Nonmyeloablative hematopoietic stem cell transplantation corrects the disease phenotype in the canine model of leukocyte adhesion deficiency

2005 ◽  
Vol 33 (6) ◽  
pp. 706-712 ◽  
Author(s):  
Thomas R. Bauer Jr. ◽  
Yu-chen Gu ◽  
Laura M. Tuschong ◽  
Tanya Burkholder ◽  
John D. Bacher ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Leukocyte Adhesion ◽  
Canine Model ◽  
Disease Phenotype ◽  
Leukocyte Adhesion Deficiency ◽  
Hematopoietic Stem

Very low levels of donor CD18+ neutrophils following allogeneic hematopoietic stem cell transplantation reverse the disease phenotype in canine leukocyte adhesion deficiency

Blood ◽  
2004 ◽  
Vol 103 (9) ◽  
pp. 3582-3589 ◽  
Author(s):  
Thomas R. Bauer ◽  
Kate E. Creevy ◽  
Yu-chen Gu ◽  
Laura M. Tuschong ◽  
Robert E. Donahue ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Leukocyte Adhesion ◽  
Disease Phenotype ◽  
Leukocyte Adhesion Deficiency ◽  
Hematopoietic Stem ◽  
Donor Chimerism

Abstract Children with the severe phenotype of the genetic immunodeficiency disease leukocyte adhesion deficiency or LAD experience life-threatening bacterial infections because of molecular defects in the leukocyte integrin CD18 molecule and the resultant failure to express the CD11/CD18 adhesion molecules on the leukocyte surface. Hematopoietic stem cell transplantation remains the only definitive therapy for LAD; however, the degree of donor chimerism and particularly the number of CD18+ donor-derived neutrophils required to reverse the disease phenotype are not known. We performed nonmyeloablative hematopoietic stem cell transplantations from healthy matched littermates in 9 dogs with the canine form of LAD known as CLAD and demonstrate that in the 3 dogs with the lowest level of donor chimerism, less than 500 CD18+ donor-derived neutrophils/μL in the peripheral blood of the CLAD recipients resulted in reversal of the CLAD disease phenotype. These results demonstrate the value of a disease-specific, large-animal model for identifying the lowest therapeutic level required for successful cellular and gene therapy. (Blood. 2004;103:3582-3589)

scholarly journals Reproductive capability in dogs with canine leukocyte adhesion deficiency treated with nonmyeloablative conditioning prior to allogeneic hematopoietic stem cell transplantation

Blood ◽  
2006 ◽  
Vol 108 (5) ◽  
pp. 1767-1769 ◽  
Author(s):  
Tanya H. Burkholder ◽  
Lyn Colenda ◽  
Laura M. Tuschong ◽  
Matthew F. Starost ◽  
Thomas R. Bauer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Leukocyte Adhesion ◽  
Reproductive Function ◽  
Leukocyte Adhesion Deficiency ◽  
Hematopoietic Stem ◽  
Conditioning Regimens

Nonmyeloablative conditioning regimens are increasingly replacing myeolablative conditioning prior to allogeneic hematopoietic stem cell transplantation (SCT). The recent advent of these conditioning regimens has limited the assessment of the long-term effects of this treatment, including analysis of reproductive function. To address the question of reproductive function after nonmyeloablative transplantation, we analyzed a cohort of young dogs with the genetic disease canine leukocyte adhesion deficiency that were treated with a nonmyeloablative dose of 200 cGy total body irradiation followed by matched-littermate SCT. Five males and 5 females entered puberty; all 5 males and 4 females subsequently sired or delivered litters following transplantation. We demonstrate that fertility is intact and dogs have uncomplicated parturitions following nonmyeloablative conditioning for SCT. These results are encouraging for children and adults of childbearing age who receive similar conditioning regimens prior to allogeneic transplantation.

scholarly journals Allogeneic Hematopoietic Stem-Cell Transplantation for Leukocyte Adhesion Deficiency

PEDIATRICS ◽  
2009 ◽  
Vol 123 (3) ◽  
pp. 836-840 ◽  
Author(s):  
W. Qasim ◽  
M. Cavazzana-Calvo ◽  
E. G. Davies ◽  
J. Davis ◽  
M. Duval ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Leukocyte Adhesion ◽  
Leukocyte Adhesion Deficiency ◽  
Hematopoietic Stem

Correction of the murine Wiskott-Aldrich syndrome phenotype by hematopoietic stem cell transplantation

Blood ◽  
2002 ◽  
Vol 99 (12) ◽  
pp. 4626-4628 ◽  
Author(s):  
Ted S. Strom ◽  
Xiuling Li ◽  
John M. Cunningham ◽  
Arthur W. Nienhuis
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Disease Phenotype ◽  
Hematopoietic Stem ◽  
Wiskott Aldrich Syndrome ◽  
Radiation Induced ◽  
Deficient Mice

Allogeneic hematopoietic stem cell transplantation (HSCT) corrects the Wiskott-Aldrich syndrome (WAS) phenotype. However, the toxicity and mortality frequently associated with this approach warrant the exploration of new therapeutic strategies. Transplantation studies of a murine model of WAS deficiency have been limited by the occurrence of a radiation-induced fatal exacerbation of a pre-existing colitis in the peritransplantation period. Here we demonstrate that when crossed to a C57/B6 background, WAS-deficient males show little if any colitis and reliably survive HSCT. We show that HSCT corrects the hematologic and functional deficiencies of WAS knockout mice. These results strengthen the analogy between murine and human WAS and provide a basis for the use of WAS-deficient mice to explore novel approaches for correction of the disease phenotype.

scholarly journals Long-term management of leukocyte adhesion deficiency type III without hematopoietic stem cell transplantation

Haematologica ◽  
2018 ◽  
Vol 103 (6) ◽  
pp. e264-e267 ◽  
Author(s):  
Paul Saultier ◽  
Sarah Szepetowski ◽  
Matthias Canault ◽  
Céline Falaise ◽  
Marjorie Poggi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Leukocyte Adhesion ◽  
Leukocyte Adhesion Deficiency ◽  
Hematopoietic Stem ◽  
Deficiency Type ◽  
Term Management
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