Recombinant Human Interleukin-3 in Patients with Hematopoietic Failure

Ganser, Arnold; Lindemann, A; Seipelt, G.; Ottmann, O. G.; Eder, Matthias; Herrmann, F.; Frisch, Jürgen; Schulz, G.; Mertelsmann, R; Hoelzer, Dieter

doi:10.1007/978-3-642-84138-5_18

Cited by 18 publications

(22 citation statements)

References 33 publications

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“…Of particular interest is the rhIL-3 related toxicity observed in the two studies. In the small cell tumour study the observed toxicity in patients treated with rhIL-3 up to a dose of 7.5 jig kg/d was similar to that reported by others (Ganser et al, 1990a;Kurzrock et al, 1991;Biesma et al, 1992). In the ovarian carcinoma study, the adverse events considered to be related to rhIL-3 were more pronounced and severe toxicity was encountered.…”

Section: Discussionsupporting

confidence: 86%

“…RhIL-3 stimulates haematopoiesis at the level of the multipotent and lineagecommitted progenitor cells, resulting in a gradual appearance (after 5 -10 days) of neutrophils, platelets and reticulocytes in the peripheral blood (Leary et al, 1987;Messner et al, 1987;Sonoda et al, 1988). In the study of Ganser et al in patients with normal haematopoiesis elevation of neutrophil and platelet counts was observed 1 week after the start of rhIL-3 treatment and maximum counts were reached between days 15 and 20 (Ganser et al, 1990a). In the small cell tumour study, where rhIL-3 was begun 6 days after the first day of chemotherapy, the median time between the start of rhIL-3 treatment and occurrence of the nadir was 6 days (range, 5-7 days) and for the ovarian carcinoma study, where rhIL-3 began within 48 h of chemotherapy, this was 15 days (range, 13-17 days).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies with rhIL-3 have been reported, including studies in patients with advanced malignancies (Ganser et al, 1990a;Kurzrock et al, 1991), myelodysplastic syndromes (Ganser et al, 1990c), and aplastic anaemia (Ganser et al, 1990b). Only a few studies have reported rhIL-3 administration in patients with chemotherapy-induced myelosuppression (Kurzrock et al, 1991;Biesma et al, 1992).…”

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confidence: 99%

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Effects of interleukin-3 on myelosuppression induced by chemotherapy for ovarian cancer and small cell undifferentiated tumours

Dercksen

Hoekman²,

Huinink³

et al. 1993

Br J Cancer

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Summary Two clinical studies were undertaken to study the toxicity profile and effects of interleukin-3 (rhIL-3) on chemotherapy-induced myelosuppression.Fifteen patients with recurrent ovarian carcinoma were treated with high dose carboplatin (800 mg m-2). All patients received 5.0 fig/kg/d rhIL-3 subcutaneously but timing and duration of rhIL-3 treatment differed.Constitutional symptoms were the major toxicity and in addition to the carboplatin-induced nausea and vomiting the combination was poorly tolerated. In 5/15 patients receiving high dose carboplatin rhIL-3 administration was discontinued due to nephrotoxicity (2 x ), hypotension, severe malaise and bone pain. In this study, rhIL-3 ameliorated chemotherapy-induced neutropenia as well as thrombocytopenia and reduced the requirement for platelet transfusions in the second cycle of chemotherapy. However, rhlL-3 failed to prevent cumulative platelet toxicity. In the second study 12 patients with small cell undifferentiated cancers were treated with carboplatin, etoposide and ifosfamide. Three dose levels of rhIL-3 were explored (0.125, 5.0 and 7.5 pg/kg/d). In this study, toxicity of the treatment was mild, however, no beneficial haematologic effects of rhIL-3 could be demonstrated.In conclusion, the haematological effects of rhIL-3 were modest and dependent on the chemotherapeutic regimen, timing and duration of rhIL-3 treatment (in relation to the expected nadir). In general rhIL-3-induced toxicity was mild, but combination with high dose carboplatin could be hazardous if rhIL-3 is initiated at 24 h after the cytostatic agent.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of interleukin-3 on myelosuppression induced by chemotherapy for ovarian cancer and small cell undifferentiated tumours

Dercksen

Hoekman²,

Huinink³

et al. 1993

Br J Cancer

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“…Umetsu et al (21) showed that an HLA-DR-specific CD4 § T cell clone induced proliferation of some follicular lymphoma cells in vitro. Hoelzer and colleagues (22) recently conducted a clinical trial using II.-3 in patients with normal hematopoiesis or bone marrow failure. 19 patients with advanced tumors were treated with IL-3 to assess its toxicity and biological effects.…”

Section: Resultsmentioning

confidence: 99%

Interleukin 3 is a growth factor for human follicular B cell lymphoma.

