Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency

Amel Hassan; Claire Booth; Alex Brightwell; Zoe Allwood; Paul Veys; Kanchan Rao; Manfred Hönig; Wilhelm Friedrich; Andrew Gennery; Mary Slatter; Robbert Bredius; Andrea Finocchi; Caterina Cancrini; Alessandro Aiuti; Fulvio Porta; Arnalda Lanfranchi; Michela Ridella; Colin Steward; Alexandra Filipovich; Rebecca Marsh; Victoria Bordon; Saleh Al-Muhsen; Hamoud Al-Mousa; Zobaida Alsum; Hasan Al-Dhekri; Abdulaziz Al Ghonaium; Carsten Speckmann; Alain Fischer; Nizar Mahlaoui; Kim E Nichols; Eyal Grunebaum; Daifulah Al Zahrani; Chaim M Roifman; Jaap Boelens; E Graham Davies; Marina Cavazzana-Calvo; Luigi Notarangelo; H Bobby Gaspar

doi:10.1182/blood-2011-12-396879

Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency

Amel Hassan, Claire Booth, Alex Brightwell, Zoe Allwood, Paul Veys, Kanchan Rao, Manfred Hönig, Wilhelm Friedrich, Andrew Gennery, Mary Slatter, Robbert Bredius, Andrea Finocchi, Caterina Cancrini, Alessandro Aiuti, Fulvio Porta, Arnalda Lanfranchi, Michela Ridella, Colin Steward, Alexandra Filipovich, Rebecca MarshVictoria Bordon, Saleh Al-Muhsen, Hamoud Al-Mousa, Zobaida Alsum, Hasan Al-Dhekri, Abdulaziz Al Ghonaium, Carsten Speckmann, Alain Fischer, Nizar Mahlaoui, Kim E Nichols, Eyal Grunebaum, Daifulah Al Zahrani, Chaim M Roifman, Jaap Boelens, E Graham Davies, Marina Cavazzana-Calvo, Luigi Notarangelo, H Bobby Gaspar,

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

Abstract

Deficiency of the purine salvage enzyme adenosine deaminase leads to SCID (ADA-SCID). Hematopoietic cell transplantation (HCT) can lead to a permanent cure of SCID; however, little data are available on outcome of HCT for ADA-SCID in particular. In this multicenter retrospective study, we analyzed outcome of HCT in 106 patients with ADA-SCID who received a total of 119 transplants. HCT from matched sibling and family donors (MSDs, MFDs) had significantly better overall survival (86% and 81%) in comparison with HCT from matched unrelated (66%; P < .05) and haploidentical donors (43%; P < .001). Superior overall survival was also seen in patients who received unconditioned transplants in comparison with myeloablative procedures (81% vs 54%; P < .003), although in unconditioned haploidentical donor HCT, nonengraftment was a major problem. Long-term immune recovery showed that regardless of transplant type, overall T-cell numbers were similar, although a faster rate of T-cell recovery was observed after MSD/MFD HCT. Humoral immunity and donor B-cell engraftment was achieved in nearly all evaluable surviving patients and was seen even after unconditioned HCT. These data detail for the first time the outcomes of HCT for ADA-SCID and show that, if patients survive HCT, long-term cellular and humoral immune recovery is achieved.

Original language	English
Pages (from-to)	3615-24; quiz 3626
Journal	Blood
Volume	120
Issue number	17
DOIs	https://doi.org/10.1182/blood-2011-12-396879
Publication status	Published - 2012

Keywords

Adenosine Deaminase
Agammaglobulinemia
Child
Child, Preschool
Female
Graft Survival
Hematopoietic Stem Cell Transplantation
Histocompatibility Testing
Humans
Immunity, Cellular
Immunity, Humoral
Infant
Infant, Newborn
Kaplan-Meier Estimate
Lymphocyte Count
Male
Myeloablative Agonists
Retrospective Studies
Severe Combined Immunodeficiency
Siblings
T-Lymphocytes
Transplantation Conditioning
Treatment Outcome
Unrelated Donors

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10.1182/blood-2011-12-396879

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Hassan, A., Booth, C., Brightwell, A., Allwood, Z., Veys, P., Rao, K., Hönig, M., Friedrich, W., Gennery, A., Slatter, M., Bredius, R., Finocchi, A., Cancrini, C., Aiuti, A., Porta, F., Lanfranchi, A., Ridella, M., Steward, C., Filipovich, A. (2012). Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency. Blood, 120(17), 3615-24; quiz 3626. https://doi.org/10.1182/blood-2011-12-396879

