Relapse and Disease-Free Survival in Patients With Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation Using Older Matched Sibling Donors vs Younger Matched Unrelated Donors

Guru Subramanian Guru Murthy; Soyoung Kim; Zhen Huan Hu; Noel Estrada-Merly; Muhammad Bilal Abid; Mahmoud Aljurf; Ulrike Bacher; Sherif M. Badawy; Amer Beitinjaneh; Chris Bredeson; Jean Yves Cahn; Jan Cerny; Miguel Angel Diaz Perez; Nosha Farhadfar; Robert Peter Gale; Siddhartha Ganguly; Usama Gergis; Gerhard C. Hildebrandt; Michael R. Grunwald; Shahrukh Hashmi; Nasheed M. Hossain; Matt Kalaycio; Rammurti T. Kamble; Mohamed A. Kharfan-Dabaja; Betty Ky Hamilton; Hillard M. Lazarus; Jane Liesveld; Mark Litzow; David I. Marks; Hemant S. Murthy; Sunita Nathan; Aziz Nazha; Taiga Nishihori; Sagar S. Patel; Attaphol Pawarode; David Rizzieri; Bipin Savani; Sachiko Seo; Melhem Solh; Celalettin Ustun; Marjolein van der Poel; Leo F. Verdonck; Ravi Vij; Baldeep Wirk; Betul Oran; Ryotaro Nakamura; Bart Scott; Wael Saber

doi:10.1001/jamaoncol.2021.6846

Relapse and Disease-Free Survival in Patients With Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation Using Older Matched Sibling Donors vs Younger Matched Unrelated Donors

Guru Subramanian Guru Murthy, Soyoung Kim, Zhen Huan Hu, Noel Estrada-Merly, Muhammad Bilal Abid, Mahmoud Aljurf, Ulrike Bacher, Sherif M. Badawy, Amer Beitinjaneh, Chris Bredeson, Jean Yves Cahn, Jan Cerny, Miguel Angel Diaz Perez, Nosha Farhadfar, Robert Peter Gale, Siddhartha Ganguly, Usama Gergis, Gerhard C. Hildebrandt, Michael R. Grunwald, Shahrukh HashmiNasheed M. Hossain, Matt Kalaycio, Rammurti T. Kamble, Mohamed A. Kharfan-Dabaja, Betty Ky Hamilton, Hillard M. Lazarus, Jane Liesveld, Mark Litzow, David I. Marks, Hemant S. Murthy, Sunita Nathan, Aziz Nazha, Taiga Nishihori, Sagar S. Patel, Attaphol Pawarode, David Rizzieri, Bipin Savani, Sachiko Seo, Melhem Solh, Celalettin Ustun, Marjolein van der Poel, Leo F. Verdonck, Ravi Vij, Baldeep Wirk, Betul Oran, Ryotaro Nakamura, Bart Scott, Wael Saber

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

44 Scopus citations

Abstract

IMPORTANCE: Matched sibling donors (MSDs) are preferred for allogeneic hematopoietic cell transplantation (allo-HCT) in myelodysplastic syndrome even if they are older. However, whether older MSDs or younger human leukocyte antigen-matched unrelated donors (MUDs) are associated with better outcomes remains unclear.

OBJECTIVE: To investigate whether allo-HCT for myelodysplastic syndrome using younger MUDs would be associated with improved disease-free survival and less relapse compared with older MSDs.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study assessed data reported to the Center for International Blood and Marrow Transplant Research database from 1761 adults 50 years or older with myelodysplastic syndrome who underwent allo-HCT using an older MSD or younger MUD between January 1, 2011, and December 31, 2017, with a median follow-up of 48 months. Data analysis was performed from January 8, 2019, to December 30, 2020.

INTERVENTIONS/EXPOSURES: Allo-HCT from an older MSD (donor age ≥50 years) or a younger MUD (donor age ≤35 years).

MAIN OUTCOMES AND MEASURES: The primary outcome was disease-free survival. Secondary outcomes were overall survival, relapse, nonrelapse mortality, acute graft-vs-host disease (GVHD), chronic GVHD, and GVHD-free relapse-free survival.

