Alternative donor transplantation for myelodysplastic syndromes: Haploidentical relative and matched unrelated donors

Michael R. Grunwald; Mei Jie Zhang; Hany Elmariah; Mariam H. Johnson; Andrew St Martin; Asad Bashey; Minoo Battiwalla; Christopher N. Bredeson; Edward Copelan; Corey S. Cutler; Biju R. George; Vikas Gupta; Christopher Kanakry; Rohtesh S. Mehta; Filippo Milano; Alberto Mussetti; Ryotaro Nakamura; Taiga Nishihori; Wael Saber; Melhem Solh; Daniel J. Weisdorf; Mary Eapen

doi:10.1182/bloodadvances.2020003654

Alternative donor transplantation for myelodysplastic syndromes: Haploidentical relative and matched unrelated donors

Michael R. Grunwald, Mei Jie Zhang, Hany Elmariah, Mariam H. Johnson, Andrew St Martin, Asad Bashey, Minoo Battiwalla, Christopher N. Bredeson, Edward Copelan, Corey S. Cutler, Biju R. George, Vikas Gupta, Christopher Kanakry, Rohtesh S. Mehta, Filippo Milano, Alberto Mussetti, Ryotaro Nakamura, Taiga Nishihori, Wael Saber, Melhem SolhDaniel J. Weisdorf, Mary Eapen

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

Abstract

We compared outcomes in 603 patients with myelodysplastic syndrome (MDS) after HLA-haploidentical relative (n = 176) and HLA-matched unrelated (n = 427) donor hematopoietic cell transplantation (HCT) from 2012 to 2017, using the Center for International Blood and Marrow Transplant Research database. All transplantations used reduced-intensity conditioning regimens. Total-body irradiation plus cyclophosphamide and fludarabine was the predominant regimen for HLA-haploidentical relative donor HCT, and graft-versus-host disease (GVHD) prophylaxis was uniformly posttransplantation cyclophosphamide, calcineurin inhibitor, and mycophenolate. Fludarabine with busulfan or melphalan was the predominant regimen for HLA-matched unrelated donor HCT, and GVHD prophylaxis was calcineurin inhibitor with mycophenolate or methotrexate. Results of multivariate analysis revealed higher relapse (hazard ratio [HR], 1.56; P = .0055; 2-year relapse rate, 48% vs 33%) and lower disease-free survival (DFS) rates after HLA-haploidentical relative donor HCT (HR, 1.29; P = .042; 2-year DFS, 29% vs 36%). However, overall survival (OS) rates did not differ between donor type (HR, 0.94; P = .65; 2-year OS, 46% for HLA-haploidentical and 44% for HLA-matched unrelated donor HCT) because of mortality associated with chronic GVHD. Acute grade 2 to 4 GVHD (HR, 0.44; P < .0001) and chronic GVHD (HR, 0.36; P < .0001) were lower after HLA-haploidentical relative donor HCT. By 2 years, probability of death resulting from chronic GVHD was lower after HLA-haploidentical relative compared with HLA-matched unrelated donor HCT (6% vs 21%), negating any potential survival advantage from better relapse control. Both donor types extend access to transplantation for patients with MDS; strategies for better relapse control are desirable for HLA-haploidentical relative donor HCT, and effective GVHD prophylaxis regimens are needed for unrelated donor HCT.

Original language	English (US)
Pages (from-to)	975-983
Number of pages	9
Journal	Blood Advances
Volume	5
Issue number	4
DOIs	https://doi.org/10.1182/bloodadvances.2020003654
State	Published - Feb 23 2021

Bibliographical note

Publisher Copyright:
© 2021 American Society of Hematology. All rights reserved.

Keywords

Graft vs Host Disease
Histocompatibility Testing
Humans
Myelodysplastic Syndromes/therapy
Transplantation Conditioning
Unrelated Donors

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Publisher link

10.1182/bloodadvances.2020003654

Find It

Find It at U of M Libraries

Cite this

Grunwald, M. R., Zhang, M. J., Elmariah, H., Johnson, M. H., Martin, A. S., Bashey, A., Battiwalla, M., Bredeson, C. N., Copelan, E., Cutler, C. S., George, B. R., Gupta, V., Kanakry, C., Mehta, R. S., Milano, F., Mussetti, A., Nakamura, R., Nishihori, T., Saber, W., ... Eapen, M. (2021). Alternative donor transplantation for myelodysplastic syndromes: Haploidentical relative and matched unrelated donors. Blood Advances, 5(4), 975-983. https://doi.org/10.1182/bloodadvances.2020003654

