Influence of severe combined immunodeficiency phenotype on the outcome of HLA non-identical, T-cell–depleted bone marrow transplantationA retrospective European survey from the European Group for Bone Marrow Transplantation and the European Society for Immunodeficiency,☆☆,

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Abstract

We analyzed the outcomes of 214 HLA non-identical T-cell–depleted bone marrow transplantations (BMTs), performed in 178 consecutive patients for treatment of severe combined immunodeficiencies (SCID). Patients were treated in 18 European centers between 1981 and March 1995. SCID variants, that is, absence of T and B lymphocytes (B–) or absence of T cells with presence of B lymphocytes (B+) were found to have a major influence on outcome. The disease-free survival was significantly better for patients with B+ SCID (60%) as compared with patients with B– SCID (35%) (P = .002), with a median follow-up of 57 months and 52 months, respectively. Other factors associated with a poor prognosis were the presence of a lung infection before BMT (odds ratio = 2.47 [1.99-2.94]) and the use of monoclonal antibodies for T-cell depletion of the graft (odds ratio = 1.67 [1.18-2.15]). Additional factors influencing outcome were age at BMT (<6 months) and period during which BMT was performed. Better results were achieved after 1991. Reduced survival of patients with B– SCID was associated with a higher incidence of early deaths from infection, a diminished rate of marrow engraftment, a trend to a higher incidence of chronic graft-versus-host disease, and slower kinetics of T/B immune function development. In both groups of patients, the use of busulfan (8 mg/kg total dose) and cyclophosphamide (200 mg/kg total dose) as a conditioning regimen provided the best cure rate (74% for patients with B+ SCID and 43% for patients with B– SCID, respectively), although results were not statistically significantly different from other regimens. This retrospective analysis should lead to the design of adapted measures to the performance of HLA non-identical BMT in patients with distinct SCID conditions. (J Pediatr 1999;134:740-8)

Section snippets

PATIENTS AND METHODS

Between 1981 and March 1995, 178 patients with B– or B+ SCID received HLA non-identical T-cell–depleted BMT in 18 cooperating centers in Europe. Data on all BMTs performed during this period were collected from members of the EBMT/ESID. The analysis was performed on data available up to December 1, 1995, giving a minimum follow-up period of 6 months and a maximum of 14 years. B+ SCID was defined as blood T-cell counts (excluding maternal T cells) <250/μL and B-cell counts >50/μL. B– SCID was

Evidence of Better Prognosis for Patients with B+ SCID

As of December 1, 1995, 73 of 122 patients with B+ SCID and 20 of 56 patients with B– SCID were alive with T-cell engraftment, after T-cell–depleted non-identical BMT with a median follow-up of 57 months (range, 6 to 162 months) and 52 months (range, 6 to 161 months), respectively. Two additional patients with B+ SCID were alive and well after receiving a second BMT with a matched unrelated donor. The survival with T-cell engraftment/function was significantly better for patients with B+ SCID

DISCUSSION

In this retrospective study we found that the results of HLA non-identical T-cell–depleted BMT were significantly better for the group of patients with B+ SCID than for the group of patients with B– SCID. The 2 populations of patients were comparable for age at BMT, clinical status before BMT (including frequency of lung infection associated with poor prognosis), period during which BMT was performed, HLA incompatibility, conditioning regimen, modalities of T-cell depletion, donor/recipient sex

Acknowledgements

The following European centers have contributed to this study: Barcelona (Dr T. Espanol); Bruxelles (Dr A. Ferster); Belgrad (Dr M. Abinun); Brescia (Dr F. Porta); Gotebörg (Dr A. Fasth); Hannover (Dr W. Ebell); Leiden (Dr J. Vossen, Dr B. Gerritsen); London (Dr G. Morgan, Dr P. Veys); Lyon (Dr G. Souillet); Mainz (Dr O. Schofer); Nancy (Dr P. Bordigoni); Newcastle (Dr A. Cant); Paris (Dr A. Fischer); Pavia (Dr Locatelli); Ulm (Dr W. Friedrich); Utrecht (Dr B. Zegers); Zurich (Dr R. Seger).

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    Supported by the European Group for Bone Marrow Transplanation, the European Society for Immunodeficiency, and the Biomed 2PL 96007 concerted action.

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    Reprint requests: A. Fischer. Unité d’Immunologie et d’Hématologie Pédiatriques, Département de Pédiatrie, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France.

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