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Sequential interleukin 3 and granulocyte-macrophage–colony stimulating factor therapy in patients with bone marrow failure with long-term follow-up of responses

  1. Hillary H. Wu M.D.1,
  2. Moshe Talpaz M.D.1,
  3. Richard E. Champlin M.D.2,
  4. Susan R. Pilat R.N.1,
  5. Razelle Kurzrock M.D.1,†,*

Article first published online: 17 NOV 2003

DOI: 10.1002/cncr.11810

Issue

Cancer

Cancer

Volume 98, Issue 11, pages 2410–2419, 1 December 2003

Additional Information

How to Cite

Wu, H. H., Talpaz, M., Champlin, R. E., Pilat, S. R. and Kurzrock, R. (2003), Sequential interleukin 3 and granulocyte-macrophage–colony stimulating factor therapy in patients with bone marrow failure with long-term follow-up of responses. Cancer, 98: 2410–2419. doi: 10.1002/cncr.11810

Author Information

  1. 1

    Department of Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, Houston, Texas

  2. 2

    Department of Bone Marrow Transplantation, University of Texas M. D. Anderson Cancer Center, Houston, Texas

  1. †

    Fax: (713) 745-2374

*Department of Bioimmunotherapy, Box 422, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030

Publication History

  1. Issue published online: 17 NOV 2003
  2. Article first published online: 17 NOV 2003
  3. Manuscript Accepted: 28 AUG 2003
  4. Manuscript Received: 20 AUG 2003

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Keywords:

  • aplastic anemia;
  • bone marrow transplantation;
  • hemoglobin;
  • myelodysplastic syndrome;
  • platelets;
  • response;
  • stem cell factor

Abstract

BACKGROUND

Interleukin-3 (IL-3) and granulocyte-macrophage–colony stimulating factor (GM-CSF) have synergistic, hematopoietic growth-promoting activity in preclinical studies. Because of the paucity of effective therapies for patients with chronic bone marrow failure states, the authors studied the biologic activity of sequential IL-3/GM-CSF in such patients.

METHODS

IL-3 was given subcutaneously for 5 days (at escalating doses of 0.15 μg/kg, 0.3 μg/kg, 0.6 μg/kg, 1.2 μg/kg, 2.5 μg/kg, 5.0 μg/kg, 10.0 μg/kg, or 15.0 μg/kg per day), and GM-CSF for was given subcutaneously for 9 days (at a dose of 5 μg/kg per day; Phase I 3 + 3 design) followed by 14 days of rest (total, 2 courses), then maintenance therapy.

RESULTS

The majority of 38 evaluable patients had aplastic anemia or myelodysplastic syndrome. Most patients (79%) had neutrophil responses. Ten patients (26%), all of whom were treated with IL-3 doses ≥ 1.2 μg/kg per day, had platelet responses, with a median increase of 132 × 109/L (range, 41–180 × 109/L) over baseline in responders. Six patients (16%) had trilineage recovery, which could be durable (the longest ongoing at 6.5 years after therapy completion). The most common toxicities were low-grade fever, headache, and fatigue. The maximum tolerated doses were IL-3 at 10 μg/kg per day and GM-CSF at 5 μg/kg per day.

CONCLUSIONS

Sequential IL-3/GM-CSF effectively raised blood counts in some patients with bone marrow failure at doses that were tolerated well. These results indicate that early-acting growth factors can induce durable, multilineage responses in a subset of individuals with bone marrow failure. Cancer 2003. © 2003 American Cancer Society.

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