Allogeneic Hematopoietic Cell Transplantation Using Treosulfan-Based Conditioning for Treatment of Marrow Failure Disorders

Lauri M. Burroughs; Akiko Shimamura; Julie An Talano; Jennifer A. Domm; Kelsey K. Baker; Colleen Delaney; Haydar Frangoul; David A. Margolis; K. Scott Baker; Eneida R. Nemecek; Amy E. Geddis; Brenda M. Sandmaier; H. Joachim Deeg; Rainer Storb; Ann E. Woolfrey

doi:10.1016/j.bbmt.2017.06.002

Allogeneic Hematopoietic Cell Transplantation Using Treosulfan-Based Conditioning for Treatment of Marrow Failure Disorders

Lauri M. Burroughs, Akiko Shimamura, Julie An Talano, Jennifer A. Domm, Kelsey K. Baker, Colleen Delaney, Haydar Frangoul, David A. Margolis, K. Scott Baker, Eneida R. Nemecek, Amy E. Geddis, Brenda M. Sandmaier, H. Joachim Deeg, Rainer Storb, Ann E. Woolfrey

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

42 Scopus citations

Abstract

Hematopoietic cell transplantation (HCT) is effective in the treatment of inherited marrow failure disorders and other nonmalignant diseases. Conventional myeloablative conditioning regimens have been associated with high transplant-related mortality, particularly in patients with comorbid conditions. Here we report on 14 patients with marrow failure disorders (Shwachman-Diamond syndrome, n = 3; Diamond Blackfan anemia, n = 4; GATA2 deficiency, n = 2; paroxysmal nocturnal hemoglobinuria, n = 4; and an undefined marrow failure disorder, n = 1) who underwent HCT on a prospective, phase II, multicenter clinical trial. Patients were given HLA-matched related (n = 2) or unrelated (n = 12) grafts after conditioning with treosulfan (42 g/m²), fludarabine (150 mg/m²), ± thymoglobulin (n = 11; 6 mg/kg). All patients engrafted. At a median follow-up of 3 years, 13 patients are alive with complete correction of their underlying disease. These results indicate that the combination of treosulfan, fludarabine, and thymoglobulin is effective at establishing donor engraftment with a low toxicity profile and excellent disease-free survival in patients with marrow failure disorders.

Original language	English (US)
Pages (from-to)	1669-1677
Number of pages	9
Journal	Biology of Blood and Marrow Transplantation
Volume	23
Issue number	10
DOIs	https://doi.org/10.1016/j.bbmt.2017.06.002
State	Published - Oct 2017

Keywords

Bone marrow failure
Diamond Blackfan Anemia
Reduced-toxicity conditioning in nonmalignant diseases
Shwachman-Diamond Syndrome

ASJC Scopus subject areas

Hematology
Transplantation

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10.1016/j.bbmt.2017.06.002

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Burroughs, L. M., Shimamura, A., Talano, J. A., Domm, J. A., Baker, K. K., Delaney, C., Frangoul, H., Margolis, D. A., Baker, K. S., Nemecek, E. R., Geddis, A. E., Sandmaier, B. M., Deeg, H. J., Storb, R., & Woolfrey, A. E. (2017). Allogeneic Hematopoietic Cell Transplantation Using Treosulfan-Based Conditioning for Treatment of Marrow Failure Disorders. Biology of Blood and Marrow Transplantation, 23(10), 1669-1677. https://doi.org/10.1016/j.bbmt.2017.06.002

Burroughs, LM, Shimamura, A, Talano, JA, Domm, JA, Baker, KK, Delaney, C, Frangoul, H, Margolis, DA, Baker, KS, Nemecek, ER, Geddis, AE, Sandmaier, BM, Deeg, HJ, Storb, R & Woolfrey, AE 2017, 'Allogeneic Hematopoietic Cell Transplantation Using Treosulfan-Based Conditioning for Treatment of Marrow Failure Disorders', Biology of Blood and Marrow Transplantation, vol. 23, no. 10, pp. 1669-1677. https://doi.org/10.1016/j.bbmt.2017.06.002