RESULTS: Of 1761 patients (1162 [66%] male; median [range] age, 64.9 [50.2-77.6] years in the MSD cohort and 66.5 [50.4-80.9] years in MUD cohort), 646 underwent allo-HCT with an older MSD and 1115 with a younger MUD. In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio [HR], 1.17; 95% CI, 1.02-1.34; P = .02), whereas the difference in overall survival rate of allo-HCT with younger MUDs vs older MSDs was not statistically significant (HR, 1.13; 95% CI, 0.98-1.29; P = .07). Allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62; 95% CI, 1.32-1.97; P < .001), lower nonrelapse mortality (HR, 0.76; 95% CI, 0.59-0.96; P = .02), lower acute GVHD (HR, 0.52; 95% CI, 0.42-0.65; P < .001), chronic GVHD (HR, 0.77; 95% CI, 0.64-0.92; P = .005), and a lower rate of GVHD-free relapse-free survival beyond 12 months after allo-HCT (HR, 1.42; 95% CI, 1.02-1.98; P = .04).

CONCLUSIONS AND RELEVANCE: This cohort study found higher disease-free survival and lower relapse for allo-HCT in myelodysplastic syndrome using younger MUDs compared with older MSDs. The risk of nonrelapse mortality and GVHD was lower with older MSDs. These results suggest that the use of younger MUDs should be considered in the donor selection algorithm for myelodysplastic syndrome, in which it is pivotal to minimize relapse given limited treatment options for managing relapsed disease.

Original language	English (US)
Pages (from-to)	404-411
Number of pages	8
Journal	JAMA oncology
Volume	8
Issue number	3
DOIs	https://doi.org/10.1001/jamaoncol.2021.6846
State	Published - Mar 1 2022

Keywords

Adult
Aged
Cohort Studies
Disease-Free Survival
Graft vs Host Disease/etiology
Hematopoietic Stem Cell Transplantation/methods
Humans
Male
Middle Aged
Myelodysplastic Syndromes/therapy
Neoplasm Recurrence, Local
Retrospective Studies
Siblings
Transplantation Conditioning/methods
Unrelated Donors

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1001/jamaoncol.2021.6846

Cite this

Guru Murthy, G. S., Kim, S., Hu, Z. H., Estrada-Merly, N., Abid, M. B., Aljurf, M., Bacher, U., Badawy, S. M., Beitinjaneh, A., Bredeson, C., Cahn, J. Y., Cerny, J., Diaz Perez, M. A., Farhadfar, N., Gale, R. P., Ganguly, S., Gergis, U., Hildebrandt, G. C., Grunwald, M. R., ... Saber, W. (2022). Relapse and Disease-Free Survival in Patients With Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation Using Older Matched Sibling Donors vs Younger Matched Unrelated Donors. JAMA oncology, 8(3), 404-411. https://doi.org/10.1001/jamaoncol.2021.6846

Relapse and Disease-Free Survival in Patients With Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation Using Older Matched Sibling Donors vs Younger Matched Unrelated Donors. / Guru Murthy, Guru Subramanian; Kim, Soyoung; Hu, Zhen Huan et al.
In: JAMA oncology, Vol. 8, No. 3, 01.03.2022, p. 404-411.

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

Guru Murthy, GS, Kim, S, Hu, ZH, Estrada-Merly, N, Abid, MB, Aljurf, M, Bacher, U, Badawy, SM, Beitinjaneh, A, Bredeson, C, Cahn, JY, Cerny, J, Diaz Perez, MA, Farhadfar, N, Gale, RP, Ganguly, S, Gergis, U, Hildebrandt, GC, Grunwald, MR, Hashmi, S, Hossain, NM, Kalaycio, M, Kamble, RT, Kharfan-Dabaja, MA, Hamilton, BK, Lazarus, HM, Liesveld, J, Litzow, M, Marks, DI, Murthy, HS, Nathan, S, Nazha, A, Nishihori, T, Patel, SS, Pawarode, A, Rizzieri, D, Savani, B, Seo, S, Solh, M, Ustun, C, van der Poel, M, Verdonck, LF, Vij, R, Wirk, B, Oran, B, Nakamura, R, Scott, B & Saber, W 2022, 'Relapse and Disease-Free Survival in Patients With Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation Using Older Matched Sibling Donors vs Younger Matched Unrelated Donors', JAMA oncology, vol. 8, no. 3, pp. 404-411. https://doi.org/10.1001/jamaoncol.2021.6846

