Choice of conditioning regimens for bone marrow transplantation in severe aplastic anemia

Nelli Bejanyan; Soyoung Kim; Kyle M. Hebert; Natasha Kekre; Hisham Abdel-Azim; Ibrahim Ahmed; Mahmoud Aljurf; Sherif M. Badawy; Amer Beitinjaneh; Jaap Jan Boelens; Miguel Angel Diaz; Christopher C. Dvorak; Shahinaz Gadalla; James Gajewski; Robert Peter Gale; Siddhartha Ganguly; Andrew R. Gennery; Biju George; Usama Gergis; David Gómez-Almaguer; Marta Gonzalez Vicent; Hasan Hashem; Rammurti T. Kamble; Kimberly A. Kasow; Hillard M. Lazarus; Vikram Mathews; Paul J. Orchard; Michael Pulsipher; Olle Ringden; Kirk Schultz; Pierre Teira; Ann E. Woolfrey; Blachy Dávila Saldaña; Bipin Savani; Jacek Winiarski; Jean Yared; Daniel J. Weisdorf; Joseph H. Antin; Mary Eapen

doi:10.1182/bloodadvances.2019000722

Choice of conditioning regimens for bone marrow transplantation in severe aplastic anemia

Nelli Bejanyan, Soyoung Kim, Kyle M. Hebert, Natasha Kekre, Hisham Abdel-Azim, Ibrahim Ahmed, Mahmoud Aljurf, Sherif M. Badawy, Amer Beitinjaneh, Jaap Jan Boelens, Miguel Angel Diaz, Christopher C. Dvorak, Shahinaz Gadalla, James Gajewski, Robert Peter Gale, Siddhartha Ganguly, Andrew R. Gennery, Biju George, Usama Gergis, David Gómez-AlmaguerMarta Gonzalez Vicent, Hasan Hashem, Rammurti T. Kamble, Kimberly A. Kasow, Hillard M. Lazarus, Vikram Mathews, Paul J. Orchard, Michael Pulsipher, Olle Ringden, Kirk Schultz, Pierre Teira, Ann E. Woolfrey, Blachy Dávila Saldaña, Bipin Savani, Jacek Winiarski, Jean Yared, Daniel J. Weisdorf, Joseph H. Antin, Mary Eapen^*

^*Corresponding author for this work

Pediatrics

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

43 Scopus citations

Abstract

Allogeneic bone marrow transplantation (BMT) is curative therapy for the treatment of patients with severe aplastic anemia (SAA). However, several conditioning regimens can be used for BMT. We evaluated transplant conditioning regimens for BMT in SAA after HLA-matched sibling and unrelated donor BMT. For recipients of HLA-matched sibling donor transplantation (n 5 955), fludarabine (Flu)/cyclophosphamide (Cy)/antithymocyte globulin (ATG) or Cy/ATG led to the best survival. The 5-year probabilities of survival with Flu/Cy/ATG, Cy/ATG, Cy 6 Flu, and busulfan/Cy were 91%, 91%, 80%, and 84%, respectively (P 5 .001). For recipients of 8/8 and 7/8 HLA allele-matched unrelated donor transplantation (n 5 409), there were no differences in survival between regimens. The 5-year probabilities of survival with Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG, and Cy/ATG were 77%, 80%, 75%, and 72%, respectively (P 5 .61). Rabbit-derived ATG compared with equine-derived ATG was associated with a lower risk of grade II to IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 0.39; P, .001) but not chronic GVHD. Independent of conditioning regimen, survival was lower in patients aged .30 years after HLA-matched sibling (HR, 2.74; P, .001) or unrelated donor (HR, 1.98; P 5 .001) transplantation. These data support Flu/Cy/ATG and Cy/ATG as optimal regimens for HLA-matched sibling BMT. Although survival after an unrelated donor BMT did not differ between regimens, use of rabbit-derived ATG may be preferred because of lower risks of acute GVHD.

