Aydin, Susanne E.; Freeman, Alexandra F.; Al-Herz, Waleed; Al-Mousa, Hamoud A.; Arnaout, Rand K.; Aydin, Roland C.; Barlogis, Vincent; Belohradsky, Bernd H.; Bonfim, Carmem; Bredius, Robbert G.; Chu, Julia I.; Ciocarlie, Oana C.; Dogu, Figen; Gaspar, Hubert B.; Geha, Raif S.; Gennery, Andrew R.; Hauck, Fabian; Hawwari, Abbas; Hickstein, Dennis D.; Hönig, Manfred; Ikinciogullari, Aydan; Klein, Christoph; Kumar, Ashish; Ifversen, Marianne R. S.; Matthes, Susanne; Metin, Ayse; Neven, Benedicte; Pai, Sung-Yun; Parikh, Suhag H.; Picard, Capucine; Renner, Ellen D.; Sanal, Özden; Schulz, Ansgar S.; Schuster, Friedhelm; Shah, Nirali N.; Shereck, Evan B.; Slatter, Mary A.; Su, Helen C.; Montfrans, Joris van; Woessmann, Wilhelm; Ziegler, John B.; Albert, Michael H. (2018): Hematopoietic stem cell transplantation as treatment for patients with DOCK8 deficiency. In: Journal of Allergy and Clinical Immunology |
Abstract
BACKGROUND: Biallelic variations in the DOCK8 gene cause a combined immunodeficiency with eczema, recurrent bacterial and viral infections, and malignancy. Natural disease outcome is dismal, but allogeneic hematopoietic stem cell transplantation (HSCT) can cure the disease. OBJECTIVE: To determine outcome of HSCT for DOCK8 deficiency and define possible outcome variables. METHODS: We performed a retrospective study of the results of HSCT in a large international cohort of DOCK8 deficient patients. RESULTS: We identified 81 patients from 22 centers transplanted at a median age of 9.7 years (range: 0.7-27.2) between 1995 and 2015. After median follow-up of 26 months (3-135), 68 of 81 patients are alive (84%). Severe acute (III-IV) or chronic graft versus host disease (GVHD) occurred in 11% and 10% respectively. Causes of death wereinfections (n=5), GVHD (5), multi-organ failure (2) and pre-existent lymphoma (1). Survival after matched related (n=40) or unrelated (35) HSCT was 89% and 81%, respectively. Reduced toxicity conditioning based on either treosulfan or reduced-dose busulfan resulted in superior survival compared to fully myeloablative busulfan-based regimens (97% vs. 78%; p=0.049). 96% of patients aged <8 years at HSCT survived, compared to 78% of those >=8 years (p=0.06). Of 73 patients with chimerism data available, 65 (89%) had >90% donor T-cell chimerism at last follow-up. Not all disease manifestations responded equally well to HSCT: eczema, infections and Mollusca resolved better than food allergies or failure to thrive. CONCLUSION: HSCT is curative in most DOCK8 deficient patients, confirming this approach as the treatment of choice. HSCT using a reduced toxicity regimen may offer the best chance for survival.
Item Type: | Journal article |
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Faculties: | Medicine > Medical Center of the University of Munich > Pediatric Clinic and Outpatient Clinic in the Dr. von Hauner Children‘s Hospital |
Subjects: | 600 Technology > 610 Medicine and health |
ISSN: | 0091-6749 |
Language: | German |
ID Code: | 59388 |
Deposited On: | 07. Dec 2018 10:26 |
Last Modified: | 04. Nov 2020 13:38 |
- BASE
- Aydin, Susanne E.
- Freeman, Alexandra F.
- Al-Herz, Waleed
- Al-Mousa, Hamoud A.
- Arnaout, Rand K.
- Aydin, Roland C.
- Barlogis, Vincent
- Belohradsky, Bernd H.
- Bonfim, Carmem
- Bredius, Robbert G.
- Chu, Julia I.
- Ciocarlie, Oana C.
- Dogu, Figen
- Gaspar, Hubert B.
- Geha, Raif S.
- Gennery, Andrew R.
- Hauck, Fabian
- Hawwari, Abbas
- Hickstein, Dennis D.
- Hönig, Manfred
- Ikinciogullari, Aydan
- Klein, Christoph
- Kumar, Ashish
- Ifversen, Marianne R. S.
- Matthes, Susanne
- Metin, Ayse
- Neven, Benedicte
- Pai, Sung-Yun
- Parikh, Suhag H.
- Picard, Capucine
- Renner, Ellen D.
- Sanal, Özden
- Schulz, Ansgar S.
- Schuster, Friedhelm
- Shah, Nirali N.
- Shereck, Evan B.
- Slatter, Mary A.
- Su, Helen C.
- Montfrans, Joris van
- Woessmann, Wilhelm
- Ziegler, John B.
- Albert, Michael H.
- Google Scholar
- Aydin, Susanne E.
- Freeman, Alexandra F.
- Al-Herz, Waleed
- Al-Mousa, Hamoud A.
- Arnaout, Rand K.
- Aydin, Roland C.
- Barlogis, Vincent
- Belohradsky, Bernd H.
- Bonfim, Carmem
- Bredius, Robbert G.
- Chu, Julia I.
- Ciocarlie, Oana C.
- Dogu, Figen
- Gaspar, Hubert B.
- Geha, Raif S.
- Gennery, Andrew R.
- Hauck, Fabian
- Hawwari, Abbas
- Hickstein, Dennis D.
- Hönig, Manfred
- Ikinciogullari, Aydan
- Klein, Christoph
- Kumar, Ashish
- Ifversen, Marianne R. S.
- Matthes, Susanne
- Metin, Ayse
- Neven, Benedicte
- Pai, Sung-Yun
- Parikh, Suhag H.
- Picard, Capucine
- Renner, Ellen D.
- Sanal, Özden
- Schulz, Ansgar S.
- Schuster, Friedhelm
- Shah, Nirali N.
- Shereck, Evan B.
- Slatter, Mary A.
- Su, Helen C.
- Montfrans, Joris van
- Woessmann, Wilhelm
- Ziegler, John B.
- Albert, Michael H.