Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score

Inborn Errors, Clinical, and Registry Working Parties of the European Society for Blood and Marrow Transplantation and the European Society for Immunodeficiencies

doi:10.1016/j.jaci.2019.12.896

Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score

Inborn Errors, Clinical, and Registry Working Parties of the European Society for Blood and Marrow Transplantation and the European Society for Immunodeficiencies

Pediatrics

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

116 Scopus citations

Abstract

Background: Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant. Objective: This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant. Method: We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices. Results: Of 76 patients with LRBA deficiency from 29 centers (median follow-up, 10 years; range, 1-52), 24 underwent HSCT from 2005 to 2019. The overall survival rate after HSCT (median follow-up, 20 months) was 70.8% (17 of 24 patients); all deaths were due to nonspecific, early, transplant-related mortality. Currently, 82.7% of patients who did not receive a transplant (43 of 52; age range, 3-69 years) are alive. Of 17 HSCT survivors, 7 are in complete remission and 5 are in good partial remission without treatment (together, 12 of 17 [70.6%]). In contrast, only 5 of 43 patients who did not receive a transplant (11.6%) are without immunosuppression. Immune deficiency and dysregulation activity scores were significantly lower in patients who survived HSCT than in those receiving conventional treatment (P = .005) or in patients who received abatacept or sirolimus as compared with other therapies, and in patients with residual LRBA expression. Higher disease burden, longer duration before HSCT, and lung involvement were associated with poor outcome. Conclusion: The lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT.

Original language	English (US)
Pages (from-to)	1452-1463
Number of pages	12
Journal	Journal of Allergy and Clinical Immunology
Volume	145
Issue number	5
DOIs	https://doi.org/10.1016/j.jaci.2019.12.896
State	Published - May 2020

Funding

M.G. Seidel and the Research Unit for Pediatric Hematology and Immunology are supported in part by the Styrian Children's Cancer Aid Foundation. M. Avbeli Stefanija was supported by the Slovenian Research Agency (grant P3-0343). H. Abolhassani was supported by the Jonas Söderquist Foundation. S. Baris was supported by the Scientific and Technological Research Council of Turkey for the diagnosis of patients with LRBA deficiency (grants 217S847 and 318S202). B. Grimbacher receives support through the Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy (CIBSS-EXC-2189-Project ID 390939984 and RESIST-EXC 2155- Project ID 39087428); through the E-Rare program of the European Union, managed by the Deutsche Forschungsgemeinschaft (grant GR1617/14-1/iPAD); and through the Netzwerke Seltener Erkrankungen of the German Ministry of Education and Research (grant GAIN_ 01GM1910A). M.R.J. Seppänen was supported by the Finnish Foundation for Pediatric Research and Pediatric Research Center, HUS Helsinki University Hospital. I. Meyts is a member of the ERN-RITA network (project identification number 739543). B. Shadur is supported by a Graduate Research Training Scholarship of the Australian government and by Hadassah Australia. M.G. Seidel and the Research Unit for Pediatric Hematology and Immunology are supported in part by the Styrian Children’s Cancer Aid Foundation . M. Avbeli Stefanija was supported by the Slovenian Research Agency (grant P3-0343 ). H. Abolhassani was supported by the Jonas Söderquist Foundation . S. Baris was supported by the Scientific and Technological Research Council of Turkey for the diagnosis of patients with LRBA deficiency (grants 217S847 and 318S202 ). B. Grimbacher receives support through the Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy (CIBSS-EXC-2189-Project ID 390939984 and RESIST-EXC 2155- Project ID 39087428 ); through the E-Rare program of the European Union, managed by the Deutsche Forschungsgemeinschaft (grant GR1617/14-1/iPAD ); and through the Netzwerke Seltener Erkrankungen of the German Ministry of Education and Research (grant GAIN_ 01GM1910A ). M.R.J. Seppänen was supported by the Finnish Foundation for Pediatric Research and Pediatric Research Center , HUS Helsinki University Hospital . I. Meyts is a member of the ERN-RITA network (project identification number 739543 ). B. Shadur is supported by a Graduate Research Training Scholarship of the Australian government and by Hadassah Australia.

Keywords

CTLA4
Inborn error of immunity
abatacept
clinical score
combined immunodeficiency
hematopoietic stem cell transplantation
immune dysregulation
performance scale
primary immunodeficiency disorder
sirolimus

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1016/j.jaci.2019.12.896

Cite this

Inborn Errors, Clinical, and Registry Working Parties of the European Society for Blood and Marrow Transplantation and the European Society for Immunodeficiencies (2020). Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score. Journal of Allergy and Clinical Immunology, 145(5), 1452-1463. https://doi.org/10.1016/j.jaci.2019.12.896

Inborn Errors, Clinical, and Registry Working Parties of the European Society for Blood and Marrow Transplantation and the European Society for Immunodeficiencies. / Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score. In: Journal of Allergy and Clinical Immunology. 2020 ; Vol. 145, No. 5. pp. 1452-1463.

