Allogeneic peripheral blood stem cell transplantation with CD34(+)-cell selection and delayed T-cell add-back in adults. Results of a single center pilot study

Background and Objectives. Allogeneic peripheral blood stem cell transplant ation with CD34(+) cell-selection (CD34(+)-PBSCT) allows rapid hematologic engraftment with a reduction in graft-versus-host disease (GVHD), although concerns exist regarding the increased risk of tumor relapse associated wit h T-cell depletion of the graft. Delayed T-cell add-back (TCAB) after such transplants may restore the graft-versus-tumor effect while achieving a red uced early transplant-related mortality due to less GVHD in a group of pati ents at high risk of early death (i.e., age greater than or equal to 45 yea rs). Design and Methods. Ten patients 45 years of age or older with hematologic malignancies received a CD34(+)-PBSCT and cyclosporin A (CyA) to prevent ac ute GVHD, followed by a planned delayed donor TCAB of 10(7) T-cells/kg to r estore the graft-versus-tumor effect. The infused graft included a median o f 6.3 x 10(6) CD34(+) cells/kg and 4.4 x 10(4) CD3(+) cells/kg. Results. Engraftment was prompt in all cases. Four patients developed acute GVHD after the CD34(+)-PBSCT and/or chronic GVHD after CyA withdrawal and did not proceed to TCAB, and two patients died early before the planned TCA B. Four patients proceeded to TCAB at a median of day +104 after CD34(+)-PB SCT (+92 to +150). Two of these patients developed acute GVHD grades I-II ( IBMTR Index B) after TCAB and all four developed chronic GVHD, which was ex tensive in two. With a median follow-up of 611 days (range 499-847) after t ransplant in the seven survivors, there have been no disease progressions, and all patients show a pattern of complete donor chimerism in bone marrow and peripheral blood. Interpretations and Conclusions. The results of our pilot study suggest tha t this protocol produces an; acceptable transplant-related morbidity and mo rtality in patients 45 years and older. However, there may be benefit in in fusing CD34(+)-selected PBSCT with even lower T-cell contents and further d elaying the TCAB. (C) 2000 Ferrata Storti Foundation.