Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation

M. Teresa de la Morena*, David Leonard, Troy R. Torgerson, Otavio Cabral-Marques, Mary Slatter, Asghar Aghamohammadi, Sharat Chandra, Luis Murguia-Favela, Francisco A. Bonilla, Maria Kanariou, Rongras Damrongwatanasuk, Caroline Y. Kuo, Christopher C. Dvorak, Isabelle Meyts, Karin Chen, Lisa Kobrynski, Neena Kapoor, Darko Richter, Daniela DiGiovanni, Fatima Dhalla & 43 others Evangelia Farmaki, Carsten Speckmann, Teresa Español, Anna Shcherbina, Imelda Celine Hanson, Jiri Litzman, John M. Routes, Melanie Wong, Ramsay Fuleihan, Suranjith L. Seneviratne, Trudy N. Small, Ales Janda, Liliana Bezrodnik, Reinhard Seger, Andrea Gomez Raccio, J. David M Edgar, Janet Chou, Jordan K. Abbott, Joris van Montfrans, Luis Ignacio González-Granado, Nancy Bunin, Necil Kutukculer, Paul Gray, Gisela Seminario, Srdjan Pasic, Victor Aquino, Christian Wysocki, Hassan Abolhassani, Morna Dorsey, Charlotte Cunningham-Rundles, Alan P. Knutsen, John Sleasman, Beatriz Tavares Costa Carvalho, Antonio Condino-Neto, Eyal Grunebaum, Helen Chapel, Hans D. Ochs, Alexandra Filipovich, Mort Cowan, Andrew Gennery, Andrew Cant, Luigi D. Notarangelo, Chaim M. Roifman

*Corresponding author for this work

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Background X-linked hyper-IgM syndrome (XHIGM) is a primary immunodeficiency with high morbidity and mortality compared with those seen in healthy subjects. Hematopoietic cell transplantation (HCT) has been considered a curative therapy, but the procedure has inherent complications and might not be available for all patients. Objectives We sought to collect data on the clinical presentation, treatment, and follow-up of a large sample of patients with XHIGM to (1) compare long-term overall survival and general well-being of patients treated with or without HCT along with clinical factors associated with mortality and (2) summarize clinical practice and risk factors in the subgroup of patients treated with HCT. Methods Physicians caring for patients with primary immunodeficiency diseases were identified through the Jeffrey Modell Foundation, United States Immunodeficiency Network, Latin American Society for Immunodeficiency, and Primary Immune Deficiency Treatment Consortium. Data were collected with a Research Electronic Data Capture Web application. Survival from time of diagnosis or transplantation was estimated by using the Kaplan-Meier method compared with log-rank tests and modeled by using proportional hazards regression. Results Twenty-eight clinical sites provided data on 189 patients given a diagnosis of XHIGM between 1964 and 2013; 176 had valid follow-up and vital status information. Sixty-seven (38%) patients received HCT. The average follow-up time was 8.5 ± 7.2 years (range, 0.1-36.2 years). No difference in overall survival was observed between patients treated with or without HCT (P = .671). However, risk associated with HCT decreased for diagnosis years 1987-1995; the hazard ratio was significantly less than 1 for diagnosis years 1995-1999. Liver disease was a significant predictor of overall survival (hazard ratio, 4.9; 95% confidence limits, 2.2-10.8; P < .001). Among survivors, those treated with HCT had higher median Karnofsky/Lansky scores than those treated without HCT (P < .001). Among patients receiving HCT, 27 (40%) had graft-versus-host disease, and most deaths occurred within 1 year of transplantation. Conclusion No difference in survival was observed between patients treated with or without HCT across all diagnosis years (1964-2013). However, survivors treated with HCT experienced somewhat greater well-being, and hazards associated with HCT decreased, reaching levels of significantly less risk in the late 1990s. Among patients treated with HCT, treatment at an early age is associated with improved survival. Optimism remains guarded as additional evidence accumulates.

