Allogeneic hemopoietic stem cell transplantation for patients with high risk acute lymphoblastic leukemia

Favorable impact of chronic graft-versus- host disease on survival and relapse

Panagiotis Zikos, Maria Teresa Van Lint, Tommaso Lamparelli, Francesca Gualandi, Domenico Occhini, Stefania Bregante, Gianni Berisso, Nicola Mordini, Massimo Incagliato, Giusy Fugazza, Mario Sessarego, Andrea Bacigalupo

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Abstract

Background and Objective. The best post-remission therapy for patients with acute lymphoblastic leukemia (ALL) is controversial, and hemopoietic stem cell transplantation (HSCT) is one therapeutic option. The goal of this study is to describe long term results of HSCT in high risk ALL patients. Design and Methods. Between 1978 and 1996, 170 patient with ALL and a median age of 22 years (1-49), underwent an allogeneic HSCT from HLA-identical siblings (n=149), family mismatched donors (n=18) or unrelated HLA matched donors (n=3); 92% of patients had at least one adverse prognostic factor for high risk ALL at diagnosis; one third (33%) were in first remission (CR1) and the majority (85%) received an unmanipulated HSCT with cyclosporin- methotrexate prophylaxis of graft-versus-host disease (GVHD). Results. After a median follow-up of over 6 years, 59 patients are alive and 111 patients have died of leukemia (46%) or transplant related complications (54%). The actuarial 10 year survival is 53%, 38% and 20%, for patients in CR1, CR2 or advanced phase, respectively. The actuarial survival of patients with (n=24) or without (n=46) cytogenetic abnormalities, grafted in CR1/CR2 was respectively 45% and 48% (p=0.5). The year of transplant had a significant impact in multivariate analysis on transplant related mortality (TRM) (p=0.0009) but not on relapse (p=0.3). Chronic GvHD was the most important favorable prognostic factor for survival (p=0.0014) and relapse (p=0.0019). Interpretation and Conclusions. This study confirms that long term survival can be achieved with HSCT in ALL patients, even those with cytogenetic abnormalities. Transplant mortality has been significantly reduced in recent years, whereas leukemia rate relapse has remained unchanged: the latter is influenced by the occurrence of chronic GvHD. Immune intervention post-HSCT may be considered to address this problem.

Original languageEnglish
Pages (from-to)896-903
Number of pages8
JournalHaematologica
Volume83
Issue number10
Publication statusPublished - Oct 1998

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Stem Cell Transplantation
Graft vs Host Disease
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Recurrence
Survival
Transplants
Chromosome Aberrations
Leukemia
Tissue Donors
Mortality
Methotrexate
Cyclosporine
Siblings
Multivariate Analysis
Therapeutics

Keywords

  • Acute lymphoblastic leukemia
  • Graft- versus-host disease
  • Graft-versus leukemia
  • Hemopoietic stem cell transplant

ASJC Scopus subject areas

  • Hematology

Cite this

Allogeneic hemopoietic stem cell transplantation for patients with high risk acute lymphoblastic leukemia : Favorable impact of chronic graft-versus- host disease on survival and relapse. / Zikos, Panagiotis; Van Lint, Maria Teresa; Lamparelli, Tommaso; Gualandi, Francesca; Occhini, Domenico; Bregante, Stefania; Berisso, Gianni; Mordini, Nicola; Incagliato, Massimo; Fugazza, Giusy; Sessarego, Mario; Bacigalupo, Andrea.

In: Haematologica, Vol. 83, No. 10, 10.1998, p. 896-903.

Research output: Contribution to journalArticle

Zikos, Panagiotis ; Van Lint, Maria Teresa ; Lamparelli, Tommaso ; Gualandi, Francesca ; Occhini, Domenico ; Bregante, Stefania ; Berisso, Gianni ; Mordini, Nicola ; Incagliato, Massimo ; Fugazza, Giusy ; Sessarego, Mario ; Bacigalupo, Andrea. / Allogeneic hemopoietic stem cell transplantation for patients with high risk acute lymphoblastic leukemia : Favorable impact of chronic graft-versus- host disease on survival and relapse. In: Haematologica. 1998 ; Vol. 83, No. 10. pp. 896-903.
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abstract = "Background and Objective. The best post-remission therapy for patients with acute lymphoblastic leukemia (ALL) is controversial, and hemopoietic stem cell transplantation (HSCT) is one therapeutic option. The goal of this study is to describe long term results of HSCT in high risk ALL patients. Design and Methods. Between 1978 and 1996, 170 patient with ALL and a median age of 22 years (1-49), underwent an allogeneic HSCT from HLA-identical siblings (n=149), family mismatched donors (n=18) or unrelated HLA matched donors (n=3); 92{\%} of patients had at least one adverse prognostic factor for high risk ALL at diagnosis; one third (33{\%}) were in first remission (CR1) and the majority (85{\%}) received an unmanipulated HSCT with cyclosporin- methotrexate prophylaxis of graft-versus-host disease (GVHD). Results. After a median follow-up of over 6 years, 59 patients are alive and 111 patients have died of leukemia (46{\%}) or transplant related complications (54{\%}). The actuarial 10 year survival is 53{\%}, 38{\%} and 20{\%}, for patients in CR1, CR2 or advanced phase, respectively. The actuarial survival of patients with (n=24) or without (n=46) cytogenetic abnormalities, grafted in CR1/CR2 was respectively 45{\%} and 48{\%} (p=0.5). The year of transplant had a significant impact in multivariate analysis on transplant related mortality (TRM) (p=0.0009) but not on relapse (p=0.3). Chronic GvHD was the most important favorable prognostic factor for survival (p=0.0014) and relapse (p=0.0019). Interpretation and Conclusions. This study confirms that long term survival can be achieved with HSCT in ALL patients, even those with cytogenetic abnormalities. Transplant mortality has been significantly reduced in recent years, whereas leukemia rate relapse has remained unchanged: the latter is influenced by the occurrence of chronic GvHD. Immune intervention post-HSCT may be considered to address this problem.",
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AU - Van Lint, Maria Teresa

