We studied the outcome of 24 peripheral blood stem cell (PBSC) graft recipients, who were T‐cell depleted (TCD) with either 20 mg (n = 14) or 10 mg (n = 10) Campath‐1H in vitro, in comparison with a ...retrospective cohort of 23 unmanipulated (UM) PBSC recipients. While the neutrophil engraftment was similar, the platelet engraftment occurred earlier in the TCD group (d 11 vs 14). The incidence of acute and chronic graft‐versus‐host‐disease (GVHD) was 8·7% and 4·4% in the TCD group, respectively, compared with 47·7% and 56·3% in UM group (P < 0·001). In the TCD group, 5/6 chronic myeloid leukaemia (CML) and 4/18 non‐CML patients relapsed (vs 0/6 and 3/17 in UM group, P = 0·06). All four molecular or cytogenetic relapses of CML were disease‐free survivors following donor lymphocyte infusion. There was no difference in the incidence of serious infection between the TCD and UM groups and the lymphocyte recovery at 100 d was comparable. In the TCD cohort, the lymphocyte recovery was quicker in the 10 mg Campath‐1H group. The non‐relapse mortality (19·1%vs 66·3%) and 3 year survival (73·1 vs 19·2) were improved in the TCD group (P = 0·05). Thus elimination of late mortalities related to chronic GVHD and a rapid immune reconstitution, limiting either infection or relapse related deaths, contributed to an improved outcome following T‐cell depletion with Campath‐1H ‘in the bag’.
There is controversy regarding the best approach to the management of patients with acute myeloid leukaemia (AML) in first remission (CR1). The impact of matched related allogeneic transplant in CR1 ...on the overall survival is equivocal, but what is not in doubt is a significant reduction in the relapse risk, compared to both autologous transplants and intensive chemotherapy, which is because of the allogeneic or the graft-versus-leukaemia (GVL) effect. Yet, this does not always translate to improved survival. T cell depletion (TCD) can reduce deaths related to graft-versus-host disease (GVHD) and its therapy, but might increase the relapse risk. The existing literature suggests that TCD is associated with a disease-free survival (DFS) of 53-80% and is associated with a lower relapse risk than anticipated (0-30%). We discuss the evolution of TCD in allogeneic transplantation and its relevance in AML-CR1 with regard to GVHD, DFS, immune reconstitution and GVL effect. It is possible that by reducing TRM related to GVHD and extramedullary toxicities, particularly in the older patients, TCD might improve the impact of allogeneic transplantation in AML-CR1, provided the immune reconstitution and the relapse risk are not adversely affected. Randomised studies are underway to address these issues.
Little is known about the role of cellular immunity in respiratory virus infections after bone marrow transplantation.
Forty allograft recipients T-cell depleted with Campath antibodies were ...evaluated for respiratory virus infections in an active surveillance program with early initiation of antiviral therapy.
Eighteen episodes of respiratory virus infection were detected in nine patients (22%) at a median of 95 days, with lower respiratory involvement in 44%. Fourteen episodes were treated with antiviral therapy for 7 to 46 days, with 11% mortality. Respiratory virus infections were more common in patients receiving Campath 100 mg in vivo, but delayed CD4+ recovery was the most significant risk factor.
Respiratory virus infections are common and often recurrent in patients with severe CD4+ T lymphopenia. However, the mortality was low, which may have been due to early institution of antiviral treatment or reduced inflammatory damage to the lungs due to severe lymphopenia.
PDF
