Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: A PIDTC natural history study

Jennifer Heimall, Brent R. Logan, Morton J. Cowan, Luigi D. Notarangelo, Linda M. Griffith, Jennifer M. Puck, Donald B. Kohn, Michael A. Pulsipher, Suhag Parikh, Caridad Martinez, Neena Kapoor, Richard O'Reilly, Michael Boyer, Sung Yun Pai, Frederick Goldman, Lauri Burroughs, Sharat Chandra, Morris Kletzel, Monica Thakar, James ConnellyGeoff Cuvelier, Blachy J.Davila Saldana, Evan Shereck, Alan Knutsen, Kathleen E. Sullivan, Kenneth Desantes, Alfred Gillio, Elie Haddad, Aleksandra Petrovic, Troy Quigg, Angela R. Smith, Elizabeth Stenger, Ziyan Yin, William T. Shearer, Thomas Fleisher, Rebecca H. Buckley, Christopher C. Dvorak

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

The Primary Immune Deficiency Treatment Consortium (PIDTC) is enrolling children with severe combined immunodeficiency (SCID) to a prospective natural history study. We analyzed patients treatedwith allogeneic hematopoietic cell transplantation (HCT) from 2010 to 2014, including 68 patientswith typical SCID and 32 with leaky SCID, Omenn syndrome, or reticular dysgenesis. Most (59%) patients were diagnosed by newborn screening or family history. The 2-year overall survivalwas 90%, but was 95%for thosewhowere infection-free at HCTvs 81%for those withactive infection (P5.009). Other factors, including thediagnosis of typical vs leaky SCID/Omenn syndrome, diagnosis via family history or newborn screening, useofpreparative chemotherapy,or thetypeof donorused,did not impact survival.Although 1-year post-HCT median CD4 counts and freedom from IV immunoglobulin were improved after the use of preparative chemotherapy, other immunologic reconstitution parameters were not affected, and the potential for late sequelae in extremely young infants requires additional evaluation. After a T-cell-replete graft, landmark analysis at day 1100 post-HCT revealed that CD3 < 300 cells/mL, CD8 < 50 cells/mL, CD45RA < 10%, or a restricted Vb T-cell receptor repertoire (<13 of 24 families) were associated with the need for a second HCT or death. In the modern era, active infection continues to pose the greatest threat to survival for SCID patients. Although newborn screening has been effective in diagnosing SCID patients early in life, there is an urgent need to identify validated approaches through prospective trials to ensure that patients proceed to HCT infection free.

Original languageEnglish (US)
Pages (from-to)2718-2727
Number of pages10
JournalBlood
Volume130
Issue number25
DOIs
StatePublished - Dec 21 2017

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Severe Combined Immunodeficiency
Transplants
Natural History
Screening
Chemotherapy
Cell Transplantation
Survival
T-cells
Intravenous Immunoglobulins
T-Cell Antigen Receptor
Grafts
Newborn Infant
Therapeutics
Infection
Drug Therapy
CD4 Lymphocyte Count
Cell Death
T-Lymphocytes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Heimall, J., Logan, B. R., Cowan, M. J., Notarangelo, L. D., Griffith, L. M., Puck, J. M., ... Dvorak, C. C. (2017). Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: A PIDTC natural history study. Blood, 130(25), 2718-2727. https://doi.org/10.1182/blood-2017-05-781849

Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant : A PIDTC natural history study. / Heimall, Jennifer; Logan, Brent R.; Cowan, Morton J.; Notarangelo, Luigi D.; Griffith, Linda M.; Puck, Jennifer M.; Kohn, Donald B.; Pulsipher, Michael A.; Parikh, Suhag; Martinez, Caridad; Kapoor, Neena; O'Reilly, Richard; Boyer, Michael; Pai, Sung Yun; Goldman, Frederick; Burroughs, Lauri; Chandra, Sharat; Kletzel, Morris; Thakar, Monica; Connelly, James; Cuvelier, Geoff; Saldana, Blachy J.Davila; Shereck, Evan; Knutsen, Alan; Sullivan, Kathleen E.; Desantes, Kenneth; Gillio, Alfred; Haddad, Elie; Petrovic, Aleksandra; Quigg, Troy; Smith, Angela R.; Stenger, Elizabeth; Yin, Ziyan; Shearer, William T.; Fleisher, Thomas; Buckley, Rebecca H.; Dvorak, Christopher C.

In: Blood, Vol. 130, No. 25, 21.12.2017, p. 2718-2727.