@article{e96cf13931644c229fa5ea476cfe3d7c,

title = "Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score",

abstract = "Background: Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant. Objective: This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant. Method: We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices. Results: Of 76 patients with LRBA deficiency from 29 centers (median follow-up, 10 years; range, 1-52), 24 underwent HSCT from 2005 to 2019. The overall survival rate after HSCT (median follow-up, 20 months) was 70.8% (17 of 24 patients); all deaths were due to nonspecific, early, transplant-related mortality. Currently, 82.7% of patients who did not receive a transplant (43 of 52; age range, 3-69 years) are alive. Of 17 HSCT survivors, 7 are in complete remission and 5 are in good partial remission without treatment (together, 12 of 17 [70.6%]). In contrast, only 5 of 43 patients who did not receive a transplant (11.6%) are without immunosuppression. Immune deficiency and dysregulation activity scores were significantly lower in patients who survived HSCT than in those receiving conventional treatment (P = .005) or in patients who received abatacept or sirolimus as compared with other therapies, and in patients with residual LRBA expression. Higher disease burden, longer duration before HSCT, and lung involvement were associated with poor outcome. Conclusion: The lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT.",

keywords = "CTLA4, Inborn error of immunity, abatacept, clinical score, combined immunodeficiency, hematopoietic stem cell transplantation, immune dysregulation, performance scale, primary immunodeficiency disorder, sirolimus",

author = "{Inborn Errors, Clinical, and Registry Working Parties of the European Society for Blood and Marrow Transplantation and the European Society for Immunodeficiencies} and Tesch, {Victoria Katharina} and Hassan Abolhassani and Bella Shadur and Joachim Zobel and Yuliya Mareika and Svetlana Sharapova and Elif Karakoc-Aydiner and Rivi{\`e}re, {Jacques G.} and Marina Garcia-Prat and Nicolette Moes and Filomeen Haerynck and Gonzales-Granado, {Luis I.} and {Santos P{\'e}rez}, {Juan Luis} and Anna Mukhina and Anna Shcherbina and Asghar Aghamohammadi and Lennart Hammarstr{\"o}m and Figen Dogu and Sule Haskologlu and Aydan İkincioğulları and {K{\"o}stel Bal}, Sevgi and Safa Baris and Kilic, {Sara Sebnem} and Karaca, {Neslihan Edeer} and Necil Kutukculer and Hermann Girschick and Antonios Kolios and Sevgi Keles and Vedat Uygun and Polina Stepensky and Austen Worth and {van Montfrans}, {Joris M.} and Peters, {Anke M.J.} and Isabelle Meyts and Mehdi Adeli and Antonio Marzollo and Nurcicek Padem and Khojah, {Amer M.} and Zahra Chavoshzadeh and {Avbelj Stefanija}, Magdalena and Shahrzad Bakhtiar and Benoit Florkin and Marie Meeths and Laura Gamez and Bodo Grimbacher and Sepp{\"a}nen, {Mikko R.J.} and Arjan Lankester and Gennery, {Andrew R.} and Seidel, {Markus G.}",

note = "Publisher Copyright: {\textcopyright} 2019 The Authors",

year = "2020",

month = may,

doi = "10.1016/j.jaci.2019.12.896",

language = "English (US)",

volume = "145",

pages = "1452--1463",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Elsevier Inc.",

number = "5",

}

Inborn Errors, Clinical, and Registry Working Parties of the European Society for Blood and Marrow Transplantation and the European Society for Immunodeficiencies 2020, 'Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score', Journal of Allergy and Clinical Immunology, vol. 145, no. 5, pp. 1452-1463. https://doi.org/10.1016/j.jaci.2019.12.896

Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score. / Inborn Errors, Clinical, and Registry Working Parties of the European Society for Blood and Marrow Transplantation and the European Society for Immunodeficiencies.
In: Journal of Allergy and Clinical Immunology, Vol. 145, No. 5, 05.2020, p. 1452-1463.

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

TY - JOUR

T1 - Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score

AU - Inborn Errors, Clinical, and Registry Working Parties of the European Society for Blood and Marrow Transplantation and the European Society for Immunodeficiencies

AU - Tesch, Victoria Katharina

AU - Abolhassani, Hassan

AU - Shadur, Bella

AU - Zobel, Joachim

AU - Mareika, Yuliya

AU - Sharapova, Svetlana

AU - Karakoc-Aydiner, Elif

AU - Rivière, Jacques G.

