Risk-stratified outcomes of nonmyeloablative HLA-haploidentical BMT with high-dose posttransplantation cyclophosphamide

Shannon R. McCurdy, Jennifer A. Kanakry, Margaret Showel, Hua Ling Tsai, F Javier Bolanos Meade, Gary Rosner, Christopher G. Kanakry, Karlo Perica, Heather Symons, Robert A Brodsky, Douglas Gladstone, Carol Ann Huff, Keith Pratz, Gabrielle T. Prince, Amy Dezern, Ivana Gojo, William H. Matsui, Ivan M Borrello, Michael A. McDevitt, Lode SwinnenB Douglas Smith, Mark J Levis, Richard F Ambinder, Leo Luznik, Richard J Jones, Ephraim J Fuchs, Yvette L. Kasamon

Research output: Contribution to journalArticle

Abstract

Related HLA-haploidentical blood or marrow transplantation (BMT) with high-dose posttransplantation cyclophosphamide (PTCy) is being increasingly used because of its acceptable safety profile. To better define outcomes of nonmyeloablative (NMA) HLA-haploidentical BMT with PTCy, 372 consecutive adult hematologic malignancy patients who underwent this procedure were retrospectively studied. Risk-stratified outcomes were evaluated using the refined Disease Risk Index (DRI), developed to stratify disease risk across histologies and allogeneic BMT regimens. Patients received uniform conditioning, T-cell-replete allografting, then PTCy, mycophenolate mofetil, and tacrolimus. Six-month probabilities of nonrelapse mortality and severe acute graft-versus-host disease were 8% and 4%. With 4.1-year median follow-up, 3-year probabilities of relapse, progression-free survival (PFS), and overall survival (OS) were 46%, 40%, and 50%, respectively. By refined DRI group, low (n = 71), intermediate (n = 241), and high/very high (n = 60) risk groups had 3-year PFS estimates of 65%, 37%, and 22% (P <.0001), with corresponding 3-year OS estimates of 71%, 48%, and 35% (P = .0001). On multivariable analyses, the DRI was statistically significantly associated with relapse, PFS, and OS (each P <.001). This analysis demonstrates that the DRI effectively risk stratifies recipients of NMA HLA-haploidentical BMT with PTCy and also suggests that this transplantation platform yields similar survivals to those seen with HLA-matched BMT.

Original languageEnglish (US)
Pages (from-to)3024-3031
Number of pages8
JournalBlood
Volume125
Issue number19
DOIs
StatePublished - May 7 2015

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Cyclophosphamide
Blood
Transplantation
Bone Marrow
Disease-Free Survival
Survival
Mycophenolic Acid
Recurrence
Histology
T-cells
Homologous Transplantation
Tacrolimus
Graft vs Host Disease
Hematologic Neoplasms
Grafts
T-Lymphocytes
Safety
Mortality

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Risk-stratified outcomes of nonmyeloablative HLA-haploidentical BMT with high-dose posttransplantation cyclophosphamide. / McCurdy, Shannon R.; Kanakry, Jennifer A.; Showel, Margaret; Tsai, Hua Ling; Bolanos Meade, F Javier; Rosner, Gary; Kanakry, Christopher G.; Perica, Karlo; Symons, Heather; Brodsky, Robert A; Gladstone, Douglas; Huff, Carol Ann; Pratz, Keith; Prince, Gabrielle T.; Dezern, Amy; Gojo, Ivana; Matsui, William H.; Borrello, Ivan M; McDevitt, Michael A.; Swinnen, Lode; Smith, B Douglas; Levis, Mark J; Ambinder, Richard F; Luznik, Leo; Jones, Richard J; Fuchs, Ephraim J; Kasamon, Yvette L.

In: Blood, Vol. 125, No. 19, 07.05.2015, p. 3024-3031.

