Inhibition of hematopoiesis by a plasma factor in a case of aplastic anemia associated with systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) may be associated with inhibition of hematopoiesis mediated by antibodies, T-cells or both. A 41-year-old woman with a five-year history of SLE treated with prednisone was admitted to Cabrini Medical Center in New York. The patient complained of fever, chills, arthralgias, general malaise, weakness and dyspnea on exertion, and showed malar rash, pallor, and a systolic ejection murmur along the left sternal border. Admission work up included a CBC with evidence of moderate pancytopenia, a normal EKG, and a normal chest X-ray. The patient's anemia was symptomatic and required a transfusion of packed red blood cells (PRBC's). Bone marrow biopsy and aspiration revealed an aplastic marrow with few hypoplastic islands of hematopoietic elements. The patient was treated with plasmapheresis, achieving immediate progress towards recovery. Bone marrow culture studies (erythroid BFU-E, and myeloid CFU-GM) were done by incubating various titers of the patient's acute phase plasma with normal bone marrow cells. This was done to determine if the patient's plasma contained any hematopoietic inhibitory activity, as has been reported in other cases. Our experiments demonstrated marked inhibition of erymathropoiesis and myelopoiesis in vitro, when various titers of the patient's plasma were included in the culture media. Control plasma produced no inhibition. These studies support the hypothesis that a circulating antibody which inhibits hematopoiesis may be produced in SLE patients with aplastic anemia, and be responsible for it.

Skin manifestation of agnogenic myeloid metaplasia.

Agnogenic myeloid metaplasia (AMN) with myelofibrosis is a clonal malignancy of the hematopoietic stem cell. The disease is characterized by increased endothelial cell and fibroblast proliferation, resulting in increased deposition of fibronectin, laminin, and collagen in the bone marrow. In advanced disease, extramedullary hematopoiesis (EMH) is invariably seen in the spleen and liver. The lymph nodes are also frequent sites of EMH, but other organs, especially the kidneys, arenals, lungs, pleura, ovaries, gastrointestinal tract, and dura, may also be involved. Skin manifestations are rare. They may present in several ways: erythematous plaques, nodules, diffuse or papular erythema, ulcers, and bullae. Histopathology of these lesions reveals cells from one or more myeloid lineage in the dermis, erythroid, or megakaryocytic series alone or in combination. In rare cases, all three cell lines are demonstrated.

Specificity of heme for hemopoietic recovery from AZT toxicity.

The toxicity of azidothymidine (AZT) was studied on normal human bone marrow hemopoietic colony growth as determined by assays of CFU-E, BFU-E, and CFU-GM. The potential sparing effect of hemin and heme analogues on AZT-suppressed bone marrow was also investigated. AZT at a lower concentration (0.1 mumol/L) inhibited CFU-E by 68%, BFU-E by 84%, and CFU-GM by 59%. AZT at a higher concentration (1.0 mumol/L) inhibited CFU-E by 88%, BFU-E by 90%, and CFU-GM by 69%. Addition of hemin (10 mumol/L) to cultures containing AZT (0.1 mumol/L) increased CFU-E growth by 279%, BFU-E by 282%, and CFU-GM by 72%. A similar concentration of heme analogues did not have an enhancing effect; in contrast, zinc protoporphyrin (ZnPP) was inhibitory to bone marrow progenitors CFU-E, BFU-E, and CFU-GM. In addition, no enhancement of colony growth was obtained when progenitor cells were cultured in the presence of 10(-2)-10(-5) M iron. These results demonstrate that exogenous hemin has a specific beneficial effect on human bone marrow hematopoietic progenitor cells which is not seen with iron or other metalloporphyrins. Furthermore, this beneficial effect includes a reversal of the cytotoxic effect of AZT on bone marrow progenitors.

Hodgkin's disease and AIDS. Twenty-three new cases and a review of the literature.

Despite numerous reports suggesting an association of Hodgkin's disease (HD) with the acquired immunodeficiency syndrome (AIDS), HD in an individual seropositive for the human immunodeficiency virus (HIV) still is not considered a criterion for the diagnosis of AIDS. The authors report 23 new cases of HD in individuals at risk for AIDS and review the literature. As a group, individuals at risk for AIDS who develop HD have a more aggressive form of the illness (82% with stage III or IV), have or develop AIDS-related opportunistic infections (54%), second neoplasms (10%), and /or profound cytopenias (32%), and 85 to 90% are HIV positive when tested. More than two thirds die within 1 year of the diagnosis of HD. The authors conclude that HIV infection alters the clinical course of HD, that advanced or high-grade HD in HIV-infected individuals should be considered indicative of AIDS, and all patients with HD should be tested for HIV.

Splenectomy in patients with AIDS.

To establish the indications for splenectomy in patients with human immunodeficiency virus (HIV) infection we retrospectively analyzed 12 patients who underwent splenectomy. Patients with HIV infection who had immune thrombocytopenic purpura (ITP) were excluded as they had no splenomegaly and a definite indication for splenectomy exists in some of these patients. All 12 patients were anemic; 6 were thrombocytopenic and 6 leukopenic. All patients had splenomegaly and all were febrile. At surgery 3 patients were found to have Mycobacterium avium intracellulare (MAI) infection; 2 had splenic abscess due to Salmonella group D; 1 each had cytomegalovirus (CMV) splenitis and localized Kaposi's sarcoma (KS) of the spleen. No definite histopathologic diagnosis could be made in five patients, all of whom had evidence of extramedullary hematopoiesis. The degree of splenic enlargement did not correlate with the outcome. Both clinical and hematologic improvements were achieved in patients with splenic abscess and in patients who had splenomegaly, anemia, and thrombocytopenia. The presence of either of these findings constitutes an indication for splenectomy. Anemia and/or leukopenia without thrombocytopenia failed to improve; the presence of MAI and active CMV infection also resulted in failure. The presence of either of these conditions may be considered a contraindication to splenectomy.

