Combination therapy with arsenic trioxide, all-trans retinoic acid, and gemtuzumab ozogamicin in recurrent acute promyelocytic leukemia

Ahmed Aribi, Hagop M. Kantarjian, Elihu H. Estey, Charles A. Koller, Deborah A. Thomas, Steven M. Kornblau, Stefan H. Faderl, Nakia M. Laddie, Guillermo Garcia-Manero, Jorge E. Cortes

Research output: Contribution to journalArticle

Abstract

BACKGROUND. From 20% to 30% of patients with acute promyelocytic leukemia (APL) who are treated with all-trans retinoic acid (ATRA) develop recurrent disease. Arsenic trioxide (ATO) is an effective agent for the salvage of patients with recurrent APL, and gemtuzumab ozogamicin (GO) has shown activity in patients with APL. METHODS. The authors investigated the efficacy of a combination of ATO, ATRA, and GO in 8 patients with APL in first recurrence (7 patients with hematologic recurrences and 1 patient with a molecular recurrence). All patients had received previous treatment with ATRA either alone or in combination with other agents. Patients received ATO 0.15 mg/kg intravenously until they achieved a bone marrow complete remission (CR). Once in CR, patients received consolidation with ATO, ATRA, and GO for 10 months. Patients then received maintenance with idarubicin, ATRA, 6-marcaptopurine, and oral methotrexate for 11 months. RESULTS. All 7 patients who had hematologic recurrences achieved CR after a median of 39 days (range, 21-56 days). After a median follow-up of ≥36 months (range, 4-55 months), 6 patients remained alive in CR, and 2 patients died in CR. Six of 8 patients remained in second CR that was longer than their first CR. All 7 evaluable patients achieved molecular remission. There were no grade 3 or 4 extramedullary toxicities. Two patients died, 1 secondary to a complication of metastatic lung adenocarcinoma, and the other of sepsis. CONCLUSIONS. The combination of ATO, ATRA, and GO was effective and may achieve durable remissions in patients with APL in first recurrence. It should be considered as an effective alternative to allogeneic or autologous transplantation.

Original languageEnglish (US)
Pages (from-to)1355-1359
Number of pages5
JournalCancer
Volume109
Issue number7
DOIs
StatePublished - Apr 1 2007
Externally publishedYes

Fingerprint

Acute Promyelocytic Leukemia
Tretinoin
Therapeutics
Recurrence
gemtuzumab
arsenic trioxide
Idarubicin
Autologous Transplantation
Homologous Transplantation
Proxy

Keywords

  • Acute promyelocytic leukemia
  • All-trans retinoic acid
  • And molecular remission
  • Arsenic trioxide
  • Gemtuzumab ozogamycin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Combination therapy with arsenic trioxide, all-trans retinoic acid, and gemtuzumab ozogamicin in recurrent acute promyelocytic leukemia. / Aribi, Ahmed; Kantarjian, Hagop M.; Estey, Elihu H.; Koller, Charles A.; Thomas, Deborah A.; Kornblau, Steven M.; Faderl, Stefan H.; Laddie, Nakia M.; Garcia-Manero, Guillermo; Cortes, Jorge E.

In: Cancer, Vol. 109, No. 7, 01.04.2007, p. 1355-1359.

Research output: Contribution to journalArticle

Aribi, A, Kantarjian, HM, Estey, EH, Koller, CA, Thomas, DA, Kornblau, SM, Faderl, SH, Laddie, NM, Garcia-Manero, G & Cortes, JE 2007, 'Combination therapy with arsenic trioxide, all-trans retinoic acid, and gemtuzumab ozogamicin in recurrent acute promyelocytic leukemia', Cancer, vol. 109, no. 7, pp. 1355-1359. https://doi.org/10.1002/cncr.22524
Aribi, Ahmed ; Kantarjian, Hagop M. ; Estey, Elihu H. ; Koller, Charles A. ; Thomas, Deborah A. ; Kornblau, Steven M. ; Faderl, Stefan H. ; Laddie, Nakia M. ; Garcia-Manero, Guillermo ; Cortes, Jorge E. / Combination therapy with arsenic trioxide, all-trans retinoic acid, and gemtuzumab ozogamicin in recurrent acute promyelocytic leukemia. In: Cancer. 2007 ; Vol. 109, No. 7. pp. 1355-1359.
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T1 - Combination therapy with arsenic trioxide, all-trans retinoic acid, and gemtuzumab ozogamicin in recurrent acute promyelocytic leukemia

AU - Aribi, Ahmed

AU - Kantarjian, Hagop M.