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title = "Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency",

abstract = "Deficiency of the purine salvage enzyme adenosine deaminase leads to SCID (ADA-SCID). Hematopoietic cell transplantation (HCT) can lead to a permanent cure of SCID; however, little data are available on outcome of HCT for ADA-SCID in particular. In this multicenter retrospective study, we analyzed outcome of HCT in 106 patients with ADA-SCID who received a total of 119 transplants. HCT from matched sibling and family donors (MSDs, MFDs) had significantly better overall survival (86% and 81%) in comparison with HCT from matched unrelated (66%; P < .05) and haploidentical donors (43%; P < .001). Superior overall survival was also seen in patients who received unconditioned transplants in comparison with myeloablative procedures (81% vs 54%; P < .003), although in unconditioned haploidentical donor HCT, nonengraftment was a major problem. Long-term immune recovery showed that regardless of transplant type, overall T-cell numbers were similar, although a faster rate of T-cell recovery was observed after MSD/MFD HCT. Humoral immunity and donor B-cell engraftment was achieved in nearly all evaluable surviving patients and was seen even after unconditioned HCT. These data detail for the first time the outcomes of HCT for ADA-SCID and show that, if patients survive HCT, long-term cellular and humoral immune recovery is achieved.",

keywords = "Adenosine Deaminase, Agammaglobulinemia, Child, Child, Preschool, Female, Graft Survival, Hematopoietic Stem Cell Transplantation, Histocompatibility Testing, Humans, Immunity, Cellular, Immunity, Humoral, Infant, Infant, Newborn, Kaplan-Meier Estimate, Lymphocyte Count, Male, Myeloablative Agonists, Retrospective Studies, Severe Combined Immunodeficiency, Siblings, T-Lymphocytes, Transplantation Conditioning, Treatment Outcome, Unrelated Donors",

author = "Amel Hassan and Claire Booth and Alex Brightwell and Zoe Allwood and Paul Veys and Kanchan Rao and Manfred H{\"o}nig and Wilhelm Friedrich and Andrew Gennery and Mary Slatter and Robbert Bredius and Andrea Finocchi and Caterina Cancrini and Alessandro Aiuti and Fulvio Porta and Arnalda Lanfranchi and Michela Ridella and Colin Steward and Alexandra Filipovich and Rebecca Marsh and Victoria Bordon and Saleh Al-Muhsen and Hamoud Al-Mousa and Zobaida Alsum and Hasan Al-Dhekri and {Al Ghonaium}, Abdulaziz and Carsten Speckmann and Alain Fischer and Nizar Mahlaoui and Nichols, {Kim E} and Eyal Grunebaum and {Al Zahrani}, Daifulah and Roifman, {Chaim M} and Jaap Boelens and Davies, {E Graham} and Marina Cavazzana-Calvo and Luigi Notarangelo and Gaspar, {H Bobby}",

year = "2012",

doi = "10.1182/blood-2011-12-396879",

language = "English",

volume = "120",

pages = "3615--24; quiz 3626",

journal = "Blood",

issn = "0006-4971",

publisher = "American Society of Hematology",

number = "17",

}

Hassan, A, Booth, C, Brightwell, A, Allwood, Z, Veys, P, Rao, K, Hönig, M, Friedrich, W, Gennery, A, Slatter, M, Bredius, R, Finocchi, A, Cancrini, C, Aiuti, A, Porta, F, Lanfranchi, A, Ridella, M, Steward, C, Filipovich, A, Marsh, R, Bordon, V, Al-Muhsen, S, Al-Mousa, H, Alsum, Z, Al-Dhekri, H, Al Ghonaium, A, Speckmann, C, Fischer, A, Mahlaoui, N, Nichols, KE, Grunebaum, E, Al Zahrani, D, Roifman, CM, Boelens, J, Davies, EG, Cavazzana-Calvo, M, Notarangelo, L, Gaspar, HB 2012, 'Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency', Blood, vol. 120, no. 17, pp. 3615-24; quiz 3626. https://doi.org/10.1182/blood-2011-12-396879

