Mitoxantrone and cyclophosphamide combination chemotherapy for the treatment of various canine malignancies

1999 ◽  
Vol 35 (3) ◽  
pp. 236-239 ◽  
Author(s):  
CJ Henry ◽  
MS Buss ◽  
KA Potter ◽  
KJ Wardrop
Keyword(s):  
Pilot Study ◽  
Combination Therapy ◽  
Combination Chemotherapy ◽  
Tumor Response ◽  
Single Agent ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Tumor Bearing ◽  
Stimulating Factor

Thirteen dogs with histopathologically confirmed malignancies were treated with mitoxantrone and cyclophosphamide combination therapy. One to four doses were administered at 21-day intervals. Recombinant human granulocyte colony-stimulating factor was administered to ameliorate myelosuppression in dogs with neutrophil nadirs less than 1,000/microl. While the protocol appears to be safe for use in tumor-bearing dogs, an advantage over mitoxantrone single-agent protocols in terms of tumor response was not demonstrated in this initial pilot study.

scholarly journals Combination therapy for radiation-induced bone marrow aplasia in nonhuman primates using synthokine SC-55494 and recombinant human granulocyte colony-stimulating factor

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4129-4135 ◽  
Author(s):  
TJ MacVittie ◽  
AM Farese ◽  
F Herodin ◽  
LB Grab ◽  
CM Baum ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Combination Therapy ◽  
Nonhuman Primates ◽  
Single Agent ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Transfusion Requirements ◽  
Radiation Induced ◽  
60Co Gamma Radiation ◽  
Stimulating Factor

Combination cytokine therapy continues to be evaluated in an effort to stimulate multilineage hematopoietic reconstitution after bone marrow myelosuppression. This study evaluated the efficacy of combination therapy with the synthetic interleukin-3 receptor agonist, Synthokine- SC55494, and recombinant methionyl human granulocyte colony-stimulating factor (rhG-CSF) on platelet and neutrophil recovery in nonhuman primates exposed to total body 700 cGy 60Co gamma radiation. After irradiation on day (d) 0, cohorts of animals subcutaneously received single-agent protocols of either human serum albumin (HSA; every day [QD], 15 micrograms/kg/d, n = 10), Synthokine (twice daily [BID], 100, micrograms/kg/d, n = 15), rhG-CSF (QD, 10 micrograms/kg/d, n = 5), or a combination of Synthokine and rhG-CSF (BID, 100 and 10 micrograms/kg/d, respectively, n = 5) for 23 days beginning on d1. Complete blood counts were monitored for 60 days postirradiation and the durations of neutropenia (absolute neutrophil count < 500/microL) and thrombocytopenia (platelet count < 20,000/microL) were assessed. Animals were provided clinical support in the form of antibiotics, fresh irradiated whole blood, and fluids. All cytokine protocols significantly (P < .05) reduced the duration thrombocytopenia versus the HSA-treated animals. Only the combination protocol of Synthokine + rhG-CSF and rhG-CSF alone significantly shortened the period neutropenia (P < .05). The combined Synthokine/rhG-CSF protocol significantly improved platelet nadir versus Synthokine alone and HSA controls and neutrophil nadir versus rhG-CSF alone and HSA controls. All cytokine protocols decreased the time to recovery to preirradiation neutrophil and platelet values. The Synthokine/rhG-CSF protocol also reduced the transfusion requirements per treatment group to 0 among 5 animals as compared with 2 among 5 animals for Synthokine alone, 8 among 5 animals for rhG-CSF, and 17 among 10 animals for HSA. These data showed that the combination of Synthokine, SC-55494, and rhG-CSF further decreased the cytopenic periods and nadirs for both platelets and neutrophils relative to Synthokine and rhG-CSF monotherapy and suggest that this combination therapy would be effective against both neutropenia and thrombocytopenia consequent to drug- or radiation- induced myelosuppression.

Antilymphocyte globulin, cyclosporin, and granulocyte colony- stimulating factor in patients with acquired severe aplastic anemia (SAA): a pilot study of the EBMT SAA Working Party

Blood ◽  
1995 ◽  
Vol 85 (5) ◽  
pp. 1348-1353 ◽  
Author(s):  
A Bacigalupo ◽  
G Broccia ◽  
G Corda ◽  
W Arcese ◽  
M Carotenuto ◽  
...  
Keyword(s):  
Pilot Study ◽  
Aplastic Anemia ◽  
Working Party ◽  
Early Mortality ◽  
Severe Aplastic Anemia ◽  
Granulocyte Colony Stimulating Factor ◽  
Antilymphocyte Globulin ◽  
Colony Stimulating Factor ◽  
Stimulating Factor

