No abstract

Fifty-one patients with acute nonlymphocytic leukemia (16 with end-stage disease, 17 in second or third remission or in early relapse, and 18 in first remission) were given infusions of HLA-identical sibling marrow after cytoreduction with high doses of busulfan and cyclophosphamide. Actuarial two-year survival rates were 0 per cent, 29 per cent, and 44 per cent, respectively. Twelve patients are still alive and in remission after 327 to 1488 days, with 10 surviving beyond two years. Acute graft-versus-host disease and viral pneumonia were the major causes of death. Leukemic cells failed to clear in one patient with end-stage disease, and a relapse with meningeal leukemia occurred in another. Only one other relapse was seen--in a patient given a transplant during a third remission. Survival was favorably affected by younger age and transplantation during first remission. We conclude that high-dose chemotherapy with busulfan and cyclophosphamide, followed by allogeneic-marrow transplantation, can produce long-term remission of acute leukemia. Chemotherapy with high-dose busulfan and cyclophosphamide before transplantation provides an effective alternative to cyclophosphamide and total-body irradiation before transplantation for the treatment of acute nonlymphocytic leukemia.

In this preliminary trial, thalidomide appeared to be safe and effective for the treatment of chronic GVHD. A trial comparing thalidomide with prednisone in patients with newly diagnosed chronic GVHD will be required to demonstrate its relative efficacy.

The records of 549 bone marrow transplant (BMT) patients at The Johns Hopkins Oncology Center during a 9-year period were reviewed to determine the incidence of bronchiolitis obliterans (BrOb). Seven patients had BrOb. All seven died, and BrOb was a contributing cause of death in six patients. Only recipients of allogeneic BMT were at risk for developing BrOb (2% incidence). Three cases were incidentally discovered at autopsy in patients who died less than 120 days after BMT from ventilatory failure owing to interstitial pneumonitis. Four cases were patients who died greater than 120 days after BMT. Of this latter group, all had overt chronic graft-v-host disease (CGVHD). Among 120 day survivors of allogeneic BMT, 6% of those with CGVHD developed BrOb as compared with none of those without CGVHD (P = .008). Five percent of patients with reduced IgG levels at day 120 developed BrOb as compared with none of those with normal IgG (P = .04). The incidence of BrOb in 120-day survivors was 14% (4 of 29) in patients with both CGVHD and decreased serum IgG, whereas patients with CGVHD only (0 of 25), those with decreased IgG levels only (0 of 53), and those with no CGVHD and normal IgG levels (0 of 70) did not develop BrOb.

Graft-versus-host disease, a complication of allogeneic bone-marrow transplantation, involves primarily the skin, liver and intestines, but may also be associated with pneumonia. To determine the relation of graft-versus-host disease with pneumonia, we evaluated the autopsies of 59 allogeneic and two autologous recipients and 74 control patients with various pulmonary diseases, who had not received a bone-marrow transplant. Lymphocytic bronchitis, characterized by lymphocyte-associated necrosis of the bronchial mucosa and often the submucosal glands, was present in 12 of 20 patients with Grade 2 or greater graft-versus-host disease but in only three of 39 with Grade 0 to 1 disease (P less than 0.0005). Onset of respiratory disease correlated with the time of onset of graft-versus-host disease. Patients with lymphocytic bronchitis had a higher incidence of bronchopneumonia and acute bronchitis of the lower respiratory tract. Lymphocytic bronchitis did not occur in the controls and appears to be a component of graft-versus-host disease that leads to bronchopneumonia, probably through destruction of the mucociliary apparatus.

Among 78 patients who died after bone marrow transplantation, neurologic complications were present in 55 (70%) and were the cause of death in 5 (6%). Metabolic encephalopathy occurred in 29 patients (37%). CNS infections included aspergillosis (3), herpes simplex encephalitis (2), and Listeria monocytogenes meningitis (1). Six additional patients had neuropathologic changes possibly due to cytomegalovirus infection. Cerebrovascular complications occurred in five patients (two hemorrhages and three infarcts). All infarcts were associated with endocarditis. The rate of nonbacterial thrombotic endocarditis was significantly higher (p less than 0.001) than in the general autopsy population. CNS leukemia and therapy-induced injury were rare. There was no evidence of graft-versus-host disease involving the CNS.

This study demonstrates that cardiotropic virus infection and myocarditis may be important in the pathogenesis of symptomatic HIV-associated cardiomyopathy.

Lethally irradiated rats reconstituted with syngeneic bone marrow and treated with cyclosporine (CsA) for 40 d develop a graft-vs.-host disease-like syndrome (GVHD) after CsA therapy. We attempted to assess the development of autoreactivity in these animals. Results revealed that a majority of the animals with syngeneic GVHD develop autocytotoxic T lymphocytes of the OX8 phenotype. In addition to reactivity with self, these cells were capable of lysing appropriate target cells from a variety of different rat strains. The target antigens appeared to be class II major histocompatibility antigens, because lysis could be effectively blocked by an anti-Ia monoclonal antibody. Cold target inhibition studies indicated that one effector cell was capable of lysing various target cells, and provided evidence against a polyclonal activation of multiple anti-Ia-reactive cells. These results suggested that the anti-class II autoreactive cell associated with syngeneic GVHD either recognizes a common class II determinant ("public" epitope) shared by multiple strains of rats, or was polyspecific with respect to "private" class II determinants.