Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab

Yasmin Abaza, Hagop Kantarjian, Guillermo Garcia-Manero, Elihu Estey, Gautam Borthakur, Elias Jabbour, Stefan Faderl, Susan O'Brien, William Wierda, Sherry Pierce, Mark Brandt, Deborah McCue, Rajyalakshmi Luthra, Keyur Patel, Steven Kornblau, Tapan Kadia, Naval Daver, Courtney DiNardo, Nitin Jain, Srdan VerstovsekAlessandra Ferrajoli, Michael Andreeff, Marina Konopleva, Zeev Estrov, Maria Foudray, David McCue, Jorge Cortes, Farhad Ravandil

Research output: Contribution to journalArticle

Abstract

The combination of all-trans-retinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of standard-risk patients with newly diagnosed acute promyelocytic leukemia (APL). A recent study demonstrated the efficacy of this regimen with added gemtuzumab ozogamicin (GO) in high-risk patients. We examined the long-term outcome of patients with newly diagnosed APL treated at our institution on 3 consecutive prospective clinical trials, using the combination of ATRA and ATO, with or without GO. For induction, all patients received ATRA (45 mg/m2 daily) and ATO (0.15 mg/kg daily) with a dose of GO (9 mg/m2 on day 1) added to high-risk patients (white blood cell count, >10 × 109/L), as well as low-risk patients who experienced leukocytosis during induction. Once in complete remission, patients received 4 cycles of ATRA plus ATO consolidation. One hundred eighty-seven patients, including 54 with high-risk and 133 with low-risk disease, have been treated. The complete remission rate was 96% (52 of 54 in high-risk and 127 of 133 in low-risk patients). Induction mortality was 4%, with only 7 relapses. Among low-risk patients, 60 patients (45%) required either GO or idarubicin for leukocytosis. Median duration of follow-up was 47.6 months. The 5-year event-free, disease-free, and overall survival rates are 85%, 96%, and 88%, respectively. Late hematological relapses beyond 1 year occurred in 3 patients. Fourteen deaths occurred beyond 1 year; 12 were related to other causes. This study confirms the durability of responses with this regimen.

Original languageEnglish (US)
Pages (from-to)1275-1283
Number of pages9
JournalBlood
Volume129
Issue number10
DOIs
StatePublished - Mar 9 2017
Externally publishedYes

Fingerprint

Acute Promyelocytic Leukemia
Tretinoin
Leukocytosis
Idarubicin
gemtuzumab
arsenic trioxide
Chemotherapy
Recurrence
Consolidation
Durability
Blood
Leukocyte Count
Cells
Disease-Free Survival
Survival Rate

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Abaza, Y., Kantarjian, H., Garcia-Manero, G., Estey, E., Borthakur, G., Jabbour, E., ... Ravandil, F. (2017). Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab. Blood, 129(10), 1275-1283. https://doi.org/10.1182/blood-2016-09-736686

Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab. / Abaza, Yasmin; Kantarjian, Hagop; Garcia-Manero, Guillermo; Estey, Elihu; Borthakur, Gautam; Jabbour, Elias; Faderl, Stefan; O'Brien, Susan; Wierda, William; Pierce, Sherry; Brandt, Mark; McCue, Deborah; Luthra, Rajyalakshmi; Patel, Keyur; Kornblau, Steven; Kadia, Tapan; Daver, Naval; DiNardo, Courtney; Jain, Nitin; Verstovsek, Srdan; Ferrajoli, Alessandra; Andreeff, Michael; Konopleva, Marina; Estrov, Zeev; Foudray, Maria; McCue, David; Cortes, Jorge; Ravandil, Farhad.

In: Blood, Vol. 129, No. 10, 09.03.2017, p. 1275-1283.

