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Two thoracic organ-transplant recipients with persistent cytomegalovirus infection developed morphologic abnormalities in their circulating neutrophils while receiving either ganciclovir or its prodrug valganciclovir. Neither patient was receiving concomitant treatment with mycophenolate mofetil or azathioprine. In both patients, the morphologic abnormalities preceded the development of neutropenia and bone-marrow hypoplasia. The morphologic changes most likely reflected interference of DNA polymerization within bone marrow progenitor cells. The changes resolved completely after the drug was withdrawn.

A retrospective study of the 99 surviving heart and lung transplant (HLT) recipients at one center showed that 31% had significant anemia (hemoglobin less than 100g/L) six months after transplantation. Chronic anemia persisted in 18% of HLT recipients two years posttransplantation. A similar study of 100 heart transplant recipients showed no unexplained anemic patients. The prevalence of anemia after HLT was unrelated to the original diagnosis, immunosuppression, or acute rejection. All HLT recipients appeared to be unduly sensitive to the myelosuppressive effects of azathioprine. Detailed studies in 16 representative patients showed a normochromic, anisocytotic anemia with normal reticulocyte counts, B12 and folate levels, and haptoglobin levels and appropriate erythropoietin levels--but increased ESRs, low/normal iron levels and low/normal total iron binding capacity, normal or raised ferritin levels, and autoantibodies in 4 (25%). Bone marrow aspirates in 10 patients showed dyshemopoiesis out of proportion to the degree of anemia and colonies of activated lymphoid cells. The cause for this anemia appears to be a combination of anemia of chronic disease and dyshemopoiesis, both of uncertain etiology.

Two transplant recipients developed striking morphological abnormalities in their circulating neutrophils while receiving mycophenolate. The changes included nuclear hypolobulation and abnormal clumping of nuclear chromatin and were presumably related to inhibition of guanosine nucleoside synthesis. In both cases the neutrophil abnormalities preceded the development of neutropenia and were thus a sign of impending hematological toxicity. The hematological changes resolved after the drug was discontinued.

The development and persistence of clinically significant red cell alloantibodies were studied in 1132 patients who underwent a heart and/or lung transplant at Harefield Hospital. Clinically significant antibodies were detected in 15 patients (1.3%) preoperatively and appeared in a further 15 (2.1%) of 704 patients followed up 1-404 weeks after surgery. Anti-D developed in only 1 of 52 D-negative recipients of a D-positive donor graft and in only 2 of 6 D-negative patients who were transfused with between 6 and 32 units of D-positive red cells. Most antibodies that appeared after transplantation remained detectable for only a few weeks. Antibodies detected preoperatively that reacted only with papain-treated cells became persistently undetectable in 4 patients who were transfused with red cells expressing the corresponding antigen specificity. By contrast, antibodies detected preoperatively by indirect antiglobulin test were still detectable after periods of up to 260 weeks in 4 patients who received only antigen-negative red cells. Immunosuppressive therapy appeared to profoundly affect the natural history of red cell alloantibody production in these patients. The underlying mechanisms warrant further study.

It is widely recommended that, during concurrent therapy with allopurinol, the azathioprine dosage should be decreased by at least two thirds. We retrospectively studied compliance with this guideline in 24 patients who had commenced allopurinol at a median of 33 months (range, 2-145 months) after heart and/or lung transplantation. The median reduction in azathioprine dose at initiation of allopurinol was 73.3% but ranged from 0% to 90% (>67% in 14 patients). Within 3 months, 11 (46%) of the patients became leukopenic (white blood cell count