Ex Vivo CD34+–Selected T Cell–Depleted Peripheral Blood Stem Cell Grafts for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia and Myelodysplastic Syndrome Is Associated with Low Incidence of Acute and Chronic Graft-versus-Host Disease and High Treatment Response

Pere Barba; Patrick Hilden; Sean M. Devlin; Molly Maloy; Djamilia Dierov; Jimmy Nieves; Matthew D. Garrett; Julie Sogani; Christina Cho; Juliet N. Barker; Nancy A. Kernan; Hugo Castro-Malaspina; Ann A. Jakubowski; Guenther Koehne; Esperanza B. Papadopoulos; Susan Prockop; Craig Sauter; Roni Tamari; Marcel R.M. van den Brink; Scott T. Avecilla; Richard Meagher; Richard J. O'Reilly; Jenna D. Goldberg; James W. Young; Sergio Giralt; Miguel Angel Perales; Doris M. Ponce

doi:10.1016/j.bbmt.2016.12.633

Ex Vivo CD34⁺–Selected T Cell–Depleted Peripheral Blood Stem Cell Grafts for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia and Myelodysplastic Syndrome Is Associated with Low Incidence of Acute and Chronic Graft-versus-Host Disease and High Treatment Response

Pere Barba, Patrick Hilden, Sean M. Devlin, Molly Maloy, Djamilia Dierov, Jimmy Nieves, Matthew D. Garrett, Julie Sogani, Christina Cho, Juliet N. Barker, Nancy A. Kernan, Hugo Castro-Malaspina, Ann A. Jakubowski, Guenther Koehne, Esperanza B. Papadopoulos, Susan Prockop, Craig Sauter, Roni Tamari, Marcel R.M. van den Brink, Scott T. AvecillaRichard Meagher, Richard J. O'Reilly, Jenna D. Goldberg, James W. Young, Sergio Giralt, Miguel Angel Perales, Doris M. Ponce

Department of Medicine

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

12 Citations (Scopus)

Abstract

© 2017 The American Society for Blood and Marrow Transplantation Ex vivo CD34+–selected T cell depletion (TCD) has been developed as a strategy to reduce the incidence of graft-versus-host disease (GVHD) after allogeneic (allo) hematopoietic stem cell transplantation (HSCT). Clinical characteristics, treatment responses, and outcomes of patients developing acute (aGVHD) and chronic GVHD (cGVHD) after TCD allo-HSCT have not been well established. We evaluated 241 consecutive patients (median age, 57 years) with acute leukemia (n = 191, 79%) or myelodysplastic syndrome (MDS) (n = 50, 21%) undergoing CD34+–selected TCD allo-HSCT without post-HCST immunosuppression in a single institution. Cumulative incidences of grades II-IV and III-IV aGVHD at 180 days were 16% (95% confidence interval [CI], 12 to 21) and 5% (95% CI, 3 to 9), respectively. The skin was the most frequent organ involved, followed by the gastrointestinal tract. Patients were treated with topical corticosteroids, poorly absorbed corticosteroids (budesonide), and/or systemic corticosteroids. The overall day 28 treatment response was high at 82%. The cumulative incidence of any cGVHD at 3 years was 5% (95% CI, 3 to 9), with a median time of onset of 256 days (range, 95 to 1645). The 3-year transplant-related mortality, relapse, overall survival, and disease-free survival were 24% (95% CI, 18 to 30), 22% (95% CI, 17 to 27), 57% (95% CI, 50 to 64), and 54% (95% CI, 47 to 61), respectively. The 1-year and 3-year probabilities of cGVHD-free/relapse-free survival were 65% (95% CI, 59 to 71) and 52% (95% CI, 45 to 59), respectively. Our findings support the use of ex vivo CD34+–selected TCD allograft as a calcineurin inhibitor–free intervention for the prevention of GVHD in patients with acute leukemia and MDS.

