In an effort to reduce allogeneic bone marrow transplant-associated mortality, less intensive and non-ablative conditioning regimens have been utilized. These have been associated with minimal toxicity, high incidence of donor engraftment, and GVL effect. We have developed a novel, less toxic preparative regimen consisting of extracorporeal photopheresis (days-5,-4), pentostatin 4mg/m2 CIVI (days-3,-2), and TBI (200cGy x 3, days-2,-1 ), followed by allogeneic bone mairow infusion and CSA and methotrexate for GVHD prophylaxis. Eligibility included prior BMT, age >55, hepatitis C, renal insufficiency. Nine of 13 patients are évaluable. There were 6 CR (3 AML, 1 MM, 1 CML, l NHL), 2PR (1 HD, 1 CLL) and 1 PD (NHL), and grade I acute GVHD limited to skin was seen in 5. Engraftment and immunologie reconstitution was studied in 10 patients. In 5 sex-mismatched transplants, 99% donor chimerism was established by day 100. In 5 sex matched transplants, mixed chimerism at day 60 was found by PCR in 4, one of which progressed to full donor engraftment between days 60-100. Using PCR-based RFLP analysis.the fifth patient lost donor engraftment and developed recurrent disease after day 60. Although hematopoietic recovery was rapid ( WBC >500 between days 13 and 27) and linear, we observed a biphasic recovery of the lymphocyte population, with initial recovery paralleling the total leukocyte recovery ( lymphocytes 377-2280/ml days 30-60), followed by a depression in lymphocytes ( range 160-584/ml ) on day 100. Helper and cytotoxic T-cell populations as well as CD56+NK cells similarly decreased after day 60 despite the absence of significant GVHD in the majority of patients. Delayed lymphopenia may be related to exposure of the graft to pentostatin if detectable drug levels persisted until day 0. Pharmaockinetic studies are underway to evaluate this. The decrease in acute GvHD may be related to the modulation of antigen-presenting host cells by either pentostatin or photopheresis. We conclude that in this modified conditioning regimen, adequate immunosuppression is achieved to establish donor chimerism with minimal GvHD.
|Original language||English (US)|
|Issue number||11 PART II|
|State||Published - Dec 1 2000|
ASJC Scopus subject areas
- Cell Biology