Transplantation outcomes for severe combined immunodeficiency, 2000-2009

Sung Yun Pai, Brent R. Logan, Linda M. Griffith, Rebecca H. Buckley, Roberta E. Parrott, Christopher C. Dvorak, Neena Kapoor, Imelda C. Hanson, Alexandra H. Filipovich, Soma Jyonouchi, Kathleen E. Sullivan, Trudy N. Small, Lauri Burroughs, Suzanne Skoda-Smith, Ann E. Haight, Audrey Grizzle, Michael A. Pulsipher, Ka Wah Chan, Ramsay L. Fuleihan, Elie Haddad & 19 others Brett Loechelt, Victor M. Aquino, Alfred Gillio, Jeffrey Davis, Alan Knutsen, Angela R. Smith, Theodore B. Moore, Marlis L. Schroeder, Frederick D. Goldman, James A. Connelly, Matthew H. Porteus, Qun Xiang, William T. Shearer, Thomas A. Fleisher, Donald B. Kohn, Jennifer M. Puck, Luigi D. Notarangelo, Morton J. Cowan, Richard J. O'Reilly*

*Corresponding author for this work

Research output: Contribution to journalArticle

252 Citations (Scopus)

Abstract

Background: The Primary Immune Deficiency Treatment Consortium was formed to analyze the results of hematopoietic-cell transplantation in children with severe combined immunodeficiency (SCID) and other primary immunodeficiencies. Factors associated with a good transplantation outcome need to be identified in order to design safer and more effective curative therapy, particularly for children with SCID diagnosed at birth. Methods: We collected data retrospectively from 240 infants with SCID who had received transplants at 25 centers during a 10-year period (2000 through 2009). Results: Survival at 5 years, freedom from immunoglobulin substitution, and CD3+ T-cell and IgA recovery were more likely among recipients of grafts from matched sibling donors than among recipients of grafts from alternative donors. However, the survival rate was high regardless of donor type among infants who received transplants at 3.5 months of age or younger (94%) and among older infants without prior infection (90%) or with infection that had resolved (82%). Among actively infected infants without a matched sibling donor, survival was best among recipients of haploidentical T-cell - depleted transplants in the absence of any pretransplantation conditioning. Among survivors, reduced-intensity or myeloablative pretransplantation conditioning was associated with an increased likelihood of a CD3+ T-cell count of more than 1000 per cubic millimeter, freedom from immunoglobulin substitution, and IgA recovery but did not significantly affect CD4+ T-cell recovery or recovery of phytohemagglutinin- induced T-cell proliferation. The genetic subtype of SCID affected the quality of CD3+ T-cell recovery but not survival. Conclusions: Transplants from donors other than matched siblings were associated with excellent survival among infants with SCID identified before the onset of infection. All available graft sources are expected to lead to excellent survival among asymptomatic infants. (Funded by the National Institute of Allergy and Infectious Diseases and others.)

Original languageEnglish (US)
Pages (from-to)434-446
Number of pages13
JournalNew England Journal of Medicine
Volume371
Issue number5
DOIs
StatePublished - Jan 1 2014

