Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency.

نویسندگان

  • Amel Hassan
  • Claire Booth
  • Alex Brightwell
  • Zoe Allwood
  • Paul Veys
  • Kanchan Rao
  • Manfred Hönig
  • Wilhelm Friedrich
  • Andrew Gennery
  • Mary Slatter
  • Robbert Bredius
  • Andrea Finocchi
  • Caterina Cancrini
  • Alessandro Aiuti
  • Fulvio Porta
  • Arnalda Lanfranchi
  • Michela Ridella
  • Colin Steward
  • Alexandra Filipovich
  • Rebecca Marsh
  • Victoria Bordon
  • Saleh Al-Muhsen
  • Hamoud Al-Mousa
  • Zobaida Alsum
  • Hasan Al-Dhekri
  • Abdulaziz Al Ghonaium
  • Carsten Speckmann
  • Alain Fischer
  • Nizar Mahlaoui
  • Kim E Nichols
  • Eyal Grunebaum
  • Daifulah Al Zahrani
  • Chaim M Roifman
  • Jaap Boelens
  • E Graham Davies
  • Marina Cavazzana-Calvo
  • Luigi Notarangelo
  • H Bobby Gaspar
چکیده

Deficiency of the purine salvage enzyme adenosine deaminase leads to SCID (ADA-SCID). Hematopoietic cell transplantation (HCT) can lead to a permanent cure of SCID; however, little data are available on outcome of HCT for ADA-SCID in particular. In this multicenter retrospective study, we analyzed outcome of HCT in 106 patients with ADA-SCID who received a total of 119 transplants. HCT from matched sibling and family donors (MSDs, MFDs) had significantly better overall survival (86% and 81%) in comparison with HCT from matched unrelated (66%; P < .05) and haploidentical donors (43%; P < .001). Superior overall survival was also seen in patients who received unconditioned transplants in comparison with myeloablative procedures (81% vs 54%; P < .003), although in unconditioned haploidentical donor HCT, nonengraftment was a major problem. Long-term immune recovery showed that regardless of transplant type, overall T-cell numbers were similar, although a faster rate of T-cell recovery was observed after MSD/MFD HCT. Humoral immunity and donor B-cell engraftment was achieved in nearly all evaluable surviving patients and was seen even after unconditioned HCT. These data detail for the first time the outcomes of HCT for ADA-SCID and show that, if patients survive HCT, long-term cellular and humoral immune recovery is achieved.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

HCT survival in ADA-SCID: what's the buzz?

In this issue of Blood, Hassan et al have turned the spotlight on hematopoietic stem cell transplantation (HCT) of adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID). They opened up the curtain of beliefs on this therapy that enables facts to be separated from fiction.

متن کامل

A 24-Year Enzyme Replacement Therapy in an Adenosine-deaminase-Deficient Patient.

Severe combined immunodeficiency (SCID) is a fatal childhood disease unless immune reconstitution is performed early in life, with either hematopoietic stem cell transplantation or gene therapy. One of its subtypes is caused by adenosine deaminase (ADA) enzyme deficiency, which leads to the accumulation of toxic metabolites that impair lymphocyte development and function. With the development o...

متن کامل

Patients with adenosine deaminase deficiency surviving after hematopoietic stem cell transplantation are at high risk of CNS complications.

Adenosine deaminase (ADA) deficiency is a systemic metabolic disease that causes an autosomal recessive variant of severe combined immunodeficiency (SCID) and less consistently other complications including neurologic abnormalities. Hematopoietic stem cell transplantation (HSCT) is able to correct the immunodeficiency, whereas control of nonimmunologic complications has not been extensively exp...

متن کامل

First Occurrence of Plasmablastic Lymphoma in Adenosine Deaminase-Deficient Severe Combined Immunodeficiency Disease Patient and Review of the Literature

Adenosine deaminase-deficient severe combined immunodeficiency disease (ADA-SCID) is a primary immune deficiency characterized by mutations in the ADA gene resulting in accumulation of toxic compounds affecting multiple districts. Hematopoietic stem cell transplantation (HSCT) from a matched donor and hematopoietic stem cell gene therapy are the preferred options for definitive treatment. Enzym...

متن کامل

Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans.

We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34(+) cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (mont...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Blood

دوره 120 17  شماره 

صفحات  -

تاریخ انتشار 2012