Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis

Guru Subramanian Guru Murthy; Soyoung Kim; Noel Estrada-Merly; Muhammad Bilal Abid; Mahmoud Aljurf; Amer Assal; Talha Badar; Sherif M. Badawy; Karen Ballen; Amer Beitinjaneh; Jan Cerny; Saurabh Chhabra; Zachariah DeFilipp; Bhagirathbhai Dholaria; Miguel Angel Diaz Perez; Shatha Farhan; Cesar O. Freytes; Robert Peter Gale; Siddhartha Ganguly; Vikas Gupta; Michael R. Grunwald; Nada Hamad; Gerhard C. Hildebrandt; Yoshihiro Inamoto; Tania Jain; Omer Jamy; Mark Juckett; Matt Kalaycio; Maxwell M. Krem; Hillard M. Lazarus; Mark Litzow; Reinhold Munker; Hemant S. Murthy; Sunita Nathan; Taiga Nishihori; Guillermo Ortí; Sagar S. Patel; Marjolein van der Poel; David A. Rizzieri; Bipin N. Savani; Sachiko Seo; Melhem Solh; Leo F. Verdonck; Baldeep Wirk; Jean A. Yared; Ryotaro Nakamura; Betul Oran; Bart Scott; Wael Saber

doi:10.3324/haematol.2022.281958

Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis

Guru Subramanian Guru Murthy, Soyoung Kim, Noel Estrada-Merly, Muhammad Bilal Abid, Mahmoud Aljurf, Amer Assal, Talha Badar, Sherif M. Badawy, Karen Ballen, Amer Beitinjaneh, Jan Cerny, Saurabh Chhabra, Zachariah DeFilipp, Bhagirathbhai Dholaria, Miguel Angel Diaz Perez, Shatha Farhan, Cesar O. Freytes, Robert Peter Gale, Siddhartha Ganguly, Vikas GuptaMichael R. Grunwald, Nada Hamad, Gerhard C. Hildebrandt, Yoshihiro Inamoto, Tania Jain, Omer Jamy, Mark Juckett, Matt Kalaycio, Maxwell M. Krem, Hillard M. Lazarus, Mark Litzow, Reinhold Munker, Hemant S. Murthy, Sunita Nathan, Taiga Nishihori, Guillermo Ortí, Sagar S. Patel, Marjolein van der Poel, David A. Rizzieri, Bipin N. Savani, Sachiko Seo, Melhem Solh, Leo F. Verdonck, Baldeep Wirk, Jean A. Yared, Ryotaro Nakamura, Betul Oran, Bart Scott, Wael Saber

Stem Cell Transplantation

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

11 Scopus citations

Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, theoptimal conditioning regimen either with reduced-intensity conditioning (RIC) or myeloablative conditioning (MAC) is not wellknown. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged =18years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MACcohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (fludarabine/busulfan n=166, fludarabine/melphalan n=327) and 379 using MAC (fludarabine/busulfan n=247, busulfan/cyclophosphamide n=132). In multivariable analysis with RIC, fludarabine/melphalan was associated with inferior overall survival (hazardratio [HR]=1.80; 95% confidenec interval [CI]: 1.15-2.81; P=0.009), higher early non-relapse mortality (HR=1.81; 95% CI: 1.12-2.91;P=0.01) and higher acute graft-versus-host disease (GvHD) (grade 2-4 HR=1.45; 95% CI: 1.03-2.03; P=0.03; grade 3-4 HR=2.21;95%CI: 1.28-3.83; P=0.004) compared to fludarabine/busulfan. In the MAC setting, busulfan/cyclophosphamide was associatedwith a higher acute GvHD (grade 2-4 HR=2.33; 95% CI: 1.67-3.25; P<0.001; grade 3-4 HR=2.31; 95% CI: 1.52-3.52; P<0.001) andinferior GvHD-free relapse-free survival (GRFS) (HR=1.94; 95% CI: 1.49-2.53; P<0.001) as compared to fludarabine/busulfan.Hence, our study suggests that fludarabine/busulfan is associated with better outcomes in RIC (better overall survival, lowerearly non-relapse mortality, lower acute GvHD) and MAC (lower acute GvHD and better GRFS) in myelofibrosis.