Clayberger

Luna‐Fineman

Lee

et al. 1992

The Journal of Experimental Medicine

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SummaryMore than one-half of adults with non-Hodgkin's B cell lymphomas present with low-grade follicular lymphomas. These tumor cells are found in dose association with follicular T lymphocytes and dendritic cells, suggesting that the surrounding ceils may play a role in the support of follicular tumors. Supernatants from activated human peripheral blood lymphocytes were found to promote the in vitro proliferation of follicular tumor cells. This effect was entirely due to interleukin 3 (IL-3), a factor generally thought to cause the growth and differentiation of immature hematopoietic cells. II.-3 receptors were detected on fresh isolates of all primary follicular cell tumors examined. These findings suggest that follicular cell tumors may be dependent in vivo on II.-3 and that therapies directed against I1.-3, its receptor, or the T cells that produce it may be effective treatment for follicular lymphoma.

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“…In addition, IL-3 has been used in culture to produce blood cells of various lineages, including neutrophils, monocytes, erythrocytes, megakaryocytes, basophils, eosinophils, mast cells, and B-lymphoid cells [2,5,[9][10][11][12][13]. Administration of IL-3 to human and primate subjects has enhanced multilineage-hematopoiesis [14][15][16][17]. Autologous progeny cells after culture/expansion in cytokine combination including IL-3 have been successfully infused into patients after a nonmyeloablative conditioning regimen [18].…”

Section: Introductionmentioning

confidence: 99%

Correlation Between IL‐3 Receptor Expression and Growth Potential of Human CD34 ⁺ Hematopoietic Cells from Different Tissues

Huang¹,

Chen²,

Yu³

et al. 1999

STEM CELLS

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CD123 (␣-subunit of IL-3 receptor) expression on primitive and committed human hematopoietic cells was studied by multicolor sorting and single-cell culture. The sources of cells included fetal liver (FLV), fetal bone marrow, umbilical cord blood, adult bone marrow and mobilized peripheral blood. Three subsets of CD34 + cells were defined by the levels of surface CD123: CD123 negative , CD123 low , and CD123 bright . Coexpression of lineage markers showed that a majority of CD34 + CD123 bright cells were myeloid and B-lymphoid progenitors, while erythroid progenitors were mainly in the CD34 + CD123 negative subset. The CD34 + CD123 low subset contained a heterogeneous distribution of early and committed progenitor cells. Single CD34 + cells from the CD123 subsets were cultured in a cytokine cocktail of stem cell factor, interleukin 3 (IL-3), IL-6, GM-CSF, erythropoietin, insulin-like growth factor-1, and basic fibroblast growth factor. After 14 days of incubation, a higher cloning efficiency (CE) was observed in the CD34 + CD123 negative and CD34 + CD123 low fractions (37 ± 23% and 44 ± 23%, respectively) than in the CD34 + CD123 bright fraction (15 ± 21%). Using previously published criteria that colonies containing dispersed, translucent cells (dispersed growth pattern, DGP) were derived from primitive cells and that colonies composed solely of clusters were from committed cells, early precursors were distributed evenly in the CD34 + CD123 negative and CD34 + CD123 low subsets. When CD38 and CD90 (Thy-1) were used for further characterization of CD34 + cells from FLV, CE increased from 37 ± 23% in CD123 negative to 70 ± 19% in CD123 negative CD38 -and from 44 ± 23% in CD123 low to 66 ± 19% in CD123 low CD38 -. No significant increase in CE or DGP progenitors was observed when CD34 + cells were sorted by CD90 and CD123. We concluded that: A) high levels of CD123 were expressed on B-lymphoid and myeloid progenitors; B) early erythroid progenitors had little or no surface CD123, and C) primitive hematopoietic cells are characterized by CD123 negative/low expression.

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Recombinant Human Interleukin-3 in Patients with Hematopoietic Failure

Cited by 18 publications

References 33 publications

Effects of interleukin-3 on myelosuppression induced by chemotherapy for ovarian cancer and small cell undifferentiated tumours

Effects of interleukin-3 on myelosuppression induced by chemotherapy for ovarian cancer and small cell undifferentiated tumours

Interleukin 3 is a growth factor for human follicular B cell lymphoma.

Correlation Between IL‐3 Receptor Expression and Growth Potential of Human CD34 ⁺ Hematopoietic Cells from Different Tissues

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Recombinant Human Interleukin-3 in Patients with Hematopoietic Failure

Cited by 18 publications

References 33 publications

Effects of interleukin-3 on myelosuppression induced by chemotherapy for ovarian cancer and small cell undifferentiated tumours

Effects of interleukin-3 on myelosuppression induced by chemotherapy for ovarian cancer and small cell undifferentiated tumours

Interleukin 3 is a growth factor for human follicular B cell lymphoma.

Correlation Between IL‐3 Receptor Expression and Growth Potential of Human CD34 + Hematopoietic Cells from Different Tissues

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Product

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Correlation Between IL‐3 Receptor Expression and Growth Potential of Human CD34 ⁺ Hematopoietic Cells from Different Tissues