Hematopoietic Retroviral Gene Marking in Patients with Follicular Non-Hodgkin's Lymphoma

Hematopoietic Retroviral Gene Marking in Patients with Follicular Non-Hodgkin's Lymphoma

We conducted a double retroviral vector (RV) gene marking trial to test for the possible contribution to relapse of follicular non-Hodgkin's lymphoma (FNHL) cells present in bone marrow (BM) and peripheral blood (PB) grafts used for hematopoietic reconstitution of patients undergoing myelaoblat...

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Bibliographic Details
Published in:Leukemia & lymphoma Vol. 32; no. 3-4; pp. 279 - 288
Main Authors: Bachier, Carlos R., Giles, Richard E., Ellerson, Deborah, Hanania, Ellie G., Garcia-Sanchez, Felix, Andreeff, Michael, Cabanillas, Fernando, Champlin, Richard, Choudhury, Raja, Berenson, Ronald, Heimfeld, Shelly, Deisseroth, Albert B.
Format: Journal Article
Language:English
Published: United States Informa UK Ltd 1999
Taylor & Francis
Subjects:
Adult
Antigens, CD34 - analysis
Bone Marrow Transplantation - adverse effects
follicular non-hodgkin's lymphoma
Genetic Vectors
Graft Survival
hematopietic gene marking
Hematopoietic Stem Cell Transplantation - adverse effects
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - immunology
Hematopoietic Stem Cells - virology
Humans
Lymphoma, Follicular - genetics
Lymphoma, Follicular - therapy
Middle Aged
retroviral gene marking
Retroviridae - genetics
Retrovirus
Transduction, Genetic
Treatment Outcome
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Summary:We conducted a double retroviral vector (RV) gene marking trial to test for the possible contribution to relapse of follicular non-Hodgkin's lymphoma (FNHL) cells present in bone marrow (BM) and peripheral blood (PB) grafts used for hematopoietic reconstitution of patients undergoing myelaoblative chemotherapy and autologous transplant. CD34 positive selection using the CellPro Ceprate CD34 column was performed on PB mononuclear cells obtained after cyclophosphamide/G-CSF mobilization. CD34 positive cells were exposed for 4-6 hours to the LNL6 or G1 Na RV in the absence of growth factors or stromal monolayers. One week later, BM mononuclear cells were similarly processed. Patients then received total body irradiation (TBI), cyclophosphamide, and etoposide followed by infusion of both PB and BM CD34 positive cells. Semiquantitative Southern blot analysis of DNA t(14;18) amplification products showed approximately a three log reduction in t(14;18) positive cells after CD34 positive selection. The first patient showed evidence of engraftment with RV positive BM and PB cells for 9 months. He relapsed one year after transplant. At relapse, one year after transplant, he had lost evidence of RV positive cells in ficolled mononuclear BM and PB cells as well as in CD19 positive cells. The second and third patients showed evidence of engraftment with RV positive cells up to 9 and 6 months post BMT respectively. The second and third patients are still in clinical remission. Our results demonstrate engraftment of RV transduced hematopoietic cells in the PB and BM for up to 9 months.
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ISSN:1042-8194
1029-2403
DOI:10.3109/10428199909167388