Original languageEnglish (US)
Pages (from-to)1282-1292
Number of pages11
JournalJournal of Allergy and Clinical Immunology
Volume139
Issue number4
DOIs
StatePublished - Apr 1 2017

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Type 1 Hyper-IgM Immunodeficiency Syndrome
Cell Transplantation
Survival
Survivors
Transplantation
Mortality

Keywords

  • CD40 ligand
  • Karnofsky/Lansky scores
  • X-linked hyper-IgM syndrome
  • defects in class-switch recombination
  • hematopoietic cell transplantation
  • long-term outcomes
  • primary immunodeficiency

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

de la Morena, M. T., Leonard, D., Torgerson, T. R., Cabral-Marques, O., Slatter, M., Aghamohammadi, A., ... Roifman, C. M. (2017). Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation. Journal of Allergy and Clinical Immunology, 139(4), 1282-1292. https://doi.org/10.1016/j.jaci.2016.07.039
de la Morena, M. Teresa ; Leonard, David ; Torgerson, Troy R. ; Cabral-Marques, Otavio ; Slatter, Mary ; Aghamohammadi, Asghar ; Chandra, Sharat ; Murguia-Favela, Luis ; Bonilla, Francisco A. ; Kanariou, Maria ; Damrongwatanasuk, Rongras ; Kuo, Caroline Y. ; Dvorak, Christopher C. ; Meyts, Isabelle ; Chen, Karin ; Kobrynski, Lisa ; Kapoor, Neena ; Richter, Darko ; DiGiovanni, Daniela ; Dhalla, Fatima ; Farmaki, Evangelia ; Speckmann, Carsten ; Español, Teresa ; Shcherbina, Anna ; Hanson, Imelda Celine ; Litzman, Jiri ; Routes, John M. ; Wong, Melanie ; Fuleihan, Ramsay ; Seneviratne, Suranjith L. ; Small, Trudy N. ; Janda, Ales ; Bezrodnik, Liliana ; Seger, Reinhard ; Raccio, Andrea Gomez ; Edgar, J. David M ; Chou, Janet ; Abbott, Jordan K. ; van Montfrans, Joris ; González-Granado, Luis Ignacio ; Bunin, Nancy ; Kutukculer, Necil ; Gray, Paul ; Seminario, Gisela ; Pasic, Srdjan ; Aquino, Victor ; Wysocki, Christian ; Abolhassani, Hassan ; Dorsey, Morna ; Cunningham-Rundles, Charlotte ; Knutsen, Alan P. ; Sleasman, John ; Costa Carvalho, Beatriz Tavares ; Condino-Neto, Antonio ; Grunebaum, Eyal ; Chapel, Helen ; Ochs, Hans D. ; Filipovich, Alexandra ; Cowan, Mort ; Gennery, Andrew ; Cant, Andrew ; Notarangelo, Luigi D. ; Roifman, Chaim M. / Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation. In: Journal of Allergy and Clinical Immunology. 2017 ; Vol. 139, No. 4. pp. 1282-1292.
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title = "Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation",
abstract = "Background X-linked hyper-IgM syndrome (XHIGM) is a primary immunodeficiency with high morbidity and mortality compared with those seen in healthy subjects. Hematopoietic cell transplantation (HCT) has been considered a curative therapy, but the procedure has inherent complications and might not be available for all patients. Objectives We sought to collect data on the clinical presentation, treatment, and follow-up of a large sample of patients with XHIGM to (1) compare long-term overall survival and general well-being of patients treated with or without HCT along with clinical factors associated with mortality and (2) summarize clinical practice and risk factors in the subgroup of patients treated with HCT. Methods Physicians caring for patients with primary immunodeficiency diseases were identified through the Jeffrey Modell Foundation, United States Immunodeficiency Network, Latin American Society for Immunodeficiency, and Primary Immune Deficiency Treatment Consortium. Data were collected with a Research Electronic Data Capture Web application. Survival from time of diagnosis or transplantation was estimated by using the Kaplan-Meier method compared with log-rank tests and modeled by using proportional hazards regression. Results Twenty-eight clinical sites provided data on 189 patients given a diagnosis of XHIGM between 1964 and 2013; 176 had valid follow-up and vital status information. Sixty-seven (38{\%}) patients received HCT. The average follow-up time was 8.5 ± 7.2 years (range, 0.1-36.2 years). No difference in overall survival was observed between patients treated with or without HCT (P = .671). However, risk associated with HCT decreased for diagnosis years 1987-1995; the hazard ratio was significantly less than 1 for diagnosis years 1995-1999. Liver disease was a significant predictor of overall survival (hazard ratio, 4.9; 95{\%} confidence limits, 2.2-10.8; P < .001). Among survivors, those treated with HCT had higher median Karnofsky/Lansky scores than those treated without HCT (P < .001). Among patients receiving HCT, 27 (40{\%}) had graft-versus-host disease, and most deaths occurred within 1 year of transplantation. Conclusion No difference in survival was observed between patients treated with or without HCT across all diagnosis years (1964-2013). However, survivors treated with HCT experienced somewhat greater well-being, and hazards associated with HCT decreased, reaching levels of significantly less risk in the late 1990s. Among patients treated with HCT, treatment at an early age is associated with improved survival. Optimism remains guarded as additional evidence accumulates.",
keywords = "CD40 ligand, Karnofsky/Lansky scores, X-linked hyper-IgM syndrome, defects in class-switch recombination, hematopoietic cell transplantation, long-term outcomes, primary immunodeficiency",
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de la Morena, MT, Leonard, D, Torgerson, TR, Cabral-Marques, O, Slatter, M, Aghamohammadi, A, Chandra, S, Murguia-Favela, L, Bonilla, FA, Kanariou, M, Damrongwatanasuk, R, Kuo, CY, Dvorak, CC, Meyts, I, Chen, K, Kobrynski, L, Kapoor, N, Richter, D, DiGiovanni, D, Dhalla, F, Farmaki, E, Speckmann, C, Español, T, Shcherbina, A, Hanson, IC, Litzman, J, Routes, JM, Wong, M, Fuleihan, R, Seneviratne, SL, Small, TN, Janda, A, Bezrodnik, L, Seger, R, Raccio, AG, Edgar, JDM, Chou, J, Abbott, JK, van Montfrans, J, González-Granado, LI, Bunin, N, Kutukculer, N, Gray, P, Seminario, G, Pasic, S, Aquino, V, Wysocki, C, Abolhassani, H, Dorsey, M, Cunningham-Rundles, C, Knutsen, AP, Sleasman, J, Costa Carvalho, BT, Condino-Neto, A, Grunebaum, E, Chapel, H, Ochs, HD, Filipovich, A, Cowan, M, Gennery, A, Cant, A, Notarangelo, LD & Roifman, CM 2017, 'Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation', Journal of Allergy and Clinical Immunology, vol. 139, no. 4, pp. 1282-1292. https://doi.org/10.1016/j.jaci.2016.07.039

Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation. / de la Morena, M. Teresa; Leonard, David; Torgerson, Troy R.; Cabral-Marques, Otavio; Slatter, Mary; Aghamohammadi, Asghar; Chandra, Sharat; Murguia-Favela, Luis; Bonilla, Francisco A.; Kanariou, Maria; Damrongwatanasuk, Rongras; Kuo, Caroline Y.; Dvorak, Christopher C.; Meyts, Isabelle; Chen, Karin; Kobrynski, Lisa; Kapoor, Neena; Richter, Darko; DiGiovanni, Daniela; Dhalla, Fatima; Farmaki, Evangelia; Speckmann, Carsten; Español, Teresa; Shcherbina, Anna; Hanson, Imelda Celine; Litzman, Jiri; Routes, John M.; Wong, Melanie; Fuleihan, Ramsay; Seneviratne, Suranjith L.; Small, Trudy N.; Janda, Ales; Bezrodnik, Liliana; Seger, Reinhard; Raccio, Andrea Gomez; Edgar, J. David M; Chou, Janet; Abbott, Jordan K.; van Montfrans, Joris; González-Granado, Luis Ignacio; Bunin, Nancy; Kutukculer, Necil; Gray, Paul; Seminario, Gisela; Pasic, Srdjan; Aquino, Victor; Wysocki, Christian; Abolhassani, Hassan; Dorsey, Morna; Cunningham-Rundles, Charlotte; Knutsen, Alan P.; Sleasman, John; Costa Carvalho, Beatriz Tavares; Condino-Neto, Antonio; Grunebaum, Eyal; Chapel, Helen; Ochs, Hans D.; Filipovich, Alexandra; Cowan, Mort; Gennery, Andrew; Cant, Andrew; Notarangelo, Luigi D.; Roifman, Chaim M.