Original language	English (US)
Pages (from-to)	3123-3131
Number of pages	9
Journal	Blood Advances
Volume	3
Issue number	20
DOIs	https://doi.org/10.1182/bloodadvances.2019000722
State	Published - 2019

Funding

1Department of Blood and Marrow Transplant and Cellular Therapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; 2Division of Biostatistics and 3Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI; 4The Ottawa Hospital Blood & Marrow Transplant Program, University of Ottawa, Ottawa, ON, Canada; 5Children’s Center for Cancer and Blood Diseases, Children’s Hospital of Los Angeles, Los Angeles, CA; 6Division of Pediatric Hematology/Oncology, Children’s Mercy Hospital, Kansas City, MO; 7King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia; 8Hematology, Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University, Evanston, IL; 9Department of Medicine, University of Miami, Miami, FL; 10Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY; 11Hospital Niño Jesus, Madrid, Spain; 12Division of Pediatric Blood and Marrow Transplantation, University of California San Francisco Medical Center, San Francisco, CA; 13Clinical Genetics Branch, National Cancer Institute, Rockville, MD; 14Department of Medicine, Oregon Health & Science University, Portland, OR; 15Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom; 16Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas, Kansas City, KS; 17Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; 18Department of Hematology, Christian Medical College Hospital, Vellore, India; 19Department of Medicine, Weill Cornell Medical College, New York, NY; 20HospitalUniversitarioJoséE.González,UniversidadAutónomadeNuevoLeón,Monterrey,Mexico;21DivisionofHematologyandOncology,NationwideChildren’sHospital, Columbus, OH; 22Department of Medicine. Baylor College of Medicine Center for Cell and Gene Therapy, Houston, TX; 23Department of Pediatrics, University of North Carolina Hospitals, Chapel Hill, NC; 24Department of Medicine, Case Western Reserve University, Cleveland, OH; 25Department of Medicine, University of Minnesota, Minneapolis, MN; 26Division of Therapeutic Immunology, Karolinska Institutet, Stockholm, Sweden; 27British Columbia Children’s Hospital, University of British Columbia, Vancouver, BC, Canada; 28Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC, Canada; 29Fred Hutchinson Cancer Research Center, Seattle, WA; 30Children’s National Medical Center, Washington, DC; 31Vanderbilt University Medical Center, Nashville, TN; 32Greenebaum Cancer Center, University of Maryland, Baltimore, MD; and 33Stem Cell Transplantation, Dana-Farber Cancer Institute, Boston, MA. The Center for International Blood and Marrow Transplant Research is supported by U24-CA76518 from the National Institutes of Health, National Cancer Institute, National Heart, Lung, and Blood Institute, and National Institute of Allergy and Infectious Diseases, and HHSH 250201200016C from Health Services Research Administration, Department of Health and Human Services.

ASJC Scopus subject areas

Hematology

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10.1182/bloodadvances.2019000722

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Bejanyan, N., Kim, S., Hebert, K. M., Kekre, N., Abdel-Azim, H., Ahmed, I., Aljurf, M., Badawy, S. M., Beitinjaneh, A., Boelens, J. J., Diaz, M. A., Dvorak, C. C., Gadalla, S., Gajewski, J., Gale, R. P., Ganguly, S., Gennery, A. R., George, B., Gergis, U., ... Eapen, M. (2019). Choice of conditioning regimens for bone marrow transplantation in severe aplastic anemia. Blood Advances, 3(20), 3123-3131. https://doi.org/10.1182/bloodadvances.2019000722

@article{af95881b22fe4944a636a7a4bf9d4ff3,

title = "Choice of conditioning regimens for bone marrow transplantation in severe aplastic anemia",

