Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: Dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation

Marcos De Lima, Athanasios Anagnostopoulos, Mark Munsell, Munir Shahjahan, Naoto Ueno, Cindy Ippoliti, Borje S. Andersson, James Gajewski, Daniel Couriel, Jorge Cortes, Michele Donato, Joyce Neumann, Richard Champlin, Sergio Giralt

Research output: Contribution to journalArticle

Abstract

Intensity of the preparative regimen is an important component of allogeneic transplantations for myelodysplasia (MDS) or acute myelogenous leukemia (AML). We compared outcomes after a truly nonablative regimen (120 mg/m2 fludarabine, 4 g/m2 cytarabine, and 36 mg/m 2 idarubicin [FAI]) and a more myelosuppressive, reduced-intensity regimen (100 to 150 mg/m2 fludarabine and 140 or 180 mg/m2 melphalan [FM]). We performed a retrospective analysis of 94 patients with MDS (n = 26) and AML (n = 68) treated with FM (n = 62) and FAI (n = 32). The FAI group had a higher proportion of patients in complete remission (CR) at transplantation (44% versus 16%, P = .006), patients in first CR (28% versus 3%, P = .008), and HLA-matched sibling donors (81% versus 40%, P = .001). Median follow-up is 40 months. FM was significantly associated with a higher degree of donor cell engraftment, higher cumulative incidence of treatment-related mortality (TRM; P = .036), and lower cumulative incidence of relapse-related mortality (P = .029). Relapse rate after FAI and FM was 61% and 30%, respectively. Actuarial 3-year survival rate was 30% after FAI and 35% following FM. In a multivariate analysis of patient- and treatment-related prognostic factors, progression-free survival was improved after FM, for patients in CR at transplantation, and for those with intermediate-risk cytogenetics. Survival was improved for patients in CR at transplantation. In conclusion, FM provided better disease control though at a cost of increased TRM and morbidity.

Original languageEnglish (US)
Pages (from-to)865-872
Number of pages8
JournalBlood
Volume104
Issue number3
DOIs
StatePublished - Aug 1 2004

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Disease control
Hematopoietic Stem Cell Transplantation
Myelodysplastic Syndromes
Stem cells
Acute Myeloid Leukemia
Idarubicin
Melphalan
Cytarabine
Transplantation
Therapeutics
Tissue Donors
Costs
Recurrence
Mortality
Incidence
Homologous Transplantation
Cytogenetics
Disease-Free Survival
Conditioning (Psychology)
fludarabine

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome : Dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. / De Lima, Marcos; Anagnostopoulos, Athanasios; Munsell, Mark; Shahjahan, Munir; Ueno, Naoto; Ippoliti, Cindy; Andersson, Borje S.; Gajewski, James; Couriel, Daniel; Cortes, Jorge; Donato, Michele; Neumann, Joyce; Champlin, Richard; Giralt, Sergio.

In: Blood, Vol. 104, No. 3, 01.08.2004, p. 865-872.

Research output: Contribution to journalArticle

De Lima, M, Anagnostopoulos, A, Munsell, M, Shahjahan, M, Ueno, N, Ippoliti, C, Andersson, BS, Gajewski, J, Couriel, D, Cortes, J, Donato, M, Neumann, J, Champlin, R & Giralt, S 2004, 'Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: Dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation', Blood, vol. 104, no. 3, pp. 865-872. https://doi.org/10.1182/blood-2003-11-3750
De Lima, Marcos ; Anagnostopoulos, Athanasios ; Munsell, Mark ; Shahjahan, Munir ; Ueno, Naoto ; Ippoliti, Cindy ; Andersson, Borje S. ; Gajewski, James ; Couriel, Daniel ; Cortes, Jorge ; Donato, Michele ; Neumann, Joyce ; Champlin, Richard ; Giralt, Sergio. / Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome : Dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. In: Blood. 2004 ; Vol. 104, No. 3. pp. 865-872.
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abstract = "Intensity of the preparative regimen is an important component of allogeneic transplantations for myelodysplasia (MDS) or acute myelogenous leukemia (AML). We compared outcomes after a truly nonablative regimen (120 mg/m2 fludarabine, 4 g/m2 cytarabine, and 36 mg/m 2 idarubicin [FAI]) and a more myelosuppressive, reduced-intensity regimen (100 to 150 mg/m2 fludarabine and 140 or 180 mg/m2 melphalan [FM]). We performed a retrospective analysis of 94 patients with MDS (n = 26) and AML (n = 68) treated with FM (n = 62) and FAI (n = 32). The FAI group had a higher proportion of patients in complete remission (CR) at transplantation (44{\%} versus 16{\%}, P = .006), patients in first CR (28{\%} versus 3{\%}, P = .008), and HLA-matched sibling donors (81{\%} versus 40{\%}, P = .001). Median follow-up is 40 months. FM was significantly associated with a higher degree of donor cell engraftment, higher cumulative incidence of treatment-related mortality (TRM; P = .036), and lower cumulative incidence of relapse-related mortality (P = .029). Relapse rate after FAI and FM was 61{\%} and 30{\%}, respectively. Actuarial 3-year survival rate was 30{\%} after FAI and 35{\%} following FM. In a multivariate analysis of patient- and treatment-related prognostic factors, progression-free survival was improved after FM, for patients in CR at transplantation, and for those with intermediate-risk cytogenetics. Survival was improved for patients in CR at transplantation. In conclusion, FM provided better disease control though at a cost of increased TRM and morbidity.",
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T1 - Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome

T2 - Dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation

AU - De Lima, Marcos

AU - Anagnostopoulos, Athanasios

AU - Munsell, Mark

AU - Shahjahan, Munir

AU - Ueno, Naoto

AU - Ippoliti, Cindy

AU - Andersson, Borje S.

AU - Gajewski, James

AU - Couriel, Daniel

AU - Cortes, Jorge

AU - Donato, Michele

AU - Neumann, Joyce

AU - Champlin, Richard

AU - Giralt, Sergio

PY - 2004/8/1

Y1 - 2004/8/1

N2 - Intensity of the preparative regimen is an important component of allogeneic transplantations for myelodysplasia (MDS) or acute myelogenous leukemia (AML). We compared outcomes after a truly nonablative regimen (120 mg/m2 fludarabine, 4 g/m2 cytarabine, and 36 mg/m 2 idarubicin [FAI]) and a more myelosuppressive, reduced-intensity regimen (100 to 150 mg/m2 fludarabine and 140 or 180 mg/m2 melphalan [FM]). We performed a retrospective analysis of 94 patients with MDS (n = 26) and AML (n = 68) treated with FM (n = 62) and FAI (n = 32). The FAI group had a higher proportion of patients in complete remission (CR) at transplantation (44% versus 16%, P = .006), patients in first CR (28% versus 3%, P = .008), and HLA-matched sibling donors (81% versus 40%, P = .001). Median follow-up is 40 months. FM was significantly associated with a higher degree of donor cell engraftment, higher cumulative incidence of treatment-related mortality (TRM; P = .036), and lower cumulative incidence of relapse-related mortality (P = .029). Relapse rate after FAI and FM was 61% and 30%, respectively. Actuarial 3-year survival rate was 30% after FAI and 35% following FM. In a multivariate analysis of patient- and treatment-related prognostic factors, progression-free survival was improved after FM, for patients in CR at transplantation, and for those with intermediate-risk cytogenetics. Survival was improved for patients in CR at transplantation. In conclusion, FM provided better disease control though at a cost of increased TRM and morbidity.

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