Functional and morphological suppressor T cell deficit in acute GVHD.

Bone marrow transplantation (BMT) is currently used to treat patients with severe haematological disorders. One of its major complications is acute graft versus host disease (aGVHD). In this report we show that, during the early stages of lymphoid cell repopulation, an excess of suppressor T cell activity and a deficit of helper T cell activity are easily demonstrated by functional studies in healthy BMT recipients. On the contrary, in patients with active signs of aGVHD, a loss of suppressor T cells, as assessed by coculturing recipient T cells with donor B cells in an in vitro pokeweed mitogen (PWM) dependent Ig secreting assay, is detected. The loss of suppressor T cells in these patients is revealed also by the analysis of peripheral blood lymphocytes with the OKT5 suppressor cytotoxic monoclonal antibody (MoAb) but not with the OKT8 suppressor cytotoxic MoAb. Our data demonstrate that in several BMT recipients, during active aGVHD, a suppressor T cell deficit can be demonstrated both functionally and phenotypically.

[Bone marrow transplantation in acute lymphatic leukemia during the first remission]. / Knochenmarktransplantation bei akuter lymphatischer Leukämie in erster Remission.

9 patients with acute lymphoblastic leukaemia (ALL) were transplanted in first remission. There were no leukaemic relapses and 6 patients became longterm survivors. Causes of death were GvHD in 2 and interstitial pneumonia in 1. 14 patients with ALL were grafted in later stages of the disease. 10 had a leukaemic relapse. One attained longlasting remission with chemotherapy, while 9 died. One patient died of CMV infection. Cotton wool lesions and haemorrhages in the retina posed a problem in patients with previous cranial irradiation. We recommend transplantation of ALL in first remission if a syngeneic or HLA-identical sibling is available, particularly if the patient has poor risk factors for chemotherapy. Prophylactic cranial irradiation should be replaced by intrathecal methotrexate and/or cytosin arabinoside in these patients.

[Bone marrow transplants--quo vadis?]. / Knochenmarktransplantation quo vadis?

Early bone marrow transplantation (BMT) in leukaemia has enormously improved the results. Leukaemic relapse is rare, as is transplant-related mortality from interstitial pneumonia and severe graft-versus-host disease (GvHD). In aplastic anaemia the most important development is that treatment with ALG offers a real alternative to BMT which is of crucial importance for all patients without a histo-compatible family donor. The main problems of BMT are the lack of histocompatible donors and GvHD. In leukaemia, relapse is still an additional problem. The new immunosuppressive agent cyclosporin-A (CyA) has made an important contribution to the prophylaxis of severe GvHD. In future the results with CyA are potentially improvable by combination with other immunosuppressive agents. It is important that the use of HLA-semicompatible family donors, unrelated donors or alternative stem cell sources should become feasible. The value of autologous BMT is difficult to judge because in most instances it has been performed in patients with endstage disease. In several congenital diseases there are alternatives to BMT, such as genetic engineering. Although many problems of BMT still have to be solved, this procedure has an important place in modern medicine.

Can whole blood be used instead of separated low density cells for examination of the mitogen response?

The response of whole blood and separated low density cells to 3 mitogenic lectins [Phytohaemagglutinin (PHA), Pokeweed mitogen (PWM) and Concanavalin (Con-A)] was tested in 133 normal individual of all ages, including cord blood. The results obtained with the two methods correlated poorly (r = 0.16 for PHA; 0.47 for PWM and 0.42 for Con-A). Thus, the two methods measure different things and results are not comparable.

High T cell colony numbers do not reflect immune competence.

The number of T cell colonies growing from ficoll separated PHA-stimulated peripheral blood cells was compared to 3H-thymidine uptake in 133 normal donors of all ages. Unexpectedly, the two parameters did not correlate: The tendency of growing cells to aggregate during the incubation period resulted in few, but large spherical colonies in persons who by young age and high counts for thymidine uptake were judged to have good T cell function. This clustering effect was less pronounced in old persons and those with a low PHA response; it was virtually absent in 17 of 18 patients with undoubted cellular immune deficiency early after allogeneic bone marrow transplantation. This resulted in a growth pattern consisting of a high number of small scattered colonies. The capacity of growing cells to aggregate was sensitive to sublethal irradiation. We conclude that the number of T cell colonies growing from a given cell suspension not only depends on the number of lymphocytes responding to the mitogen. It is negatively determined by the drive of growing cells to cluster. This phenomenon deserves further study, since it appears to be a parameter of cellular immune competence which is not readily recognized with 3H thymidine incorporation.