Engraftment of marrow allografts treated with Campath-1 monoclonal antibodies

We have analyzed the factors associated with engraftment in 216 recipients of T-cell depleted allogeneic HLA identical sibling marrow transplants usin g 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 m arrow with Campath-1G (IgG2b isotype). Patients with durable engraftment ha d fast hematopoietic recovery: SAA patients reached ANC > 0.5x10(6)/L on Da y 14; those with leukemia attained ANC > 0.5X10(6)/L on Days 18, 17, and 15 for ANLL, ALL and CML respectively, while patients with thalasemia reached ANC > 0.5 X 10(6)/L on Day 21. Overall, 24 patients (17 with leukemia, 4 w ith SAA, and 3 with thalassemia) suffered graft failure: 10 patients tall g rafted with Campath-1M) rejected their grafts, while 14 others (9 grafted w ith Campath-1M, and 5 with 1G isotype) never engrafted (p = 0.009). Multiva riate analysis revealed that neither pretransplant protocol, nor stage of d isease 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). Pat ients with ANLL or SAA had a better chance to engraft (p = 0.027, RR = 1.40 0; and p = 0.003, RR = 2.677, respectively) compared to patients with thala ssemia (p = 0.001, RR = 0.551). A higher concentration of Campath-1 antibod y in vitro and in vivo adversely affected engraftment. Our data show that s atisfactory engraftment can be achieved in patients transplanted with Campa th-1 treated marrow allografts. However, despite the measures undertaken to prevent rejection, graft failure still poses a problem, Further pretranspl ant immunosuppression and perhaps more selective T-cell depletion may reduc e the increased graft failure in these patients. (C) 1999 International Soc iety for Experimental Hematology. Published by Elsevier Science Inc.