SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery

Elie Haddad, Brent R. Logan, Linda M. Griffith, Rebecca H. Buckley, Roberta E. Parrott, Susan E. Prockop, Trudy N. Small, Jessica Chaisson, Christopher C. Dvorak, Megan Murnane, Neena Kapoor, Hisham Abdel-Azim, Imelda C. Hanson, Caridad Martinez, Jack J.H. Bleesing, Sharat Chandra, Angela R. Smith, Matthew E. Cavanaugh, Soma Jyonouchi, Kathleen E. Sullivan & 45 others Lauri Burroughs, Suzanne Skoda-Smith, Ann E. Haight, Audrey G. Tumlin, Troy C. Quigg, Candace Taylor, Blachy J. Dávila Saldaña, Michael D. Keller, Christine M. Seroogy, Kenneth B. Desantes, Aleksandra Petrovic, Jennifer W. Leiding, David C. Shyr, Hélène Decaluwe, Pierre Teira, Alfred P. Gillio, Alan P. Knutsen, Theodore B. Moore, Morris Kletzel, John A. Craddock, Victor Aquino, Jeffrey H. Davis, Lolie C. Yu, Geoffrey D.E. Cuvelier, Jeffrey J. Bednarski, Frederick D. Goldman, Elizabeth M. Kang, Evan Shereck, Matthew H. Porteus, James A. Connelly, Thomas A. Fleisher, Harry L. Malech, William T. Shearer, Paul Szabolcs, Monica S. Thakar, Mark T. Vander Lugt, Jennifer Heimall, Ziyan Yin, Michael A. Pulsipher, Sung Yun Pai, Donald B. Kohn, Jennifer M. Puck, Morton J. Cowan, Richard J. O’Reilly, Luigi D. Notarangelo

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The Primary Immune Deficiency Treatment Consortium (PIDTC) performed a retrospective analysis of 662 patients with severe combined immunodeficiency (SCID) who received a hematopoietic cell transplantation (HCT) as first-line treatment between 1982 and 2012 in 33 North American institutions. Overall survival was higher after HCT from matched-sibling donors (MSDs). Among recipients of non-MSD HCT, multivariate analysis showed that the SCID genotype strongly influenced survival and immune reconstitution. Overall survival was similar for patients with RAG, IL2RG, or JAK3 defects and was significantly better compared with patients with ADA or DCLRE1C mutations. Patients with RAG or DCLRE1C mutations had poorer immune reconstitution than other genotypes. Although survival did not correlate with the type of conditioning regimen, recipients of reduced-intensity or myeloablative conditioning had a lower incidence of treatment failure and better T- and B-cell reconstitution, but a higher risk for graft-versus-host disease, compared with those receiving no conditioning or immunosuppression only. Infection-free status and younger age at HCT were associated with improved survival. Typical SCID, leaky SCID, and Omenn syndrome had similar outcomes. Landmark analysis identified CD41 and CD41CD45RA1 cell counts at 6 and 12 months post-HCT as biomarkers predictive of overall survival and long-term T-cell reconstitution. Our data emphasize the need for patient-tailored treatment strategies depending upon the underlying SCID genotype. The prognostic significance of CD41 cell counts as early as 6 months after HCT emphasizes the importance of close follow-up of immune reconstitution to identify patients who may need additional intervention to prevent poor long-term outcome.

Original languageEnglish (US)
Pages (from-to)1737-1749
Number of pages13
JournalBlood
Volume132
Issue number17
DOIs
StatePublished - Oct 25 2018

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X-Linked Combined Immunodeficiency Diseases
Patient treatment
Severe Combined Immunodeficiency
T-cells
Cell Transplantation
Biomarkers
CD4 Lymphocyte Count
Grafts
Genotype
Cells
Recovery
Defects
Survival
Siblings
Cell Count
Tissue Donors
Mutation
Graft vs Host Disease
Treatment Failure
Immunosuppression

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Haddad, E., Logan, B. R., Griffith, L. M., Buckley, R. H., Parrott, R. E., Prockop, S. E., ... Notarangelo, L. D. (2018). SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery. Blood, 132(17), 1737-1749. https://doi.org/10.1182/blood-2018-03-840702

SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery. / Haddad, Elie; Logan, Brent R.; Griffith, Linda M.; Buckley, Rebecca H.; Parrott, Roberta E.; Prockop, Susan E.; Small, Trudy N.; Chaisson, Jessica; Dvorak, Christopher C.; Murnane, Megan; Kapoor, Neena; Abdel-Azim, Hisham; Hanson, Imelda C.; Martinez, Caridad; Bleesing, Jack J.H.; Chandra, Sharat; Smith, Angela R.; Cavanaugh, Matthew E.; Jyonouchi, Soma; Sullivan, Kathleen E.; Burroughs, Lauri; Skoda-Smith, Suzanne; Haight, Ann E.; Tumlin, Audrey G.; Quigg, Troy C.; Taylor, Candace; Dávila Saldaña, Blachy J.; Keller, Michael D.; Seroogy, Christine M.; Desantes, Kenneth B.; Petrovic, Aleksandra; Leiding, Jennifer W.; Shyr, David C.; Decaluwe, Hélène; Teira, Pierre; Gillio, Alfred P.; Knutsen, Alan P.; Moore, Theodore B.; Kletzel, Morris; Craddock, John A.; Aquino, Victor; Davis, Jeffrey H.; Yu, Lolie C.; Cuvelier, Geoffrey D.E.; Bednarski, Jeffrey J.; Goldman, Frederick D.; Kang, Elizabeth M.; Shereck, Evan; Porteus, Matthew H.; Connelly, James A.; Fleisher, Thomas A.; Malech, Harry L.; Shearer, William T.; Szabolcs, Paul; Thakar, Monica S.; Vander Lugt, Mark T.; Heimall, Jennifer; Yin, Ziyan; Pulsipher, Michael A.; Pai, Sung Yun; Kohn, Donald B.; Puck, Jennifer M.; Cowan, Morton J.; O’Reilly, Richard J.; Notarangelo, Luigi D.

In: Blood, Vol. 132, No. 17, 25.10.2018, p. 1737-1749.

