TY - JOUR
T1 - Engraftment of marrow allografts treated with Campath-1 monoclonal antibodies
AU - Naparstek, Elizabeth
AU - Delukina, Maria
AU - Or, Reuven
AU - Nagler, Arnon
AU - Kapelushnik, Joseph
AU - Varadi, Gabor
AU - Strauss, Nurit
AU - Cividalli, Gabriel
AU - Aker, Mahmed
AU - Brautbar, Chaim
AU - Waldmann, Herman
AU - Hale, Geoff
AU - Slavin, Shimon
PY - 1999/7
Y1 - 1999/7
N2 - We have analyzed the factors associated with engraftment in 216 recipients of T-cell depleted allogeneic HLA identical sibling marrow transplants using Campath 1 monoclonal antihuman lymphocyte (CD52) antibodies. The patient population consisted of 168 patients with hematologic malignancies, 26 with severe aplastic anemia (SAA), and 22 with hemoglobinopathies, half of whom received marrow treated in vitro with Campath-1M (IgM) and half received marrow with Campath-1G (IgG2b isotype). Patients with durable engraftment had fast hematopoietic recovery: SAA patients reached ANC > 0.5 X 106/L on Day 14; those with leukemia attained ANC > 0.5 X 106/L on Days 18, 17, and 15 for ANLL, ALL and CML respectively, while patients with thalasemia reached ANC > 0.5 X 106/L on Day 21. Overall, 24 patients (17 with leukemia, 4 with SAA, and 3 with thalassemia) suffered graft failure: 10 patients (all grafted with Campath-1M) rejected their grafts, while 14 others (9 grafted with Campath-1M, and 5 with 1G isotype) never engrafted (p = 0.009). Multivariate analysis revealed that neither pretransplant protocol, nor stage of disease or type of antibody used, donor sex and ABO match had any impact on engraftment. The variables favorably associated with engraftment were older age (p = 0.030, RR = 1.016) and CFU- GM number (p = 0.013, RR = 1.001). Patients with ANLL or SAA had a better chance to engraft (p = 0.027, RR = 1.400; and p = 0.003, RR = 2.677, respectively) compared to patients with thalassemia (p = 0.001, RR = 0.551). A higher concentration of Campath-1 antibody in vitro and in vivo adversely affected engraftment. Our data show that satisfactory engraftment can be achieved in patients transplanted with Campath-1 treated marrow allografts. However, despite the measures undertaken to prevent rejection, graft failure still poses a problem. Further pretransplant immunosuppression and perhaps more selective T-cell depletion may reduce the increased graft failure in these patients.
AB - We have analyzed the factors associated with engraftment in 216 recipients of T-cell depleted allogeneic HLA identical sibling marrow transplants using Campath 1 monoclonal antihuman lymphocyte (CD52) antibodies. The patient population consisted of 168 patients with hematologic malignancies, 26 with severe aplastic anemia (SAA), and 22 with hemoglobinopathies, half of whom received marrow treated in vitro with Campath-1M (IgM) and half received marrow with Campath-1G (IgG2b isotype). Patients with durable engraftment had fast hematopoietic recovery: SAA patients reached ANC > 0.5 X 106/L on Day 14; those with leukemia attained ANC > 0.5 X 106/L on Days 18, 17, and 15 for ANLL, ALL and CML respectively, while patients with thalasemia reached ANC > 0.5 X 106/L on Day 21. Overall, 24 patients (17 with leukemia, 4 with SAA, and 3 with thalassemia) suffered graft failure: 10 patients (all grafted with Campath-1M) rejected their grafts, while 14 others (9 grafted with Campath-1M, and 5 with 1G isotype) never engrafted (p = 0.009). Multivariate analysis revealed that neither pretransplant protocol, nor stage of disease or type of antibody used, donor sex and ABO match had any impact on engraftment. The variables favorably associated with engraftment were older age (p = 0.030, RR = 1.016) and CFU- GM number (p = 0.013, RR = 1.001). Patients with ANLL or SAA had a better chance to engraft (p = 0.027, RR = 1.400; and p = 0.003, RR = 2.677, respectively) compared to patients with thalassemia (p = 0.001, RR = 0.551). A higher concentration of Campath-1 antibody in vitro and in vivo adversely affected engraftment. Our data show that satisfactory engraftment can be achieved in patients transplanted with Campath-1 treated marrow allografts. However, despite the measures undertaken to prevent rejection, graft failure still poses a problem. Further pretransplant immunosuppression and perhaps more selective T-cell depletion may reduce the increased graft failure in these patients.
KW - Campath-1
KW - Engraftment
KW - T-cell depletion
UR - http://www.scopus.com/inward/record.url?scp=20244383278&partnerID=8YFLogxK
U2 - 10.1016/S0301-472X(99)00052-1
DO - 10.1016/S0301-472X(99)00052-1
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AN - SCOPUS:20244383278
SN - 0301-472X
VL - 27
SP - 1210
EP - 1218
JO - Experimental Hematology
JF - Experimental Hematology
IS - 7
ER -
