Unrelated partially matched peripheral blood stem cell transplantation with highly purified CD34+ cells in a child with Wiskott–Aldrich syndrome

Schwinger, Wolfgang; Urban, Ch.; Lackner, Herwig; Kerbl, Reinhold; Benesch, Martin; Dornbusch, HJ; Sovinz, Petra; Schumm, Michael; Handgretinger, Rupert

doi:10.1038/sj.bmt.1702473

Cited by 4 publications

(3 citation statements)

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“…Stable host–recipient chimaerism is acceptable, as long as there are sufficient donor cells for normal function. Therefore non‐myeloablative transplantation is particularly appropriate for patients, such as ours, with non‐malignant conditions (Amrolia et al , 2000; Schwinger et al , 2000).…”

Section: Discussionmentioning

confidence: 99%

Non‐myeloablative bone marrow transplantation in an adult with Wiskott–Aldrich syndrome

Longhurst¹,

Taussig

Haque

et al. 2002

Br J Haematol

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Summary. Early bone marrow transplant is now standard treatment for infants with severe immunode®ciencies such as Wiskott±Aldrich Syndrome (WAS), but results in older children and adults are poor. Non-myeloablative transplant has shown promise in the treatment of older children, who are likely to have active infections and organ damage. We describe a non-myeloablative transplant of a 26-year-old man with WAS, undertaken because of severe infections and vasculitis. Partial engraftment and immunorestoration were achieved. The patient is well 1 year post transplantation.Keywords: immunological de®ciency syndromes, Wiskott± Aldrich syndrome, vasculitis, bone marrow transplantation, transplantation chimaera.A 26-year-old man with Wiskott±Aldrich Syndrome (WAS) had recurrent bacterial respiratory tract infections and bronchiectasis, despite intravenous immunoglobulin (i.v. Ig) replacement. Two years previously, he had undergone splenectomy to treat life-threatening thrombocytopenia and had subsequently developed antineutrophil cytoplasmic antibody (ANCA)-negative necrotizing vasculitis. Smalland medium-sized arteries of the intestinal tract and kidneys were affected, with aneurysmal dilatation and massive haemorrhage. Corticosteroids (prednisolone 30 mg/d) and cyclophosphamide (50 mg´3/d) were required. Full details have previously been published (McCluggage et al, 1999). At the age of 25 years, he suffered Pneumocystis pneumonia, requiring ventilatory support.Because of severe immunode®ciency and high risk of Epstein±Barr virus (EBV)-related malignancy, conferred by WAS and cyclophosphamide treatment, the patient was assessed for bone marrow transplantation. There was no suitable related donor but an unrelated donor, mismatched at a single Cw locus, was available. Computerized tomography of the lungs con®rmed severe bronchiectasis.Because of frequent infections and pre-existing lung damage, we felt that conditioning associated with conventional regimens would not be tolerated. Therefore the patient was conditioned according to a non-myeloablative protocol, namely anti-CD52 (CAMPATH-1H, 10 mg, d )10 to )6),¯udarabine (25 mg/m 2 , d )6 to )2) and cyclophosphamide (1 g/m 2 , d )3 and )2 with MESNA). The donor was EBV seropositive and the patient EBV indeterminate, as he was receiving i.v. Ig. EBV-speci®c cytotoxic T-lymphocytes were generated in vitro from the bone marrow donor, for use in case of EBV-associated lymphoproliferation (Haque & Crawford, 1999). The transplant (d 0) was red cell-depleted bone marrow; 1´10 6 CD34 + cells/kg recipient weight. Cyclosporine was given from d )1 for graftversus-host prophylaxis.Penicillin V, cotrimoxazole and i.v. Ig (at an increased dose of 0á4 g/kg weekly) were continued. Valaciclovir, itraconazole, cipro¯oxacin and colistin were commenced as viral, fungal and bacterial prophylaxis respectively. RESULTSThere was early regeneration of all cell lines with neutrophil numbers above 1´10 9 /l at d 8. However, invasive bacterial infections occurred from the day of the transplant. Infe...

