Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency

Claudia Wehr; Andrew R. Gennery; Caroline Lindemans; Ansgar Schulz; Manfred Hoenig; Reinhard Marks; Mike Recher; Bernd Gruhn; Andreas Holbro; Ingmar Heijnen; Deborah Meyer; Goetz Grigoleit; Hermann Einsele; Ulrich Baumann; Thorsten Witte; Karl-Walter Sykora; Sigune Goldacker; Lorena Regairaz; Serap Aksoylar; Omur Ardeniz; Marco Zecca; Przemyslaw Zdziarski; Isabelle Meyts; Susanne Matthes-Martin; Kohsuke Imai; Chikako Kamae; Adele Fielding; Suranjith Seneviratne; Nizar Mahlaoui; Mary A. Slatter; Tayfun Gungor; Peter D. Arkwright; JM van Montfrans; Kathleen E. Sullivan; Bodo Grimbacher; Andrew Cant; Hans-Hartmut Peter; Juergen Finke; H. Bobby Gaspar; Klaus Warnatz; Marta Rizzi

doi:10.1016/j.jaci.2014.11.029

Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency

Claudia Wehr
, Andrew R. Gennery
, Caroline Lindemans
, Ansgar Schulz
, Manfred Hoenig
, Reinhard Marks
, Mike Recher
, Bernd Gruhn
, Andreas Holbro
, Ingmar Heijnen
, Deborah Meyer
, Goetz Grigoleit
, Hermann Einsele
, Ulrich Baumann
, Thorsten Witte
, Karl-Walter Sykora
, Sigune Goldacker
, Lorena Regairaz
, Serap Aksoylar
, Omur Ardeniz

Marco Zecca, Przemyslaw Zdziarski, Isabelle Meyts, Susanne Matthes-Martin, Kohsuke Imai, Chikako Kamae, Adele Fielding, Suranjith Seneviratne, Nizar Mahlaoui, Mary A. Slatter, Tayfun Gungor, Peter D. Arkwright, JM van Montfrans, Kathleen E. Sullivan, Bodo Grimbacher, Andrew Cant, Hans-Hartmut Peter, Juergen Finke, H. Bobby Gaspar, Klaus Warnatz, Marta Rizzi^*, ,

^*Corresponding author for this work

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

Abstract

Background: Common variable immunodeficiency (CVID) is usually well controlled with immunoglobulin substitution and immunomodulatory drugs. A subgroup of patients has a complicated disease course with high mortality. For these patients, investigation of more invasive, potentially curative treatments, such as allogeneic hematopoietic stem cell transplantation (HSCT), is warranted.

Objective: We sought to define the outcomes of HSCT for patients with CVID.

Methods: Retrospective data were collected from 14 centers worldwide on patients with CVID receiving HSCT between 1993 and 2012.

Results: Twenty-five patients with CVID, which was defined according to international criteria, aged 8 to 50 years at the time of transplantation were included in the study. The indication for HSCT was immunologic dysregulation in the majority of patients. The overall survival rate was 48%, and the survival rate for patients undergoing transplantation for lymphoma was 83%. The major causes of death were treatment-refractory graft-versus-host disease accompanied by poor immune reconstitution and infectious complications. Immunoglobulin substitution was stopped in 50% of surviving patients. In 92% of surviving patients, the condition constituting the indication for HSCT resolved.

Conclusion: This multicenter study demonstrated that HSCT in patients with CVID was beneficial in most surviving patients; however, there was a high mortality associated with the procedure. Therefore this therapeutic approach should only be considered in carefully selected patients in whom there has been extensive characterization of the immunologic and/or genetic defect underlying the CVID diagnosis. Criteria for patient selection, refinement of the transplantation protocol, and timing are needed for an improved outcome.

Original language	English
Pages (from-to)	988-997.e6
Number of pages	16
Journal	Journal of Allergy and Clinical Immunology
Volume	135
Issue number	4
DOIs	https://doi.org/10.1016/j.jaci.2014.11.029
Publication status	Published - Apr 2015

Keywords

Common variable immunodeficiency
hypogammaglobulinemia
hematopoietic stem cell transplantation
immunologic reconstitution
immunoglobulin substitution/replacement
outcome
mortality
survival
BONE-MARROW-TRANSPLANTATION
SEVERE APLASTIC-ANEMIA
VERSUS-HOST-DISEASE
B-CELL
EUROPEAN GROUP
WORKING PARTY
ACUTE GVHD
DISORDERS
BLOOD
CLASSIFICATION

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10.1016/j.jaci.2014.11.029

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Wehr, C., Gennery, A. R., Lindemans, C., Schulz, A., Hoenig, M., Marks, R., Recher, M., Gruhn, B., Holbro, A., Heijnen, I., Meyer, D., Grigoleit, G., Einsele, H., Baumann, U., Witte, T., Sykora, K.-W., Goldacker, S., Regairaz, L., Aksoylar, S. (2015). Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency. Journal of Allergy and Clinical Immunology, 135(4), 988-997.e6. https://doi.org/10.1016/j.jaci.2014.11.029