Research output: Contribution to journalArticle

Abaza, Y, Kantarjian, H, Garcia-Manero, G, Estey, E, Borthakur, G, Jabbour, E, Faderl, S, O'Brien, S, Wierda, W, Pierce, S, Brandt, M, McCue, D, Luthra, R, Patel, K, Kornblau, S, Kadia, T, Daver, N, DiNardo, C, Jain, N, Verstovsek, S, Ferrajoli, A, Andreeff, M, Konopleva, M, Estrov, Z, Foudray, M, McCue, D, Cortes, J & Ravandil, F 2017, 'Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab', Blood, vol. 129, no. 10, pp. 1275-1283. https://doi.org/10.1182/blood-2016-09-736686
Abaza Y, Kantarjian H, Garcia-Manero G, Estey E, Borthakur G, Jabbour E et al. Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab. Blood. 2017 Mar 9;129(10):1275-1283. https://doi.org/10.1182/blood-2016-09-736686
Abaza, Yasmin ; Kantarjian, Hagop ; Garcia-Manero, Guillermo ; Estey, Elihu ; Borthakur, Gautam ; Jabbour, Elias ; Faderl, Stefan ; O'Brien, Susan ; Wierda, William ; Pierce, Sherry ; Brandt, Mark ; McCue, Deborah ; Luthra, Rajyalakshmi ; Patel, Keyur ; Kornblau, Steven ; Kadia, Tapan ; Daver, Naval ; DiNardo, Courtney ; Jain, Nitin ; Verstovsek, Srdan ; Ferrajoli, Alessandra ; Andreeff, Michael ; Konopleva, Marina ; Estrov, Zeev ; Foudray, Maria ; McCue, David ; Cortes, Jorge ; Ravandil, Farhad. / Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab. In: Blood. 2017 ; Vol. 129, No. 10. pp. 1275-1283.
@article{091321eab2c140278c2555687ac17bd1,
title = "Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab",
abstract = "The combination of all-trans-retinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of standard-risk patients with newly diagnosed acute promyelocytic leukemia (APL). A recent study demonstrated the efficacy of this regimen with added gemtuzumab ozogamicin (GO) in high-risk patients. We examined the long-term outcome of patients with newly diagnosed APL treated at our institution on 3 consecutive prospective clinical trials, using the combination of ATRA and ATO, with or without GO. For induction, all patients received ATRA (45 mg/m2 daily) and ATO (0.15 mg/kg daily) with a dose of GO (9 mg/m2 on day 1) added to high-risk patients (white blood cell count, >10 × 109/L), as well as low-risk patients who experienced leukocytosis during induction. Once in complete remission, patients received 4 cycles of ATRA plus ATO consolidation. One hundred eighty-seven patients, including 54 with high-risk and 133 with low-risk disease, have been treated. The complete remission rate was 96{\%} (52 of 54 in high-risk and 127 of 133 in low-risk patients). Induction mortality was 4{\%}, with only 7 relapses. Among low-risk patients, 60 patients (45{\%}) required either GO or idarubicin for leukocytosis. Median duration of follow-up was 47.6 months. The 5-year event-free, disease-free, and overall survival rates are 85{\%}, 96{\%}, and 88{\%}, respectively. Late hematological relapses beyond 1 year occurred in 3 patients. Fourteen deaths occurred beyond 1 year; 12 were related to other causes. This study confirms the durability of responses with this regimen.",
author = "Yasmin Abaza and Hagop Kantarjian and Guillermo Garcia-Manero and Elihu Estey and Gautam Borthakur and Elias Jabbour and Stefan Faderl and Susan O'Brien and William Wierda and Sherry Pierce and Mark Brandt and Deborah McCue and Rajyalakshmi Luthra and Keyur Patel and Steven Kornblau and Tapan Kadia and Naval Daver and Courtney DiNardo and Nitin Jain and Srdan Verstovsek and Alessandra Ferrajoli and Michael Andreeff and Marina Konopleva and Zeev Estrov and Maria Foudray and David McCue and Jorge Cortes and Farhad Ravandil",
year = "2017",
month = "3",
day = "9",
doi = "10.1182/blood-2016-09-736686",
language = "English (US)",
volume = "129",
pages = "1275--1283",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "10",