Patients with severe aplastic anemia (SAA) and a neutrophil (PMN) count of less than 0.5 x 10(9)/L are exposed to a high risk of early mortality when treated with antilymphocyte globulin (ALG) and steroids, with the major problem being infectious complications. The addition of human recombinant granulocyte colony-stimulating factor (rhG-CSF) to ALG may reduce early mortality by improving neutrophil counts in the short term. To test the feasibility of this approach, the SAA Working Party of the European Group for Blood and Marrow Transplantation (EBMT) designed a pilot study that included rhG-CSF (5 micrograms/kg/d, days 1 through 90), horse ALG (HALG; 15 mg/kg/d, days 1 through 5), methylprednisolone (2 mg/kg/d, days 1 through 5, then tapering the dose), and cyclosporin A (CyA; 5 mg/kg/d orally, days 1 through 180). Patients with newly diagnosed acquired SAA (untreated) and with neutrophil counts of < or = 0.5 x 10(9)/L were eligible. Forty consecutive patients entered this study and are evaluable with a minimum follow up of 120 days: the median age was 16 years (range, 2 to 72 years), the interval from diagnosis to treatment was 24 days, and the median PMN count was 0.19 x 10(9)/L. Twenty-one patients had hemorrhages, and 19 were infected at the time of treatment. Overall, treatment was well tolerated: the median maximum PMN count during rhG- CSF administration was 12 x 10(9)/L (range, 0.4 x 10(9)/L to 44 x 10(9)/L). There were three early deaths (8%) due to infection. Four patients (10%) showed no recovery, whereas 33 patients (82%) had trilineage hematologic reconstitution and became transfusion- independent at a median interval of 115 days from treatment. Median follow up for surviving patients is 428 days (range, 122 to 1,005). Actuarial survival is 92%: 86% and 100% for patients with PMN counts less than 0.2 x 10(9)/L or between 0.2 x 10(9)/L and 0.5 x 10(9)/L, respectively. This study suggests that the addition of rhG-CSF to ALG and CyA is well tolerated, is associated with a low risk of mortality, and offers a good chance of hematologic response. This protocol would appear to be an interesting alternative treatment for SAA patients with a low PMN count who lack an HLA-identical sibling.

scholarly journals Flt-3 Ligand Synergizes With Granulocyte Colony-Stimulating Factor to Increase Neutrophil Numbers and to Mobilize Peripheral Blood Stem Cells With Long-Term Repopulating Potential

Blood ◽  
1997 ◽  
Vol 89 (11) ◽  
pp. 3998-4004 ◽  
Author(s):  
Graham Molineux ◽  
Clay McCrea ◽  
Xiao Qiang Yan ◽  
Patrick Kerzic ◽  
Ian McNiece
Keyword(s):  
Peripheral Blood ◽  
Single Agent ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells ◽  
Short And Long Term ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Flt-3 ligand (FL) shares many features with stem cell factor (SCF), a widely documented cofactor for peripheral blood progenitor cell (PBPC) mobilization. We investigated the mobilization of PBPCs by FL in combination with granulocyte colony-stimulating factor (G-CSF). As a single agent, FL was a relatively modest mobilizer of PBPCs, resulting in 360 granulocyte/macrophage colony-forming cells (GM-CFCs)/mL blood (control, 155 GM-CFCs/mL blood) and no advantage in leukocyte recovery when these PBPCs were transplanted to irradiated recipient mice. G-CSF, on the other hand, mobilized over 20,000 GM-CFCs/mL blood, and the combination of G-CSF + FL resulted in over 100,000 GM-CFCs/mL blood. The combination of G-CSF + FL stimulated increased levels of monocytes and basophils in the peripheral blood. The performance of the mobilized PBPC product in irradiated hosts correlated with progenitor numbers resulting in long-term engraftment in association with accelerated short-term recovery of both leukocytes and platelets. These data demonstrate the potential of FL to synergize with G-CSF to mobilize PBPCs with both short- and long-term engraftment potential. The effect is similar to the synergistic interaction of G-CSF and SCF on PBPC mobilization. The use of FL as opposed to SCF may elicit a different spectrum of toxicities including lymphoid proliferation effects, in contrast to the mast cell degranulation effects of SCF. Clinical studies of FL are needed to evaluate its usefulness in man.

Combination Therapy With Recombinant Human Granulocyte Colony-Stimulating Factor and Erythropoietin in Aplastic Anemia

1995 ◽  
Vol 48 (1) ◽  
pp. 29-33 ◽  
Author(s):  
Masahiro Imamura ◽  
Masanobu Kobayashi ◽  
Sumiko Kobayashi ◽  
Kohki Yoshida ◽  
Chikara Mikuni ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Aplastic Anemia ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor
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