From 10/94 to 12/99, 219 patients underwent BMT from a partially mismatch;d related donor (PMRD)using a single protocol. The median patient age was 28 y (range: 1-54). 136 patients were transplanted for acute leukemia, 54 for chronic leukemia, 24 for other malignancies and 5 for non-malignant disease. 166 patients (76%) were classified as high risk; 117 patients (53%) were in relapse at BMT. The median donor age was 29 y (range: 4-67). In 80% there was a HLA-mismatch of a2 ag. Conditioning comprised T! H, VP16, Ara-C, Cyclophosphamide, ATG, and Methylprednisolone (MP). The marrow was T-depleted with OKT3 (median log depletion 1.78; range 0.7-3.0). Further GVKD prophylaxis comprised cyclosporin, ATG and MP. The probab. of engraftment was 98%. The cumulative incidence (CI) of aGVHDH-IV was only 17% (grd IIl-IV 9%). The CI of cGVHD at 1 y was 40% with a CI of limited/severe to extensive cGVHD of only 16%. There was a trend to a higher CI of aGVHD with older donors (20 y CI 20% vs <20y CI of 10%, p=0.07). The CI of relapse at 5 y was 23%;a plateau was reached at 2 y Relapse was influenced by type of leukemia (acute leukemia 27% vs chronic leukemia 12%, p=0.03). TRM was 56% at 5 y, and was higher in patients who received less than tie median CD34+ dose of 1.8xl06/kg (65% vs 48%, p=0.004). The probabilities of survival and DFS at 5 y were 21 and 14%. In Cox analysis the relative risk (RR) of treatment failure was determined by patient and donor age, donor CMV status and risk group. The RR of treatment failure was 1.63 for patients aged 20-50 y and a donor 20-40 y (p=0.01)wh;n compared to the reference group of patients less than 20 years with a donor < 50 y or patients 20-40 y with a donor < 20 y (RR=1.0). The RR of treatment failure was 1.93 for patients who were patients 50 y of age, or patients with a donor 40 y (p=0.0002). T le RR of treatment failure was increased for patients transplanted from a CMV negati re (RR=1.0) donor as opposed to a CMV positive donor (RR=0.74, p=0.05). We conclule that the current protocol allows for transplantation across major MHC barriers with excellent engraftment and a low risk of aGVHD. Donor age is an important determinant rf outcome and younger donors should be preferentially selected. The present data are inconclusive regarding use of high doses of CD34+ cell for PMRD transplantation.
|Original language||English (US)|
|Issue number||11 PART I|
|State||Published - Dec 1 2000|
ASJC Scopus subject areas
- Cell Biology