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title = "Relapse and Disease-Free Survival in Patients With Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation Using Older Matched Sibling Donors vs Younger Matched Unrelated Donors",

abstract = "IMPORTANCE: Matched sibling donors (MSDs) are preferred for allogeneic hematopoietic cell transplantation (allo-HCT) in myelodysplastic syndrome even if they are older. However, whether older MSDs or younger human leukocyte antigen-matched unrelated donors (MUDs) are associated with better outcomes remains unclear.OBJECTIVE: To investigate whether allo-HCT for myelodysplastic syndrome using younger MUDs would be associated with improved disease-free survival and less relapse compared with older MSDs.DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study assessed data reported to the Center for International Blood and Marrow Transplant Research database from 1761 adults 50 years or older with myelodysplastic syndrome who underwent allo-HCT using an older MSD or younger MUD between January 1, 2011, and December 31, 2017, with a median follow-up of 48 months. Data analysis was performed from January 8, 2019, to December 30, 2020.INTERVENTIONS/EXPOSURES: Allo-HCT from an older MSD (donor age ≥50 years) or a younger MUD (donor age ≤35 years).MAIN OUTCOMES AND MEASURES: The primary outcome was disease-free survival. Secondary outcomes were overall survival, relapse, nonrelapse mortality, acute graft-vs-host disease (GVHD), chronic GVHD, and GVHD-free relapse-free survival.RESULTS: Of 1761 patients (1162 [66%] male; median [range] age, 64.9 [50.2-77.6] years in the MSD cohort and 66.5 [50.4-80.9] years in MUD cohort), 646 underwent allo-HCT with an older MSD and 1115 with a younger MUD. In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio [HR], 1.17; 95% CI, 1.02-1.34; P = .02), whereas the difference in overall survival rate of allo-HCT with younger MUDs vs older MSDs was not statistically significant (HR, 1.13; 95% CI, 0.98-1.29; P = .07). Allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62; 95% CI, 1.32-1.97; P < .001), lower nonrelapse mortality (HR, 0.76; 95% CI, 0.59-0.96; P = .02), lower acute GVHD (HR, 0.52; 95% CI, 0.42-0.65; P < .001), chronic GVHD (HR, 0.77; 95% CI, 0.64-0.92; P = .005), and a lower rate of GVHD-free relapse-free survival beyond 12 months after allo-HCT (HR, 1.42; 95% CI, 1.02-1.98; P = .04).CONCLUSIONS AND RELEVANCE: This cohort study found higher disease-free survival and lower relapse for allo-HCT in myelodysplastic syndrome using younger MUDs compared with older MSDs. The risk of nonrelapse mortality and GVHD was lower with older MSDs. These results suggest that the use of younger MUDs should be considered in the donor selection algorithm for myelodysplastic syndrome, in which it is pivotal to minimize relapse given limited treatment options for managing relapsed disease.",

keywords = "Adult, Aged, Cohort Studies, Disease-Free Survival, Graft vs Host Disease/etiology, Hematopoietic Stem Cell Transplantation/methods, Humans, Male, Middle Aged, Myelodysplastic Syndromes/therapy, Neoplasm Recurrence, Local, Retrospective Studies, Siblings, Transplantation Conditioning/methods, Unrelated Donors",

author = "{Guru Murthy}, {Guru Subramanian} and Soyoung Kim and Hu, {Zhen Huan} and Noel Estrada-Merly and Abid, {Muhammad Bilal} and Mahmoud Aljurf and Ulrike Bacher and Badawy, {Sherif M.} and Amer Beitinjaneh and Chris Bredeson and Cahn, {Jean Yves} and Jan Cerny and {Diaz Perez}, {Miguel Angel} and Nosha Farhadfar and Gale, {Robert Peter} and Siddhartha Ganguly and Usama Gergis and Hildebrandt, {Gerhard C.} and Grunwald, {Michael R.} and Shahrukh Hashmi and Hossain, {Nasheed M.} and Matt Kalaycio and Kamble, {Rammurti T.} and Kharfan-Dabaja, {Mohamed A.} and Hamilton, {Betty Ky} and Lazarus, {Hillard M.} and Jane Liesveld and Mark Litzow and Marks, {David I.} and Murthy, {Hemant S.} and Sunita Nathan and Aziz Nazha and Taiga Nishihori and Patel, {Sagar S.} and Attaphol Pawarode and David Rizzieri and Bipin Savani and Sachiko Seo and Melhem Solh and Celalettin Ustun and {van der Poel}, Marjolein and Verdonck, {Leo F.} and Ravi Vij and Baldeep Wirk and Betul Oran and Ryotaro Nakamura and Bart Scott and Wael Saber",

note = "Publisher Copyright: {\textcopyright} 2022 American Medical Association",

year = "2022",

month = mar,

day = "1",

doi = "10.1001/jamaoncol.2021.6846",

language = "English (US)",

volume = "8",

pages = "404--411",

journal = "JAMA oncology",

issn = "2374-2437",

publisher = "American Medical Association",

number = "3",

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TY - JOUR

T1 - Relapse and Disease-Free Survival in Patients With Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation Using Older Matched Sibling Donors vs Younger Matched Unrelated Donors