AU - Lamparelli, Tommaso

AU - Gualandi, Francesca

AU - Occhini, Domenico

AU - Bregante, Stefania

AU - Berisso, Gianni

AU - Mordini, Nicola

AU - Incagliato, Massimo

AU - Fugazza, Giusy

AU - Sessarego, Mario

AU - Bacigalupo, Andrea

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N2 - Background and Objective. The best post-remission therapy for patients with acute lymphoblastic leukemia (ALL) is controversial, and hemopoietic stem cell transplantation (HSCT) is one therapeutic option. The goal of this study is to describe long term results of HSCT in high risk ALL patients. Design and Methods. Between 1978 and 1996, 170 patient with ALL and a median age of 22 years (1-49), underwent an allogeneic HSCT from HLA-identical siblings (n=149), family mismatched donors (n=18) or unrelated HLA matched donors (n=3); 92% of patients had at least one adverse prognostic factor for high risk ALL at diagnosis; one third (33%) were in first remission (CR1) and the majority (85%) received an unmanipulated HSCT with cyclosporin- methotrexate prophylaxis of graft-versus-host disease (GVHD). Results. After a median follow-up of over 6 years, 59 patients are alive and 111 patients have died of leukemia (46%) or transplant related complications (54%). The actuarial 10 year survival is 53%, 38% and 20%, for patients in CR1, CR2 or advanced phase, respectively. The actuarial survival of patients with (n=24) or without (n=46) cytogenetic abnormalities, grafted in CR1/CR2 was respectively 45% and 48% (p=0.5). The year of transplant had a significant impact in multivariate analysis on transplant related mortality (TRM) (p=0.0009) but not on relapse (p=0.3). Chronic GvHD was the most important favorable prognostic factor for survival (p=0.0014) and relapse (p=0.0019). Interpretation and Conclusions. This study confirms that long term survival can be achieved with HSCT in ALL patients, even those with cytogenetic abnormalities. Transplant mortality has been significantly reduced in recent years, whereas leukemia rate relapse has remained unchanged: the latter is influenced by the occurrence of chronic GvHD. Immune intervention post-HSCT may be considered to address this problem.

AB - Background and Objective. The best post-remission therapy for patients with acute lymphoblastic leukemia (ALL) is controversial, and hemopoietic stem cell transplantation (HSCT) is one therapeutic option. The goal of this study is to describe long term results of HSCT in high risk ALL patients. Design and Methods. Between 1978 and 1996, 170 patient with ALL and a median age of 22 years (1-49), underwent an allogeneic HSCT from HLA-identical siblings (n=149), family mismatched donors (n=18) or unrelated HLA matched donors (n=3); 92% of patients had at least one adverse prognostic factor for high risk ALL at diagnosis; one third (33%) were in first remission (CR1) and the majority (85%) received an unmanipulated HSCT with cyclosporin- methotrexate prophylaxis of graft-versus-host disease (GVHD). Results. After a median follow-up of over 6 years, 59 patients are alive and 111 patients have died of leukemia (46%) or transplant related complications (54%). The actuarial 10 year survival is 53%, 38% and 20%, for patients in CR1, CR2 or advanced phase, respectively. The actuarial survival of patients with (n=24) or without (n=46) cytogenetic abnormalities, grafted in CR1/CR2 was respectively 45% and 48% (p=0.5). The year of transplant had a significant impact in multivariate analysis on transplant related mortality (TRM) (p=0.0009) but not on relapse (p=0.3). Chronic GvHD was the most important favorable prognostic factor for survival (p=0.0014) and relapse (p=0.0019). Interpretation and Conclusions. This study confirms that long term survival can be achieved with HSCT in ALL patients, even those with cytogenetic abnormalities. Transplant mortality has been significantly reduced in recent years, whereas leukemia rate relapse has remained unchanged: the latter is influenced by the occurrence of chronic GvHD. Immune intervention post-HSCT may be considered to address this problem.

KW - Acute lymphoblastic leukemia

KW - Graft- versus-host disease

KW - Graft-versus leukemia

KW - Hemopoietic stem cell transplant

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