Research output: Contribution to journalArticle

Heimall, J, Logan, BR, Cowan, MJ, Notarangelo, LD, Griffith, LM, Puck, JM, Kohn, DB, Pulsipher, MA, Parikh, S, Martinez, C, Kapoor, N, O'Reilly, R, Boyer, M, Pai, SY, Goldman, F, Burroughs, L, Chandra, S, Kletzel, M, Thakar, M, Connelly, J, Cuvelier, G, Saldana, BJD, Shereck, E, Knutsen, A, Sullivan, KE, Desantes, K, Gillio, A, Haddad, E, Petrovic, A, Quigg, T, Smith, AR, Stenger, E, Yin, Z, Shearer, WT, Fleisher, T, Buckley, RH & Dvorak, CC 2017, 'Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: A PIDTC natural history study', Blood, vol. 130, no. 25, pp. 2718-2727. https://doi.org/10.1182/blood-2017-05-781849
Heimall, Jennifer ; Logan, Brent R. ; Cowan, Morton J. ; Notarangelo, Luigi D. ; Griffith, Linda M. ; Puck, Jennifer M. ; Kohn, Donald B. ; Pulsipher, Michael A. ; Parikh, Suhag ; Martinez, Caridad ; Kapoor, Neena ; O'Reilly, Richard ; Boyer, Michael ; Pai, Sung Yun ; Goldman, Frederick ; Burroughs, Lauri ; Chandra, Sharat ; Kletzel, Morris ; Thakar, Monica ; Connelly, James ; Cuvelier, Geoff ; Saldana, Blachy J.Davila ; Shereck, Evan ; Knutsen, Alan ; Sullivan, Kathleen E. ; Desantes, Kenneth ; Gillio, Alfred ; Haddad, Elie ; Petrovic, Aleksandra ; Quigg, Troy ; Smith, Angela R. ; Stenger, Elizabeth ; Yin, Ziyan ; Shearer, William T. ; Fleisher, Thomas ; Buckley, Rebecca H. ; Dvorak, Christopher C. / Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant : A PIDTC natural history study. In: Blood. 2017 ; Vol. 130, No. 25. pp. 2718-2727.
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abstract = "The Primary Immune Deficiency Treatment Consortium (PIDTC) is enrolling children with severe combined immunodeficiency (SCID) to a prospective natural history study. We analyzed patients treatedwith allogeneic hematopoietic cell transplantation (HCT) from 2010 to 2014, including 68 patientswith typical SCID and 32 with leaky SCID, Omenn syndrome, or reticular dysgenesis. Most (59{\%}) patients were diagnosed by newborn screening or family history. The 2-year overall survivalwas 90{\%}, but was 95{\%}for thosewhowere infection-free at HCTvs 81{\%}for those withactive infection (P5.009). Other factors, including thediagnosis of typical vs leaky SCID/Omenn syndrome, diagnosis via family history or newborn screening, useofpreparative chemotherapy,or thetypeof donorused,did not impact survival.Although 1-year post-HCT median CD4 counts and freedom from IV immunoglobulin were improved after the use of preparative chemotherapy, other immunologic reconstitution parameters were not affected, and the potential for late sequelae in extremely young infants requires additional evaluation. After a T-cell-replete graft, landmark analysis at day 1100 post-HCT revealed that CD3 < 300 cells/mL, CD8 < 50 cells/mL, CD45RA < 10{\%}, or a restricted Vb T-cell receptor repertoire (<13 of 24 families) were associated with the need for a second HCT or death. In the modern era, active infection continues to pose the greatest threat to survival for SCID patients. Although newborn screening has been effective in diagnosing SCID patients early in life, there is an urgent need to identify validated approaches through prospective trials to ensure that patients proceed to HCT infection free.",
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AU - Kohn, Donald B.

AU - Pulsipher, Michael A.

AU - Parikh, Suhag

AU - Martinez, Caridad

AU - Kapoor, Neena

AU - O'Reilly, Richard

AU - Boyer, Michael

AU - Pai, Sung Yun

AU - Goldman, Frederick

AU - Burroughs, Lauri

AU - Chandra, Sharat

AU - Kletzel, Morris

AU - Thakar, Monica

AU - Connelly, James

AU - Cuvelier, Geoff

AU - Saldana, Blachy J.Davila

AU - Shereck, Evan

AU - Knutsen, Alan

AU - Sullivan, Kathleen E.

AU - Desantes, Kenneth

AU - Gillio, Alfred

AU - Haddad, Elie

AU - Petrovic, Aleksandra

AU - Quigg, Troy

AU - Smith, Angela R.

AU - Stenger, Elizabeth

AU - Yin, Ziyan

AU - Shearer, William T.

AU - Fleisher, Thomas

AU - Buckley, Rebecca H.

AU - Dvorak, Christopher C.

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