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Section: Discussionmentioning

confidence: 99%

Non‐myeloablative bone marrow transplantation in an adult with Wiskott–Aldrich syndrome

Longhurst¹,

Taussig

Haque

et al. 2002

Br J Haematol

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“…These reports show a high incidence of graft failure and poor immune reconstitution following T cell-depleted haploidentical HSCTs. Schwinger, et al provided a promising case report of "megadose" purified CD34 + haploidentical grafts used to overcome the barrier to engraftment without endangering GVHD [12]. Our convenient results in this patient in a way that supports the results of Schwinger, et al can encourage further investigation of the role of using 'high doses' of related haploidentical CD34-selected peripheral blood stem cells in patients with WAS at early stages of disease before the beginning of severe, life-threatening complications.…”

Section: Resultsmentioning

confidence: 99%

Successful Haploidentical Transplantation with High Doses of CD34+-Selected Peripheral Blood Stem Cells in Wiskott-Aldrich Syndrome: A Case Report

Ae¹

2017

Ann Hematol Oncol

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Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive, primary immunodeficiency, characterized by eczema, microthrombocytopenia, recurrent infection, and increased susceptibility to autoimmune diseases and lymphoreticular malignancies. To date, HSCT is the only curative therapy. HSCT using HLA-matched related or unrelated donors is highly successful in treating WAS, but these donors may not always be available. We describe a 20 months-old-boy with WAS, who was transplanted by using highly-purified, 16.11x106/kg CD34 + stem cells from his HLA 2-loci mismatched mother, because of lacking donor and suffering life threatening, ongoing sinopulmonary infections. Conditioning consisted of busulfan (16 mg/kg), cyclophosphamide (200 mg/kg), rabbit anti-thymocyte globulin (10 mg/kg) and fludarabine (160 mg/m 2 ). He received methylprednisolone for graft-versus-host disease (GvHD) prophylaxis. The time for neutrophil, platelet and erythrocyte recovery was 11 days, 14 days and 19 days, respectively. He showed immunologic reconstitution by day +180. He developed grade II aGVHD on day +12, and grade I cGVHD on day +240, resolution achieved in aGVHD with i.v. methylprednisolone and cyclosporine, in cGVHD with oral prednisolone. He is well and alive up to now six years after transplantation. He didn't have any serious infection. Fluorescence in situ hybridization analysis revealed sustained full donor-type engraftment and flow cytometric analysis revealed sustained immunologic reconstitution. The convenient results in this patient can encourage further investigation of the role of using 'high doses' of related haploidentical CD34-selected peripheral blood stem cells in patients with WAS at early stages of disease, before the beginning of severe, life-threatening complications.

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“…Untreated patients with typical WAS have poor prognosis with the major causes of death being infection, bleeding, lymphoproliferative disorders, and malignancy (3). Allogenic HSCT is the only curative treatment which can correct both lymphoid and platelet abnormalities (2, 4). The five yr probabilities of survival have been reported to be 87% (74–94%) with HLA identical sibling donors, 52% (37–65%) with other related donors and 71% (58–80%) with unrelated donors (1).…”

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confidence: 99%

Hematopoietic stem cell transplantation from a donor with Klinefelter syndrome for Wiskott–Aldrich syndrome

Balcı¹,

Turul

Daar³

et al. 2008

Pediatric Transplantation

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WAS is a rare X-linked recessive disorder characterized by primary progressive T cell immunodeficiency, impaired antipolysaccharide antibody response, thrombocytopenia with small platelet, and eczematoid dermatitis. Untreated patients with typical WAS have poor prognosis with the major causes of death being infection, bleeding, lymphoproliferative disorders, and malignancy. Due to the increased risk of infectious and hemorrhagic episodes the best results with HSCT are achieved in patients less than five yr of age and are recommended as early as possible. Here, we report a three-yr-old boy with WAS who underwent UCB and BMT from his genotypically identical brother with Klinefelter syndrome.

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Unrelated partially matched peripheral blood stem cell transplantation with highly purified CD34+ cells in a child with Wiskott–Aldrich syndrome

Cited by 4 publications

References 20 publications

Non‐myeloablative bone marrow transplantation in an adult with Wiskott–Aldrich syndrome

Non‐myeloablative bone marrow transplantation in an adult with Wiskott–Aldrich syndrome

Successful Haploidentical Transplantation with High Doses of CD34+-Selected Peripheral Blood Stem Cells in Wiskott-Aldrich Syndrome: A Case Report

Hematopoietic stem cell transplantation from a donor with Klinefelter syndrome for Wiskott–Aldrich syndrome

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