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 | |
| 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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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
}
TY - JOUR
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
N1 - Funding Information: Financial disclosure: The CIBMTR is supported primarily by Public Health Service Grant U24CA076518 from the National Cancer Institute, the National Heart, Lung and Blood Institute, and the National Institute of Allergy and Infectious Diseases; Grant HHSH250201700006C from the Health Resources and Services Administration; and Awards N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research. Support is also provided by Be the Match Foundation, the Medical College of Wisconsin, the National Marrow Donor Program, and from the following commercial entities: AbbVie, Accenture, Actinium Pharmaceuticals, Adaptive Biotechnologies, Adienne, Allovir, Amgen, Astellas Pharma US, bluebird bio, Bristol Myers Squibb, CareDx, CSL Behring, CytoSen Therapeutics, Daiichi Sankyo, Eurofins Viracor, ExcellThera, Fate Therapeutics, Gamida Cell, Genentech, Gilead, GlaxoSmithKline, Incyte, Janssen/Johnson & Johnson, Jasper Therapeutics, Jazz Pharmaceuticals, Karyopharm Therapeutics, Kiadis Pharma; Kite Pharma, Kyowa Kirin, Magenta Therapeutics, Medac, Merck & Co, Millennium, Miltenyi Biotec, MorphoSys, Novartis, Omeros, Oncopeptides, Orca Biosystems, Pfizer, Pharmacyclics, Sanofi Genzyme, Seagen, Stemcyte, Takeda Pharmaceuticals, Tscan, Vertex, Vor Biopharma, and Xenikos. Funding Information: Financial disclosure: The CIBMTR is supported primarily by Public Health Service Grant U24CA076518 from the National Cancer Institute, the National Heart, Lung and Blood Institute, and the National Institute of Allergy and Infectious Diseases; Grant HHSH250201700006C from the Health Resources and Services Administration; and Awards N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research. Support is also provided by Be the Match Foundation, the Medical College of Wisconsin, the National Marrow Donor Program, and from the following commercial entities: AbbVie, Accenture, Actinium Pharmaceuticals, Adaptive Biotechnologies, Adienne, Allovir, Amgen, Astellas Pharma US, bluebird bio, Bristol Myers Squibb, CareDx, CSL Behring, CytoSen Therapeutics, Daiichi Sankyo, Eurofins Viracor, ExcellThera, Fate Therapeutics, Gamida Cell, Genentech, Gilead, GlaxoSmithKline, Incyte, Janssen/Johnson & Johnson, Jasper Therapeutics, Jazz Pharmaceuticals, Karyopharm Therapeutics, Kiadis Pharma; Kite Pharma, Kyowa Kirin, Magenta Therapeutics, Medac, Merck & Co, Millennium, Miltenyi Biotec, MorphoSys, Novartis, Omeros, Oncopeptides, Orca Biosystems, Pfizer, Pharmacyclics, Sanofi Genzyme, Seagen, Stemcyte, Takeda Pharmaceuticals, Tscan, Vertex, Vor Biopharma, and Xenikos. Conflict of interest statement: D.R. reports receiving personal fees from Amgen, Kite Pharma, AROG, Pharmacyclics, Seattle Genetics, Pfizer, Novartis, Sanofi-Aventis, Incyte, Gilead, Jazz Pharmaceuticals, AbbVie and Celgene and other remuneration from Celltron/Teva, Mustang, Bayer, and Stemline. G.C.H. reports receiving honoraria from Pfizer, Kite Pharma, Incyte, Jazz Pharmaceuticals, Pharmacyclics, Takeda, the Falk Foundation, and Astellas Pharma. G.A.H. reports receiving honoraria from Medpace. J.C. reports receiving personal fees from Jazz Pharmaceuticals and Amgen. J.L.L. reports receiving honoraria from Onconova. J.A.Y. reports receiving honoraria from Kite Pharma and Jazz Pharmaceutical. J.Y.-C. reports receiving honoraria from Agios, AbbVie, Otsuka and Race Oncology. J.S. reports receiving personal fees from Alexion Pharmaceuticals, Takeda Pharmaceuticals, Pfizer, Apellis Pharmaceuticals, Novartis, and Sanofi. M.R.G. reports receiving personal fees from AbbVie, Agios, Amgen, Cardinal Health, BMS/Celgene, Daiichi Sankyo, Incyte, Merck, Pfizer, Premier, Karius, Astellas, and Trovagene and honoraria from Incyte, Forma Therapeutics, Genentech/Roche, and Janssen. M.S. reports receiving personal fees from Astellas Pharma, Celgene, Pfizer, Jazz Pharmaceuticals, AbbVie, Taiho, Novartis, and Roche. N.F. reports receiving grants from CSL Behring and honoraria from Incyte. M.A.K.