TY - JOUR
T1 - Engraftment and immunologic effects of a novel less myeloablative allogeneic transplant conditioning regimen of continuous infusion pentostatin, photopheresis, and low dose tbi
AU - Alcindor, Thierry
AU - Chan, Geoffrey
AU - Al-Olama, Asma
AU - Miller, Kenneth
AU - Roberts, Todd
AU - Schenkein, David
AU - Sprague, Kelly
AU - Gorgun, Gullu
AU - Foss, Francine
PY - 2000/12/1
Y1 - 2000/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33748528635&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748528635&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:33748528635
SN - 0006-4971
VL - 96
SP - 327b
JO - Blood
JF - Blood
IS - 11 PART II
ER -