@article{a3a7824585ee4e5db58dac188d8bb267,

title = "Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency",

abstract = "Background: Common variable immunodeficiency (CVID) is usually well controlled with immunoglobulin substitution and immunomodulatory drugs. A subgroup of patients has a complicated disease course with high mortality. For these patients, investigation of more invasive, potentially curative treatments, such as allogeneic hematopoietic stem cell transplantation (HSCT), is warranted.Objective: We sought to define the outcomes of HSCT for patients with CVID.Methods: Retrospective data were collected from 14 centers worldwide on patients with CVID receiving HSCT between 1993 and 2012.Results: Twenty-five patients with CVID, which was defined according to international criteria, aged 8 to 50 years at the time of transplantation were included in the study. The indication for HSCT was immunologic dysregulation in the majority of patients. The overall survival rate was 48\%, and the survival rate for patients undergoing transplantation for lymphoma was 83\%. The major causes of death were treatment-refractory graft-versus-host disease accompanied by poor immune reconstitution and infectious complications. Immunoglobulin substitution was stopped in 50\% of surviving patients. In 92\% of surviving patients, the condition constituting the indication for HSCT resolved.Conclusion: This multicenter study demonstrated that HSCT in patients with CVID was beneficial in most surviving patients; however, there was a high mortality associated with the procedure. Therefore this therapeutic approach should only be considered in carefully selected patients in whom there has been extensive characterization of the immunologic and/or genetic defect underlying the CVID diagnosis. Criteria for patient selection, refinement of the transplantation protocol, and timing are needed for an improved outcome.",

keywords = "Common variable immunodeficiency, hypogammaglobulinemia, hematopoietic stem cell transplantation, immunologic reconstitution, immunoglobulin substitution/replacement, outcome, mortality, survival, BONE-MARROW-TRANSPLANTATION, SEVERE APLASTIC-ANEMIA, VERSUS-HOST-DISEASE, B-CELL, EUROPEAN GROUP, WORKING PARTY, ACUTE GVHD, DISORDERS, BLOOD, CLASSIFICATION",

author = "Claudia Wehr and Gennery, \{Andrew R.\} and Caroline Lindemans and Ansgar Schulz and Manfred Hoenig and Reinhard Marks and Mike Recher and Bernd Gruhn and Andreas Holbro and Ingmar Heijnen and Deborah Meyer and Goetz Grigoleit and Hermann Einsele and Ulrich Baumann and Thorsten Witte and Karl-Walter Sykora and Sigune Goldacker and Lorena Regairaz and Serap Aksoylar and Omur Ardeniz and Marco Zecca and Przemyslaw Zdziarski and Isabelle Meyts and Susanne Matthes-Martin and Kohsuke Imai and Chikako Kamae and Adele Fielding and Suranjith Seneviratne and Nizar Mahlaoui and Slatter, \{Mary A.\} and Tayfun Gungor and Arkwright, \{Peter D.\} and \{van Montfrans\}, JM and Sullivan, \{Kathleen E.\} and Bodo Grimbacher and Andrew Cant and Hans-Hartmut Peter and Juergen Finke and Gaspar, \{H. Bobby\} and Klaus Warnatz and Marta Rizzi",

year = "2015",

month = apr,

doi = "10.1016/j.jaci.2014.11.029",

language = "English",

volume = "135",

pages = "988--997.e6",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Elsevier",

number = "4",

}

Wehr, C, Gennery, AR, Lindemans, C, Schulz, A, Hoenig, M, Marks, R, Recher, M, Gruhn, B, Holbro, A, Heijnen, I, Meyer, D, Grigoleit, G, Einsele, H, Baumann, U, Witte, T, Sykora, K-W, Goldacker, S, Regairaz, L, Aksoylar, S, Ardeniz, O, Zecca, M, Zdziarski, P, Meyts, I, Matthes-Martin, S, Imai, K, Kamae, C, Fielding, A, Seneviratne, S, Mahlaoui, N, Slatter, MA, Gungor, T, Arkwright, PD, van Montfrans, JM, Sullivan, KE, Grimbacher, B, Cant, A, Peter, H-H, Finke, J, Gaspar, HB, Warnatz, K, Rizzi, M 2015, 'Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency', Journal of Allergy and Clinical Immunology, vol. 135, no. 4, pp. 988-997.e6. https://doi.org/10.1016/j.jaci.2014.11.029

TY - JOUR

T1 - Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency

AU - Wehr, Claudia

AU - Gennery, Andrew R.