Research output: Contribution to journalArticle

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abstract = "Related HLA-haploidentical blood or marrow transplantation (BMT) with high-dose posttransplantation cyclophosphamide (PTCy) is being increasingly used because of its acceptable safety profile. To better define outcomes of nonmyeloablative (NMA) HLA-haploidentical BMT with PTCy, 372 consecutive adult hematologic malignancy patients who underwent this procedure were retrospectively studied. Risk-stratified outcomes were evaluated using the refined Disease Risk Index (DRI), developed to stratify disease risk across histologies and allogeneic BMT regimens. Patients received uniform conditioning, T-cell-replete allografting, then PTCy, mycophenolate mofetil, and tacrolimus. Six-month probabilities of nonrelapse mortality and severe acute graft-versus-host disease were 8{\%} and 4{\%}. With 4.1-year median follow-up, 3-year probabilities of relapse, progression-free survival (PFS), and overall survival (OS) were 46{\%}, 40{\%}, and 50{\%}, respectively. By refined DRI group, low (n = 71), intermediate (n = 241), and high/very high (n = 60) risk groups had 3-year PFS estimates of 65{\%}, 37{\%}, and 22{\%} (P <.0001), with corresponding 3-year OS estimates of 71{\%}, 48{\%}, and 35{\%} (P = .0001). On multivariable analyses, the DRI was statistically significantly associated with relapse, PFS, and OS (each P <.001). This analysis demonstrates that the DRI effectively risk stratifies recipients of NMA HLA-haploidentical BMT with PTCy and also suggests that this transplantation platform yields similar survivals to those seen with HLA-matched BMT.",
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AU - McCurdy, Shannon R.

AU - Kanakry, Jennifer A.

AU - Showel, Margaret

AU - Tsai, Hua Ling

AU - Bolanos Meade, F Javier

AU - Rosner, Gary

AU - Kanakry, Christopher G.

AU - Perica, Karlo

AU - Symons, Heather

AU - Brodsky, Robert A

AU - Gladstone, Douglas

AU - Huff, Carol Ann

AU - Pratz, Keith

AU - Prince, Gabrielle T.

AU - Dezern, Amy

AU - Gojo, Ivana

AU - Matsui, William H.

AU - Borrello, Ivan M

AU - McDevitt, Michael A.

AU - Swinnen, Lode

AU - Smith, B Douglas

AU - Levis, Mark J

AU - Ambinder, Richard F

AU - Luznik, Leo

AU - Jones, Richard J

AU - Fuchs, Ephraim J

AU - Kasamon, Yvette L.

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N2 - Related HLA-haploidentical blood or marrow transplantation (BMT) with high-dose posttransplantation cyclophosphamide (PTCy) is being increasingly used because of its acceptable safety profile. To better define outcomes of nonmyeloablative (NMA) HLA-haploidentical BMT with PTCy, 372 consecutive adult hematologic malignancy patients who underwent this procedure were retrospectively studied. Risk-stratified outcomes were evaluated using the refined Disease Risk Index (DRI), developed to stratify disease risk across histologies and allogeneic BMT regimens. Patients received uniform conditioning, T-cell-replete allografting, then PTCy, mycophenolate mofetil, and tacrolimus. Six-month probabilities of nonrelapse mortality and severe acute graft-versus-host disease were 8% and 4%. With 4.1-year median follow-up, 3-year probabilities of relapse, progression-free survival (PFS), and overall survival (OS) were 46%, 40%, and 50%, respectively. By refined DRI group, low (n = 71), intermediate (n = 241), and high/very high (n = 60) risk groups had 3-year PFS estimates of 65%, 37%, and 22% (P <.0001), with corresponding 3-year OS estimates of 71%, 48%, and 35% (P = .0001). On multivariable analyses, the DRI was statistically significantly associated with relapse, PFS, and OS (each P <.001). This analysis demonstrates that the DRI effectively risk stratifies recipients of NMA HLA-haploidentical BMT with PTCy and also suggests that this transplantation platform yields similar survivals to those seen with HLA-matched BMT.

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