AU - Guru Murthy, Guru Subramanian

AU - Kim, Soyoung

AU - Hu, Zhen Huan

AU - Estrada-Merly, Noel

AU - Abid, Muhammad Bilal

AU - Aljurf, Mahmoud

AU - Bacher, Ulrike

AU - Badawy, Sherif M.

AU - Beitinjaneh, Amer

AU - Bredeson, Chris

AU - Cahn, Jean Yves

AU - Cerny, Jan

AU - Diaz Perez, Miguel Angel

AU - Farhadfar, Nosha

AU - Gale, Robert Peter

AU - Ganguly, Siddhartha

AU - Gergis, Usama

AU - Hildebrandt, Gerhard C.

AU - Grunwald, Michael R.

AU - Hashmi, Shahrukh

AU - Hossain, Nasheed M.

AU - Kalaycio, Matt

AU - Kamble, Rammurti T.

AU - Kharfan-Dabaja, Mohamed A.

AU - Hamilton, Betty Ky

AU - Lazarus, Hillard M.

AU - Liesveld, Jane

AU - Litzow, Mark

AU - Marks, David I.

AU - Murthy, Hemant S.

AU - Nathan, Sunita

AU - Nazha, Aziz

AU - Nishihori, Taiga

AU - Patel, Sagar S.

AU - Pawarode, Attaphol

AU - Rizzieri, David

AU - Savani, Bipin

AU - Seo, Sachiko

AU - Solh, Melhem

AU - Ustun, Celalettin

AU - van der Poel, Marjolein

AU - Verdonck, Leo F.

AU - Vij, Ravi

AU - Wirk, Baldeep

AU - Oran, Betul

AU - Nakamura, Ryotaro

AU - Scott, Bart

AU - Saber, Wael

PY - 2022/3/1

Y1 - 2022/3/1

N2 - IMPORTANCE: Matched sibling donors (MSDs) are preferred for allogeneic hematopoietic cell transplantation (allo-HCT) in myelodysplastic syndrome even if they are older. However, whether older MSDs or younger human leukocyte antigen-matched unrelated donors (MUDs) are associated with better outcomes remains unclear.OBJECTIVE: To investigate whether allo-HCT for myelodysplastic syndrome using younger MUDs would be associated with improved disease-free survival and less relapse compared with older MSDs.DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study assessed data reported to the Center for International Blood and Marrow Transplant Research database from 1761 adults 50 years or older with myelodysplastic syndrome who underwent allo-HCT using an older MSD or younger MUD between January 1, 2011, and December 31, 2017, with a median follow-up of 48 months. Data analysis was performed from January 8, 2019, to December 30, 2020.INTERVENTIONS/EXPOSURES: Allo-HCT from an older MSD (donor age ≥50 years) or a younger MUD (donor age ≤35 years).MAIN OUTCOMES AND MEASURES: The primary outcome was disease-free survival. Secondary outcomes were overall survival, relapse, nonrelapse mortality, acute graft-vs-host disease (GVHD), chronic GVHD, and GVHD-free relapse-free survival.RESULTS: Of 1761 patients (1162 [66%] male; median [range] age, 64.9 [50.2-77.6] years in the MSD cohort and 66.5 [50.4-80.9] years in MUD cohort), 646 underwent allo-HCT with an older MSD and 1115 with a younger MUD. In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio [HR], 1.17; 95% CI, 1.02-1.34; P = .02), whereas the difference in overall survival rate of allo-HCT with younger MUDs vs older MSDs was not statistically significant (HR, 1.13; 95% CI, 0.98-1.29; P = .07). Allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62; 95% CI, 1.32-1.97; P < .001), lower nonrelapse mortality (HR, 0.76; 95% CI, 0.59-0.96; P = .02), lower acute GVHD (HR, 0.52; 95% CI, 0.42-0.65; P < .001), chronic GVHD (HR, 0.77; 95% CI, 0.64-0.92; P = .005), and a lower rate of GVHD-free relapse-free survival beyond 12 months after allo-HCT (HR, 1.42; 95% CI, 1.02-1.98; P = .04).CONCLUSIONS AND RELEVANCE: This cohort study found higher disease-free survival and lower relapse for allo-HCT in myelodysplastic syndrome using younger MUDs compared with older MSDs. The risk of nonrelapse mortality and GVHD was lower with older MSDs. These results suggest that the use of younger MUDs should be considered in the donor selection algorithm for myelodysplastic syndrome, in which it is pivotal to minimize relapse given limited treatment options for managing relapsed disease.