AU - Garcia-Prat, Marina

AU - Moes, Nicolette

AU - Haerynck, Filomeen

AU - Gonzales-Granado, Luis I.

AU - Santos Pérez, Juan Luis

AU - Mukhina, Anna

AU - Shcherbina, Anna

AU - Aghamohammadi, Asghar

AU - Hammarström, Lennart

AU - Dogu, Figen

AU - Haskologlu, Sule

AU - İkincioğulları, Aydan

AU - Köstel Bal, Sevgi

AU - Baris, Safa

AU - Kilic, Sara Sebnem

AU - Karaca, Neslihan Edeer

AU - Kutukculer, Necil

AU - Girschick, Hermann

AU - Kolios, Antonios

AU - Keles, Sevgi

AU - Uygun, Vedat

AU - Stepensky, Polina

AU - Worth, Austen

AU - van Montfrans, Joris M.

AU - Peters, Anke M.J.

AU - Meyts, Isabelle

AU - Adeli, Mehdi

AU - Marzollo, Antonio

AU - Padem, Nurcicek

AU - Khojah, Amer M.

AU - Chavoshzadeh, Zahra

AU - Avbelj Stefanija, Magdalena

AU - Bakhtiar, Shahrzad

AU - Florkin, Benoit

AU - Meeths, Marie

AU - Gamez, Laura

AU - Grimbacher, Bodo

AU - Seppänen, Mikko R.J.

AU - Lankester, Arjan

AU - Gennery, Andrew R.

AU - Seidel, Markus G.

PY - 2020/5

Y1 - 2020/5

N2 - Background: Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant. Objective: This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant. Method: We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices. Results: Of 76 patients with LRBA deficiency from 29 centers (median follow-up, 10 years; range, 1-52), 24 underwent HSCT from 2005 to 2019. The overall survival rate after HSCT (median follow-up, 20 months) was 70.8% (17 of 24 patients); all deaths were due to nonspecific, early, transplant-related mortality. Currently, 82.7% of patients who did not receive a transplant (43 of 52; age range, 3-69 years) are alive. Of 17 HSCT survivors, 7 are in complete remission and 5 are in good partial remission without treatment (together, 12 of 17 [70.6%]). In contrast, only 5 of 43 patients who did not receive a transplant (11.6%) are without immunosuppression. Immune deficiency and dysregulation activity scores were significantly lower in patients who survived HSCT than in those receiving conventional treatment (P = .005) or in patients who received abatacept or sirolimus as compared with other therapies, and in patients with residual LRBA expression. Higher disease burden, longer duration before HSCT, and lung involvement were associated with poor outcome. Conclusion: The lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT.

AB - Background: Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant. Objective: This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant. Method: We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices. Results: Of 76 patients with LRBA deficiency from 29 centers (median follow-up, 10 years; range, 1-52), 24 underwent HSCT from 2005 to 2019. The overall survival rate after HSCT (median follow-up, 20 months) was 70.8% (17 of 24 patients); all deaths were due to nonspecific, early, transplant-related mortality. Currently, 82.7% of patients who did not receive a transplant (43 of 52; age range, 3-69 years) are alive. Of 17 HSCT survivors, 7 are in complete remission and 5 are in good partial remission without treatment (together, 12 of 17 [70.6%]). In contrast, only 5 of 43 patients who did not receive a transplant (11.6%) are without immunosuppression. Immune deficiency and dysregulation activity scores were significantly lower in patients who survived HSCT than in those receiving conventional treatment (P = .005) or in patients who received abatacept or sirolimus as compared with other therapies, and in patients with residual LRBA expression. Higher disease burden, longer duration before HSCT, and lung involvement were associated with poor outcome. Conclusion: The lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT.

KW - CTLA4

KW - Inborn error of immunity

KW - abatacept

KW - clinical score

KW - combined immunodeficiency

KW - hematopoietic stem cell transplantation

KW - immune dysregulation

KW - performance scale

KW - primary immunodeficiency disorder

KW - sirolimus

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U2 - 10.1016/j.jaci.2019.12.896

DO - 10.1016/j.jaci.2019.12.896

M3 - Article

C2 - 31887391

AN - SCOPUS:85078904882

SN - 0091-6749

VL - 145

SP - 1452

EP - 1463

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 5

ER -

Inborn Errors, Clinical, and Registry Working Parties of the European Society for Blood and Marrow Transplantation and the European Society for Immunodeficiencies. Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score. Journal of Allergy and Clinical Immunology. 2020 May;145(5):1452-1463. doi: 10.1016/j.jaci.2019.12.896

Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score

Abstract

Funding

Keywords

ASJC Scopus subject areas

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