Definition of relapse risk and role of nonanthracycline drags for consolidation in patients with acute promyelocytic leukemia

A joint study of the PETHEMA and GIMEMA cooperative groups

M. A. Sanz, F. Lo Coco, G. Martin, G. Avvisati, C. Rayon, T. Barbui, J. Diaz-Mediavilla, G. Fioritoni, J. D. Gonzalez, V. Liso, J. Esteve, F. Ferrara, P. Bolufer, C. Bernasconi, M. Gonzalez, F. Rodeghiero, D. Colomer, M. C. Petti, J. M. Ribera, F. Mandelli

Research output: Contribution to journalArticle

454 Citations (Scopus)

Abstract

Preliminary independent reports of the Italian GIMEMA and the Spanish PETHEMA trials for newly diagnosed acute promyelocytic leukemia (APL) indicated a similarly high antileukemic efficacy in terms of complete remission and disease-free survival rates. To better investigate these studies and the prognostic factors influencing relapse risk, this study analyzed the updated results of 217 patients with PML/RARαpositive APL enrolled in GIMEMA (n = 108) and PETHEMA (n = 109). All patients received identical induction (AIDA schedule) and maintenance. For consolidation, GIMEMA patients received 3 courses including idarubicin/cytarabine, mitoxantrone/etoposide, and idarubicin/cytarabine/thioguanine, whereas PETHEMA patients received the same drugs and dose schedule of Idarubicin and mitoxantrone with the omission of nonintercalating agents. Depending on whether molecular relapses were classified as censored or uncensored events, the 3-year Kaplan-Meier estimates of relapse-free survival (RFS) for the combined series were 90 ± 2% and 86 ± 2%, respectively. Minor differences observed between the 2 patient cohorts were negligible. Multivariate regression analysis of RFS showed that initial leukocyte (WBC) and platelet counts were the only variables with independent prognostic value. The resulting predictive model for RFS demonstrated its capability of segregating patients into low-risk (WBC count ≤ 10 x 109/L, platelet count > 40 x 109/L), intermediate-risk (WBC count ≤ 10 x 109/L, platelets ≤ 40 x 109/L), and high-risk (WBC count > 10 x 109/L.) groups, with distinctive RFS curves (P <.0001). The conclusions are that omission of nonanthracycline drugs from the AIDA regimen is not associated with reduced antileukemic efficacy and a simple predictive model may be used for risk-adapted therapy in this disease. (C) 2000 by The American Society of Hematology.

Original languageEnglish
Pages (from-to)1247-1253
Number of pages7
JournalBlood
Volume96
Issue number4
Publication statusPublished - Aug 15 2000

Fingerprint

Acute Promyelocytic Leukemia
Consolidation
Drag
Idarubicin
Recurrence
Platelets
Mitoxantrone
Cytarabine
Survival
Platelet Count
Appointments and Schedules
Thioguanine
Etoposide
Regression analysis
Pharmaceutical Preparations
Kaplan-Meier Estimate
Leukocyte Count
Disease-Free Survival
Blood Platelets
Multivariate Analysis

ASJC Scopus subject areas

  • Hematology

Cite this

Definition of relapse risk and role of nonanthracycline drags for consolidation in patients with acute promyelocytic leukemia : A joint study of the PETHEMA and GIMEMA cooperative groups. / Sanz, M. A.; Lo Coco, F.; Martin, G.; Avvisati, G.; Rayon, C.; Barbui, T.; Diaz-Mediavilla, J.; Fioritoni, G.; Gonzalez, J. D.; Liso, V.; Esteve, J.; Ferrara, F.; Bolufer, P.; Bernasconi, C.; Gonzalez, M.; Rodeghiero, F.; Colomer, D.; Petti, M. C.; Ribera, J. M.; Mandelli, F.

In: Blood, Vol. 96, No. 4, 15.08.2000, p. 1247-1253.

