Outcome of allogeneic hematopoietic cell transplantation from HLA-identical siblings for severe aplastic anemia in patients over 40 years of age

Dario Sangiolo; Rainer Storb; H. Joachim Deeg; Mary E.D. Flowers; Paul J. Martin; Brenda M. Sandmaier; Hans Peter Kiem; Richard A. Nash; Kris Doney; Wendy M. Leisenring; George Earl Georges

doi:10.1016/j.bbmt.2010.04.005

Outcome of allogeneic hematopoietic cell transplantation from HLA-identical siblings for severe aplastic anemia in patients over 40 years of age

Dario Sangiolo, Rainer Storb, H. Joachim Deeg, Mary E.D. Flowers, Paul J. Martin, Brenda M. Sandmaier, Hans Peter Kiem, Richard A. Nash, Kris Doney, Wendy M. Leisenring, George Earl Georges^*

^*Corresponding author for this work

Medicine, Hematology Oncology Division

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

38 Scopus citations

Abstract

Patients with severe aplastic anemia (SAA) over 40 years of age are often not offered treatment with hematopoietic cell transplantation (HCT) because of concerns about treatment-related morbidity or mortality. To evaluate this risk, we analyzed outcomes after allogeneic HCT from HLA-identical sibling donors for all older patients with SAA at our center since 1988. The 23 consecutive patients ranged in age from 40 to 68 years. The conditioning regimen was cyclophosphamide (200 mg/kg) and horse antithymocyte globulin. Methotrexate and cyclosporine were given for postgrafting immunosuppression. The cumulative incidences of grades II, III, and IV acute graft-versus-host-disease were 30%, 4%, and 0%, respectively; that for chronic GVHD was 26%. With a median follow-up of 9.1 years, overall survival was 65%. Documented infections within 1 month before HCT were significantly associated with risk of early treatment-related mortality (P < .001). The median time to discontinuation of posttransplant immunosuppression was 6.2 (range: 5.9-92.0) months. Three patients developed superficial basal cell carcinoma between 5.5 and 15 years after HCT. Our data favor a practice of extending HLA-identical sibling HCT for treatment of SAA in patients older than 40 years of age who are without significant medical comorbidities.

Original language	English (US)
Pages (from-to)	1411-1418
Number of pages	8
Journal	Biology of Blood and Marrow Transplantation
Volume	16
Issue number	10
DOIs	https://doi.org/10.1016/j.bbmt.2010.04.005
State	Published - Oct 2010

Funding

Financial disclosure: This work was supported by grants HL36444, CA15704 , and AI067770 National Institutes of Health , Bethesda, MD, USA. D.S. is a fellowship recipient “Assegno di Ricerca,” funded by Regione Piemonte , Italy. The authors thank the patients and their families, the transplant and long-term follow-up teams, the referring physicians, and the database managers, particularly Gary Schoch, for their invaluable help with the study, and Bonnie Larson, Helen Crawford, and Sue Carbonneau for help with manuscript preparation.

Keywords

Aplastic anemia
Cyclophosphamide/antithymocyte globulin conditioning
Human leukocyte antigen-matched bone marrow transplantation
Older age

ASJC Scopus subject areas

Transplantation
Hematology

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10.1016/j.bbmt.2010.04.005

Cite this

Sangiolo, D., Storb, R., Deeg, H. J., Flowers, M. E. D., Martin, P. J., Sandmaier, B. M., Kiem, H. P., Nash, R. A., Doney, K., Leisenring, W. M., & Georges, G. E. (2010). Outcome of allogeneic hematopoietic cell transplantation from HLA-identical siblings for severe aplastic anemia in patients over 40 years of age. Biology of Blood and Marrow Transplantation, 16(10), 1411-1418. https://doi.org/10.1016/j.bbmt.2010.04.005

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title = "Outcome of allogeneic hematopoietic cell transplantation from HLA-identical siblings for severe aplastic anemia in patients over 40 years of age",

abstract = "Patients with severe aplastic anemia (SAA) over 40 years of age are often not offered treatment with hematopoietic cell transplantation (HCT) because of concerns about treatment-related morbidity or mortality. To evaluate this risk, we analyzed outcomes after allogeneic HCT from HLA-identical sibling donors for all older patients with SAA at our center since 1988. The 23 consecutive patients ranged in age from 40 to 68 years. The conditioning regimen was cyclophosphamide (200 mg/kg) and horse antithymocyte globulin. Methotrexate and cyclosporine were given for postgrafting immunosuppression. The cumulative incidences of grades II, III, and IV acute graft-versus-host-disease were 30%, 4%, and 0%, respectively; that for chronic GVHD was 26%. With a median follow-up of 9.1 years, overall survival was 65%. Documented infections within 1 month before HCT were significantly associated with risk of early treatment-related mortality (P < .001). The median time to discontinuation of posttransplant immunosuppression was 6.2 (range: 5.9-92.0) months. Three patients developed superficial basal cell carcinoma between 5.5 and 15 years after HCT. Our data favor a practice of extending HLA-identical sibling HCT for treatment of SAA in patients older than 40 years of age who are without significant medical comorbidities.",

keywords = "Aplastic anemia, Cyclophosphamide/antithymocyte globulin conditioning, Human leukocyte antigen-matched bone marrow transplantation, Older age",

