Over the past 10 years the Ulm BMT group has pursued a strategy of in - vivo / ex - vivo T cell depletion of allogeneic bone marrow grafts and preemptive donor lymphocyte infusions in patients ( pts ) with low risk leukemias and HLA - identical sibling donors. This strategy has provided excellent control of graft rejection, acute and chronic GvHD in combination with an acceptable relapse rate. Over the past five years we have employed a similar strategy to pts receiving a peripheral blood progenitor cell transplant ( PBPCT ) and have extended the indication for this approach to pts with more advanced disease and receiving grafts from alternative donors. Here we report the outcome of 160 consecutive cases transplanted between 4 / 96 and 12 / 00. The cohort consisted of 87 men and 73 women with a median age of 42 y ( range 17 - 63 y ). 109 of these pts were considered to be at high - risk of treatment failure because of advanced disease and / or an alternative stem cell donor. The conditioning consisted of TBI 12 Gy or Bu 12,8 mg / kg i.v. + CTX 120 mg / kg Â±Thiotepa 10 mg / kg, 52 pts at high risk of relapse were additionally treated with Re -188 labelled anti - CD66 monoclonal antibody. Donors consisted of HLA - identical siblings ( n = 80 ), matched unrelated donors (MUD, n = 45 ),mismatched family donors ( n = 21 )and haploidentical family donors ( n = 14 ). In - vivo T cell depletion was performed with rabbit ATG ( n = 108 ) or Campath 1 H ( n = 52 ). Three methods of ex - vivo T cell depletion were used : CD34+ selection with the CEPRATE device + CD2 / CD3 depletion ( n = 47 ), CD34+ selection with the CliniMACS device ( n = 61 )and Campath 1 H in the bag ( n = 52 ). Rapid and stable engraftment was achieved in 96 % of pts. The actuarial risk of acute GvHD grade II was 23 %, no patient suffered grade III or IV acute GvHD. The actuarial risk of chronic GvHD was 47%. After a median follow - up of 26 mo ( range 8 - 61 mo) 54% pts are alive, 65% in the low risk group and 49% in the high - risk group. TRM was the cause of death in 35 % of pts, relapse caused the death of 11% of pts. The most frequent causes of death were sepsis and aspergillus nfections. Autoimmune disease developed in 15% of pts ( autoimmunethyroiditis, AIHA , ITP ). Overall we observed no significant differences between the different T cell depletion modalities with respect to engraftment and GvHD control.Overall outcome was determined by the stage of disease ( AML 1. CR 61%, 2.CR 41 %, CML c.P. 71%) and the type of donor ( HLA - id sib. 62 % , MUD 47% , haploid. 43% ). In summary,in - vivo / ex - vivo T cell depleted PBPCT is associated with a low risk of graft failure , a low risk of severe acute GvHD, a significant risk of chronic GvHD and a moderate risk of autoimmune disease.
Full conference title:
43rd American Society of Hematology (ASH) Annual Meeting
- ASH 43rd (2001)