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Severe Combined Immunodeficiency
Transplantation
T-Lymphocytes
Transplants
Tissue Donors
Survival
Siblings
Immunoglobulin A
Immunoglobulins
National Institute of Allergy and Infectious Diseases (U.S.)
Infection
Cell Transplantation
Phytohemagglutinins
Survivors
Survival Rate
Cell Count
Cell Proliferation
Parturition
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Pai, S. Y., Logan, B. R., Griffith, L. M., Buckley, R. H., Parrott, R. E., Dvorak, C. C., ... O'Reilly, R. J. (2014). Transplantation outcomes for severe combined immunodeficiency, 2000-2009. New England Journal of Medicine, 371(5), 434-446. https://doi.org/10.1056/NEJMoa1401177
Pai, Sung Yun ; Logan, Brent R. ; Griffith, Linda M. ; Buckley, Rebecca H. ; Parrott, Roberta E. ; Dvorak, Christopher C. ; Kapoor, Neena ; Hanson, Imelda C. ; Filipovich, Alexandra H. ; Jyonouchi, Soma ; Sullivan, Kathleen E. ; Small, Trudy N. ; Burroughs, Lauri ; Skoda-Smith, Suzanne ; Haight, Ann E. ; Grizzle, Audrey ; Pulsipher, Michael A. ; Chan, Ka Wah ; Fuleihan, Ramsay L. ; Haddad, Elie ; Loechelt, Brett ; Aquino, Victor M. ; Gillio, Alfred ; Davis, Jeffrey ; Knutsen, Alan ; Smith, Angela R. ; Moore, Theodore B. ; Schroeder, Marlis L. ; Goldman, Frederick D. ; Connelly, James A. ; Porteus, Matthew H. ; Xiang, Qun ; Shearer, William T. ; Fleisher, Thomas A. ; Kohn, Donald B. ; Puck, Jennifer M. ; Notarangelo, Luigi D. ; Cowan, Morton J. ; O'Reilly, Richard J. / Transplantation outcomes for severe combined immunodeficiency, 2000-2009. In: New England Journal of Medicine. 2014 ; Vol. 371, No. 5. pp. 434-446.
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title = "Transplantation outcomes for severe combined immunodeficiency, 2000-2009",
abstract = "Background: The Primary Immune Deficiency Treatment Consortium was formed to analyze the results of hematopoietic-cell transplantation in children with severe combined immunodeficiency (SCID) and other primary immunodeficiencies. Factors associated with a good transplantation outcome need to be identified in order to design safer and more effective curative therapy, particularly for children with SCID diagnosed at birth. Methods: We collected data retrospectively from 240 infants with SCID who had received transplants at 25 centers during a 10-year period (2000 through 2009). Results: Survival at 5 years, freedom from immunoglobulin substitution, and CD3+ T-cell and IgA recovery were more likely among recipients of grafts from matched sibling donors than among recipients of grafts from alternative donors. However, the survival rate was high regardless of donor type among infants who received transplants at 3.5 months of age or younger (94{\%}) and among older infants without prior infection (90{\%}) or with infection that had resolved (82{\%}). Among actively infected infants without a matched sibling donor, survival was best among recipients of haploidentical T-cell - depleted transplants in the absence of any pretransplantation conditioning. Among survivors, reduced-intensity or myeloablative pretransplantation conditioning was associated with an increased likelihood of a CD3+ T-cell count of more than 1000 per cubic millimeter, freedom from immunoglobulin substitution, and IgA recovery but did not significantly affect CD4+ T-cell recovery or recovery of phytohemagglutinin- induced T-cell proliferation. The genetic subtype of SCID affected the quality of CD3+ T-cell recovery but not survival. Conclusions: Transplants from donors other than matched siblings were associated with excellent survival among infants with SCID identified before the onset of infection. All available graft sources are expected to lead to excellent survival among asymptomatic infants. (Funded by the National Institute of Allergy and Infectious Diseases and others.)",
author = "Pai, {Sung Yun} and Logan, {Brent R.} and Griffith, {Linda M.} and Buckley, {Rebecca H.} and Parrott, {Roberta E.} and Dvorak, {Christopher C.} and Neena Kapoor and Hanson, {Imelda C.} and Filipovich, {Alexandra H.} and Soma Jyonouchi and Sullivan, {Kathleen E.} and Small, {Trudy N.} and Lauri Burroughs and Suzanne Skoda-Smith and Haight, {Ann E.} and Audrey Grizzle and Pulsipher, {Michael A.} and Chan, {Ka Wah} and Fuleihan, {Ramsay L.} and Elie Haddad and Brett Loechelt and Aquino, {Victor M.} and Alfred Gillio and Jeffrey Davis and Alan Knutsen and Smith, {Angela R.} and Moore, {Theodore B.} and Schroeder, {Marlis L.} and Goldman, {Frederick D.} and Connelly, {James A.} and Porteus, {Matthew H.} and Qun Xiang and Shearer, {William T.} and Fleisher, {Thomas A.} and Kohn, {Donald B.} and Puck, {Jennifer M.} and Notarangelo, {Luigi D.} and Cowan, {Morton J.} and O'Reilly, {Richard J.}",
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Pai, SY, Logan, BR, Griffith, LM, Buckley, RH, Parrott, RE, Dvorak, CC, Kapoor, N, Hanson, IC, Filipovich, AH, Jyonouchi, S, Sullivan, KE, Small, TN, Burroughs, L, Skoda-Smith, S, Haight, AE, Grizzle, A, Pulsipher, MA, Chan, KW, Fuleihan, RL, Haddad, E, Loechelt, B, Aquino, VM, Gillio, A, Davis, J, Knutsen, A, Smith, AR, Moore, TB, Schroeder, ML, Goldman, FD, Connelly, JA, Porteus, MH, Xiang, Q, Shearer, WT, Fleisher, TA, Kohn, DB, Puck, JM, Notarangelo, LD, Cowan, MJ & O'Reilly, RJ 2014, 'Transplantation outcomes for severe combined immunodeficiency, 2000-2009', New England Journal of Medicine, vol. 371, no. 5, pp. 434-446. https://doi.org/10.1056/NEJMoa1401177

