PMID- 27438785
OWN - NLM
STAT- MEDLINE
DCOM- 20171207
LR  - 20220801
IS  - 1573-2592 (Electronic)
IS  - 0271-9142 (Linking)
VI  - 36
IP  - 7
DP  - 2016 Oct
TI  - Long-Term Outcomes of Hematopoietic Stem Cell Transplantation for ZAP70 
      Deficiency.
PG  - 713-24
LID - 10.1007/s10875-016-0316-z [doi]
AB  - ZAP70 deficiency is a rare T + B + NK+ combined immunodeficiency with limited 
      outcome data to help guide decisions around hematopoietic stem cell transplant 
      (HSCT). We sought to understand the long-term clinical and immunologic outcomes 
      of both conditioned and unconditioned HSCT for ZAP70 deficiency following 
      transplant from a variety of graft sources. We performed a retrospective, single 
      center review of all cases of HSCT for genetically confirmed ZAP70 deficiency 
      since 1992. At a median of 13.5-year post-HSCT, 8/8 (100 %) patients are alive. 
      Three received unconditioned bone marrow transplants from human leukocyte antigen 
      (HLA)-matched siblings and achieved stable mixed donor-recipient T cell chimerism 
      but low B cell (4-9 %) and absent to near-absent myeloid donor engraftment. 
      Despite this, all three have normal immunoglobulin levels, have developed 
      specific protective antibody responses to post-HSCT vaccinations, and have 
      discontinued immunoglobulin replacement. Five patients received myeloablative 
      conditioning (three T cell-depleted haploidentical and two unrelated cord blood) 
      and have full donor chimerism for T and B cells and myeloid lineages. One patient 
      experienced primary graft failure after serotherapy only. CD8 T cell count is 
      normal in 5/8, high in 1/8, and low in 2/8. Infectious complications in 5/5 and 
      autoimmune thrombocytopenia in one patient resolved post-HSCT. Mitogen 
      proliferation to phytohemagglutinin was normal after HSCT in 8/8 patients. In 
      total, seven have discontinued immunoglobulin replacement. In conclusion, HSCT 
      using a variety of graft sources and approaches, including unconditioned matched 
      sibling donor transplant, is a life-saving therapy for ZAP70 deficiency, 
      providing excellent long-term immune function and resolution of clinical 
      problems.
FAU - Cuvelier, Geoffrey D E
AU  - Cuvelier GD
AD  - Manitoba Blood and Marrow Transplant Program, Division of Pediatric 
      Hematology-Oncology, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, 
      Manitoba, Canada. gcuvelier@cancercare.mb.ca.
AD  - Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, 
      Manitoba, Canada. gcuvelier@cancercare.mb.ca.
AD  - CancerCare Manitoba, ON2011-675 McDermot Avenue, Winnipeg, Manitoba, R3E 0V9, 
      Canada. gcuvelier@cancercare.mb.ca.
FAU - Rubin, Tamar S
AU  - Rubin TS
AD  - Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, 
      Manitoba, Canada.
AD  - Division of Allergy and Clinical Immunology, University of Manitoba, Winnipeg, 
      Manitoba, Canada.
FAU - Wall, Donna A
AU  - Wall DA
AD  - Manitoba Blood and Marrow Transplant Program, Division of Pediatric 
      Hematology-Oncology, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, 
      Manitoba, Canada.
AD  - Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, 
      Manitoba, Canada.
FAU - Schroeder, Marlis L
AU  - Schroeder ML
AD  - Manitoba Blood and Marrow Transplant Program, Division of Pediatric 
      Hematology-Oncology, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, 
      Manitoba, Canada.
AD  - Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, 
      Manitoba, Canada.
LA  - eng
PT  - Journal Article
DEP - 20160720
PL  - Netherlands
TA  - J Clin Immunol
JT  - Journal of clinical immunology
JID - 8102137
RN  - 0 (Biomarkers)
RN  - EC 2.7.10.2 (ZAP-70 Protein-Tyrosine Kinase)
RN  - ZAP70 deficiency
SB  - IM
MH  - Biomarkers
MH  - Child, Preschool
MH  - Female
MH  - Follow-Up Studies
MH  - Graft vs Host Disease/etiology/prevention & control
MH  - *Hematopoietic Stem Cell Transplantation/adverse effects/methods
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Lymphocyte Count
MH  - Male
MH  - Mutation
MH  - Phenotype
MH  - Severe Combined Immunodeficiency/diagnosis/*therapy
MH  - T-Lymphocytes/immunology/metabolism
MH  - Time Factors
MH  - Transplantation Conditioning
MH  - Transplantation, Homologous
MH  - Treatment Outcome
MH  - ZAP-70 Protein-Tyrosine Kinase/*deficiency
OTO - NOTNLM
OT  - T+ SCID
OT  - ZAP70 deficiency
OT  - atypical SCID
OT  - hematopoietic stem cell transplant
OT  - leaky SCID
EDAT- 2016/07/21 06:00
MHDA- 2017/12/08 06:00
CRDT- 2016/07/21 06:00
PHST- 2016/04/18 00:00 [received]
PHST- 2016/07/07 00:00 [accepted]
PHST- 2016/07/21 06:00 [entrez]
PHST- 2016/07/21 06:00 [pubmed]
PHST- 2017/12/08 06:00 [medline]
AID - 10.1007/s10875-016-0316-z [pii]
AID - 10.1007/s10875-016-0316-z [doi]
PST - ppublish
SO  - J Clin Immunol. 2016 Oct;36(7):713-24. doi: 10.1007/s10875-016-0316-z. Epub 2016 
      Jul 20.