author = "Dario Sangiolo and Rainer Storb and Deeg, {H. Joachim} and Flowers, {Mary E.D.} and Martin, {Paul J.} and Sandmaier, {Brenda M.} and Kiem, {Hans Peter} and Nash, {Richard A.} and Kris Doney and Leisenring, {Wendy M.} and Georges, {George Earl}",

note = "Funding Information: Financial disclosure: This work was supported by grants HL36444, CA15704 , and AI067770 National Institutes of Health , Bethesda, MD, USA. D.S. is a fellowship recipient “Assegno di Ricerca,” funded by Regione Piemonte , Italy. The authors thank the patients and their families, the transplant and long-term follow-up teams, the referring physicians, and the database managers, particularly Gary Schoch, for their invaluable help with the study, and Bonnie Larson, Helen Crawford, and Sue Carbonneau for help with manuscript preparation.",

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Sangiolo, D, Storb, R, Deeg, HJ, Flowers, MED, Martin, PJ, Sandmaier, BM, Kiem, HP, Nash, RA, Doney, K, Leisenring, WM & Georges, GE 2010, 'Outcome of allogeneic hematopoietic cell transplantation from HLA-identical siblings for severe aplastic anemia in patients over 40 years of age', Biology of Blood and Marrow Transplantation, vol. 16, no. 10, pp. 1411-1418. https://doi.org/10.1016/j.bbmt.2010.04.005

TY - JOUR

T1 - Outcome of allogeneic hematopoietic cell transplantation from HLA-identical siblings for severe aplastic anemia in patients over 40 years of age

AU - Sangiolo, Dario

AU - Storb, Rainer

AU - Deeg, H. Joachim

AU - Flowers, Mary E.D.

AU - Martin, Paul J.

AU - Sandmaier, Brenda M.

AU - Kiem, Hans Peter

AU - Nash, Richard A.

AU - Doney, Kris

AU - Leisenring, Wendy M.

AU - Georges, George Earl

N1 - Funding Information: Financial disclosure: This work was supported by grants HL36444, CA15704 , and AI067770 National Institutes of Health , Bethesda, MD, USA. D.S. is a fellowship recipient “Assegno di Ricerca,” funded by Regione Piemonte , Italy. The authors thank the patients and their families, the transplant and long-term follow-up teams, the referring physicians, and the database managers, particularly Gary Schoch, for their invaluable help with the study, and Bonnie Larson, Helen Crawford, and Sue Carbonneau for help with manuscript preparation.

PY - 2010/10

Y1 - 2010/10

N2 - Patients with severe aplastic anemia (SAA) over 40 years of age are often not offered treatment with hematopoietic cell transplantation (HCT) because of concerns about treatment-related morbidity or mortality. To evaluate this risk, we analyzed outcomes after allogeneic HCT from HLA-identical sibling donors for all older patients with SAA at our center since 1988. The 23 consecutive patients ranged in age from 40 to 68 years. The conditioning regimen was cyclophosphamide (200 mg/kg) and horse antithymocyte globulin. Methotrexate and cyclosporine were given for postgrafting immunosuppression. The cumulative incidences of grades II, III, and IV acute graft-versus-host-disease were 30%, 4%, and 0%, respectively; that for chronic GVHD was 26%. With a median follow-up of 9.1 years, overall survival was 65%. Documented infections within 1 month before HCT were significantly associated with risk of early treatment-related mortality (P < .001). The median time to discontinuation of posttransplant immunosuppression was 6.2 (range: 5.9-92.0) months. Three patients developed superficial basal cell carcinoma between 5.5 and 15 years after HCT. Our data favor a practice of extending HLA-identical sibling HCT for treatment of SAA in patients older than 40 years of age who are without significant medical comorbidities.

AB - Patients with severe aplastic anemia (SAA) over 40 years of age are often not offered treatment with hematopoietic cell transplantation (HCT) because of concerns about treatment-related morbidity or mortality. To evaluate this risk, we analyzed outcomes after allogeneic HCT from HLA-identical sibling donors for all older patients with SAA at our center since 1988. The 23 consecutive patients ranged in age from 40 to 68 years. The conditioning regimen was cyclophosphamide (200 mg/kg) and horse antithymocyte globulin. Methotrexate and cyclosporine were given for postgrafting immunosuppression. The cumulative incidences of grades II, III, and IV acute graft-versus-host-disease were 30%, 4%, and 0%, respectively; that for chronic GVHD was 26%. With a median follow-up of 9.1 years, overall survival was 65%. Documented infections within 1 month before HCT were significantly associated with risk of early treatment-related mortality (P < .001). The median time to discontinuation of posttransplant immunosuppression was 6.2 (range: 5.9-92.0) months. Three patients developed superficial basal cell carcinoma between 5.5 and 15 years after HCT. Our data favor a practice of extending HLA-identical sibling HCT for treatment of SAA in patients older than 40 years of age who are without significant medical comorbidities.

KW - Aplastic anemia

KW - Cyclophosphamide/antithymocyte globulin conditioning

KW - Human leukocyte antigen-matched bone marrow transplantation

KW - Older age

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Outcome of allogeneic hematopoietic cell transplantation from HLA-identical siblings for severe aplastic anemia in patients over 40 years of age

Abstract

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