Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improve Transplantation Outcomes in Older Patients with Myelodysplastic Syndromes

Betül Oran; Kwang Woo Ahn; Caitrin Fretham; Amer Beitinjaneh; Asad Bashey; Attaphol Pawarode; Baldeep Wirk; Bart L. Scott; Bipin N. Savani; Christopher Bredeson; Daniel Weisdorf; David I. Marks; David Rizzieri; Edward Copelan; Gerhard C. Hildebrandt; Gregory A. Hale; Hemant S. Murthy; Hillard M. Lazarus; Jan Cerny; Jane L. Liesveld; Jean A. Yared; Jean Yves-Cahn; Jeffrey Szer; Leo F. Verdonck; Mahmoud Aljurf; Marjolein van der Poel; Mark Litzow; Matt Kalaycio; Michael R. Grunwald; Miguel Angel Diaz; Mitchell Sabloff; Mohamed A. Kharfan-Dabaja; Navneet S. Majhail; Nosha Farhadfar; Ran Reshef; Richard F. Olsson; Robert Peter Gale; Ryotaro Nakamura; Sachiko Seo; Saurabh Chhabra; Shahrukh Hashmi; Shatha Farhan; Siddhartha Ganguly; Sunita Nathan; Taiga Nishihori; Tania Jain; Vaibhav Agrawal; Ulrike Bacher; Uday Popat; Wael Saber

doi:10.1016/j.jtct.2021.08.007

Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improve Transplantation Outcomes in Older Patients with Myelodysplastic Syndromes

Betül Oran, Kwang Woo Ahn, Caitrin Fretham, Amer Beitinjaneh, Asad Bashey, Attaphol Pawarode, Baldeep Wirk, Bart L. Scott, Bipin N. Savani, Christopher Bredeson, Daniel Weisdorf, David I. Marks, David Rizzieri, Edward Copelan, Gerhard C. Hildebrandt, Gregory A. Hale, Hemant S. Murthy, Hillard M. Lazarus, Jan Cerny, Jane L. LiesveldJean A. Yared, Jean Yves-Cahn, Jeffrey Szer, Leo F. Verdonck, Mahmoud Aljurf, Marjolein van der Poel, Mark Litzow, Matt Kalaycio, Michael R. Grunwald, Miguel Angel Diaz, Mitchell Sabloff, Mohamed A. Kharfan-Dabaja, Navneet S. Majhail, Nosha Farhadfar, Ran Reshef, Richard F. Olsson, Robert Peter Gale, Ryotaro Nakamura, Sachiko Seo, Saurabh Chhabra, Shahrukh Hashmi, Shatha Farhan, Siddhartha Ganguly, Sunita Nathan, Taiga Nishihori, Tania Jain, Vaibhav Agrawal, Ulrike Bacher, Uday Popat, Wael Saber

Hematology

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

Abstract

Reduced-intensity conditioning (RIC) regimens developed to extend the use of allogeneic hematopoietic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the 2 most commonly used RIC regimens, i.v. fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in patients with myelodysplastic syndrome (MDS). Through the Center for International Blood and Marrow Transplant Research (CIBMTR), we identified 1045 MDS patients age ≥60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using an RIC regimen. The CIBMTR's definition of RIC was used: a regimen that incorporated an i.v. busulfan total dose ≤7.2 mg/kg or a low-dose melphalan total dose ≤150 mg/m². The 2 groups, recipients of FluBu (n = 697) and recipients of FluMel (n = 448), were comparable in terms of disease- and transplantation-related characteristics except for the more frequent use of antithymocyte globulin or alemtuzumab in the FluBu group (39% versus 31%). The median age was 67 years in both groups. FluMel was associated with a reduced relapse incidence (RI) compared with FluBu, with a 1-year adjusted incidence of 26% versus 44% (P ≤ .0001). Transplantation-related mortality (TRM) was higher in the FluMel group (26% versus 16%; P ≤ .0001). Because the magnitude of improvement with FluMel in RI was greater than the improvement in TRM with FluBu, disease-free survival (DFS) was better at 1 year and beyond with FluMel compared with FluBu (48% versus 40% at 1 year [P = .02] and 35% versus 27% at 3 years [P = .01]). Overall survival was comparable in the 2 groups at 1 year (63% versus 61%; P = .4) but was significantly improved with FluMel compared with FluBu at 3 years (46% versus 39%; P = .03). Our results suggest that FluMel is associated with superior DFS compared with FluBu owing to reduced RI in older patients with MDS patients.