Original language	English
Pages (from-to)	452-458
Journal	Biology of Blood and Marrow Transplantation
Volume	23
Issue number	3
DOIs	https://doi.org/10.1016/j.bbmt.2016.12.633
Publication status	Published - 1 Mar 2017

Keywords

Acute graft-versus-host disease
Chronic graft-versus-host disease
T cell–depleted transplantation

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Barba, P., Hilden, P., Devlin, S. M., Maloy, M., Dierov, D., Nieves, J., Garrett, M. D., Sogani, J., Cho, C., Barker, J. N., Kernan, N. A., Castro-Malaspina, H., Jakubowski, A. A., Koehne, G., Papadopoulos, E. B., Prockop, S., Sauter, C., Tamari, R., van den Brink, M. R. M., ... Ponce, D. M. (2017). Ex Vivo CD34⁺–Selected T Cell–Depleted Peripheral Blood Stem Cell Grafts for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia and Myelodysplastic Syndrome Is Associated with Low Incidence of Acute and Chronic Graft-versus-Host Disease and High Treatment Response. Biology of Blood and Marrow Transplantation, 23(3), 452-458. https://doi.org/10.1016/j.bbmt.2016.12.633

Barba, Pere ; Hilden, Patrick ; Devlin, Sean M. ; Maloy, Molly ; Dierov, Djamilia ; Nieves, Jimmy ; Garrett, Matthew D. ; Sogani, Julie ; Cho, Christina ; Barker, Juliet N. ; Kernan, Nancy A. ; Castro-Malaspina, Hugo ; Jakubowski, Ann A. ; Koehne, Guenther ; Papadopoulos, Esperanza B. ; Prockop, Susan ; Sauter, Craig ; Tamari, Roni ; van den Brink, Marcel R.M. ; Avecilla, Scott T. ; Meagher, Richard ; O'Reilly, Richard J. ; Goldberg, Jenna D. ; Young, James W. ; Giralt, Sergio ; Perales, Miguel Angel ; Ponce, Doris M. / Ex Vivo CD34⁺–Selected T Cell–Depleted Peripheral Blood Stem Cell Grafts for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia and Myelodysplastic Syndrome Is Associated with Low Incidence of Acute and Chronic Graft-versus-Host Disease and High Treatment Response. In: Biology of Blood and Marrow Transplantation. 2017 ; Vol. 23, No. 3. pp. 452-458.

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title = "Ex Vivo CD34+–Selected T Cell–Depleted Peripheral Blood Stem Cell Grafts for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia and Myelodysplastic Syndrome Is Associated with Low Incidence of Acute and Chronic Graft-versus-Host Disease and High Treatment Response",

abstract = "{\textcopyright} 2017 The American Society for Blood and Marrow Transplantation Ex vivo CD34+–selected T cell depletion (TCD) has been developed as a strategy to reduce the incidence of graft-versus-host disease (GVHD) after allogeneic (allo) hematopoietic stem cell transplantation (HSCT). Clinical characteristics, treatment responses, and outcomes of patients developing acute (aGVHD) and chronic GVHD (cGVHD) after TCD allo-HSCT have not been well established. We evaluated 241 consecutive patients (median age, 57 years) with acute leukemia (n = 191, 79%) or myelodysplastic syndrome (MDS) (n = 50, 21%) undergoing CD34+–selected TCD allo-HSCT without post-HCST immunosuppression in a single institution. Cumulative incidences of grades II-IV and III-IV aGVHD at 180 days were 16% (95% confidence interval [CI], 12 to 21) and 5% (95% CI, 3 to 9), respectively. The skin was the most frequent organ involved, followed by the gastrointestinal tract. Patients were treated with topical corticosteroids, poorly absorbed corticosteroids (budesonide), and/or systemic corticosteroids. The overall day 28 treatment response was high at 82%. The cumulative incidence of any cGVHD at 3 years was 5% (95% CI, 3 to 9), with a median time of onset of 256 days (range, 95 to 1645). The 3-year transplant-related mortality, relapse, overall survival, and disease-free survival were 24% (95% CI, 18 to 30), 22% (95% CI, 17 to 27), 57% (95% CI, 50 to 64), and 54% (95% CI, 47 to 61), respectively. The 1-year and 3-year probabilities of cGVHD-free/relapse-free survival were 65% (95% CI, 59 to 71) and 52% (95% CI, 45 to 59), respectively. Our findings support the use of ex vivo CD34+–selected TCD allograft as a calcineurin inhibitor–free intervention for the prevention of GVHD in patients with acute leukemia and MDS.",

keywords = "Acute graft-versus-host disease, Chronic graft-versus-host disease, T cell–depleted transplantation",

