T-CELL-DEPLETED ALLOGENEIC BONE-MARROW TRANSPLANTATION FOR ACUTE-LEUKEMIA USING CAMPATH-1 ANTIBODIES AND POSTTRANSPLANT ADMINISTRATION OF DONORS PERIPHERAL-BLOOD LYMPHOCYTES FOR PREVENTION OF RELAPSE
E. Naparstek et al., T-CELL-DEPLETED ALLOGENEIC BONE-MARROW TRANSPLANTATION FOR ACUTE-LEUKEMIA USING CAMPATH-1 ANTIBODIES AND POSTTRANSPLANT ADMINISTRATION OF DONORS PERIPHERAL-BLOOD LYMPHOCYTES FOR PREVENTION OF RELAPSE, British Journal of Haematology, 89(3), 1995, pp. 506-515
One hundred and forty-six patients with acute leukaemia (81 with ANLL
and 65 with ALL) received allogeneic bone marrow transplantation from
their fully matched siblings. 121 patients underwent T-cell depletion
(TCD) using Campath 1 monoclonal rat anti-human lymphocyte (CDw52) ant
ibodies; 67 with Campath 1M and 54 with Campath 1G isotypes. Patients
were conditioned for transplant using either total body irradiation co
mbined with chemotherapy (125 patients) or busulfan and cyclophosphami
de (21 patients). 112 recipients of T-cell depleted allografts receive
d in addition total lymphoid irradiation (TLI) for prevention of rejec
tion, Engraftment of neutrophils (>0.5 x 10(9)/l) and platelets (>25 x
10(9)/l) occurred on days 15 and 18, and on days 18 and 20 in recipie
nts of Campath 1M and Campath 1G treated marrows respectively. Rejecti
on was documented in 6.8% of T-cell depleted transplants. Leukaemia re
lapse-free survival at 2 years was 83% for patients transplanted in fi
rst CR, 76% in second CR (P-2 = 0.34) and 42% in advanced leukaemia (P
-2 = 0.009). 81 marrow recipients, 38 with Campath 1M and 43 with Camp
ath 1G treated marrow, received post-transplant graded increments of d
onor's peripheral blood lymphocytes (PBL) to induce graft-versus-leuka
emia (GVL) effects. Administration of donor's PBL was associated with
clinically significant GVHD and with decreased relapse rate especially
in patients with ALL. Our data suggest that in patients receiving mar
row allografts depleted of T cells by Campath 1 monoclonal antibodies,
rejection can be reduced by adequate pregrafting immunosuppression. I
n patients with advanced disease, post-transplant cell-mediated immuno
therapy (CMI) using donor's PBL may be beneficial; however, further st
udies are needed to define the optimal schedule of CMI for safe and ef
fective prevention of relapse following TCD bone marrow transplantatio
n in malignant haematological diseases.