Original language	English (US)
Pages (from-to)	921.e1-921.e10
Journal	Transplantation and Cellular Therapy
Volume	27
Issue number	11
DOIs	https://doi.org/10.1016/j.jtct.2021.08.007
State	Published - Nov 2021

Keywords

MDS
Melphalan
Relapse
Survival
Transplantation

ASJC Scopus subject areas

Immunology and Allergy
Molecular Medicine
Hematology
Cell Biology
Transplantation

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10.1016/j.jtct.2021.08.007

Cite this

Oran, B., Ahn, K. W., Fretham, C., Beitinjaneh, A., Bashey, A., Pawarode, A., Wirk, B., Scott, B. L., Savani, B. N., Bredeson, C., Weisdorf, D., Marks, D. I., Rizzieri, D., Copelan, E., Hildebrandt, G. C., Hale, G. A., Murthy, H. S., Lazarus, H. M., Cerny, J., ... Saber, W. (2021). Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improve Transplantation Outcomes in Older Patients with Myelodysplastic Syndromes. Transplantation and Cellular Therapy, 27(11), 921.e1-921.e10. https://doi.org/10.1016/j.jtct.2021.08.007

Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improve Transplantation Outcomes in Older Patients with Myelodysplastic Syndromes. / Oran, Betül; Ahn, Kwang Woo; Fretham, Caitrin et al.
In: Transplantation and Cellular Therapy, Vol. 27, No. 11, 11.2021, p. 921.e1-921.e10.

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

Oran, B, Ahn, KW, Fretham, C, Beitinjaneh, A, Bashey, A, Pawarode, A, Wirk, B, Scott, BL, Savani, BN, Bredeson, C, Weisdorf, D, Marks, DI, Rizzieri, D, Copelan, E, Hildebrandt, GC, Hale, GA, Murthy, HS, Lazarus, HM, Cerny, J, Liesveld, JL, Yared, JA, Yves-Cahn, J, Szer, J, Verdonck, LF, Aljurf, M, van der Poel, M, Litzow, M, Kalaycio, M, Grunwald, MR, Diaz, MA, Sabloff, M, Kharfan-Dabaja, MA, Majhail, NS, Farhadfar, N, Reshef, R, Olsson, RF, Gale, RP, Nakamura, R, Seo, S, Chhabra, S, Hashmi, S, Farhan, S, Ganguly, S, Nathan, S, Nishihori, T, Jain, T, Agrawal, V, Bacher, U, Popat, U & Saber, W 2021, 'Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improve Transplantation Outcomes in Older Patients with Myelodysplastic Syndromes', Transplantation and Cellular Therapy, vol. 27, no. 11, pp. 921.e1-921.e10. https://doi.org/10.1016/j.jtct.2021.08.007

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abstract = "Reduced-intensity conditioning (RIC) regimens developed to extend the use of allogeneic hematopoietic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the 2 most commonly used RIC regimens, i.v. fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in patients with myelodysplastic syndrome (MDS). Through the Center for International Blood and Marrow Transplant Research (CIBMTR), we identified 1045 MDS patients age ≥60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using an RIC regimen. The CIBMTR's definition of RIC was used: a regimen that incorporated an i.v. busulfan total dose ≤7.2 mg/kg or a low-dose melphalan total dose ≤150 mg/m2. The 2 groups, recipients of FluBu (n = 697) and recipients of FluMel (n = 448), were comparable in terms of disease- and transplantation-related characteristics except for the more frequent use of antithymocyte globulin or alemtuzumab in the FluBu group (39% versus 31%). The median age was 67 years in both groups. FluMel was associated with a reduced relapse incidence (RI) compared with FluBu, with a 1-year adjusted incidence of 26% versus 44% (P ≤ .0001). Transplantation-related mortality (TRM) was higher in the FluMel group (26% versus 16%; P ≤ .0001). Because the magnitude of improvement with FluMel in RI was greater than the improvement in TRM with FluBu, disease-free survival (DFS) was better at 1 year and beyond with FluMel compared with FluBu (48% versus 40% at 1 year [P = .02] and 35% versus 27% at 3 years [P = .01]). Overall survival was comparable in the 2 groups at 1 year (63% versus 61%; P = .4) but was significantly improved with FluMel compared with FluBu at 3 years (46% versus 39%; P = .03). Our results suggest that FluMel is associated with superior DFS compared with FluBu owing to reduced RI in older patients with MDS patients.",

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doi = "10.1016/j.jtct.2021.08.007",

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T1 - Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improve Transplantation Outcomes in Older Patients with Myelodysplastic Syndromes

AU - Oran, Betül

AU - Ahn, Kwang Woo

AU - Fretham, Caitrin

AU - Beitinjaneh, Amer

AU - Bashey, Asad

AU - Pawarode, Attaphol

AU - Wirk, Baldeep

AU - Scott, Bart L.

AU - Savani, Bipin N.

AU - Bredeson, Christopher

AU - Weisdorf, Daniel

AU - Marks, David I.

AU - Rizzieri, David

AU - Copelan, Edward

AU - Hildebrandt, Gerhard C.

AU - Hale, Gregory A.