Grunwald, MR, Zhang, MJ, Elmariah, H, Johnson, MH, Martin, AS, Bashey, A, Battiwalla, M, Bredeson, CN, Copelan, E, Cutler, CS, George, BR, Gupta, V, Kanakry, C, Mehta, RS, Milano, F, Mussetti, A, Nakamura, R, Nishihori, T, Saber, W, Solh, M, Weisdorf, DJ & Eapen, M 2021, 'Alternative donor transplantation for myelodysplastic syndromes: Haploidentical relative and matched unrelated donors', Blood Advances, vol. 5, no. 4, pp. 975-983. https://doi.org/10.1182/bloodadvances.2020003654

@article{5a315bdd3e3f45a6a877bff54ddf4bac,

title = "Alternative donor transplantation for myelodysplastic syndromes: Haploidentical relative and matched unrelated donors",

abstract = "We compared outcomes in 603 patients with myelodysplastic syndrome (MDS) after HLA-haploidentical relative (n = 176) and HLA-matched unrelated (n = 427) donor hematopoietic cell transplantation (HCT) from 2012 to 2017, using the Center for International Blood and Marrow Transplant Research database. All transplantations used reduced-intensity conditioning regimens. Total-body irradiation plus cyclophosphamide and fludarabine was the predominant regimen for HLA-haploidentical relative donor HCT, and graft-versus-host disease (GVHD) prophylaxis was uniformly posttransplantation cyclophosphamide, calcineurin inhibitor, and mycophenolate. Fludarabine with busulfan or melphalan was the predominant regimen for HLA-matched unrelated donor HCT, and GVHD prophylaxis was calcineurin inhibitor with mycophenolate or methotrexate. Results of multivariate analysis revealed higher relapse (hazard ratio [HR], 1.56; P = .0055; 2-year relapse rate, 48% vs 33%) and lower disease-free survival (DFS) rates after HLA-haploidentical relative donor HCT (HR, 1.29; P = .042; 2-year DFS, 29% vs 36%). However, overall survival (OS) rates did not differ between donor type (HR, 0.94; P = .65; 2-year OS, 46% for HLA-haploidentical and 44% for HLA-matched unrelated donor HCT) because of mortality associated with chronic GVHD. Acute grade 2 to 4 GVHD (HR, 0.44; P < .0001) and chronic GVHD (HR, 0.36; P < .0001) were lower after HLA-haploidentical relative donor HCT. By 2 years, probability of death resulting from chronic GVHD was lower after HLA-haploidentical relative compared with HLA-matched unrelated donor HCT (6% vs 21%), negating any potential survival advantage from better relapse control. Both donor types extend access to transplantation for patients with MDS; strategies for better relapse control are desirable for HLA-haploidentical relative donor HCT, and effective GVHD prophylaxis regimens are needed for unrelated donor HCT.",

keywords = "Graft vs Host Disease, Histocompatibility Testing, Humans, Myelodysplastic Syndromes/therapy, Transplantation Conditioning, Unrelated Donors",

author = "Grunwald, {Michael R.} and Zhang, {Mei Jie} and Hany Elmariah and Johnson, {Mariam H.} and Martin, {Andrew St} and Asad Bashey and Minoo Battiwalla and Bredeson, {Christopher N.} and Edward Copelan and Cutler, {Corey S.} and George, {Biju R.} and Vikas Gupta and Christopher Kanakry and Mehta, {Rohtesh S.} and Filippo Milano and Alberto Mussetti and Ryotaro Nakamura and Taiga Nishihori and Wael Saber and Melhem Solh and Weisdorf, {Daniel J.} and Mary Eapen",

year = "2021",

month = feb,

day = "23",

doi = "10.1182/bloodadvances.2020003654",

language = "English (US)",

volume = "5",

pages = "975--983",

journal = "Blood Advances",

issn = "2473-9529",

publisher = "American Society of Hematology",

number = "4",

}

TY - JOUR

T1 - Alternative donor transplantation for myelodysplastic syndromes

T2 - Haploidentical relative and matched unrelated donors

AU - Grunwald, Michael R.

AU - Zhang, Mei Jie

AU - Elmariah, Hany

AU - Johnson, Mariam H.

AU - Martin, Andrew St

AU - Bashey, Asad

AU - Battiwalla, Minoo

AU - Bredeson, Christopher N.

AU - Copelan, Edward

AU - Cutler, Corey S.

AU - George, Biju R.

AU - Gupta, Vikas

AU - Kanakry, Christopher

AU - Mehta, Rohtesh S.

AU - Milano, Filippo

AU - Mussetti, Alberto

AU - Nakamura, Ryotaro

AU - Nishihori, Taiga

AU - Saber, Wael

AU - Solh, Melhem

AU - Weisdorf, Daniel J.