Research output: Contribution to journalArticle

Haddad, E, Logan, BR, Griffith, LM, Buckley, RH, Parrott, RE, Prockop, SE, Small, TN, Chaisson, J, Dvorak, CC, Murnane, M, Kapoor, N, Abdel-Azim, H, Hanson, IC, Martinez, C, Bleesing, JJH, Chandra, S, Smith, AR, Cavanaugh, ME, Jyonouchi, S, Sullivan, KE, Burroughs, L, Skoda-Smith, S, Haight, AE, Tumlin, AG, Quigg, TC, Taylor, C, Dávila Saldaña, BJ, Keller, MD, Seroogy, CM, Desantes, KB, Petrovic, A, Leiding, JW, Shyr, DC, Decaluwe, H, Teira, P, Gillio, AP, Knutsen, AP, Moore, TB, Kletzel, M, Craddock, JA, Aquino, V, Davis, JH, Yu, LC, Cuvelier, GDE, Bednarski, JJ, Goldman, FD, Kang, EM, Shereck, E, Porteus, MH, Connelly, JA, Fleisher, TA, Malech, HL, Shearer, WT, Szabolcs, P, Thakar, MS, Vander Lugt, MT, Heimall, J, Yin, Z, Pulsipher, MA, Pai, SY, Kohn, DB, Puck, JM, Cowan, MJ, O’Reilly, RJ & Notarangelo, LD 2018, 'SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery', Blood, vol. 132, no. 17, pp. 1737-1749. https://doi.org/10.1182/blood-2018-03-840702
Haddad E, Logan BR, Griffith LM, Buckley RH, Parrott RE, Prockop SE et al. SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery. Blood. 2018 Oct 25;132(17):1737-1749. https://doi.org/10.1182/blood-2018-03-840702
Haddad, Elie ; Logan, Brent R. ; Griffith, Linda M. ; Buckley, Rebecca H. ; Parrott, Roberta E. ; Prockop, Susan E. ; Small, Trudy N. ; Chaisson, Jessica ; Dvorak, Christopher C. ; Murnane, Megan ; Kapoor, Neena ; Abdel-Azim, Hisham ; Hanson, Imelda C. ; Martinez, Caridad ; Bleesing, Jack J.H. ; Chandra, Sharat ; Smith, Angela R. ; Cavanaugh, Matthew E. ; Jyonouchi, Soma ; Sullivan, Kathleen E. ; Burroughs, Lauri ; Skoda-Smith, Suzanne ; Haight, Ann E. ; Tumlin, Audrey G. ; Quigg, Troy C. ; Taylor, Candace ; Dávila Saldaña, Blachy J. ; Keller, Michael D. ; Seroogy, Christine M. ; Desantes, Kenneth B. ; Petrovic, Aleksandra ; Leiding, Jennifer W. ; Shyr, David C. ; Decaluwe, Hélène ; Teira, Pierre ; Gillio, Alfred P. ; Knutsen, Alan P. ; Moore, Theodore B. ; Kletzel, Morris ; Craddock, John A. ; Aquino, Victor ; Davis, Jeffrey H. ; Yu, Lolie C. ; Cuvelier, Geoffrey D.E. ; Bednarski, Jeffrey J. ; Goldman, Frederick D. ; Kang, Elizabeth M. ; Shereck, Evan ; Porteus, Matthew H. ; Connelly, James A. ; Fleisher, Thomas A. ; Malech, Harry L. ; Shearer, William T. ; Szabolcs, Paul ; Thakar, Monica S. ; Vander Lugt, Mark T. ; Heimall, Jennifer ; Yin, Ziyan ; Pulsipher, Michael A. ; Pai, Sung Yun ; Kohn, Donald B. ; Puck, Jennifer M. ; Cowan, Morton J. ; O’Reilly, Richard J. ; Notarangelo, Luigi D. / SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery. In: Blood. 2018 ; Vol. 132, No. 17. pp. 1737-1749.
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abstract = "The Primary Immune Deficiency Treatment Consortium (PIDTC) performed a retrospective analysis of 662 patients with severe combined immunodeficiency (SCID) who received a hematopoietic cell transplantation (HCT) as first-line treatment between 1982 and 2012 in 33 North American institutions. Overall survival was higher after HCT from matched-sibling donors (MSDs). Among recipients of non-MSD HCT, multivariate analysis showed that the SCID genotype strongly influenced survival and immune reconstitution. Overall survival was similar for patients with RAG, IL2RG, or JAK3 defects and was significantly better compared with patients with ADA or DCLRE1C mutations. Patients with RAG or DCLRE1C mutations had poorer immune reconstitution than other genotypes. Although survival did not correlate with the type of conditioning regimen, recipients of reduced-intensity or myeloablative conditioning had a lower incidence of treatment failure and better T- and B-cell reconstitution, but a higher risk for graft-versus-host disease, compared with those receiving no conditioning or immunosuppression only. Infection-free status and younger age at HCT were associated with improved survival. Typical SCID, leaky SCID, and Omenn syndrome had similar outcomes. Landmark analysis identified CD41 and CD41CD45RA1 cell counts at 6 and 12 months post-HCT as biomarkers predictive of overall survival and long-term T-cell reconstitution. Our data emphasize the need for patient-tailored treatment strategies depending upon the underlying SCID genotype. The prognostic significance of CD41 cell counts as early as 6 months after HCT emphasizes the importance of close follow-up of immune reconstitution to identify patients who may need additional intervention to prevent poor long-term outcome.",
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T1 - SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery

AU - Haddad, Elie

AU - Logan, Brent R.

AU - Griffith, Linda M.

AU - Buckley, Rebecca H.

AU - Parrott, Roberta E.

AU - Prockop, Susan E.

AU - Small, Trudy N.

AU - Chaisson, Jessica

AU - Dvorak, Christopher C.

AU - Murnane, Megan

AU - Kapoor, Neena

AU - Abdel-Azim, Hisham

AU - Hanson, Imelda C.

AU - Martinez, Caridad

AU - Bleesing, Jack J.H.

AU - Chandra, Sharat

AU - Smith, Angela R.

AU - Cavanaugh, Matthew E.

AU - Jyonouchi, Soma

AU - Sullivan, Kathleen E.

AU - Burroughs, Lauri

AU - Skoda-Smith, Suzanne

AU - Haight, Ann E.

AU - Tumlin, Audrey G.

AU - Quigg, Troy C.

AU - Taylor, Candace

AU - Dávila Saldaña, Blachy J.

AU - Keller, Michael D.

AU - Seroogy, Christine M.

AU - Desantes, Kenneth B.

AU - Petrovic, Aleksandra

AU - Leiding, Jennifer W.

AU - Shyr, David C.