-D. reports receiving honoraria from Daiichi Sankyo and Pharmacyclics. N.F.M. reports receiving personal fees from Anthem, Incyte, and Nkarta. R.R. reports receiving personal fees from Gilead, Bristol Myers Squibb, Monsanto, Incyte, Magenta, Pharmacyclics, Atara, and Novartis. R.F.O. reports receiving personal fees from AstraZeneca. R.P.G. reports receiving personal fees from BeiGene, Kite Pharma, Fusion Pharma, La Jolla NanoMedical, MingSight Pharmaceuticals, CStone Pharmaceuticals, Antengene Biotech, FFF Enterprises, AZCA, the Rak Fond Foundation, and StemRad. R.N. reports receiving grants from Miyarisan and personal fees from NapaJen, Kadmon, Viracor, and Magenta. S.S. reports receiving personal fees from Janssen Pharmaceutical KK, outside the submitted work. S.H. reports receiving grants and honoraria from Pfizer, Novartis, Therakos, Janssen, and MSD. S.G. reports receiving personal fees from Seattle Genetics, Kite Pharma, and Kadmon. T.N. reports receiving honoraria from Karyopharm, Novartis, and Null Pharma. T.J. reports receiving honoraria from Takeda Oncology, CareDx, and Bristol Myers Squibb. Authorship statement: B.O. W.S. and U.P. developed the design and concept of the study; C.F. and K.W.A. performed the statistical analysis; B.O. W.S. U.P. C.F. and K.W.A. critically reviewed the data and analysis; and all authors were involved in interpretation of the data and analysis. B.O. wrote the first draft of the manuscript. All authors reviewed/revised the manuscript. Financial disclosure: See Acknowledgments on page 921.e8. Funding Information: Conflict of interest statement: D.R. reports receiving personal fees from Amgen, Kite Pharma, AROG, Pharmacyclics, Seattle Genetics, Pfizer, Novartis, Sanofi-Aventis, Incyte, Gilead, Jazz Pharmaceuticals, AbbVie and Celgene and other remuneration from Celltron/Teva, Mustang, Bayer, and Stemline. G.C.H. reports receiving honoraria from Pfizer, Kite Pharma, Incyte, Jazz Pharmaceuticals, Pharmacyclics, Takeda, the Falk Foundation, and Astellas Pharma. G.A.H. reports receiving honoraria from Medpace. J.C. reports receiving personal fees from Jazz Pharmaceuticals and Amgen. J.L.L. reports receiving honoraria from Onconova. J.A.Y. reports receiving honoraria from Kite Pharma and Jazz Pharmaceutical. J.Y.-C. reports receiving honoraria from Agios, AbbVie, Otsuka and Race Oncology. J.S. reports receiving personal fees from Alexion Pharmaceuticals, Takeda Pharmaceuticals, Pfizer, Apellis Pharmaceuticals, Novartis, and Sanofi. M.R.G. reports receiving personal fees from AbbVie, Agios, Amgen, Cardinal Health, BMS/Celgene, Daiichi Sankyo, Incyte, Merck, Pfizer, Premier, Karius, Astellas, and Trovagene and honoraria from Incyte, Forma Therapeutics, Genentech/Roche, and Janssen. M.S. reports receiving personal fees from Astellas Pharma, Celgene, Pfizer, Jazz Pharmaceuticals, AbbVie, Taiho, Novartis, and Roche. N.F. reports receiving grants from CSL Behring and honoraria from Incyte. M.A.K.-D. reports receiving honoraria from Daiichi Sankyo and Pharmacyclics. N.F.M. reports receiving personal fees from Anthem, Incyte, and Nkarta. R.R. reports receiving personal fees from Gilead, Bristol Myers Squibb, Monsanto, Incyte, Magenta, Pharmacyclics, Atara, and Novartis. R.F.O. reports receiving personal fees from AstraZeneca. R.P.G. reports receiving personal fees from BeiGene, Kite Pharma, Fusion Pharma, La Jolla NanoMedical, MingSight Pharmaceuticals, CStone Pharmaceuticals, Antengene Biotech, FFF Enterprises, AZCA, the Rak Fond Foundation, and StemRad. R.N. reports receiving grants from Miyarisan and personal fees from NapaJen, Kadmon, Viracor, and Magenta. S.S. reports receiving personal fees from Janssen Pharmaceutical KK, outside the submitted work. S.H. reports receiving grants and honoraria from Pfizer, Novartis, Therakos, Janssen, and MSD. S.G. reports receiving personal fees from Seattle Genetics, Kite Pharma, and Kadmon. T.N. reports receiving honoraria from Karyopharm, Novartis, and Null Pharma. T.J. reports receiving honoraria from Takeda Oncology, CareDx, and Bristol Myers Squibb. Publisher Copyright: © 2021
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
UR - http://www.scopus.com/inward/record.url?scp=85121157621&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85121157621&partnerID=8YFLogxK
U2 - 10.1016/j.jtct.2021.08.007
DO - 10.1016/j.jtct.2021.08.007
M3 - Article
C2 - 34403791
AN - SCOPUS:85121157621
VL - 27
SP - 921.e1-921.e10
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
SN - 2666-6367
IS - 11
ER -