LONG-TERM IMMUNE RECONSTITUTION AND OUTCOME AFTER HLA-NONIDENTICAL T-CELL-DEPLETED BONE-MARROW TRANSPLANTATION FOR SEVERE COMBINED IMMUNODEFICIENCY - A EUROPEAN RETROSPECTIVE STUDY OF 116 PATIENTS

We have performed a retrospective analysis of the development of T-and B-cell functions after HLA-nonidentical T-cell-depleted bone marrow t ransplantation (BMT) performed in 193 patients with severe combined im munodeficiency (SCID) at 18 European centers between December 1982 and December 31, 1993. One hundred sixteen of 193 patients were alive wit h evidence of engraftment 6 months after BMT. Development of T-cell fu nction occurred earlier than B-cell function and was achieved more fre quently up to the time of last follow-up. The median time to achieve n ormal T-cell function was 8.7 months, whereas the median time to achie ve normal B-cell function was 14.9 months. Twenty-four patients died l ater than 6 months post-BMT, mainly due to chronic graft-versus-host d isease (cGVHD) and/or viral infection. Absence of T-cell reconstitutio n 6 months after BMT, unlike absence of B-cell reconstitution, was ass ociated with a poor outcome. Two additional factors were associated wi th a poor outcome: presence of cGVHD 6 months after BMT and B-SCID ver sus B+ SCID. However, two of these three factors remained as significa nt prognostic factors in a multivariate analysis: the absence of T-cel l function and the presence of cGVHD 6 months after BMT. Analysis of t he factors influencing the development of immune reconstitution showed that T-and B-cell functions occurred earlier and more frequently in B f SCID versus B-SCID patients. Acute GVHD was associated with a slower development of T-cell function at 6 months, and cGVHD had a negative influence on the development of T-cell function afterwards, but neithe r acute nor chronic GVHD was found to influence the development of B-c ell function. Once engraftment occurred, whether patients had or had n ot received Busulfan in the conditioning regimen did not influence the kinetics and quality of T-cell function development. In a multivariat e study, two factors were found to influence the T cell function 6 mon ths after BMT: type of SCID and acute GVHD. The results of this retros pective analysis should lead to new protocols adapted to SCID disease, considering that disease-related as well as BMT related parameters in fluence the development of immune function and thereby long-term outco me after HLA-nonidentical T-cell-depleted BMT. (C) 1998 by The America n Society of Hematology.