Rapid hematopoietic engraftment following fractionated TBI conditioning and transplantation with CD34 + enriched hematopoietic progenitor cells from partially mismatched related donors

Nineteen adult patients with poor-risk hematologic malignancy received T cell-depleted (TCD) hematopoietic progenitor cell (HPC) transplant from partially mismatched related donors (PMRD). The preparative regimen (FITFA) included fractionated TBI, thiotepa, fludarabine, and horse ( n = 3) or rabbit ( n = 16) anti-thymocyte anti-sera (ATG). GVHD prophylaxis consisted of TCD by positive/negative selection using the Isolex 300i system and pre-transplant ATG with no post-transplant immunosuppression. The mean number (±s.d.) of transplanted CD34 + and CD3 + cells were 8.9 × 10 6 /kg ±4.3 (range 2.6–19.3) and 1.4 × 10 4 /kg ±1.2 (range 0.3–4.6) respectively. Seventeen patients evaluable for neutrophil engraftment achieved an ANC >0.5 × 10 9 /l at a median of 12 days (range 9–27), with evidence of full donor chimerism. Thirteen patients died of the following causes: relapse ( n = 6), infections ( n = 5), interstitial pneumonia ( n = 1), and unknown causes ( n = 1) None of the recipients of rabbit ATG required therapy for acute or chronic GVHD. Five patients are alive and disease-free at a median time of 303 days post transplant (range 100–660). The FITFA preparative regimen using fractionated TBI is well tolerated and is sufficiently immunosuppressive to allow rapid and stable donor origin hematopoietic engraftment without ‘mega’ doses of CD34 + cells. Combination of stringent ex vivo TCD and pre-transplant ATG is effective GVHD prophylaxis.