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title = "Allogeneic Hematopoietic Cell Transplantation Using Treosulfan-Based Conditioning for Treatment of Marrow Failure Disorders",

abstract = "Hematopoietic cell transplantation (HCT) is effective in the treatment of inherited marrow failure disorders and other nonmalignant diseases. Conventional myeloablative conditioning regimens have been associated with high transplant-related mortality, particularly in patients with comorbid conditions. Here we report on 14 patients with marrow failure disorders (Shwachman-Diamond syndrome, n = 3; Diamond Blackfan anemia, n = 4; GATA2 deficiency, n = 2; paroxysmal nocturnal hemoglobinuria, n = 4; and an undefined marrow failure disorder, n = 1) who underwent HCT on a prospective, phase II, multicenter clinical trial. Patients were given HLA-matched related (n = 2) or unrelated (n = 12) grafts after conditioning with treosulfan (42 g/m2), fludarabine (150 mg/m2), ± thymoglobulin (n = 11; 6 mg/kg). All patients engrafted. At a median follow-up of 3 years, 13 patients are alive with complete correction of their underlying disease. These results indicate that the combination of treosulfan, fludarabine, and thymoglobulin is effective at establishing donor engraftment with a low toxicity profile and excellent disease-free survival in patients with marrow failure disorders.",

keywords = "Bone marrow failure, Diamond Blackfan Anemia, Reduced-toxicity conditioning in nonmalignant diseases, Shwachman-Diamond Syndrome",

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doi = "10.1016/j.bbmt.2017.06.002",

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AU - Burroughs, Lauri M.

AU - Shimamura, Akiko

AU - Talano, Julie An

AU - Domm, Jennifer A.

AU - Baker, Kelsey K.

AU - Delaney, Colleen

AU - Frangoul, Haydar

AU - Margolis, David A.

AU - Baker, K. Scott

AU - Nemecek, Eneida R.

AU - Geddis, Amy E.

AU - Sandmaier, Brenda M.

AU - Deeg, H. Joachim

AU - Storb, Rainer

AU - Woolfrey, Ann E.

PY - 2017/10

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N2 - Hematopoietic cell transplantation (HCT) is effective in the treatment of inherited marrow failure disorders and other nonmalignant diseases. Conventional myeloablative conditioning regimens have been associated with high transplant-related mortality, particularly in patients with comorbid conditions. Here we report on 14 patients with marrow failure disorders (Shwachman-Diamond syndrome, n = 3; Diamond Blackfan anemia, n = 4; GATA2 deficiency, n = 2; paroxysmal nocturnal hemoglobinuria, n = 4; and an undefined marrow failure disorder, n = 1) who underwent HCT on a prospective, phase II, multicenter clinical trial. Patients were given HLA-matched related (n = 2) or unrelated (n = 12) grafts after conditioning with treosulfan (42 g/m2), fludarabine (150 mg/m2), ± thymoglobulin (n = 11; 6 mg/kg). All patients engrafted. At a median follow-up of 3 years, 13 patients are alive with complete correction of their underlying disease. These results indicate that the combination of treosulfan, fludarabine, and thymoglobulin is effective at establishing donor engraftment with a low toxicity profile and excellent disease-free survival in patients with marrow failure disorders.

AB - Hematopoietic cell transplantation (HCT) is effective in the treatment of inherited marrow failure disorders and other nonmalignant diseases. Conventional myeloablative conditioning regimens have been associated with high transplant-related mortality, particularly in patients with comorbid conditions. Here we report on 14 patients with marrow failure disorders (Shwachman-Diamond syndrome, n = 3; Diamond Blackfan anemia, n = 4; GATA2 deficiency, n = 2; paroxysmal nocturnal hemoglobinuria, n = 4; and an undefined marrow failure disorder, n = 1) who underwent HCT on a prospective, phase II, multicenter clinical trial. Patients were given HLA-matched related (n = 2) or unrelated (n = 12) grafts after conditioning with treosulfan (42 g/m2), fludarabine (150 mg/m2), ± thymoglobulin (n = 11; 6 mg/kg). All patients engrafted. At a median follow-up of 3 years, 13 patients are alive with complete correction of their underlying disease. These results indicate that the combination of treosulfan, fludarabine, and thymoglobulin is effective at establishing donor engraftment with a low toxicity profile and excellent disease-free survival in patients with marrow failure disorders.

KW - Bone marrow failure

KW - Diamond Blackfan Anemia

KW - Reduced-toxicity conditioning in nonmalignant diseases

KW - Shwachman-Diamond Syndrome

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Allogeneic Hematopoietic Cell Transplantation Using Treosulfan-Based Conditioning for Treatment of Marrow Failure Disorders

Abstract

Keywords

ASJC Scopus subject areas

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