Phase II study of all-trans retinoic acid in the accelerated phase or early blastic phase of chronic myeloid leukemia: A study of the eastern cooperative oncology group (E1993)

Janice P. Dutcher, Sandra Lee, Robert E. Gallagher, Adel Z. Makary, John D. Hines, Harold Londer, John P. Farnen, John M. Bennett, Elisabeth M. Paietta, Jacob M. Rowe, Olga Goloubeva, Peter H. Wiernik

Research output: Contribution to journalArticle

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Abstract

The aims of this study were to evaluate the safety and efficacy of all-trans retinoic acid (ATRA) in the treatment of the accelerated and blastic phase of chronic myeloid leukemia (CML) and to evaluate in vitro correlates of biological activity. ATRA was administered in an intermittent schedule to patients with CML in the accelerated or blastic phases for a 6 week induction period, which was continued if there was evidence of clinical response or stable disease. If the patient was progressing at 6 weeks, interferon-α could be added to the ATRA. Laboratory correlative studies were performed prior to treatment and at intervals during treatment to evaluate effects on maturation and differentiation, and on CML progenitor cell growth by assessment of colony-forming cells (CFC). Eighteen patients were enrolled. There was 1 complete response, 1 partial response and 2 with hematological improvement. A fifth patient was stable on ATRA and interferon for several months. Laboratory data for the responders demonstrated high sensitivity of primary CFC to ATRA prior to treatment and low serial CFC counts on ATRA therapy. ATRA demonstrated clinical and hematological activity in 5 of 18 patients with the accelerated phase of CML, and there was evidence of a biological effect in laboratory studies of 3 of the 5 patients' progenitor cells. Combination therapy with other differentiating agents may be useful in this disease.

Original languageEnglish (US)
Pages (from-to)377-385
Number of pages9
JournalLeukemia and Lymphoma
Volume46
Issue number3
DOIs
StatePublished - Mar 2005

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Leukemia, Myeloid, Chronic Phase
Tretinoin
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Interferons
Therapeutics
Myeloid Progenitor Cells
Appointments and Schedules
Stem Cells
Cell Count
Safety
Growth

Keywords

  • Accelerated phase
  • All-trans retinoic acid
  • Blast crisis
  • CML

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Phase II study of all-trans retinoic acid in the accelerated phase or early blastic phase of chronic myeloid leukemia : A study of the eastern cooperative oncology group (E1993). / Dutcher, Janice P.; Lee, Sandra; Gallagher, Robert E.; Makary, Adel Z.; Hines, John D.; Londer, Harold; Farnen, John P.; Bennett, John M.; Paietta, Elisabeth M.; Rowe, Jacob M.; Goloubeva, Olga; Wiernik, Peter H.

In: Leukemia and Lymphoma, Vol. 46, No. 3, 03.2005, p. 377-385.

Research output: Contribution to journalArticle

Dutcher, JP, Lee, S, Gallagher, RE, Makary, AZ, Hines, JD, Londer, H, Farnen, JP, Bennett, JM, Paietta, EM, Rowe, JM, Goloubeva, O & Wiernik, PH 2005, 'Phase II study of all-trans retinoic acid in the accelerated phase or early blastic phase of chronic myeloid leukemia: A study of the eastern cooperative oncology group (E1993)', Leukemia and Lymphoma, vol. 46, no. 3, pp. 377-385. https://doi.org/10.1080/10428190400013100
Dutcher, Janice P. ; Lee, Sandra ; Gallagher, Robert E. ; Makary, Adel Z. ; Hines, John D. ; Londer, Harold ; Farnen, John P. ; Bennett, John M. ; Paietta, Elisabeth M. ; Rowe, Jacob M. ; Goloubeva, Olga ; Wiernik, Peter H. / Phase II study of all-trans retinoic acid in the accelerated phase or early blastic phase of chronic myeloid leukemia : A study of the eastern cooperative oncology group (E1993). In: Leukemia and Lymphoma. 2005 ; Vol. 46, No. 3. pp. 377-385.
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