author = "Pere Barba and Patrick Hilden and Devlin, {Sean M.} and Molly Maloy and Djamilia Dierov and Jimmy Nieves and Garrett, {Matthew D.} and Julie Sogani and Christina Cho and Barker, {Juliet N.} and Kernan, {Nancy A.} and Hugo Castro-Malaspina and Jakubowski, {Ann A.} and Guenther Koehne and Papadopoulos, {Esperanza B.} and Susan Prockop and Craig Sauter and Roni Tamari and {van den Brink}, {Marcel R.M.} and Avecilla, {Scott T.} and Richard Meagher and O'Reilly, {Richard J.} and Goldberg, {Jenna D.} and Young, {James W.} and Sergio Giralt and Perales, {Miguel Angel} and Ponce, {Doris M.}",

year = "2017",

month = mar,

day = "1",

doi = "10.1016/j.bbmt.2016.12.633",

language = "English",

volume = "23",

pages = "452--458",

journal = "Biology of Blood and Marrow Transplantation",

issn = "1083-8791",

number = "3",

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Barba, P, Hilden, P, Devlin, SM, Maloy, M, Dierov, D, Nieves, J, Garrett, MD, Sogani, J, Cho, C, Barker, JN, Kernan, NA, Castro-Malaspina, H, Jakubowski, AA, Koehne, G, Papadopoulos, EB, Prockop, S, Sauter, C, Tamari, R, van den Brink, MRM, Avecilla, ST, Meagher, R, O'Reilly, RJ, Goldberg, JD, Young, JW, Giralt, S, Perales, MA & Ponce, DM 2017, 'Ex Vivo CD34⁺–Selected T Cell–Depleted Peripheral Blood Stem Cell Grafts for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia and Myelodysplastic Syndrome Is Associated with Low Incidence of Acute and Chronic Graft-versus-Host Disease and High Treatment Response', Biology of Blood and Marrow Transplantation, vol. 23, no. 3, pp. 452-458. https://doi.org/10.1016/j.bbmt.2016.12.633

Ex Vivo CD34⁺–Selected T Cell–Depleted Peripheral Blood Stem Cell Grafts for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia and Myelodysplastic Syndrome Is Associated with Low Incidence of Acute and Chronic Graft-versus-Host Disease and High Treatment Response. / Barba, Pere; Hilden, Patrick; Devlin, Sean M.; Maloy, Molly; Dierov, Djamilia; Nieves, Jimmy; Garrett, Matthew D.; Sogani, Julie; Cho, Christina; Barker, Juliet N.; Kernan, Nancy A.; Castro-Malaspina, Hugo; Jakubowski, Ann A.; Koehne, Guenther; Papadopoulos, Esperanza B.; Prockop, Susan; Sauter, Craig; Tamari, Roni; van den Brink, Marcel R.M.; Avecilla, Scott T.; Meagher, Richard; O'Reilly, Richard J.; Goldberg, Jenna D.; Young, James W.; Giralt, Sergio; Perales, Miguel Angel; Ponce, Doris M.

In: Biology of Blood and Marrow Transplantation, Vol. 23, No. 3, 01.03.2017, p. 452-458.

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

TY - JOUR

T1 - Ex Vivo CD34+–Selected T Cell–Depleted Peripheral Blood Stem Cell Grafts for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia and Myelodysplastic Syndrome Is Associated with Low Incidence of Acute and Chronic Graft-versus-Host Disease and High Treatment Response

AU - Barba, Pere

AU - Hilden, Patrick

AU - Devlin, Sean M.

AU - Maloy, Molly

AU - Dierov, Djamilia

AU - Nieves, Jimmy

AU - Garrett, Matthew D.

AU - Sogani, Julie

AU - Cho, Christina

AU - Barker, Juliet N.

AU - Kernan, Nancy A.

AU - Castro-Malaspina, Hugo

AU - Jakubowski, Ann A.

AU - Koehne, Guenther

AU - Papadopoulos, Esperanza B.

AU - Prockop, Susan

AU - Sauter, Craig

AU - Tamari, Roni

AU - van den Brink, Marcel R.M.

AU - Avecilla, Scott T.

AU - Meagher, Richard

AU - O'Reilly, Richard J.

AU - Goldberg, Jenna D.

AU - Young, James W.