TY - JOUR

T1 - Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency

AU - Hassan, Amel

AU - Booth, Claire

AU - Brightwell, Alex

AU - Allwood, Zoe

AU - Veys, Paul

AU - Rao, Kanchan

AU - Hönig, Manfred

AU - Friedrich, Wilhelm

AU - Gennery, Andrew

AU - Slatter, Mary

AU - Bredius, Robbert

AU - Finocchi, Andrea

AU - Cancrini, Caterina

AU - Aiuti, Alessandro

AU - Porta, Fulvio

AU - Lanfranchi, Arnalda

AU - Ridella, Michela

AU - Steward, Colin

AU - Filipovich, Alexandra

AU - Marsh, Rebecca

AU - Bordon, Victoria

AU - Al-Muhsen, Saleh

AU - Al-Mousa, Hamoud

AU - Alsum, Zobaida

AU - Al-Dhekri, Hasan

AU - Al Ghonaium, Abdulaziz

AU - Speckmann, Carsten

AU - Fischer, Alain

AU - Mahlaoui, Nizar

AU - Nichols, Kim E

AU - Grunebaum, Eyal

AU - Al Zahrani, Daifulah

AU - Roifman, Chaim M

AU - Boelens, Jaap

AU - Davies, E Graham

AU - Cavazzana-Calvo, Marina

AU - Notarangelo, Luigi

AU - Gaspar, H Bobby

PY - 2012

Y1 - 2012

N2 - Deficiency of the purine salvage enzyme adenosine deaminase leads to SCID (ADA-SCID). Hematopoietic cell transplantation (HCT) can lead to a permanent cure of SCID; however, little data are available on outcome of HCT for ADA-SCID in particular. In this multicenter retrospective study, we analyzed outcome of HCT in 106 patients with ADA-SCID who received a total of 119 transplants. HCT from matched sibling and family donors (MSDs, MFDs) had significantly better overall survival (86% and 81%) in comparison with HCT from matched unrelated (66%; P < .05) and haploidentical donors (43%; P < .001). Superior overall survival was also seen in patients who received unconditioned transplants in comparison with myeloablative procedures (81% vs 54%; P < .003), although in unconditioned haploidentical donor HCT, nonengraftment was a major problem. Long-term immune recovery showed that regardless of transplant type, overall T-cell numbers were similar, although a faster rate of T-cell recovery was observed after MSD/MFD HCT. Humoral immunity and donor B-cell engraftment was achieved in nearly all evaluable surviving patients and was seen even after unconditioned HCT. These data detail for the first time the outcomes of HCT for ADA-SCID and show that, if patients survive HCT, long-term cellular and humoral immune recovery is achieved.

AB - Deficiency of the purine salvage enzyme adenosine deaminase leads to SCID (ADA-SCID). Hematopoietic cell transplantation (HCT) can lead to a permanent cure of SCID; however, little data are available on outcome of HCT for ADA-SCID in particular. In this multicenter retrospective study, we analyzed outcome of HCT in 106 patients with ADA-SCID who received a total of 119 transplants. HCT from matched sibling and family donors (MSDs, MFDs) had significantly better overall survival (86% and 81%) in comparison with HCT from matched unrelated (66%; P < .05) and haploidentical donors (43%; P < .001). Superior overall survival was also seen in patients who received unconditioned transplants in comparison with myeloablative procedures (81% vs 54%; P < .003), although in unconditioned haploidentical donor HCT, nonengraftment was a major problem. Long-term immune recovery showed that regardless of transplant type, overall T-cell numbers were similar, although a faster rate of T-cell recovery was observed after MSD/MFD HCT. Humoral immunity and donor B-cell engraftment was achieved in nearly all evaluable surviving patients and was seen even after unconditioned HCT. These data detail for the first time the outcomes of HCT for ADA-SCID and show that, if patients survive HCT, long-term cellular and humoral immune recovery is achieved.

KW - Adenosine Deaminase

KW - Agammaglobulinemia

KW - Child

KW - Child, Preschool

KW - Female

KW - Graft Survival

KW - Hematopoietic Stem Cell Transplantation

KW - Histocompatibility Testing

KW - Humans

KW - Immunity, Cellular

KW - Immunity, Humoral

KW - Infant

KW - Infant, Newborn

KW - Kaplan-Meier Estimate

KW - Lymphocyte Count

KW - Male

KW - Myeloablative Agonists

KW - Retrospective Studies

KW - Severe Combined Immunodeficiency

KW - Siblings

KW - T-Lymphocytes

KW - Transplantation Conditioning

KW - Treatment Outcome

KW - Unrelated Donors

U2 - 10.1182/blood-2011-12-396879

DO - 10.1182/blood-2011-12-396879

M3 - Article

C2 - 22791287

SN - 0006-4971

VL - 120

SP - 3615-24; quiz 3626

JO - Blood

JF - Blood

IS - 17

ER -

Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency

Abstract

Keywords

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