AB - IMPORTANCE: Matched sibling donors (MSDs) are preferred for allogeneic hematopoietic cell transplantation (allo-HCT) in myelodysplastic syndrome even if they are older. However, whether older MSDs or younger human leukocyte antigen-matched unrelated donors (MUDs) are associated with better outcomes remains unclear.OBJECTIVE: To investigate whether allo-HCT for myelodysplastic syndrome using younger MUDs would be associated with improved disease-free survival and less relapse compared with older MSDs.DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study assessed data reported to the Center for International Blood and Marrow Transplant Research database from 1761 adults 50 years or older with myelodysplastic syndrome who underwent allo-HCT using an older MSD or younger MUD between January 1, 2011, and December 31, 2017, with a median follow-up of 48 months. Data analysis was performed from January 8, 2019, to December 30, 2020.INTERVENTIONS/EXPOSURES: Allo-HCT from an older MSD (donor age ≥50 years) or a younger MUD (donor age ≤35 years).MAIN OUTCOMES AND MEASURES: The primary outcome was disease-free survival. Secondary outcomes were overall survival, relapse, nonrelapse mortality, acute graft-vs-host disease (GVHD), chronic GVHD, and GVHD-free relapse-free survival.RESULTS: Of 1761 patients (1162 [66%] male; median [range] age, 64.9 [50.2-77.6] years in the MSD cohort and 66.5 [50.4-80.9] years in MUD cohort), 646 underwent allo-HCT with an older MSD and 1115 with a younger MUD. In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio [HR], 1.17; 95% CI, 1.02-1.34; P = .02), whereas the difference in overall survival rate of allo-HCT with younger MUDs vs older MSDs was not statistically significant (HR, 1.13; 95% CI, 0.98-1.29; P = .07). Allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62; 95% CI, 1.32-1.97; P < .001), lower nonrelapse mortality (HR, 0.76; 95% CI, 0.59-0.96; P = .02), lower acute GVHD (HR, 0.52; 95% CI, 0.42-0.65; P < .001), chronic GVHD (HR, 0.77; 95% CI, 0.64-0.92; P = .005), and a lower rate of GVHD-free relapse-free survival beyond 12 months after allo-HCT (HR, 1.42; 95% CI, 1.02-1.98; P = .04).CONCLUSIONS AND RELEVANCE: This cohort study found higher disease-free survival and lower relapse for allo-HCT in myelodysplastic syndrome using younger MUDs compared with older MSDs. The risk of nonrelapse mortality and GVHD was lower with older MSDs. These results suggest that the use of younger MUDs should be considered in the donor selection algorithm for myelodysplastic syndrome, in which it is pivotal to minimize relapse given limited treatment options for managing relapsed disease.

KW - Adult

KW - Aged

KW - Cohort Studies

KW - Disease-Free Survival

KW - Graft vs Host Disease/etiology

KW - Hematopoietic Stem Cell Transplantation/methods

KW - Humans

KW - Male

KW - Middle Aged

KW - Myelodysplastic Syndromes/therapy

KW - Neoplasm Recurrence, Local

KW - Retrospective Studies

KW - Siblings

KW - Transplantation Conditioning/methods

KW - Unrelated Donors

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DO - 10.1001/jamaoncol.2021.6846

M3 - Article

C2 - 35024768

AN - SCOPUS:85123085547

SN - 2374-2437

VL - 8

SP - 404

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JO - JAMA oncology

JF - JAMA oncology

IS - 3

ER -

Relapse and Disease-Free Survival in Patients With Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation Using Older Matched Sibling Donors vs Younger Matched Unrelated Donors

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