}

TY - JOUR

T1 - Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab

AU - Abaza, Yasmin

AU - Kantarjian, Hagop

AU - Garcia-Manero, Guillermo

AU - Estey, Elihu

AU - Borthakur, Gautam

AU - Jabbour, Elias

AU - Faderl, Stefan

AU - O'Brien, Susan

AU - Wierda, William

AU - Pierce, Sherry

AU - Brandt, Mark

AU - McCue, Deborah

AU - Luthra, Rajyalakshmi

AU - Patel, Keyur

AU - Kornblau, Steven

AU - Kadia, Tapan

AU - Daver, Naval

AU - DiNardo, Courtney

AU - Jain, Nitin

AU - Verstovsek, Srdan

AU - Ferrajoli, Alessandra

AU - Andreeff, Michael

AU - Konopleva, Marina

AU - Estrov, Zeev

AU - Foudray, Maria

AU - McCue, David

AU - Cortes, Jorge

AU - Ravandil, Farhad

PY - 2017/3/9

Y1 - 2017/3/9

N2 - The combination of all-trans-retinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of standard-risk patients with newly diagnosed acute promyelocytic leukemia (APL). A recent study demonstrated the efficacy of this regimen with added gemtuzumab ozogamicin (GO) in high-risk patients. We examined the long-term outcome of patients with newly diagnosed APL treated at our institution on 3 consecutive prospective clinical trials, using the combination of ATRA and ATO, with or without GO. For induction, all patients received ATRA (45 mg/m2 daily) and ATO (0.15 mg/kg daily) with a dose of GO (9 mg/m2 on day 1) added to high-risk patients (white blood cell count, >10 × 109/L), as well as low-risk patients who experienced leukocytosis during induction. Once in complete remission, patients received 4 cycles of ATRA plus ATO consolidation. One hundred eighty-seven patients, including 54 with high-risk and 133 with low-risk disease, have been treated. The complete remission rate was 96% (52 of 54 in high-risk and 127 of 133 in low-risk patients). Induction mortality was 4%, with only 7 relapses. Among low-risk patients, 60 patients (45%) required either GO or idarubicin for leukocytosis. Median duration of follow-up was 47.6 months. The 5-year event-free, disease-free, and overall survival rates are 85%, 96%, and 88%, respectively. Late hematological relapses beyond 1 year occurred in 3 patients. Fourteen deaths occurred beyond 1 year; 12 were related to other causes. This study confirms the durability of responses with this regimen.

AB - The combination of all-trans-retinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of standard-risk patients with newly diagnosed acute promyelocytic leukemia (APL). A recent study demonstrated the efficacy of this regimen with added gemtuzumab ozogamicin (GO) in high-risk patients. We examined the long-term outcome of patients with newly diagnosed APL treated at our institution on 3 consecutive prospective clinical trials, using the combination of ATRA and ATO, with or without GO. For induction, all patients received ATRA (45 mg/m2 daily) and ATO (0.15 mg/kg daily) with a dose of GO (9 mg/m2 on day 1) added to high-risk patients (white blood cell count, >10 × 109/L), as well as low-risk patients who experienced leukocytosis during induction. Once in complete remission, patients received 4 cycles of ATRA plus ATO consolidation. One hundred eighty-seven patients, including 54 with high-risk and 133 with low-risk disease, have been treated. The complete remission rate was 96% (52 of 54 in high-risk and 127 of 133 in low-risk patients). Induction mortality was 4%, with only 7 relapses. Among low-risk patients, 60 patients (45%) required either GO or idarubicin for leukocytosis. Median duration of follow-up was 47.6 months. The 5-year event-free, disease-free, and overall survival rates are 85%, 96%, and 88%, respectively. Late hematological relapses beyond 1 year occurred in 3 patients. Fourteen deaths occurred beyond 1 year; 12 were related to other causes. This study confirms the durability of responses with this regimen.

UR - http://www.scopus.com/inward/record.url?scp=85015251442&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85015251442&partnerID=8YFLogxK

U2 - 10.1182/blood-2016-09-736686

DO - 10.1182/blood-2016-09-736686

M3 - Article

C2 - 28003274

AN - SCOPUS:85015251442

VL - 129

SP - 1275

EP - 1283

JO - Blood

JF - Blood

SN - 0006-4971

IS - 10

ER -