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

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

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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

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© 2019 American Society of Hematology. All rights reserved.

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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

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

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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",

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doi = "10.1182/bloodadvances.2019000722",

language = "English (US)",

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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

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

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