Hematopoietic stem cell transplantation in patients with gain-of-function signal transducer and activator of transcription 1 mutations
Por:
Leiding, JW, Okada, S, Hagin, D, Abinun, M, Shcherbina, A, Balashov, DN, Kim, VHD, Ovadia, A, Guthery, SL, Pulsipher, M, Lilic, D, Devlin, LA, Christie, S, Depner, M, Fuchs, S, van Royen-Kerkhof, A, Lindemans, C, Petrovic, A, Sullivan, KE, Bunin, N, Kilic, SS, Arpaci, F, de la Calle-Martin, O, Martinez-Martinez, L, Aldave, JC, Kobayashi, M, Ohkawa, T, Imai, K, Iguchi, A, Roifman, CM, Gennery, AR, Slatter, M, Ochs, HD, Morio, T, Torgerson, TR, Inborn Errors Working Party, European Soc Blood Marrow, Primary Immune Deficiency
Publicada:
1 feb 2018
Resumen:
Background: Gain-of-function (GOF) mutations in signal transducer and activator of transcription 1 (STAT1) cause susceptibility to a range of infections, autoimmunity, immune dysregulation, and combined immunodeficiency. Disease manifestations can be mild or severe and life-threatening. Hematopoietic stem cell transplantation (HSCT) has been used in some patients with more severe symptoms to treat and cure the disorder. However, the outcome of HSCT for this disorder is not well established.
Objective: We sought to aggregate the worldwide experience of HSCT in patients with GOF-STAT1 mutations and to assess outcomes, including donor engraftment, overall survival, graft-versus-host disease, and transplant-related complications.
Methods: Data were collected from an international cohort of 15 patients with GOF-STAT1 mutations who had undergone HSCT-using a variety of conditioning regimens and donor sources. Retrospective data collection allowed the outcome of transplantation to be assessed. In vitro functional testing was performed to confirm that each of the identified STAT1 variants was in fact a GOF mutation.
Results: Primary donor engraftment in this cohort of 15 patients with GOF-STAT1 mutations was 74%, and overall survival was only 40%. Secondary graft failure was common (50%), and posttransplantation event-free survival was poor (10% by 100 days). Asubset of patients had hemophagocytic lymphohistiocytosis before transplant, contributing to their poor outcomes.
Conclusion: Our data indicate that HSCT for patients with GOF-STAT1 mutations is curative but has significant risk of secondary graft failure and death.
Filiaciones:
Leiding, JW:
Univ South Florida Johns Hopkins, All Childrens Hosp, Dept Pediat, Div Allergy & Immunol, St Petersburg, FL USA
Okada, S:
Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Pediat, Hiroshima, Japan
Hagin, D:
Univ Washington, Dept Pediat, Seattle, WA 98195 USA
Seattle Childrens Res Inst, 1900 9th Ave,JMB 7, Seattle, WA 98101 USA
Abinun, M:
Great North Childrens Hosp, RVI, Newcastle Upon Tyne, Tyne & Wear, England
Newcastle Univ, ICM, Primary Immunodeficiency Grp, Newcastle Upon Tyne, Tyne & Wear, England
Shcherbina, A:
Fed Res & Clin Ctr Pediat Hematol Oncol & Immunol, Moscow, Russia
Balashov, DN:
Fed Res & Clin Ctr Pediat Hematol Oncol & Immunol, Moscow, Russia
Kim, VHD:
Hosp Sick Children, Canadian Ctr Primary Immunodeficiency, Toronto, ON, Canada
Ovadia, A:
Hosp Sick Children, Canadian Ctr Primary Immunodeficiency, Toronto, ON, Canada
Guthery, SL:
Univ Utah, Dept Pediat, Div Pediat Gastroenterol Hepatol & Nutr, Salt Lake City, UT USA
Pulsipher, M:
Univ Southern Calif, Keck Sch Med, Childrens Hosp Los Angeles, Div Hematol Oncol & Blood & Marrow Transplantat, Los Angeles, CA USA
Lilic, D:
Newcastle Univ, ICM, Primary Immunodeficiency Grp, Newcastle Upon Tyne, Tyne & Wear, England
Devlin, LA:
Royal Hosp, Reg Immunol Serv, Belfast, Antrim, North Ireland
Christie, S:
Royal Hosp, Dept Pediat, Belfast, Antrim, North Ireland
Depner, M:
Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Freiburg, Germany
Univ Freiburg, Freiburg, Germany
Fuchs, S:
Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Freiburg, Germany
Univ Freiburg, Freiburg, Germany
van Royen-Kerkhof, A:
Univ Med Ctr Utrecht, Pediat Blood & Marrow Transplantat Program, Utrecht, Netherlands
Lindemans, C:
Univ Med Ctr Utrecht, Pediat Blood & Marrow Transplantat Program, Utrecht, Netherlands
Petrovic, A:
Univ Washington, Dept Pediat, Seattle, WA 98195 USA
Seattle Childrens Res Inst, 1900 9th Ave,JMB 7, Seattle, WA 98101 USA
All Childrens Hosp, Johns Hopkins Med, Blood & Bone Marrow Transplant Program, St Petersburg, FL USA
Sullivan, KE:
Univ Penn, Dept Pediat, Perelman Sch Med, Div Allergy & Immunol, Philadelphia, PA 19104 USA
Bunin, N:
Univ Penn, Dept Pediat, Perelman Sch Med, Div Oncol, Philadelphia, PA 19104 USA
Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA
Kilic, SS:
Uludag Univ, Med Fac, Dept Pediat, Div Pediat Immunol, Gorukle, Turkey
Arpaci, F:
GATA Fac, Bone Marrow Transplant Ctr, Ankara, Turkey
de la Calle-Martin, O:
Hosp Santa Creu & Sant Pau, Dept Immunol, Barcelona, Spain
Martinez-Martinez, L:
Hosp Santa Creu & Sant Pau, Dept Immunol, Barcelona, Spain
Aldave, JC:
Hosp Rebagliati, Allergy & Immunol, Lima, Peru
Kobayashi, M:
Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Pediat, Hiroshima, Japan
Ohkawa, T:
Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Pediat & Dev Biol, Tokyo, Japan
Imai, K:
Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Pediat & Dev Biol, Tokyo, Japan
Iguchi, A:
Hokkaido Univ, Grad Sch Med, Dept Pediat, Sapporo, Hokkaido, Japan
Roifman, CM:
Hosp Sick Children, Canadian Ctr Primary Immunodeficiency, Toronto, ON, Canada
Gennery, AR:
Great North Childrens Hosp, RVI, Newcastle Upon Tyne, Tyne & Wear, England
Newcastle Univ, ICM, Primary Immunodeficiency Grp, Newcastle Upon Tyne, Tyne & Wear, England
Slatter, M:
Great North Childrens Hosp, RVI, Newcastle Upon Tyne, Tyne & Wear, England
Newcastle Univ, ICM, Primary Immunodeficiency Grp, Newcastle Upon Tyne, Tyne & Wear, England
Ochs, HD:
Univ Washington, Dept Pediat, Seattle, WA 98195 USA
Seattle Childrens Res Inst, 1900 9th Ave,JMB 7, Seattle, WA 98101 USA
Morio, T:
Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Pediat & Dev Biol, Tokyo, Japan
Torgerson, TR:
Univ Washington, Dept Pediat, Seattle, WA 98195 USA
Seattle Childrens Res Inst, 1900 9th Ave,JMB 7, Seattle, WA 98101 USA
Bronze, Green Accepted
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