AU - Murthy, Hemant S.

AU - Lazarus, Hillard M.

AU - Cerny, Jan

AU - Liesveld, Jane L.

AU - Yared, Jean A.

AU - Yves-Cahn, Jean

AU - Szer, Jeffrey

AU - Verdonck, Leo F.

AU - Aljurf, Mahmoud

AU - van der Poel, Marjolein

AU - Litzow, Mark

AU - Kalaycio, Matt

AU - Grunwald, Michael R.

AU - Diaz, Miguel Angel

AU - Sabloff, Mitchell

AU - Kharfan-Dabaja, Mohamed A.

AU - Majhail, Navneet S.

AU - Farhadfar, Nosha

AU - Reshef, Ran

AU - Olsson, Richard F.

AU - Gale, Robert Peter

AU - Nakamura, Ryotaro

AU - Seo, Sachiko

AU - Chhabra, Saurabh

AU - Hashmi, Shahrukh

AU - Farhan, Shatha

AU - Ganguly, Siddhartha

AU - Nathan, Sunita

AU - Nishihori, Taiga

AU - Jain, Tania

AU - Agrawal, Vaibhav

AU - Bacher, Ulrike

AU - Popat, Uday

AU - Saber, Wael

PY - 2021/11

Y1 - 2021/11

N2 - Reduced-intensity conditioning (RIC) regimens developed to extend the use of allogeneic hematopoietic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the 2 most commonly used RIC regimens, i.v. fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in patients with myelodysplastic syndrome (MDS). Through the Center for International Blood and Marrow Transplant Research (CIBMTR), we identified 1045 MDS patients age ≥60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using an RIC regimen. The CIBMTR's definition of RIC was used: a regimen that incorporated an i.v. busulfan total dose ≤7.2 mg/kg or a low-dose melphalan total dose ≤150 mg/m2. The 2 groups, recipients of FluBu (n = 697) and recipients of FluMel (n = 448), were comparable in terms of disease- and transplantation-related characteristics except for the more frequent use of antithymocyte globulin or alemtuzumab in the FluBu group (39% versus 31%). The median age was 67 years in both groups. FluMel was associated with a reduced relapse incidence (RI) compared with FluBu, with a 1-year adjusted incidence of 26% versus 44% (P ≤ .0001). Transplantation-related mortality (TRM) was higher in the FluMel group (26% versus 16%; P ≤ .0001). Because the magnitude of improvement with FluMel in RI was greater than the improvement in TRM with FluBu, disease-free survival (DFS) was better at 1 year and beyond with FluMel compared with FluBu (48% versus 40% at 1 year [P = .02] and 35% versus 27% at 3 years [P = .01]). Overall survival was comparable in the 2 groups at 1 year (63% versus 61%; P = .4) but was significantly improved with FluMel compared with FluBu at 3 years (46% versus 39%; P = .03). Our results suggest that FluMel is associated with superior DFS compared with FluBu owing to reduced RI in older patients with MDS patients.

AB - Reduced-intensity conditioning (RIC) regimens developed to extend the use of allogeneic hematopoietic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the 2 most commonly used RIC regimens, i.v. fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in patients with myelodysplastic syndrome (MDS). Through the Center for International Blood and Marrow Transplant Research (CIBMTR), we identified 1045 MDS patients age ≥60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using an RIC regimen. The CIBMTR's definition of RIC was used: a regimen that incorporated an i.v. busulfan total dose ≤7.2 mg/kg or a low-dose melphalan total dose ≤150 mg/m2. The 2 groups, recipients of FluBu (n = 697) and recipients of FluMel (n = 448), were comparable in terms of disease- and transplantation-related characteristics except for the more frequent use of antithymocyte globulin or alemtuzumab in the FluBu group (39% versus 31%). The median age was 67 years in both groups. FluMel was associated with a reduced relapse incidence (RI) compared with FluBu, with a 1-year adjusted incidence of 26% versus 44% (P ≤ .0001). Transplantation-related mortality (TRM) was higher in the FluMel group (26% versus 16%; P ≤ .0001). Because the magnitude of improvement with FluMel in RI was greater than the improvement in TRM with FluBu, disease-free survival (DFS) was better at 1 year and beyond with FluMel compared with FluBu (48% versus 40% at 1 year [P = .02] and 35% versus 27% at 3 years [P = .01]). Overall survival was comparable in the 2 groups at 1 year (63% versus 61%; P = .4) but was significantly improved with FluMel compared with FluBu at 3 years (46% versus 39%; P = .03). Our results suggest that FluMel is associated with superior DFS compared with FluBu owing to reduced RI in older patients with MDS patients.

KW - MDS

KW - Melphalan

KW - Relapse

KW - Survival

KW - Transplantation

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Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improve Transplantation Outcomes in Older Patients with Myelodysplastic Syndromes

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