abstract = "Allogeneic bone marrow transplantation (BMT) is curative therapy for the treatment of patients with severe aplastic anemia (SAA). However, several conditioning regimens can be used for BMT. We evaluated transplant conditioning regimens for BMT in SAA after HLA-matched sibling and unrelated donor BMT. For recipients of HLA-matched sibling donor transplantation (n 5 955), fludarabine (Flu)/cyclophosphamide (Cy)/antithymocyte globulin (ATG) or Cy/ATG led to the best survival. The 5-year probabilities of survival with Flu/Cy/ATG, Cy/ATG, Cy 6 Flu, and busulfan/Cy were 91%, 91%, 80%, and 84%, respectively (P 5 .001). For recipients of 8/8 and 7/8 HLA allele-matched unrelated donor transplantation (n 5 409), there were no differences in survival between regimens. The 5-year probabilities of survival with Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG, and Cy/ATG were 77%, 80%, 75%, and 72%, respectively (P 5 .61). Rabbit-derived ATG compared with equine-derived ATG was associated with a lower risk of grade II to IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 0.39; P, .001) but not chronic GVHD. Independent of conditioning regimen, survival was lower in patients aged .30 years after HLA-matched sibling (HR, 2.74; P, .001) or unrelated donor (HR, 1.98; P 5 .001) transplantation. These data support Flu/Cy/ATG and Cy/ATG as optimal regimens for HLA-matched sibling BMT. Although survival after an unrelated donor BMT did not differ between regimens, use of rabbit-derived ATG may be preferred because of lower risks of acute GVHD.",

author = "Nelli Bejanyan and Soyoung Kim and Hebert, {Kyle M.} and Natasha Kekre and Hisham Abdel-Azim and Ibrahim Ahmed and Mahmoud Aljurf and Badawy, {Sherif M.} and Amer Beitinjaneh and Boelens, {Jaap Jan} and Diaz, {Miguel Angel} and Dvorak, {Christopher C.} and Shahinaz Gadalla and James Gajewski and Gale, {Robert Peter} and Siddhartha Ganguly and Gennery, {Andrew R.} and Biju George and Usama Gergis and David G{\'o}mez-Almaguer and Vicent, {Marta Gonzalez} and Hasan Hashem and Kamble, {Rammurti T.} and Kasow, {Kimberly A.} and Lazarus, {Hillard M.} and Vikram Mathews and Orchard, {Paul J.} and Michael Pulsipher and Olle Ringden and Kirk Schultz and Pierre Teira and Woolfrey, {Ann E.} and Salda{\~n}a, {Blachy D{\'a}vila} and Bipin Savani and Jacek Winiarski and Jean Yared and Weisdorf, {Daniel J.} and Antin, {Joseph H.} and Mary Eapen",

year = "2019",

doi = "10.1182/bloodadvances.2019000722",

language = "English (US)",

volume = "3",

pages = "3123--3131",

journal = "Blood Advances",

issn = "2473-9529",

publisher = "American Society of Hematology",

number = "20",

}

Bejanyan, N, Kim, S, Hebert, KM, Kekre, N, Abdel-Azim, H, Ahmed, I, Aljurf, M, Badawy, SM, Beitinjaneh, A, Boelens, JJ, Diaz, MA, Dvorak, CC, Gadalla, S, Gajewski, J, Gale, RP, Ganguly, S, Gennery, AR, George, B, Gergis, U, Gómez-Almaguer, D, Vicent, MG, Hashem, H, Kamble, RT, Kasow, KA, Lazarus, HM, Mathews, V, Orchard, PJ, Pulsipher, M, Ringden, O, Schultz, K, Teira, P, Woolfrey, AE, Saldaña, BD, Savani, B, Winiarski, J, Yared, J, Weisdorf, DJ, Antin, JH & Eapen, M 2019, 'Choice of conditioning regimens for bone marrow transplantation in severe aplastic anemia', Blood Advances, vol. 3, no. 20, pp. 3123-3131. https://doi.org/10.1182/bloodadvances.2019000722

TY - JOUR

T1 - Choice of conditioning regimens for bone marrow transplantation in severe aplastic anemia

AU - Bejanyan, Nelli

AU - Kim, Soyoung

AU - Hebert, Kyle M.

AU - Kekre, Natasha

AU - Abdel-Azim, Hisham

AU - Ahmed, Ibrahim

AU - Aljurf, Mahmoud

AU - Badawy, Sherif M.

AU - Beitinjaneh, Amer

AU - Boelens, Jaap Jan

AU - Diaz, Miguel Angel

AU - Dvorak, Christopher C.

AU - Gadalla, Shahinaz

AU - Gajewski, James

AU - Gale, Robert Peter

AU - Ganguly, Siddhartha

AU - Gennery, Andrew R.

