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MER administered prophylactically prolonged the survival of BALB/c mice challenged with transplants of syngeneic plasmacytomas to a moderate but significant extent. In contrast, MER exerted little therapeutic action when given alone at or after tumor implantation.

Bone marrow examination of a patient with a myeloproliferative disorder revealed monosomy for chromosome No. 6 (45,XX,-6). Two months later, during blastic crisis, reinvestigation of the bone marrow showed the presence of the Ph-1 chromosome in the previously aneuploid cell line (45,XX,-6,-22,+Ph-1). This case differs from those previously published in that the Ph-1 chromosome appeared de novo during the development of frank acute myelogenous leukemia.

The relationship between expression of xenotropic virus and the development of autoimmunization was studied in the progeny of crosses between New Zealand Black (NZB) and SWR mice. The (F1 X SWR) and F2 progeny segregated into three phenotypes: high-virus, low-virus, and virus-negative; F1 and (F1 X NZB) progeny were always high-virus. Autoantibodies, immune deposit nephritis and lymphomas developed in the progeny of these crosses. The virological phenotype of the animal could be dissociated from the presence of either autoantibodies or nephritis. For example, mice that expressed titers of virus as high as the NZB parent failed to develop signs of autoimmunization, even up to 24 mo of age. By contrast, some (F1 X SWR) and F2 mice that expressed low titers of virus developed autoimmune disease. Furthermore, a proportion of virus-negative mice produced autoantibodies and were found to have typical immune deposit nephritis. No viral antigens could be detected in the renal lesions of such virus-negative animals. By contrast with the dissociation between expression of virus and occurrence of nephritis, the presence of antibodies to DNA correlated with the development of renal lesions. We conclude that the genes that determine the expression of infectious xenotropic virus in NZB mice segregate independently from those that are involved in the autoimmune disease of these animals.

The retroviral envelope glycoprotein, gp70 was measured in the serum of New Zealand Black (NZB) and SWR mice and the progeny of their crosses. The serum gp70 values segregated to "NZB-like" and "SWR-like" levels in these mice. A complex mechanism determined the inheritance of NZB-like serum gp70 levels. We found that the factors determining the expression of this retroviral protein were independent of the genes (Nzv-1 and Nzv-2) that determined the expression of infectious xenotropic virus. Autoimmune disease, including immune deposit nephritis could be dissociated from the degree of expression of serum gp70. By contrast, presence of circulating immune complexes and anti-DNA antibody did correlate with the development of nephritis in these crosses. A significant correlation was found between high grade expression of serum gp70 and the presence of lymphomas in these mice.

A transferrin-free serum, produced by removing the siderophilin with a specific antitransferrin antibody, was incapable of stimulating the entry of iron into reticulocytes, unless it was reconstituted with pure transferrin-iron complex. These observations militate against the existence of serum factor(s), other than transferrin, capable of stimulating the incorporation of iron into reticulocytes. Comparing the effects of whole serum, pure transferrin, transferrin-free serum, and the latter reconstituted with pure transferrin, it was found that normal, pooled human serum augmented the utilization of intracellular iron for heme production, which transferrin alone did not achieve.

A transferrin-free serum, produced by removing the siderophilin with a specific antitransferrin antibody, was incapable of stimulating the entry of iron into reticulocytes, unless it was reconstituted with pure transferrin-iron complex. These observations militate against the existence of serum factor(s), other than transferrin, capable of stimulating the incorporation of iron into reticulocytes. Comparing the effects of whole serum, pure transferrin, transferrin-free serum, and the latter reconstituted with pure transferrin, it was found that normal, pooled human serum augmented the utilization of intracellular iron for heme production, which transferrin alone did not achieve.

Pre-transfusion and post-transfusion blood samples from eight individuals were typed at 10 PCR amplified loci. In no case did the PCR DNA profile of the post-transfusion blood sample differ from that of the pre-transfusion profile.