AU - Lindemans, Caroline

AU - Schulz, Ansgar

AU - Hoenig, Manfred

AU - Marks, Reinhard

AU - Recher, Mike

AU - Gruhn, Bernd

AU - Holbro, Andreas

AU - Heijnen, Ingmar

AU - Meyer, Deborah

AU - Grigoleit, Goetz

AU - Einsele, Hermann

AU - Baumann, Ulrich

AU - Witte, Thorsten

AU - Sykora, Karl-Walter

AU - Goldacker, Sigune

AU - Regairaz, Lorena

AU - Aksoylar, Serap

AU - Ardeniz, Omur

AU - Zecca, Marco

AU - Zdziarski, Przemyslaw

AU - Meyts, Isabelle

AU - Matthes-Martin, Susanne

AU - Imai, Kohsuke

AU - Kamae, Chikako

AU - Fielding, Adele

AU - Seneviratne, Suranjith

AU - Mahlaoui, Nizar

AU - Slatter, Mary A.

AU - Gungor, Tayfun

AU - Arkwright, Peter D.

AU - van Montfrans, JM

AU - Sullivan, Kathleen E.

AU - Grimbacher, Bodo

AU - Cant, Andrew

AU - Peter, Hans-Hartmut

AU - Finke, Juergen

AU - Gaspar, H. Bobby

AU - Warnatz, Klaus

AU - Rizzi, Marta

PY - 2015/4

Y1 - 2015/4

N2 - Background: Common variable immunodeficiency (CVID) is usually well controlled with immunoglobulin substitution and immunomodulatory drugs. A subgroup of patients has a complicated disease course with high mortality. For these patients, investigation of more invasive, potentially curative treatments, such as allogeneic hematopoietic stem cell transplantation (HSCT), is warranted.Objective: We sought to define the outcomes of HSCT for patients with CVID.Methods: Retrospective data were collected from 14 centers worldwide on patients with CVID receiving HSCT between 1993 and 2012.Results: Twenty-five patients with CVID, which was defined according to international criteria, aged 8 to 50 years at the time of transplantation were included in the study. The indication for HSCT was immunologic dysregulation in the majority of patients. The overall survival rate was 48%, and the survival rate for patients undergoing transplantation for lymphoma was 83%. The major causes of death were treatment-refractory graft-versus-host disease accompanied by poor immune reconstitution and infectious complications. Immunoglobulin substitution was stopped in 50% of surviving patients. In 92% of surviving patients, the condition constituting the indication for HSCT resolved.Conclusion: This multicenter study demonstrated that HSCT in patients with CVID was beneficial in most surviving patients; however, there was a high mortality associated with the procedure. Therefore this therapeutic approach should only be considered in carefully selected patients in whom there has been extensive characterization of the immunologic and/or genetic defect underlying the CVID diagnosis. Criteria for patient selection, refinement of the transplantation protocol, and timing are needed for an improved outcome.

AB - Background: Common variable immunodeficiency (CVID) is usually well controlled with immunoglobulin substitution and immunomodulatory drugs. A subgroup of patients has a complicated disease course with high mortality. For these patients, investigation of more invasive, potentially curative treatments, such as allogeneic hematopoietic stem cell transplantation (HSCT), is warranted.Objective: We sought to define the outcomes of HSCT for patients with CVID.Methods: Retrospective data were collected from 14 centers worldwide on patients with CVID receiving HSCT between 1993 and 2012.Results: Twenty-five patients with CVID, which was defined according to international criteria, aged 8 to 50 years at the time of transplantation were included in the study. The indication for HSCT was immunologic dysregulation in the majority of patients. The overall survival rate was 48%, and the survival rate for patients undergoing transplantation for lymphoma was 83%. The major causes of death were treatment-refractory graft-versus-host disease accompanied by poor immune reconstitution and infectious complications. Immunoglobulin substitution was stopped in 50% of surviving patients. In 92% of surviving patients, the condition constituting the indication for HSCT resolved.Conclusion: This multicenter study demonstrated that HSCT in patients with CVID was beneficial in most surviving patients; however, there was a high mortality associated with the procedure. Therefore this therapeutic approach should only be considered in carefully selected patients in whom there has been extensive characterization of the immunologic and/or genetic defect underlying the CVID diagnosis. Criteria for patient selection, refinement of the transplantation protocol, and timing are needed for an improved outcome.

KW - Common variable immunodeficiency

KW - hypogammaglobulinemia

KW - hematopoietic stem cell transplantation

KW - immunologic reconstitution

KW - immunoglobulin substitution/replacement

KW - outcome

KW - mortality

KW - survival

KW - BONE-MARROW-TRANSPLANTATION

KW - SEVERE APLASTIC-ANEMIA

KW - VERSUS-HOST-DISEASE

KW - B-CELL

KW - EUROPEAN GROUP

KW - WORKING PARTY

KW - ACUTE GVHD

KW - DISORDERS

KW - BLOOD

KW - CLASSIFICATION

U2 - 10.1016/j.jaci.2014.11.029

DO - 10.1016/j.jaci.2014.11.029

M3 - Article

C2 - 25595268

SN - 0091-6749

VL - 135

SP - 988-997.e6

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 4

ER -

Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency

Abstract

Keywords

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