Mixed hematologic chimerism after allogeneic marrow transplantation for severe aplastic anemia is associated with a higher risk of graft rejection and a lessened incidence of acute graft-versus-host disease

Ninety-six patients with severe aplastic anemia who received a sex- mismatched, HLA-identical allogeneic sibling marrow transplant had sequential cytogenetic analyses performed to determine the incidence and implications of posttransplant mixed hematologic chimerism. Of the 96 patients, 56 (58.3%) became mixed chimeras with coexisting host and donor cells detected in peripheral blood or marrow 14 days or later after transplant, and 40 patients (41.7%) were complete chimeras with 100% donor-type hematopoietic cells. The incidence of mixed chimerism was independent of prior blood production transfusions and infusion of donor buffy coat. The rejection rate was significantly increased in the mixed chimeric group, particularly in patients not receiving buffy coat (14 of 36 rejecting), although overall, the majority (69.7%) retained their first graft. Rejection was seen almost exclusively in patients exposed to multiple transfusions before transplantation. If patients who reject their first graft are censored, the overall incidence of grades II through IV acute graft-v-host disease (GVHD) was significantly reduced in those with mixed chimerism. Transfused patients with mixed chimerism in particular were less likely to develop grades II through IV acute GVHD. The incidence of chronic GVHD was similar in the two groups and did not significantly influence survival. In this study, mixed chimerism persisted for up to 395 days posttransplant, either the first graft being rejected or, more commonly, hematopoiesis reverting to 100% donor-type cells. Mixed lymphohematopoietic chimerism may persist in patients with aplastic anemia who have received matched allogeneic marrow transplants for significant periods before hematopoiesis reverts to donor cell type.     

LAV/HTLV III presence in peripheral blood lymphocytes of seropositive young hemophiliacs

Recent studies indicate a high prevalence of seropositivity to the lymphadenopathy-associated virus/human T-lymphotropic virus (type III) among individuals with hemophilia exposed to clotting factor concentrates prepared from large donor pools. The peripheral blood lymphocytes of 19 young seropositive patients with inherited bleeding disorders were examined for the presence of this virus by coculture with phytohemagglutinin-stimulated lymphocytes. Viral isolates were obtained from six of 19 patients. While none of these patients have developed the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex, five of them had lymphadenopathy in two noncontiguous areas, and two showed clinically symptomatic enlarged tonsils and adenoids. Of the 13 patients in whom virus was not demonstrated, five were judged clinically normal and five had mild lymphadenopathy in one anatomical area. These results suggest that as many as 33% of hemophiliacs (six of 19 patients studied), who have circulating antibodies to mature viral proteins, have viral-infected peripheral blood lymphocytes capable of infecting other lymphocytes in vitro.     

Cyclosporin-A abrogates transfusion-induced sensitization and prevents marrow graft rejection in DLA-identical canine littermates

Previous studies had shown that marrow graft rejection generally did not occur in untransfused dogs given 900-rad total body irradiation and hemopoietic grafts from DLA identical littermates (only 1 of 59 rejected), but was seen in all instances after three preceding transfusions of whole blood from the marrow donor on days -24, -17, and -10 before transplantation (19 of 19 rejected). The present study was undertaken to investigate whether immunization by 3 preceding transfusions of whole blood from the DLA-identical littermate marrow donor could be abrogated by administration of the immunosuppressive agent cyclo-sporin-A, 20 mg/kg/day intramuscularly on days -5 to 0. Seven of 10 dogs showed sustained marrow engraftment. 2 failed to engraft, and 1 dog died to early to be evaluated. It was concluded that immunization to non-DLA antigens by preceding whole blood transfusions could be abrogated in most cases by a short-course of cyclosporin-A before total body irradiation and marrow transplantation, resulting in successful and sustained marrow engraftment.     

On the development and psychometric testing of the WHO screening instrument to assess disablement in the general population

The development and psychometric testing of the new World Health Organization (WHO) disablement screening instrument for the general population is described. Two samples were used for the empirical tests: the cross-cultural sample of the WHO Disablement Assessment Schedule (WHO-DAS II) field tests in 19 countries (N = 1323), and an Ontario (Canada) general population sample (N = 802). Psychometric tests included procedures from classical test theory as well as analyses based on item response theory (IRT), both parametric and non-parametric. Results showed that the disablement screener had good properties with respect to classical test theory, but lacked compatibility with respect to IRT criteria. This lack of compatibility with IRT criteria generally leads to a test that must be redefined for each new sample and each time it is administered. Hence, the results reported in this paper suggest that the WHO disablement screener needs revision, if it is to serve as an international cross-cultural instrument. Copyright © 1999 Whurr Publishers Ltd.