Transplantation outcomes for severe combined immunodeficiency, 2000-2009. / Pai, Sung Yun; Logan, Brent R.; Griffith, Linda M.; Buckley, Rebecca H.; Parrott, Roberta E.; Dvorak, Christopher C.; Kapoor, Neena; Hanson, Imelda C.; Filipovich, Alexandra H.; Jyonouchi, Soma; Sullivan, Kathleen E.; Small, Trudy N.; Burroughs, Lauri; Skoda-Smith, Suzanne; Haight, Ann E.; Grizzle, Audrey; Pulsipher, Michael A.; Chan, Ka Wah; Fuleihan, Ramsay L.; Haddad, Elie; Loechelt, Brett; Aquino, Victor M.; Gillio, Alfred; Davis, Jeffrey; Knutsen, Alan; Smith, Angela R.; Moore, Theodore B.; Schroeder, Marlis L.; Goldman, Frederick D.; Connelly, James A.; Porteus, Matthew H.; Xiang, Qun; Shearer, William T.; Fleisher, Thomas A.; Kohn, Donald B.; Puck, Jennifer M.; Notarangelo, Luigi D.; Cowan, Morton J.; O'Reilly, Richard J.

In: New England Journal of Medicine, Vol. 371, No. 5, 01.01.2014, p. 434-446.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Transplantation outcomes for severe combined immunodeficiency, 2000-2009

AU - Pai, Sung Yun

AU - Logan, Brent R.

AU - Griffith, Linda M.

AU - Buckley, Rebecca H.

AU - Parrott, Roberta E.

AU - Dvorak, Christopher C.

AU - Kapoor, Neena

AU - Hanson, Imelda C.

AU - Filipovich, Alexandra H.

AU - Jyonouchi, Soma

AU - Sullivan, Kathleen E.

AU - Small, Trudy N.

AU - Burroughs, Lauri

AU - Skoda-Smith, Suzanne

AU - Haight, Ann E.

AU - Grizzle, Audrey

AU - Pulsipher, Michael A.

AU - Chan, Ka Wah

AU - Fuleihan, Ramsay L.

AU - Haddad, Elie

AU - Loechelt, Brett

AU - Aquino, Victor M.

AU - Gillio, Alfred

AU - Davis, Jeffrey

AU - Knutsen, Alan

AU - Smith, Angela R.

AU - Moore, Theodore B.

AU - Schroeder, Marlis L.

AU - Goldman, Frederick D.

AU - Connelly, James A.

AU - Porteus, Matthew H.