AU - Giralt, Sergio

AU - Perales, Miguel Angel

AU - Ponce, Doris M.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - © 2017 The American Society for Blood and Marrow Transplantation Ex vivo CD34+–selected T cell depletion (TCD) has been developed as a strategy to reduce the incidence of graft-versus-host disease (GVHD) after allogeneic (allo) hematopoietic stem cell transplantation (HSCT). Clinical characteristics, treatment responses, and outcomes of patients developing acute (aGVHD) and chronic GVHD (cGVHD) after TCD allo-HSCT have not been well established. We evaluated 241 consecutive patients (median age, 57 years) with acute leukemia (n = 191, 79%) or myelodysplastic syndrome (MDS) (n = 50, 21%) undergoing CD34+–selected TCD allo-HSCT without post-HCST immunosuppression in a single institution. Cumulative incidences of grades II-IV and III-IV aGVHD at 180 days were 16% (95% confidence interval [CI], 12 to 21) and 5% (95% CI, 3 to 9), respectively. The skin was the most frequent organ involved, followed by the gastrointestinal tract. Patients were treated with topical corticosteroids, poorly absorbed corticosteroids (budesonide), and/or systemic corticosteroids. The overall day 28 treatment response was high at 82%. The cumulative incidence of any cGVHD at 3 years was 5% (95% CI, 3 to 9), with a median time of onset of 256 days (range, 95 to 1645). The 3-year transplant-related mortality, relapse, overall survival, and disease-free survival were 24% (95% CI, 18 to 30), 22% (95% CI, 17 to 27), 57% (95% CI, 50 to 64), and 54% (95% CI, 47 to 61), respectively. The 1-year and 3-year probabilities of cGVHD-free/relapse-free survival were 65% (95% CI, 59 to 71) and 52% (95% CI, 45 to 59), respectively. Our findings support the use of ex vivo CD34+–selected TCD allograft as a calcineurin inhibitor–free intervention for the prevention of GVHD in patients with acute leukemia and MDS.

AB - © 2017 The American Society for Blood and Marrow Transplantation Ex vivo CD34+–selected T cell depletion (TCD) has been developed as a strategy to reduce the incidence of graft-versus-host disease (GVHD) after allogeneic (allo) hematopoietic stem cell transplantation (HSCT). Clinical characteristics, treatment responses, and outcomes of patients developing acute (aGVHD) and chronic GVHD (cGVHD) after TCD allo-HSCT have not been well established. We evaluated 241 consecutive patients (median age, 57 years) with acute leukemia (n = 191, 79%) or myelodysplastic syndrome (MDS) (n = 50, 21%) undergoing CD34+–selected TCD allo-HSCT without post-HCST immunosuppression in a single institution. Cumulative incidences of grades II-IV and III-IV aGVHD at 180 days were 16% (95% confidence interval [CI], 12 to 21) and 5% (95% CI, 3 to 9), respectively. The skin was the most frequent organ involved, followed by the gastrointestinal tract. Patients were treated with topical corticosteroids, poorly absorbed corticosteroids (budesonide), and/or systemic corticosteroids. The overall day 28 treatment response was high at 82%. The cumulative incidence of any cGVHD at 3 years was 5% (95% CI, 3 to 9), with a median time of onset of 256 days (range, 95 to 1645). The 3-year transplant-related mortality, relapse, overall survival, and disease-free survival were 24% (95% CI, 18 to 30), 22% (95% CI, 17 to 27), 57% (95% CI, 50 to 64), and 54% (95% CI, 47 to 61), respectively. The 1-year and 3-year probabilities of cGVHD-free/relapse-free survival were 65% (95% CI, 59 to 71) and 52% (95% CI, 45 to 59), respectively. Our findings support the use of ex vivo CD34+–selected TCD allograft as a calcineurin inhibitor–free intervention for the prevention of GVHD in patients with acute leukemia and MDS.

KW - Acute graft-versus-host disease

KW - Chronic graft-versus-host disease

KW - T cell–depleted transplantation

U2 - 10.1016/j.bbmt.2016.12.633

DO - 10.1016/j.bbmt.2016.12.633

M3 - Article

VL - 23

SP - 452

EP - 458

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 3

ER -

Barba P, Hilden P, Devlin SM, Maloy M, Dierov D, Nieves J et al. Ex Vivo CD34⁺–Selected T Cell–Depleted Peripheral Blood Stem Cell Grafts for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia and Myelodysplastic Syndrome Is Associated with Low Incidence of Acute and Chronic Graft-versus-Host Disease and High Treatment Response. Biology of Blood and Marrow Transplantation. 2017 Mar 1;23(3):452-458. https://doi.org/10.1016/j.bbmt.2016.12.633