Graft versus host disease prophylaxis with low-dose cyclosporine-A reduces the risk of relapse in children with acute leukemia given HLA- identical sibling bone marrow transplantation: Results of a randomized trial

Franco Locatelli, Marco Zecca, Roberto Rondelli, Federico Bonetti, Giorgio Dini, Arcangelo Prete, Chiara Messina, Cornelio Uderzo, Mimmo Ripaldi, Fulvio Porta, Giovanna Giorgiani, Eugenia Giraldi, Andrea Pession

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

Leukemia relapse is a major cause of treatment failure for patients with acute leukemia given allogeneic bone marrow transplantation (BMT). This study evaluated whether a reduction of the dosage of cyclosporine-A (Cs-A) used for graft versus host disease (GVHD) prophylaxis could reduce relapse rate (RR) in children with acute leukemia given BMT. Fifty-nine children who had transplantation from HLA-identical siblings were randomized to receive Cs-A intravenously at a dosage of 1 mg/kg/d (Cs-A1) or of 3 mg/kg/d (Cs-A3) until patients were able to tolerate oral intake. Subsequently, both groups received Cs-A orally at a dosage of 6 mg/kg/d, with discontinuation 5 months after BMT. The probability of developing grade II-IV acute GVHD was 57% for the Cs-A1 group versus 38% for the Cs-A3 group (P = .06); the probability of developing chronic GVHD was 30% for the Cs-A1 group and 26% for the Cs-A3 group (P = NS). Three patients died of grade IV acute GVHD: 2 were in the Cs- A1 and the third in the Cs-A3 group. The RR was 15% for the Cs-A1 group and 41% for the Cs-A3 group (P = .034); 1-year transplant-related mortality estimates were 17% and 7%, respectively (P = NS). With a median observation time of 44 months from BMT, the 5-year event-free survival for children belonging to Cs-A1 and Cs-A3 groups was 70% and 51%, respectively (P = .15). Our data demonstrate that the use of low Cs-A doses is associated with a statistically significant reduction of leukemia relapse, probably due to an increased graft versus leukemia effect. (C) 2000 by The American Society of Hematology.

Original languageEnglish
Pages (from-to)1572-1579
Number of pages8
JournalBlood
Volume95
Issue number5
Publication statusPublished - Mar 1 2000

Fingerprint

Graft vs Host Disease
Bone Marrow Transplantation
Grafts
Cyclosporine
Siblings
Bone
Leukemia
Recurrence
Transplants
Homologous Transplantation
Treatment Failure
Disease-Free Survival
Transplantation
Observation
Mortality

ASJC Scopus subject areas

  • Hematology

Cite this

Graft versus host disease prophylaxis with low-dose cyclosporine-A reduces the risk of relapse in children with acute leukemia given HLA- identical sibling bone marrow transplantation : Results of a randomized trial. / Locatelli, Franco; Zecca, Marco; Rondelli, Roberto; Bonetti, Federico; Dini, Giorgio; Prete, Arcangelo; Messina, Chiara; Uderzo, Cornelio; Ripaldi, Mimmo; Porta, Fulvio; Giorgiani, Giovanna; Giraldi, Eugenia; Pession, Andrea.

In: Blood, Vol. 95, No. 5, 01.03.2000, p. 1572-1579.

Research output: Contribution to journalArticle

Locatelli, Franco ; Zecca, Marco ; Rondelli, Roberto ; Bonetti, Federico ; Dini, Giorgio ; Prete, Arcangelo ; Messina, Chiara ; Uderzo, Cornelio ; Ripaldi, Mimmo ; Porta, Fulvio ; Giorgiani, Giovanna ; Giraldi, Eugenia ; Pession, Andrea. / Graft versus host disease prophylaxis with low-dose cyclosporine-A reduces the risk of relapse in children with acute leukemia given HLA- identical sibling bone marrow transplantation : Results of a randomized trial. In: Blood. 2000 ; Vol. 95, No. 5. pp. 1572-1579.
@article{91aba2bdf28c49e5affc72d8d1154eb7,
title = "Graft versus host disease prophylaxis with low-dose cyclosporine-A reduces the risk of relapse in children with acute leukemia given HLA- identical sibling bone marrow transplantation: Results of a randomized trial",
abstract = "Leukemia relapse is a major cause of treatment failure for patients with acute leukemia given allogeneic bone marrow transplantation (BMT). This study evaluated whether a reduction of the dosage of cyclosporine-A (Cs-A) used for graft versus host disease (GVHD) prophylaxis could reduce relapse rate (RR) in children with acute leukemia given BMT. Fifty-nine children who had transplantation from HLA-identical siblings were randomized to receive Cs-A intravenously at a dosage of 1 mg/kg/d (Cs-A1) or of 3 mg/kg/d (Cs-A3) until patients were able to tolerate oral intake. Subsequently, both groups received Cs-A orally at a dosage of 6 mg/kg/d, with discontinuation 5 months after BMT. The probability of developing grade II-IV acute GVHD was 57{\%} for the Cs-A1 group versus 38{\%} for the Cs-A3 group (P = .06); the probability of developing chronic GVHD was 30{\%} for the Cs-A1 group and 26{\%} for the Cs-A3 group (P = NS). Three patients died of grade IV acute GVHD: 2 were in the Cs- A1 and the third in the Cs-A3 group. The RR was 15{\%} for the Cs-A1 group and 41{\%} for the Cs-A3 group (P = .034); 1-year transplant-related mortality estimates were 17{\%} and 7{\%}, respectively (P = NS). With a median observation time of 44 months from BMT, the 5-year event-free survival for children belonging to Cs-A1 and Cs-A3 groups was 70{\%} and 51{\%}, respectively (P = .15). Our data demonstrate that the use of low Cs-A doses is associated with a statistically significant reduction of leukemia relapse, probably due to an increased graft versus leukemia effect. (C) 2000 by The American Society of Hematology.",
author = "Franco Locatelli and Marco Zecca and Roberto Rondelli and Federico Bonetti and Giorgio Dini and Arcangelo Prete and Chiara Messina and Cornelio Uderzo and Mimmo Ripaldi and Fulvio Porta and Giovanna Giorgiani and Eugenia Giraldi and Andrea Pession",
year = "2000",
month = "3",
day = "1",
language = "English",
volume = "95",
pages = "1572--1579",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "5",