AU - Xiang, Qun

AU - Shearer, William T.

AU - Fleisher, Thomas A.

AU - Kohn, Donald B.

AU - Puck, Jennifer M.

AU - Notarangelo, Luigi D.

AU - Cowan, Morton J.

AU - O'Reilly, Richard J.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background: The Primary Immune Deficiency Treatment Consortium was formed to analyze the results of hematopoietic-cell transplantation in children with severe combined immunodeficiency (SCID) and other primary immunodeficiencies. Factors associated with a good transplantation outcome need to be identified in order to design safer and more effective curative therapy, particularly for children with SCID diagnosed at birth. Methods: We collected data retrospectively from 240 infants with SCID who had received transplants at 25 centers during a 10-year period (2000 through 2009). Results: Survival at 5 years, freedom from immunoglobulin substitution, and CD3+ T-cell and IgA recovery were more likely among recipients of grafts from matched sibling donors than among recipients of grafts from alternative donors. However, the survival rate was high regardless of donor type among infants who received transplants at 3.5 months of age or younger (94%) and among older infants without prior infection (90%) or with infection that had resolved (82%). Among actively infected infants without a matched sibling donor, survival was best among recipients of haploidentical T-cell - depleted transplants in the absence of any pretransplantation conditioning. Among survivors, reduced-intensity or myeloablative pretransplantation conditioning was associated with an increased likelihood of a CD3+ T-cell count of more than 1000 per cubic millimeter, freedom from immunoglobulin substitution, and IgA recovery but did not significantly affect CD4+ T-cell recovery or recovery of phytohemagglutinin- induced T-cell proliferation. The genetic subtype of SCID affected the quality of CD3+ T-cell recovery but not survival. Conclusions: Transplants from donors other than matched siblings were associated with excellent survival among infants with SCID identified before the onset of infection. All available graft sources are expected to lead to excellent survival among asymptomatic infants. (Funded by the National Institute of Allergy and Infectious Diseases and others.)

AB - Background: The Primary Immune Deficiency Treatment Consortium was formed to analyze the results of hematopoietic-cell transplantation in children with severe combined immunodeficiency (SCID) and other primary immunodeficiencies. Factors associated with a good transplantation outcome need to be identified in order to design safer and more effective curative therapy, particularly for children with SCID diagnosed at birth. Methods: We collected data retrospectively from 240 infants with SCID who had received transplants at 25 centers during a 10-year period (2000 through 2009). Results: Survival at 5 years, freedom from immunoglobulin substitution, and CD3+ T-cell and IgA recovery were more likely among recipients of grafts from matched sibling donors than among recipients of grafts from alternative donors. However, the survival rate was high regardless of donor type among infants who received transplants at 3.5 months of age or younger (94%) and among older infants without prior infection (90%) or with infection that had resolved (82%). Among actively infected infants without a matched sibling donor, survival was best among recipients of haploidentical T-cell - depleted transplants in the absence of any pretransplantation conditioning. Among survivors, reduced-intensity or myeloablative pretransplantation conditioning was associated with an increased likelihood of a CD3+ T-cell count of more than 1000 per cubic millimeter, freedom from immunoglobulin substitution, and IgA recovery but did not significantly affect CD4+ T-cell recovery or recovery of phytohemagglutinin- induced T-cell proliferation. The genetic subtype of SCID affected the quality of CD3+ T-cell recovery but not survival. Conclusions: Transplants from donors other than matched siblings were associated with excellent survival among infants with SCID identified before the onset of infection. All available graft sources are expected to lead to excellent survival among asymptomatic infants. (Funded by the National Institute of Allergy and Infectious Diseases and others.)

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DO - 10.1056/NEJMoa1401177

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Pai SY, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC et al. Transplantation outcomes for severe combined immunodeficiency, 2000-2009. New England Journal of Medicine. 2014 Jan 1;371(5):434-446. https://doi.org/10.1056/NEJMoa1401177