vector-marked leukemic blasts have been detected.

AB - To evaluate whether marrow contributes to relapse after autologous bone marrow transplantation (AuBMT) for acute leukemia, transplanted marrow was marked with the G1N retroviral vector (Genetic Therapy Inc.) containing the neomycin phosphotransferase gene (neo). Between April 1992 and August 1993, 4 patients were transplanted for acute myeloid leukemia (AML) in second complete remission (CR) and 1 patient for acute lymphoid leukemia in first CR. An average of 12.4% (range 5-19%) of transplanted marrow mononuclear cells were exposed to G1N vector for 4 hr. In the vector-treated portion of the marrow, 4.9% of GM-CFU and 3.6% of erythroid burst-forming units (BFU-E) were resistant to G418 in vitro. In the 5 patients, the polymerase chain reaction (PCR) detected the neo sequence on only two occasions after AuBMT. Of 4 patients surviving 1 year after transplantation, only 1 had evidence of gene marked cells by PCR. Two AML patients have relapsed, one of whom had evidence of neo sequences in the bone marrow at day 100 but not at relapse 11 months after AuBMT. The second patient relapsed 18 months after AuBMT but never had PCR evidence of neo sequences before or after relapse. Our results indicate vector-transduced autologous bone marrow from heavily pretreated adults with acute leukemia mark with low efficiency, although vector sequences have been detected in bone marrow and peripheral blood up to 1 year after transplant. Of the 2 relapsed patients, no evidence of vector-marked leukemic blasts have been detected.

UR - http://www.scopus.com/inward/record.url?scp=19244362468&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=19244362468&partnerID=8YFLogxK

U2 - 10.1089/hum.1996.7.11-1323

DO - 10.1089/hum.1996.7.11-1323

M3 - Article

C2 - 8818719

AN - SCOPUS:19244362468

VL - 7

SP - 1323

EP - 1329

JO - Human Gene Therapy

JF - Human Gene Therapy

SN - 1043-0342

IS - 11

ER -