Original language	English (US)
Pages (from-to)	1900-1908
Number of pages	9
Journal	Haematologica
Volume	108
Issue number	7
DOIs	https://doi.org/10.3324/haematol.2022.281958
State	Published - Jul 2023

ASJC Scopus subject areas

Hematology

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10.3324/haematol.2022.281958

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Murthy, G. S. G., Kim, S., Estrada-Merly, N., Abid, M. B., Aljurf, M., Assal, A., Badar, T., Badawy, S. M., Ballen, K., Beitinjaneh, A., Cerny, J., Chhabra, S., DeFilipp, Z., Dholaria, B., Perez, M. A. D., Farhan, S., Freytes, C. O., Gale, R. P., Ganguly, S., ... Saber, W. (2023). Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis. Haematologica, 108(7), 1900-1908. https://doi.org/10.3324/haematol.2022.281958

Murthy, GSG, Kim, S, Estrada-Merly, N, Abid, MB, Aljurf, M, Assal, A, Badar, T, Badawy, SM, Ballen, K, Beitinjaneh, A, Cerny, J, Chhabra, S, DeFilipp, Z, Dholaria, B, Perez, MAD, Farhan, S, Freytes, CO, Gale, RP, Ganguly, S, Gupta, V, Grunwald, MR, Hamad, N, Hildebrandt, GC, Inamoto, Y, Jain, T, Jamy, O, Juckett, M, Kalaycio, M, Krem, MM, Lazarus, HM, Litzow, M, Munker, R, Murthy, HS, Nathan, S, Nishihori, T, Ortí, G, Patel, SS, van der Poel, M, Rizzieri, DA, Savani, BN, Seo, S, Solh, M, Verdonck, LF, Wirk, B, Yared, JA, Nakamura, R, Oran, B, Scott, B & Saber, W 2023, 'Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis', Haematologica, vol. 108, no. 7, pp. 1900-1908. https://doi.org/10.3324/haematol.2022.281958

@article{d7aec0bbf15d4031be490f98172984ba,

title = "Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis",

abstract = "Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, theoptimal conditioning regimen either with reduced-intensity conditioning (RIC) or myeloablative conditioning (MAC) is not wellknown. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged =18years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MACcohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (fludarabine/busulfan n=166, fludarabine/melphalan n=327) and 379 using MAC (fludarabine/busulfan n=247, busulfan/cyclophosphamide n=132). In multivariable analysis with RIC, fludarabine/melphalan was associated with inferior overall survival (hazardratio [HR]=1.80; 95% confidenec interval [CI]: 1.15-2.81; P=0.009), higher early non-relapse mortality (HR=1.81; 95% CI: 1.12-2.91;P=0.01) and higher acute graft-versus-host disease (GvHD) (grade 2-4 HR=1.45; 95% CI: 1.03-2.03; P=0.03; grade 3-4 HR=2.21;95%CI: 1.28-3.83; P=0.004) compared to fludarabine/busulfan. In the MAC setting, busulfan/cyclophosphamide was associatedwith a higher acute GvHD (grade 2-4 HR=2.33; 95% CI: 1.67-3.25; P<0.001; grade 3-4 HR=2.31; 95% CI: 1.52-3.52; P<0.001) andinferior GvHD-free relapse-free survival (GRFS) (HR=1.94; 95% CI: 1.49-2.53; P<0.001) as compared to fludarabine/busulfan.Hence, our study suggests that fludarabine/busulfan is associated with better outcomes in RIC (better overall survival, lowerearly non-relapse mortality, lower acute GvHD) and MAC (lower acute GvHD and better GRFS) in myelofibrosis.",

author = "Murthy, {Guru Subramanian Guru} and Soyoung Kim and Noel Estrada-Merly and Abid, {Muhammad Bilal} and Mahmoud Aljurf and Amer Assal and Talha Badar and Badawy, {Sherif M.} and Karen Ballen and Amer Beitinjaneh and Jan Cerny and Saurabh Chhabra and Zachariah DeFilipp and Bhagirathbhai Dholaria and Perez, {Miguel Angel Diaz} and Shatha Farhan and Freytes, {Cesar O.} and Gale, {Robert Peter} and Siddhartha Ganguly and Vikas Gupta and Grunwald, {Michael R.} and Nada Hamad and Hildebrandt, {Gerhard C.} and Yoshihiro Inamoto and Tania Jain and Omer Jamy and Mark Juckett and Matt Kalaycio and Krem, {Maxwell M.} and Lazarus, {Hillard M.} and Mark Litzow and Reinhold Munker and Murthy, {Hemant S.} and Sunita Nathan and Taiga Nishihori and Guillermo Ort{\'i} and Patel, {Sagar S.} and {van der Poel}, Marjolein and Rizzieri, {David A.} and Savani, {Bipin N.} and Sachiko Seo and Melhem Solh and Verdonck, {Leo F.} and Baldeep Wirk and Yared, {Jean A.} and Ryotaro Nakamura and Betul Oran and Bart Scott and Wael Saber",

year = "2023",

month = jul,

doi = "10.3324/haematol.2022.281958",

language = "English (US)",

volume = "108",

pages = "1900--1908",

journal = "Haematologica",

issn = "0390-6078",

publisher = "Ferrata Storti Foundation",

number = "7",

}

TY - JOUR

T1 - Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis

AU - Murthy, Guru Subramanian Guru

AU - Kim, Soyoung

AU - Estrada-Merly, Noel

AU - Abid, Muhammad Bilal

AU - Aljurf, Mahmoud

AU - Assal, Amer

AU - Badar, Talha

AU - Badawy, Sherif M.