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Increased risk of delayed hemolysis following conventional minor ABO mismatched allogeneic bone marrow transplantation (BMT) has been found to be associated with peripheral blood stem cell transplantation (PBSCT), non-T-cell depletion, and immunosuppression by Cyclosporin A (CSA) or FK506. We recently demonstrated that it is possible to achieve stable engraftment with mixed or complete chimerism using nonmyeloablative conditioning consisting of Fludarabine, Busulfan and ATG followed by G-CSF mobilized PBSCT, with CSA as the sole anti-GVHD prophylaxis. Four patients (pts.) who under went NST and developed delayed hemolysis are reviewed here. All were male, of median age 18 (4–56) years. Two suffered from βThalassemia major, 1 from AML, and 1 from CML. Three were transplanted from fully matched sibling donors (2 male, 1 female), and one from a 1 locus mismatched family-related female donor. All pts. engrafted with mixed (n=3) or complete (n=1) chimerism. The donors' engrafted with mixed (n=3) or complete (n=1) chimerism. The donors' blood groups were A− (n=2), A+ (n=1) and B+ (n=1), while the recipients' were B−, A+, O+ and AB+, respectively. Clinically significant hemolysis occurred at day 173 (66–240) post-NST. Hemoglobin dropped to 5.3 (5.2–6.3) g/dL, hematocrit to 15.4 (15.3–18.9) %, with 4.1 (2.7–7.8) reticulocytes. All pts. had hyperbilirubinemia and increased LDH levels. Their haptoglobulin dropped to less than 50 mg%. In 3 recipients increased levels of isohemagglutinin IgG titers were observed. The pts. were treated successfully with multiple RBC transfusions, fluids, diuretics, plasma exchange, high dose immunoglobulins, steroids and erythropoietin. Since NST achieves a state of mixed chimerism without ablation of the recipients' B cell response to RBC-mismatched antigens, we conclude that as it may be associated with an increased risk of delayed hemolysis.

Summary A 23-year-old Ashkenazi woman with Gaucher's disease developed Coombs-positive warm-type autoimmune hemolytic anemia. Treatment with high-dose steroids resulted in complete remission within 2 weeks. Study of an additional 72 patients with Gaucher's disease revealed another case of Coombs-positive warm-type autoimmune hemolytic anemia; other autoimmune disorders were found in 17 of these patients. The possible association of Coombs-positive hemolytic anemia and Gaucher's disease is discussed.

Although full blood counts (FBC) are among the most commonly performed laboratory tests, the contribution of routine FBCs to the diagnosis of new problems is controversial. This study represents a unique linkage of a consultant haematology team, reviewing all abnormal blood counts, to an organization providing ambulatory health care to 350 000 patients. The objective was to establish the underlying clinical disorders responsible for all abnormal FBCs during a 2-month period, and to estimate the impact of the haematology team on the diagnostic work-up and management of newly identified problems. 572 (2.55%) of the 22 454 FBCs were abnormal. Of these, 357 showed microcytosis, caused by iron deficiency (58%), thalassaemia minor (35%), inflammation (6%) or chronic renal failure (1%). The most common causes of normocytic anaemia (25 patients) were disseminated malignancy and acute blood loss; of macrocytosis (27 patients), chronic liver disease and cancer; of erythrocytosis (16 patients), chronic hypoxia; of thrombocytopaenia (48 patients), chronic liver disease and ITP; of thrombocytosis (47 patients), iron deficiency and inflammation; of leukopaenia or pancytopaenia (20 patients), cirrhosis and disseminated malignancy; and of leukocytosis (26 patients), chronic leukaemias in the elderly and infection in children. Major new haematological abnormalities were encountered in 0.24% of all blood counts, representing about one new diagnosis per day. Routine blood counts do contribute to the health care of a population. Screening for haematological disease through a central clinical laboratory covering a large high-risk ambulatory population offers a cost-effective way of searching for serious clinical problems, alerting the primary physicians of their existence, and offering advice in continued evaluation and problem management.