AU - Eapen, Mary

PY - 2021/2/23

Y1 - 2021/2/23

N2 - We compared outcomes in 603 patients with myelodysplastic syndrome (MDS) after HLA-haploidentical relative (n = 176) and HLA-matched unrelated (n = 427) donor hematopoietic cell transplantation (HCT) from 2012 to 2017, using the Center for International Blood and Marrow Transplant Research database. All transplantations used reduced-intensity conditioning regimens. Total-body irradiation plus cyclophosphamide and fludarabine was the predominant regimen for HLA-haploidentical relative donor HCT, and graft-versus-host disease (GVHD) prophylaxis was uniformly posttransplantation cyclophosphamide, calcineurin inhibitor, and mycophenolate. Fludarabine with busulfan or melphalan was the predominant regimen for HLA-matched unrelated donor HCT, and GVHD prophylaxis was calcineurin inhibitor with mycophenolate or methotrexate. Results of multivariate analysis revealed higher relapse (hazard ratio [HR], 1.56; P = .0055; 2-year relapse rate, 48% vs 33%) and lower disease-free survival (DFS) rates after HLA-haploidentical relative donor HCT (HR, 1.29; P = .042; 2-year DFS, 29% vs 36%). However, overall survival (OS) rates did not differ between donor type (HR, 0.94; P = .65; 2-year OS, 46% for HLA-haploidentical and 44% for HLA-matched unrelated donor HCT) because of mortality associated with chronic GVHD. Acute grade 2 to 4 GVHD (HR, 0.44; P < .0001) and chronic GVHD (HR, 0.36; P < .0001) were lower after HLA-haploidentical relative donor HCT. By 2 years, probability of death resulting from chronic GVHD was lower after HLA-haploidentical relative compared with HLA-matched unrelated donor HCT (6% vs 21%), negating any potential survival advantage from better relapse control. Both donor types extend access to transplantation for patients with MDS; strategies for better relapse control are desirable for HLA-haploidentical relative donor HCT, and effective GVHD prophylaxis regimens are needed for unrelated donor HCT.

AB - We compared outcomes in 603 patients with myelodysplastic syndrome (MDS) after HLA-haploidentical relative (n = 176) and HLA-matched unrelated (n = 427) donor hematopoietic cell transplantation (HCT) from 2012 to 2017, using the Center for International Blood and Marrow Transplant Research database. All transplantations used reduced-intensity conditioning regimens. Total-body irradiation plus cyclophosphamide and fludarabine was the predominant regimen for HLA-haploidentical relative donor HCT, and graft-versus-host disease (GVHD) prophylaxis was uniformly posttransplantation cyclophosphamide, calcineurin inhibitor, and mycophenolate. Fludarabine with busulfan or melphalan was the predominant regimen for HLA-matched unrelated donor HCT, and GVHD prophylaxis was calcineurin inhibitor with mycophenolate or methotrexate. Results of multivariate analysis revealed higher relapse (hazard ratio [HR], 1.56; P = .0055; 2-year relapse rate, 48% vs 33%) and lower disease-free survival (DFS) rates after HLA-haploidentical relative donor HCT (HR, 1.29; P = .042; 2-year DFS, 29% vs 36%). However, overall survival (OS) rates did not differ between donor type (HR, 0.94; P = .65; 2-year OS, 46% for HLA-haploidentical and 44% for HLA-matched unrelated donor HCT) because of mortality associated with chronic GVHD. Acute grade 2 to 4 GVHD (HR, 0.44; P < .0001) and chronic GVHD (HR, 0.36; P < .0001) were lower after HLA-haploidentical relative donor HCT. By 2 years, probability of death resulting from chronic GVHD was lower after HLA-haploidentical relative compared with HLA-matched unrelated donor HCT (6% vs 21%), negating any potential survival advantage from better relapse control. Both donor types extend access to transplantation for patients with MDS; strategies for better relapse control are desirable for HLA-haploidentical relative donor HCT, and effective GVHD prophylaxis regimens are needed for unrelated donor HCT.

KW - Graft vs Host Disease

KW - Histocompatibility Testing

KW - Humans

KW - Myelodysplastic Syndromes/therapy

KW - Transplantation Conditioning

KW - Unrelated Donors

UR - http://www.scopus.com/inward/record.url?scp=85102602689&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85102602689&partnerID=8YFLogxK

U2 - 10.1182/bloodadvances.2020003654

DO - 10.1182/bloodadvances.2020003654

M3 - Article

C2 - 33576783

AN - SCOPUS:85102602689

SN - 2473-9529

VL - 5

SP - 975

EP - 983

JO - Blood Advances

JF - Blood Advances

IS - 4

ER -

Alternative donor transplantation for myelodysplastic syndromes: Haploidentical relative and matched unrelated donors

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

Publisher link

Find It

Other files and links

Fingerprint

Cite this