AU - Estey, Elihu H.

AU - Koller, Charles A.

AU - Thomas, Deborah A.

AU - Kornblau, Steven M.

AU - Faderl, Stefan H.

AU - Laddie, Nakia M.

AU - Garcia-Manero, Guillermo

AU - Cortes, Jorge E.

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N2 - BACKGROUND. From 20% to 30% of patients with acute promyelocytic leukemia (APL) who are treated with all-trans retinoic acid (ATRA) develop recurrent disease. Arsenic trioxide (ATO) is an effective agent for the salvage of patients with recurrent APL, and gemtuzumab ozogamicin (GO) has shown activity in patients with APL. METHODS. The authors investigated the efficacy of a combination of ATO, ATRA, and GO in 8 patients with APL in first recurrence (7 patients with hematologic recurrences and 1 patient with a molecular recurrence). All patients had received previous treatment with ATRA either alone or in combination with other agents. Patients received ATO 0.15 mg/kg intravenously until they achieved a bone marrow complete remission (CR). Once in CR, patients received consolidation with ATO, ATRA, and GO for 10 months. Patients then received maintenance with idarubicin, ATRA, 6-marcaptopurine, and oral methotrexate for 11 months. RESULTS. All 7 patients who had hematologic recurrences achieved CR after a median of 39 days (range, 21-56 days). After a median follow-up of ≥36 months (range, 4-55 months), 6 patients remained alive in CR, and 2 patients died in CR. Six of 8 patients remained in second CR that was longer than their first CR. All 7 evaluable patients achieved molecular remission. There were no grade 3 or 4 extramedullary toxicities. Two patients died, 1 secondary to a complication of metastatic lung adenocarcinoma, and the other of sepsis. CONCLUSIONS. The combination of ATO, ATRA, and GO was effective and may achieve durable remissions in patients with APL in first recurrence. It should be considered as an effective alternative to allogeneic or autologous transplantation.

AB - BACKGROUND. From 20% to 30% of patients with acute promyelocytic leukemia (APL) who are treated with all-trans retinoic acid (ATRA) develop recurrent disease. Arsenic trioxide (ATO) is an effective agent for the salvage of patients with recurrent APL, and gemtuzumab ozogamicin (GO) has shown activity in patients with APL. METHODS. The authors investigated the efficacy of a combination of ATO, ATRA, and GO in 8 patients with APL in first recurrence (7 patients with hematologic recurrences and 1 patient with a molecular recurrence). All patients had received previous treatment with ATRA either alone or in combination with other agents. Patients received ATO 0.15 mg/kg intravenously until they achieved a bone marrow complete remission (CR). Once in CR, patients received consolidation with ATO, ATRA, and GO for 10 months. Patients then received maintenance with idarubicin, ATRA, 6-marcaptopurine, and oral methotrexate for 11 months. RESULTS. All 7 patients who had hematologic recurrences achieved CR after a median of 39 days (range, 21-56 days). After a median follow-up of ≥36 months (range, 4-55 months), 6 patients remained alive in CR, and 2 patients died in CR. Six of 8 patients remained in second CR that was longer than their first CR. All 7 evaluable patients achieved molecular remission. There were no grade 3 or 4 extramedullary toxicities. Two patients died, 1 secondary to a complication of metastatic lung adenocarcinoma, and the other of sepsis. CONCLUSIONS. The combination of ATO, ATRA, and GO was effective and may achieve durable remissions in patients with APL in first recurrence. It should be considered as an effective alternative to allogeneic or autologous transplantation.

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KW - And molecular remission

KW - Arsenic trioxide

KW - Gemtuzumab ozogamycin

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