AU - Decaluwe, Hélène

AU - Teira, Pierre

AU - Gillio, Alfred P.

AU - Knutsen, Alan P.

AU - Moore, Theodore B.

AU - Kletzel, Morris

AU - Craddock, John A.

AU - Aquino, Victor

AU - Davis, Jeffrey H.

AU - Yu, Lolie C.

AU - Cuvelier, Geoffrey D.E.

AU - Bednarski, Jeffrey J.

AU - Goldman, Frederick D.

AU - Kang, Elizabeth M.

AU - Shereck, Evan

AU - Porteus, Matthew H.

AU - Connelly, James A.

AU - Fleisher, Thomas A.

AU - Malech, Harry L.

AU - Shearer, William T.

AU - Szabolcs, Paul

AU - Thakar, Monica S.

AU - Vander Lugt, Mark T.

AU - Heimall, Jennifer

AU - Yin, Ziyan

AU - Pulsipher, Michael A.

AU - Pai, Sung Yun

AU - Kohn, Donald B.

AU - Puck, Jennifer M.

AU - Cowan, Morton J.

AU - O’Reilly, Richard J.

AU - Notarangelo, Luigi D.

PY - 2018/10/25

Y1 - 2018/10/25

N2 - The Primary Immune Deficiency Treatment Consortium (PIDTC) performed a retrospective analysis of 662 patients with severe combined immunodeficiency (SCID) who received a hematopoietic cell transplantation (HCT) as first-line treatment between 1982 and 2012 in 33 North American institutions. Overall survival was higher after HCT from matched-sibling donors (MSDs). Among recipients of non-MSD HCT, multivariate analysis showed that the SCID genotype strongly influenced survival and immune reconstitution. Overall survival was similar for patients with RAG, IL2RG, or JAK3 defects and was significantly better compared with patients with ADA or DCLRE1C mutations. Patients with RAG or DCLRE1C mutations had poorer immune reconstitution than other genotypes. Although survival did not correlate with the type of conditioning regimen, recipients of reduced-intensity or myeloablative conditioning had a lower incidence of treatment failure and better T- and B-cell reconstitution, but a higher risk for graft-versus-host disease, compared with those receiving no conditioning or immunosuppression only. Infection-free status and younger age at HCT were associated with improved survival. Typical SCID, leaky SCID, and Omenn syndrome had similar outcomes. Landmark analysis identified CD41 and CD41CD45RA1 cell counts at 6 and 12 months post-HCT as biomarkers predictive of overall survival and long-term T-cell reconstitution. Our data emphasize the need for patient-tailored treatment strategies depending upon the underlying SCID genotype. The prognostic significance of CD41 cell counts as early as 6 months after HCT emphasizes the importance of close follow-up of immune reconstitution to identify patients who may need additional intervention to prevent poor long-term outcome.

AB - The Primary Immune Deficiency Treatment Consortium (PIDTC) performed a retrospective analysis of 662 patients with severe combined immunodeficiency (SCID) who received a hematopoietic cell transplantation (HCT) as first-line treatment between 1982 and 2012 in 33 North American institutions. Overall survival was higher after HCT from matched-sibling donors (MSDs). Among recipients of non-MSD HCT, multivariate analysis showed that the SCID genotype strongly influenced survival and immune reconstitution. Overall survival was similar for patients with RAG, IL2RG, or JAK3 defects and was significantly better compared with patients with ADA or DCLRE1C mutations. Patients with RAG or DCLRE1C mutations had poorer immune reconstitution than other genotypes. Although survival did not correlate with the type of conditioning regimen, recipients of reduced-intensity or myeloablative conditioning had a lower incidence of treatment failure and better T- and B-cell reconstitution, but a higher risk for graft-versus-host disease, compared with those receiving no conditioning or immunosuppression only. Infection-free status and younger age at HCT were associated with improved survival. Typical SCID, leaky SCID, and Omenn syndrome had similar outcomes. Landmark analysis identified CD41 and CD41CD45RA1 cell counts at 6 and 12 months post-HCT as biomarkers predictive of overall survival and long-term T-cell reconstitution. Our data emphasize the need for patient-tailored treatment strategies depending upon the underlying SCID genotype. The prognostic significance of CD41 cell counts as early as 6 months after HCT emphasizes the importance of close follow-up of immune reconstitution to identify patients who may need additional intervention to prevent poor long-term outcome.

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