In: Journal of Allergy and Clinical Immunology, Vol. 139, No. 4, 01.04.2017, p. 1282-1292.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation

AU - de la Morena, M. Teresa

AU - Leonard, David

AU - Torgerson, Troy R.

AU - Cabral-Marques, Otavio

AU - Slatter, Mary

AU - Aghamohammadi, Asghar

AU - Chandra, Sharat

AU - Murguia-Favela, Luis

AU - Bonilla, Francisco A.

AU - Kanariou, Maria

AU - Damrongwatanasuk, Rongras

AU - Kuo, Caroline Y.

AU - Dvorak, Christopher C.

AU - Meyts, Isabelle

AU - Chen, Karin

AU - Kobrynski, Lisa

AU - Kapoor, Neena

AU - Richter, Darko

AU - DiGiovanni, Daniela

AU - Dhalla, Fatima

AU - Farmaki, Evangelia

AU - Speckmann, Carsten

AU - Español, Teresa

AU - Shcherbina, Anna

AU - Hanson, Imelda Celine

AU - Litzman, Jiri

AU - Routes, John M.

AU - Wong, Melanie

AU - Fuleihan, Ramsay

AU - Seneviratne, Suranjith L.

AU - Small, Trudy N.

AU - Janda, Ales

AU - Bezrodnik, Liliana

AU - Seger, Reinhard

AU - Raccio, Andrea Gomez

AU - Edgar, J. David M

AU - Chou, Janet

AU - Abbott, Jordan K.

AU - van Montfrans, Joris

AU - González-Granado, Luis Ignacio

AU - Bunin, Nancy

AU - Kutukculer, Necil

AU - Gray, Paul

AU - Seminario, Gisela

AU - Pasic, Srdjan

AU - Aquino, Victor

AU - Wysocki, Christian

AU - Abolhassani, Hassan

AU - Dorsey, Morna

AU - Cunningham-Rundles, Charlotte

AU - Knutsen, Alan P.

AU - Sleasman, John

AU - Costa Carvalho, Beatriz Tavares

AU - Condino-Neto, Antonio

AU - Grunebaum, Eyal

AU - Chapel, Helen

AU - Ochs, Hans D.

AU - Filipovich, Alexandra

AU - Cowan, Mort

AU - Gennery, Andrew

AU - Cant, Andrew

AU - Notarangelo, Luigi D.