AU - George, Biju

AU - Gergis, Usama

AU - Gómez-Almaguer, David

AU - Vicent, Marta Gonzalez

AU - Hashem, Hasan

AU - Kamble, Rammurti T.

AU - Kasow, Kimberly A.

AU - Lazarus, Hillard M.

AU - Mathews, Vikram

AU - Orchard, Paul J.

AU - Pulsipher, Michael

AU - Ringden, Olle

AU - Schultz, Kirk

AU - Teira, Pierre

AU - Woolfrey, Ann E.

AU - Saldaña, Blachy Dávila

AU - Savani, Bipin

AU - Winiarski, Jacek

AU - Yared, Jean

AU - Weisdorf, Daniel J.

AU - Antin, Joseph H.

AU - Eapen, Mary

PY - 2019

Y1 - 2019

N2 - Allogeneic bone marrow transplantation (BMT) is curative therapy for the treatment of patients with severe aplastic anemia (SAA). However, several conditioning regimens can be used for BMT. We evaluated transplant conditioning regimens for BMT in SAA after HLA-matched sibling and unrelated donor BMT. For recipients of HLA-matched sibling donor transplantation (n 5 955), fludarabine (Flu)/cyclophosphamide (Cy)/antithymocyte globulin (ATG) or Cy/ATG led to the best survival. The 5-year probabilities of survival with Flu/Cy/ATG, Cy/ATG, Cy 6 Flu, and busulfan/Cy were 91%, 91%, 80%, and 84%, respectively (P 5 .001). For recipients of 8/8 and 7/8 HLA allele-matched unrelated donor transplantation (n 5 409), there were no differences in survival between regimens. The 5-year probabilities of survival with Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG, and Cy/ATG were 77%, 80%, 75%, and 72%, respectively (P 5 .61). Rabbit-derived ATG compared with equine-derived ATG was associated with a lower risk of grade II to IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 0.39; P, .001) but not chronic GVHD. Independent of conditioning regimen, survival was lower in patients aged .30 years after HLA-matched sibling (HR, 2.74; P, .001) or unrelated donor (HR, 1.98; P 5 .001) transplantation. These data support Flu/Cy/ATG and Cy/ATG as optimal regimens for HLA-matched sibling BMT. Although survival after an unrelated donor BMT did not differ between regimens, use of rabbit-derived ATG may be preferred because of lower risks of acute GVHD.

AB - Allogeneic bone marrow transplantation (BMT) is curative therapy for the treatment of patients with severe aplastic anemia (SAA). However, several conditioning regimens can be used for BMT. We evaluated transplant conditioning regimens for BMT in SAA after HLA-matched sibling and unrelated donor BMT. For recipients of HLA-matched sibling donor transplantation (n 5 955), fludarabine (Flu)/cyclophosphamide (Cy)/antithymocyte globulin (ATG) or Cy/ATG led to the best survival. The 5-year probabilities of survival with Flu/Cy/ATG, Cy/ATG, Cy 6 Flu, and busulfan/Cy were 91%, 91%, 80%, and 84%, respectively (P 5 .001). For recipients of 8/8 and 7/8 HLA allele-matched unrelated donor transplantation (n 5 409), there were no differences in survival between regimens. The 5-year probabilities of survival with Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG, and Cy/ATG were 77%, 80%, 75%, and 72%, respectively (P 5 .61). Rabbit-derived ATG compared with equine-derived ATG was associated with a lower risk of grade II to IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 0.39; P, .001) but not chronic GVHD. Independent of conditioning regimen, survival was lower in patients aged .30 years after HLA-matched sibling (HR, 2.74; P, .001) or unrelated donor (HR, 1.98; P 5 .001) transplantation. These data support Flu/Cy/ATG and Cy/ATG as optimal regimens for HLA-matched sibling BMT. Although survival after an unrelated donor BMT did not differ between regimens, use of rabbit-derived ATG may be preferred because of lower risks of acute GVHD.

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ER -

Choice of conditioning regimens for bone marrow transplantation in severe aplastic anemia

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