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 10(6)/L on Day 14; those with
leukemia attained ANC > 0.5 x 10(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 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.