Hematopoietic recovery following high-dose combined alkylating-agent chemotherapy and autologous bone marrow support in patients in phase-I clinical trials of colony-stimulating factors: G-CSF, GM-CSF, IL-1, IL-2, M-CSF

Laughlin, Mary J.; Kirkpatrick, Gordon; Sabiston, N.; Peters, William P.; Kurtzberg, Joanne

doi:10.1007/bf01696346

Cited by 23 publications

(16 citation statements)

References 21 publications

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“…These observations are similar to those described by Laughlin et al, 26 who reported no relevant modifications of marrow regeneration using continous intravenous infusion of similar doses of IL-2 (40 000 Cetus units m 2 /day equivalent to 240 000 IU m 2 /day) early after BMT. Similarly, Meehan et al 27 observed no modification of engraftment time using higher IL-2 dosages (600 000 IU m 2 /day) subcutaneously.…”

Section: Discussionsupporting

confidence: 91%

Administration of low-dose interleukin-2 plus G-CSF/EPO early after autologous PBSC transplantation: effects on immune recovery and NK activity in a prospective study in women with breast and ovarian cancer

Perillo

Pierelli

Battaglia

et al. 2002

Bone Marrow Transplant

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Summary:This study evaluated the effects of low-dose IL-2 plus G-CSF/EPO on post-PBSC transplantation (PBSCT) immune-hematopoietic reconstitution and NK activity in patients with breast (BrCa) and ovarian cancer (OvCa). To this end, two consecutive series of patients were prospectively assigned to distinct post-PBSCT cytokine regimens (from day +1 to day +12) which consisted of G-CSF (5 g/kg/day) plus EPO (150 IU/kg/every other day) in 17 patients (13 BrCa and 4 OvCa) or G-CSF/EPO plus IL-2 (2 ؋ 10 5 IU/m 2 /day) in 15 patients (10 BrCa and 5 OvCa). Hematopoietic recovery and post-transplantation clinical courses were comparable in G-CSF/EPO-and in G-CSF/EPO plus IL-2-treated patients, without significant side-effects attributable to IL-2 administration. In the early and late post-transplant period a significantly higher PMN count was observed in G-CSF/EPO plus IL-2-treated patients (P ‫؍‬ 0.034 and P ‫؍‬ 0.040 on day +20 and +100, respectively). No significant differences were found between the two groups of patients in the kinetics of most lymphocyte subsets except naive CD45RA + T cells which had a delayed recovery in G-CSF/EPO plus IL-2 patients (P ‫؍‬ 0.021 on day +100). No significant difference was observed between NK activity in the two different groups, albeit a significantly higher NK count was observed in G-CSF/EPO plus IL-2 series on day +20 (P ‫؍‬ 0.020). These results demonstrate that low-dose IL-2 can be safely administered in combination with G-CSF/EPO early after PBSCT and that it exerts favorable effects on post-PBSCT myeloid reconstitution, but not on immune recovery.

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Section: Discussionsupporting

confidence: 91%

Administration of low-dose interleukin-2 plus G-CSF/EPO early after autologous PBSC transplantation: effects on immune recovery and NK activity in a prospective study in women with breast and ovarian cancer

Perillo

Pierelli

Battaglia

et al. 2002

Bone Marrow Transplant

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“…Acute toxicities of either IL-1α or IL-1β were greater following intravenous compared to subcutaneous injection; subcutaneous injection was associated with significant local pain, erythema and swelling. 34 Chills and fever are observed in nearly all patients, even in the 1 ng/kg dose group. 35 At 10-30 ng/kg, all patients experience chills and fever.…”