}

TY - JOUR

T1 - Graft versus host disease prophylaxis with low-dose cyclosporine-A reduces the risk of relapse in children with acute leukemia given HLA- identical sibling bone marrow transplantation

T2 - Results of a randomized trial

AU - Locatelli, Franco

AU - Zecca, Marco

AU - Rondelli, Roberto

AU - Bonetti, Federico

AU - Dini, Giorgio

AU - Prete, Arcangelo

AU - Messina, Chiara

AU - Uderzo, Cornelio

AU - Ripaldi, Mimmo

AU - Porta, Fulvio

AU - Giorgiani, Giovanna

AU - Giraldi, Eugenia

AU - Pession, Andrea

PY - 2000/3/1

Y1 - 2000/3/1

N2 - Leukemia relapse is a major cause of treatment failure for patients with acute leukemia given allogeneic bone marrow transplantation (BMT). This study evaluated whether a reduction of the dosage of cyclosporine-A (Cs-A) used for graft versus host disease (GVHD) prophylaxis could reduce relapse rate (RR) in children with acute leukemia given BMT. Fifty-nine children who had transplantation from HLA-identical siblings were randomized to receive Cs-A intravenously at a dosage of 1 mg/kg/d (Cs-A1) or of 3 mg/kg/d (Cs-A3) until patients were able to tolerate oral intake. Subsequently, both groups received Cs-A orally at a dosage of 6 mg/kg/d, with discontinuation 5 months after BMT. The probability of developing grade II-IV acute GVHD was 57% for the Cs-A1 group versus 38% for the Cs-A3 group (P = .06); the probability of developing chronic GVHD was 30% for the Cs-A1 group and 26% for the Cs-A3 group (P = NS). Three patients died of grade IV acute GVHD: 2 were in the Cs- A1 and the third in the Cs-A3 group. The RR was 15% for the Cs-A1 group and 41% for the Cs-A3 group (P = .034); 1-year transplant-related mortality estimates were 17% and 7%, respectively (P = NS). With a median observation time of 44 months from BMT, the 5-year event-free survival for children belonging to Cs-A1 and Cs-A3 groups was 70% and 51%, respectively (P = .15). Our data demonstrate that the use of low Cs-A doses is associated with a statistically significant reduction of leukemia relapse, probably due to an increased graft versus leukemia effect. (C) 2000 by The American Society of Hematology.

AB - Leukemia relapse is a major cause of treatment failure for patients with acute leukemia given allogeneic bone marrow transplantation (BMT). This study evaluated whether a reduction of the dosage of cyclosporine-A (Cs-A) used for graft versus host disease (GVHD) prophylaxis could reduce relapse rate (RR) in children with acute leukemia given BMT. Fifty-nine children who had transplantation from HLA-identical siblings were randomized to receive Cs-A intravenously at a dosage of 1 mg/kg/d (Cs-A1) or of 3 mg/kg/d (Cs-A3) until patients were able to tolerate oral intake. Subsequently, both groups received Cs-A orally at a dosage of 6 mg/kg/d, with discontinuation 5 months after BMT. The probability of developing grade II-IV acute GVHD was 57% for the Cs-A1 group versus 38% for the Cs-A3 group (P = .06); the probability of developing chronic GVHD was 30% for the Cs-A1 group and 26% for the Cs-A3 group (P = NS). Three patients died of grade IV acute GVHD: 2 were in the Cs- A1 and the third in the Cs-A3 group. The RR was 15% for the Cs-A1 group and 41% for the Cs-A3 group (P = .034); 1-year transplant-related mortality estimates were 17% and 7%, respectively (P = NS). With a median observation time of 44 months from BMT, the 5-year event-free survival for children belonging to Cs-A1 and Cs-A3 groups was 70% and 51%, respectively (P = .15). Our data demonstrate that the use of low Cs-A doses is associated with a statistically significant reduction of leukemia relapse, probably due to an increased graft versus leukemia effect. (C) 2000 by The American Society of Hematology.

UR - http://www.scopus.com/inward/record.url?scp=17744409283&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17744409283&partnerID=8YFLogxK

M3 - Article

C2 - 10688810

AN - SCOPUS:17744409283

VL - 95

SP - 1572

EP - 1579

JO - Blood

JF - Blood

SN - 0006-4971

IS - 5

ER -