Research output: Contribution to journalArticle

Sanz, MA, Lo Coco, F, Martin, G, Avvisati, G, Rayon, C, Barbui, T, Diaz-Mediavilla, J, Fioritoni, G, Gonzalez, JD, Liso, V, Esteve, J, Ferrara, F, Bolufer, P, Bernasconi, C, Gonzalez, M, Rodeghiero, F, Colomer, D, Petti, MC, Ribera, JM & Mandelli, F 2000, 'Definition of relapse risk and role of nonanthracycline drags for consolidation in patients with acute promyelocytic leukemia: A joint study of the PETHEMA and GIMEMA cooperative groups', Blood, vol. 96, no. 4, pp. 1247-1253.
Sanz, M. A. ; Lo Coco, F. ; Martin, G. ; Avvisati, G. ; Rayon, C. ; Barbui, T. ; Diaz-Mediavilla, J. ; Fioritoni, G. ; Gonzalez, J. D. ; Liso, V. ; Esteve, J. ; Ferrara, F. ; Bolufer, P. ; Bernasconi, C. ; Gonzalez, M. ; Rodeghiero, F. ; Colomer, D. ; Petti, M. C. ; Ribera, J. M. ; Mandelli, F. / Definition of relapse risk and role of nonanthracycline drags for consolidation in patients with acute promyelocytic leukemia : A joint study of the PETHEMA and GIMEMA cooperative groups. In: Blood. 2000 ; Vol. 96, No. 4. pp. 1247-1253.
@article{af94cc65699d422e8dcd1b133adab5eb,
title = "Definition of relapse risk and role of nonanthracycline drags for consolidation in patients with acute promyelocytic leukemia: A joint study of the PETHEMA and GIMEMA cooperative groups",
abstract = "Preliminary independent reports of the Italian GIMEMA and the Spanish PETHEMA trials for newly diagnosed acute promyelocytic leukemia (APL) indicated a similarly high antileukemic efficacy in terms of complete remission and disease-free survival rates. To better investigate these studies and the prognostic factors influencing relapse risk, this study analyzed the updated results of 217 patients with PML/RARαpositive APL enrolled in GIMEMA (n = 108) and PETHEMA (n = 109). All patients received identical induction (AIDA schedule) and maintenance. For consolidation, GIMEMA patients received 3 courses including idarubicin/cytarabine, mitoxantrone/etoposide, and idarubicin/cytarabine/thioguanine, whereas PETHEMA patients received the same drugs and dose schedule of Idarubicin and mitoxantrone with the omission of nonintercalating agents. Depending on whether molecular relapses were classified as censored or uncensored events, the 3-year Kaplan-Meier estimates of relapse-free survival (RFS) for the combined series were 90 ± 2{\%} and 86 ± 2{\%}, respectively. Minor differences observed between the 2 patient cohorts were negligible. Multivariate regression analysis of RFS showed that initial leukocyte (WBC) and platelet counts were the only variables with independent prognostic value. The resulting predictive model for RFS demonstrated its capability of segregating patients into low-risk (WBC count ≤ 10 x 109/L, platelet count > 40 x 109/L), intermediate-risk (WBC count ≤ 10 x 109/L, platelets ≤ 40 x 109/L), and high-risk (WBC count > 10 x 109/L.) groups, with distinctive RFS curves (P <.0001). The conclusions are that omission of nonanthracycline drugs from the AIDA regimen is not associated with reduced antileukemic efficacy and a simple predictive model may be used for risk-adapted therapy in this disease. (C) 2000 by The American Society of Hematology.",
author = "Sanz, {M. A.} and {Lo Coco}, F. and G. Martin and G. Avvisati and C. Rayon and T. Barbui and J. Diaz-Mediavilla and G. Fioritoni and Gonzalez, {J. D.} and V. Liso and J. Esteve and F. Ferrara and P. Bolufer and C. Bernasconi and M. Gonzalez and F. Rodeghiero and D. Colomer and Petti, {M. C.} and Ribera, {J. M.} and F. Mandelli",
year = "2000",
month = "8",
day = "15",
language = "English",
volume = "96",
pages = "1247--1253",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "4",

}

TY - JOUR

T1 - Definition of relapse risk and role of nonanthracycline drags for consolidation in patients with acute promyelocytic leukemia

T2 - A joint study of the PETHEMA and GIMEMA cooperative groups

AU - Sanz, M. A.

AU - Lo Coco, F.

AU - Martin, G.

AU - Avvisati, G.

AU - Rayon, C.

AU - Barbui, T.

AU - Diaz-Mediavilla, J.

AU - Fioritoni, G.

AU - Gonzalez, J. D.