Section: Interleukin-1mentioning

confidence: 98%

Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed

Dinarello¹

2004

J. Endotoxin Res.

246

210

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For many years, it was thought that bacterial products caused fever via the intermediate production of a host-derived, fever-producing molecule, called endogenous pyrogen (EP). Bacterial products and other fever-producing substances were termed exogenous pyrogens. It was considered highly unlikely that exogenous pyrogens caused fever by acting directly on the hypothalamic thermoregulatory center since there were countless fever-producing microbial products, mostly large molecules, with no common physical structure. In vivo and in vitro, lipopolysaccharides (LPSs) and other microbial products induced EP, subsequently shown to be interleukin-1 (IL-1). The concept of the 'endogenous pyrogen' cause of fever gained considerable support when pure, recombinant IL-1 produced fever in humans and in animals at subnanomolar concentrations. Subsequently, recombinant tumor necrosis factor-alpha (TNF-alpha), IL-6 and other cytokines were also shown to cause fever and EPs are now termed pyrogenic cytokines. However, the concept was challenged when specific blockade of either IL-1 or TNF activity did not diminish the febrile response to LPS, to other microbial products or to natural infections in animals and in humans. During infection, fever could occur independently of IL-1 or TNF activity. The cytokine-like property of Toll-like receptor (TLR) signal transduction provides an explanation by which any microbial product can cause fever by engaging its specific TLR on the vascular network supplying the thermoregulatory center in the anterior hypothalamus. Since fever induced by IL-1, TNF-alpha, IL-6 or TLR ligands requires cyclooxygenase-2, production of prostaglandin E2 (PGE2) and activation of hypothalamic PGE2 receptors provides a unifying mechanism for fever by endogenous and exogenous pyrogens. Thus, fever is the result of either cytokine receptor or TLR triggering; in autoimmune diseases, fever is mostly cytokine mediated whereas both cytokine and TLR account for fever during infection.

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“…Administration of recombinant human G-CSF protein has been shown to significantly accelerate the recovery of white blood cell counts, following either the administration of cytotoxic agents or bone marrow transplantation (29,30). Recombinant human G-CSF is now approved by the FDA for treatment of myelosuppression in human patients (30) and is thus relevant for use as a potential gene therapy.…”

Section: Circulating and Tissue Levels Of Human G-csf Protein Followimentioning

confidence: 99%

Cationic Liposome-mediated Intravenous Gene Delivery

Liu

Liggitt

Zhong

et al. 1995

Journal of Biological Chemistry

226

121

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Systemic gene transfer provides new opportunities for the analysis of gene function and gene regulation in vivo, as well as for human gene therapy. We used the chloramphenicol acetyltransferase reporter gene to examine several parameters important for the development of efficient, cationic liposome-mediated, intravenous (IV) gene transfer in mice. We then demonstrated that this approach can produce high level expression of biologically important genes. Specifically, we assessed the relationship of expression vector design to the level of systemic gene expression produced, and compared transfection levels produced by intravenously injecting DNA alone versus DNA⅐liposome complexes. We found that both the position of the heterologous intron, and the promoter element used in the expression plasmid, significantly affected the level of systemic gene expression produced. Although intravenous injection of plasmid DNA alone transfected every tissue analyzed, liposome-mediated delivery was much more efficient. We also established that repeated IV injection of DNA⅐liposome complexes produced high level systemic transfection. The second injection of DNA⅐liposome complexes produced levels of gene expression at least as high as those following a single IV injection. Thus, unlike some viral vectors, a neutralizing host-immune response does not limit re-expression, following reinjection of DNA⅐liposome complexes.Finally, we showed that the expression vectors which produced the highest levels of chloramphenicol acetyltransferase reporter gene expression could also produce high level expression of two colony stimulating factor genes in mice. Specifically, IV injection of liposomes complexed to expression vectors into which we had inserted either the murine granulocyte-macrophagecolony stimulating factor cDNA or the human granulocyte-CSF cDNA, produced circulating levels of the corresponding colony stimulating factor gene product comparable to levels which have been shown previously to be both biologically and therapeutically significant.

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Hematopoietic recovery following high-dose combined alkylating-agent chemotherapy and autologous bone marrow support in patients in phase-I clinical trials of colony-stimulating factors: G-CSF, GM-CSF, IL-1, IL-2, M-CSF

Cited by 23 publications

References 21 publications

Administration of low-dose interleukin-2 plus G-CSF/EPO early after autologous PBSC transplantation: effects on immune recovery and NK activity in a prospective study in women with breast and ovarian cancer

Administration of low-dose interleukin-2 plus G-CSF/EPO early after autologous PBSC transplantation: effects on immune recovery and NK activity in a prospective study in women with breast and ovarian cancer

Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed

Cationic Liposome-mediated Intravenous Gene Delivery

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