AU - Ballen, Karen

AU - Beitinjaneh, Amer

AU - Cerny, Jan

AU - Chhabra, Saurabh

AU - DeFilipp, Zachariah

AU - Dholaria, Bhagirathbhai

AU - Perez, Miguel Angel Diaz

AU - Farhan, Shatha

AU - Freytes, Cesar O.

AU - Gale, Robert Peter

AU - Ganguly, Siddhartha

AU - Gupta, Vikas

AU - Grunwald, Michael R.

AU - Hamad, Nada

AU - Hildebrandt, Gerhard C.

AU - Inamoto, Yoshihiro

AU - Jain, Tania

AU - Jamy, Omer

AU - Juckett, Mark

AU - Kalaycio, Matt

AU - Krem, Maxwell M.

AU - Lazarus, Hillard M.

AU - Litzow, Mark

AU - Munker, Reinhold

AU - Murthy, Hemant S.

AU - Nathan, Sunita

AU - Nishihori, Taiga

AU - Ortí, Guillermo

AU - Patel, Sagar S.

AU - van der Poel, Marjolein

AU - Rizzieri, David A.

AU - Savani, Bipin N.

AU - Seo, Sachiko

AU - Solh, Melhem

AU - Verdonck, Leo F.

AU - Wirk, Baldeep

AU - Yared, Jean A.

AU - Nakamura, Ryotaro

AU - Oran, Betul

AU - Scott, Bart

AU - Saber, Wael

PY - 2023/7

Y1 - 2023/7

N2 - Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, theoptimal conditioning regimen either with reduced-intensity conditioning (RIC) or myeloablative conditioning (MAC) is not wellknown. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged =18years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MACcohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (fludarabine/busulfan n=166, fludarabine/melphalan n=327) and 379 using MAC (fludarabine/busulfan n=247, busulfan/cyclophosphamide n=132). In multivariable analysis with RIC, fludarabine/melphalan was associated with inferior overall survival (hazardratio [HR]=1.80; 95% confidenec interval [CI]: 1.15-2.81; P=0.009), higher early non-relapse mortality (HR=1.81; 95% CI: 1.12-2.91;P=0.01) and higher acute graft-versus-host disease (GvHD) (grade 2-4 HR=1.45; 95% CI: 1.03-2.03; P=0.03; grade 3-4 HR=2.21;95%CI: 1.28-3.83; P=0.004) compared to fludarabine/busulfan. In the MAC setting, busulfan/cyclophosphamide was associatedwith a higher acute GvHD (grade 2-4 HR=2.33; 95% CI: 1.67-3.25; P<0.001; grade 3-4 HR=2.31; 95% CI: 1.52-3.52; P<0.001) andinferior GvHD-free relapse-free survival (GRFS) (HR=1.94; 95% CI: 1.49-2.53; P<0.001) as compared to fludarabine/busulfan.Hence, our study suggests that fludarabine/busulfan is associated with better outcomes in RIC (better overall survival, lowerearly non-relapse mortality, lower acute GvHD) and MAC (lower acute GvHD and better GRFS) in myelofibrosis.

AB - Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, theoptimal conditioning regimen either with reduced-intensity conditioning (RIC) or myeloablative conditioning (MAC) is not wellknown. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged =18years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MACcohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (fludarabine/busulfan n=166, fludarabine/melphalan n=327) and 379 using MAC (fludarabine/busulfan n=247, busulfan/cyclophosphamide n=132). In multivariable analysis with RIC, fludarabine/melphalan was associated with inferior overall survival (hazardratio [HR]=1.80; 95% confidenec interval [CI]: 1.15-2.81; P=0.009), higher early non-relapse mortality (HR=1.81; 95% CI: 1.12-2.91;P=0.01) and higher acute graft-versus-host disease (GvHD) (grade 2-4 HR=1.45; 95% CI: 1.03-2.03; P=0.03; grade 3-4 HR=2.21;95%CI: 1.28-3.83; P=0.004) compared to fludarabine/busulfan. In the MAC setting, busulfan/cyclophosphamide was associatedwith a higher acute GvHD (grade 2-4 HR=2.33; 95% CI: 1.67-3.25; P<0.001; grade 3-4 HR=2.31; 95% CI: 1.52-3.52; P<0.001) andinferior GvHD-free relapse-free survival (GRFS) (HR=1.94; 95% CI: 1.49-2.53; P<0.001) as compared to fludarabine/busulfan.Hence, our study suggests that fludarabine/busulfan is associated with better outcomes in RIC (better overall survival, lowerearly non-relapse mortality, lower acute GvHD) and MAC (lower acute GvHD and better GRFS) in myelofibrosis.

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DO - 10.3324/haematol.2022.281958

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JO - Haematologica

JF - Haematologica

IS - 7

ER -

Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis

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