AU - Liso, V.

AU - Esteve, J.

AU - Ferrara, F.

AU - Bolufer, P.

AU - Bernasconi, C.

AU - Gonzalez, M.

AU - Rodeghiero, F.

AU - Colomer, D.

AU - Petti, M. C.

AU - Ribera, J. M.

AU - Mandelli, F.

PY - 2000/8/15

Y1 - 2000/8/15

N2 - Preliminary independent reports of the Italian GIMEMA and the Spanish PETHEMA trials for newly diagnosed acute promyelocytic leukemia (APL) indicated a similarly high antileukemic efficacy in terms of complete remission and disease-free survival rates. To better investigate these studies and the prognostic factors influencing relapse risk, this study analyzed the updated results of 217 patients with PML/RARαpositive APL enrolled in GIMEMA (n = 108) and PETHEMA (n = 109). All patients received identical induction (AIDA schedule) and maintenance. For consolidation, GIMEMA patients received 3 courses including idarubicin/cytarabine, mitoxantrone/etoposide, and idarubicin/cytarabine/thioguanine, whereas PETHEMA patients received the same drugs and dose schedule of Idarubicin and mitoxantrone with the omission of nonintercalating agents. Depending on whether molecular relapses were classified as censored or uncensored events, the 3-year Kaplan-Meier estimates of relapse-free survival (RFS) for the combined series were 90 ± 2% and 86 ± 2%, respectively. Minor differences observed between the 2 patient cohorts were negligible. Multivariate regression analysis of RFS showed that initial leukocyte (WBC) and platelet counts were the only variables with independent prognostic value. The resulting predictive model for RFS demonstrated its capability of segregating patients into low-risk (WBC count ≤ 10 x 109/L, platelet count > 40 x 109/L), intermediate-risk (WBC count ≤ 10 x 109/L, platelets ≤ 40 x 109/L), and high-risk (WBC count > 10 x 109/L.) groups, with distinctive RFS curves (P <.0001). The conclusions are that omission of nonanthracycline drugs from the AIDA regimen is not associated with reduced antileukemic efficacy and a simple predictive model may be used for risk-adapted therapy in this disease. (C) 2000 by The American Society of Hematology.

AB - Preliminary independent reports of the Italian GIMEMA and the Spanish PETHEMA trials for newly diagnosed acute promyelocytic leukemia (APL) indicated a similarly high antileukemic efficacy in terms of complete remission and disease-free survival rates. To better investigate these studies and the prognostic factors influencing relapse risk, this study analyzed the updated results of 217 patients with PML/RARαpositive APL enrolled in GIMEMA (n = 108) and PETHEMA (n = 109). All patients received identical induction (AIDA schedule) and maintenance. For consolidation, GIMEMA patients received 3 courses including idarubicin/cytarabine, mitoxantrone/etoposide, and idarubicin/cytarabine/thioguanine, whereas PETHEMA patients received the same drugs and dose schedule of Idarubicin and mitoxantrone with the omission of nonintercalating agents. Depending on whether molecular relapses were classified as censored or uncensored events, the 3-year Kaplan-Meier estimates of relapse-free survival (RFS) for the combined series were 90 ± 2% and 86 ± 2%, respectively. Minor differences observed between the 2 patient cohorts were negligible. Multivariate regression analysis of RFS showed that initial leukocyte (WBC) and platelet counts were the only variables with independent prognostic value. The resulting predictive model for RFS demonstrated its capability of segregating patients into low-risk (WBC count ≤ 10 x 109/L, platelet count > 40 x 109/L), intermediate-risk (WBC count ≤ 10 x 109/L, platelets ≤ 40 x 109/L), and high-risk (WBC count > 10 x 109/L.) groups, with distinctive RFS curves (P <.0001). The conclusions are that omission of nonanthracycline drugs from the AIDA regimen is not associated with reduced antileukemic efficacy and a simple predictive model may be used for risk-adapted therapy in this disease. (C) 2000 by The American Society of Hematology.

UR - http://www.scopus.com/inward/record.url?scp=0034663162&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034663162&partnerID=8YFLogxK

M3 - Article

VL - 96

SP - 1247

EP - 1253

JO - Blood

JF - Blood

SN - 0006-4971

IS - 4

ER -