title: Cytotoxic T lymphocyte precursor frequency analyses in bone marrow transplantation with volunteer unrelated donors. Value in donor selection.
abstract: Between May 1989 and February 1994, we performed 48 volunteer unrelated donor BMTs for first chronic phase chronic myeloid leukemia using in vivo T cell depletion for acute graft-versus-host disease (aGvHD) prophylaxis. In 40 cases, adequate material was available to measure the frequency of antirecipient MHC cytotoxic T lymphocyte precursor (CTLp) cells in the blood of potential donors. This supplemented standard serological typing, one-dimensional isoelectric focusing for class I proteins, and allogenotyping for DR and DQ alleles using DNA RFLP analysis in the donor selection process. All recipients were conditioned with cyclophosphamide 120 mg/kg, TBI 1320 cGy, and intravenous Campath 1G. GvHD prophylaxis consisted of CsA, short-course methotrexate, and intravenous Campath 1G. Minimum follow-up in all surviving recipients was 100 days. The development of aGvHD and the probability of leukemia-free survival were compared between the high frequency group (CTLp > 1 in 100,000) (n = 15) and the low frequency group (CTLp < 1 in 100,000) (n = 25). There was a trend for increasing grade of aGvHD, which was statistically significant in the high frequency group when compared with the low frequency group (P = 0.003). Both a high frequency of CTLp (relative risk [RR] = 9.0, P = 0.016) and HLA mismatch (RR = 6.7, P = 0.023) were predictors of severe aGvHD (grade III or IV). Multivariate analysis showed that CTLp group (RR = 3.4, P = 0.015) and CMV status (RR = 3.9, P = 0.008) were predictors of leukemia-free survival. Further investigation showed an interaction between the two, such that CMV seropositive recipients in the high frequency group had a relative risk of 9.4 (P = 0.0001) of treatment failure (death or relapse) when compared with other combinations. We conclude that with our present GvHD prophylaxis regimen, CTLp frequency analysis predicts post-BMT outcome and is a valuable aid in donor selection.
authors.affiliation: LRF Centre for Adult Leukaemia, Royal Postgraduate Medical School, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Spencer
authors.forename: P A
authors.initials: PA
authors.lastname: Brookes
authors.forename: E
authors.initials: E
authors.lastname: Kaminski
authors.forename: J M
authors.initials: JM
authors.lastname: Hows
authors.forename: R M
authors.initials: RM
authors.lastname: Szydlo
authors.forename: F
authors.initials: F
authors.lastname: van Rhee
authors.forename: J M
authors.initials: JM
authors.lastname: Goldman
authors.forename: J R
authors.initials: JR
authors.lastname: Batchelor
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000517:prevention & control; D006650:Histocompatibility Testing; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D014019:Tissue Donors