AU - Roifman, Chaim M.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Background X-linked hyper-IgM syndrome (XHIGM) is a primary immunodeficiency with high morbidity and mortality compared with those seen in healthy subjects. Hematopoietic cell transplantation (HCT) has been considered a curative therapy, but the procedure has inherent complications and might not be available for all patients. Objectives We sought to collect data on the clinical presentation, treatment, and follow-up of a large sample of patients with XHIGM to (1) compare long-term overall survival and general well-being of patients treated with or without HCT along with clinical factors associated with mortality and (2) summarize clinical practice and risk factors in the subgroup of patients treated with HCT. Methods Physicians caring for patients with primary immunodeficiency diseases were identified through the Jeffrey Modell Foundation, United States Immunodeficiency Network, Latin American Society for Immunodeficiency, and Primary Immune Deficiency Treatment Consortium. Data were collected with a Research Electronic Data Capture Web application. Survival from time of diagnosis or transplantation was estimated by using the Kaplan-Meier method compared with log-rank tests and modeled by using proportional hazards regression. Results Twenty-eight clinical sites provided data on 189 patients given a diagnosis of XHIGM between 1964 and 2013; 176 had valid follow-up and vital status information. Sixty-seven (38%) patients received HCT. The average follow-up time was 8.5 ± 7.2 years (range, 0.1-36.2 years). No difference in overall survival was observed between patients treated with or without HCT (P = .671). However, risk associated with HCT decreased for diagnosis years 1987-1995; the hazard ratio was significantly less than 1 for diagnosis years 1995-1999. Liver disease was a significant predictor of overall survival (hazard ratio, 4.9; 95% confidence limits, 2.2-10.8; P < .001). Among survivors, those treated with HCT had higher median Karnofsky/Lansky scores than those treated without HCT (P < .001). Among patients receiving HCT, 27 (40%) had graft-versus-host disease, and most deaths occurred within 1 year of transplantation. Conclusion No difference in survival was observed between patients treated with or without HCT across all diagnosis years (1964-2013). However, survivors treated with HCT experienced somewhat greater well-being, and hazards associated with HCT decreased, reaching levels of significantly less risk in the late 1990s. Among patients treated with HCT, treatment at an early age is associated with improved survival. Optimism remains guarded as additional evidence accumulates.

AB - Background X-linked hyper-IgM syndrome (XHIGM) is a primary immunodeficiency with high morbidity and mortality compared with those seen in healthy subjects. Hematopoietic cell transplantation (HCT) has been considered a curative therapy, but the procedure has inherent complications and might not be available for all patients. Objectives We sought to collect data on the clinical presentation, treatment, and follow-up of a large sample of patients with XHIGM to (1) compare long-term overall survival and general well-being of patients treated with or without HCT along with clinical factors associated with mortality and (2) summarize clinical practice and risk factors in the subgroup of patients treated with HCT. Methods Physicians caring for patients with primary immunodeficiency diseases were identified through the Jeffrey Modell Foundation, United States Immunodeficiency Network, Latin American Society for Immunodeficiency, and Primary Immune Deficiency Treatment Consortium. Data were collected with a Research Electronic Data Capture Web application. Survival from time of diagnosis or transplantation was estimated by using the Kaplan-Meier method compared with log-rank tests and modeled by using proportional hazards regression. Results Twenty-eight clinical sites provided data on 189 patients given a diagnosis of XHIGM between 1964 and 2013; 176 had valid follow-up and vital status information. Sixty-seven (38%) patients received HCT. The average follow-up time was 8.5 ± 7.2 years (range, 0.1-36.2 years). No difference in overall survival was observed between patients treated with or without HCT (P = .671). However, risk associated with HCT decreased for diagnosis years 1987-1995; the hazard ratio was significantly less than 1 for diagnosis years 1995-1999. Liver disease was a significant predictor of overall survival (hazard ratio, 4.9; 95% confidence limits, 2.2-10.8; P < .001). Among survivors, those treated with HCT had higher median Karnofsky/Lansky scores than those treated without HCT (P < .001). Among patients receiving HCT, 27 (40%) had graft-versus-host disease, and most deaths occurred within 1 year of transplantation. Conclusion No difference in survival was observed between patients treated with or without HCT across all diagnosis years (1964-2013). However, survivors treated with HCT experienced somewhat greater well-being, and hazards associated with HCT decreased, reaching levels of significantly less risk in the late 1990s. Among patients treated with HCT, treatment at an early age is associated with improved survival. Optimism remains guarded as additional evidence accumulates.

KW - CD40 ligand

KW - Karnofsky/Lansky scores

KW - X-linked hyper-IgM syndrome

KW - defects in class-switch recombination

KW - hematopoietic cell transplantation

KW - long-term outcomes

KW - primary immunodeficiency

UR - http://www.scopus.com/inward/record.url?scp=85006809816&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85006809816&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2016.07.039

DO - 10.1016/j.jaci.2016.07.039

M3 - Article

VL - 139

SP - 1282

EP - 1292

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 4

ER -