Microenvironmental toxicity of azidothymidine: partial sparing with hemin.

Azidothymidine (AZT) is a useful drug in management of AIDS. Nevertheless, its hematologic toxicity such as anemia and neutropenia present further complications to an already compromised hematopoietic state in patients. We studied the effects of AZT on human and murine bone marrow (BM) colony growth as determined by assays of CFU-E, BFU-E, CFU-GM, and fibroblastoid stromal (CFU-Fb) colonies. Cultures were grown in methylcellulose with growth factors and scored after three- to 14-day incubation. In general, murine marrow cultures were more sensitive to AZT as compared with human marrow. Furthermore, interindividual variation in toxicity to AZT was observed between marrow samples; 1 mumol/L AZT inhibited murine CFU-E, BFU-E, and CFU-GM by 98% to 100%, whereas human marrow was inhibited by 52%, 87%, and 65%, respectively. Lower concentrations of AZT (0.1 mumol/L) inhibited murine erythroid colony growth by 85% to 90%, whereas human growth was inhibited by only 39% to 52%. Myeloid colony inhibition was similar for human and murine systems. CFU-Fb growth was markedly suppressed (75%) by 1 mumol/L AZT. Hemin, at a concentration of 10 mumol/L, overcame some of the inhibitory effects of 1 to 0.1 mumol/L AZT without hindering antiviral activity. Inhibition of human CFU-E growth was completely overcome with hemin, whereas CFU-GM growth was recovered to 66% to 74% of control. A similar but less pronounced effect was observed for BFU-E. Furthermore, hemin does not decrease AZT's effects of HIV antigen content in vitro. We conclude that anemia and neutropenia, occurring as a result of AZT, may not be as pronounced in the presence of hemin. Furthermore, CFU-Fb was significantly reduced in the presence of low concentrations of AZT. This may indicate a major target site for BM toxicity since the stromal microenvironment may be responsible for maintaining short- and long-term hematopoiesis.

A clinicopathologically distinctive primary splenic histiocytic neoplasm. Demonstration of its histiocyte derivation by immunophenotypic and molecular genetic analysis.

We describe a primary splenic neoplasm composed of cytomorphologically malignant-appearing erythrophagocytic histiocytoid cells reminiscent of those seen in malignant histiocytosis. However, this neoplasm displayed certain distinctive clinicopathologic features--including localization to the spleen, where it grew as separate discrete nodules--that distinguish it from all previously reported cases of malignant histiocytosis. The cells expressed a monocyte/histiocyte immunophenotype and lacked clonal immunoglobulin and T-cell receptor beta-chain gene rearrangements. Our results suggest that this neoplasm represents a clinicopathologically distinctive and possibly unique tumor derived from the tissue macrophage lineage.

Autoimmune thrombocytopenic purpura in homosexual men.

Since November 1980 we have diagnosed 11 cases of severe autoimmune thrombocytopenic purpura in homosexual men; their mean platelet count (+/- SE) was 16 000 +/- 3000/mm3. All patients have been sexually active with multiple partners and exposed to numerous viruses and drugs. During this period, we also have diagnosed 20 cases of classic autoimmune thrombocytopenic purpura in heterosexual persons, with a normal women to men ratio of 3:1. Eight of nine homosexual patients had elevated platelet IgG compared with normal values in eight of 10 homosexual control subjects having normal hemograms (p less than 0.01). All responded moderately or completely to steroids. The three patients who had splenectomy had excellent responses. Four of five patients had a decreased helper/suppressor T cell ratio compared to healthy controls (p less than 0.001). Circulating immune complexes and total gamma globulin levels were elevated and lymphocytes relatively decreased in homosexual patients compared with homosexual controls (p less than 0.05). Thus, some sexually-active homosexual men seem to have an increased incidence of an immune regulation disorder directed against platelets.

Production paroxysmal nocturnal hemoglobinuria-like red blood cells by tea.

Normal human red cells incubated with saline extracts of tea develop paroxysmal nocturnal hemoglobinuria-like defects as demonstrated by positive acid and sucrose hemolysis tests. All of a variety of tea preparations tested provoked a sensitivity to complement-dependent hemolysis and, with one exception, a moderate decrease in red cell acetylcholinesterase activity. Complement-dependent hemolysis in teaincubated red cells was inhibited by antisera to C3 and C3 activator, but not by antisera to C4. This suggests that incubation with tea may alter the red cell membrane in a way that specifically potentiates the lytic effects of the alternate pathway of complement, but not the classic pathway. Leupeptin, a protease inhibitor, also prevented complement-dependent hemolysis of red cells incubated with tea. Although the clinical consequences of these observations are unknown, the study was initiated following a report of a young male who had developed an acute limited intravascular hemolytic episode following ingestion of large quantities of a herbal tea.