Clinical presentation and natural history of patients with essential thrombocythemia and the Philadelphia chromosome.

Six women presented with the clinical picture of essential thrombocythemia (ET) without the anemia, marked splenomegaly, and extreme leukocytosis characteristic of chronic myelogenous leukemia (CML). All had the Philadelphia chromosome on karyotype analysis of the bone marrow. Peripheral basophilia was present in four cases, providing a clinical clue that the Philadelphia chromosome might be present. Marrow biopsy showed granulocytic hyperplasia and either small megakaryocytes or sheets of megakaryocytes with marked atypia, findings that are more typical of CML than ET. The clinical importance of finding the Philadelphia chromosome in patients who seem to have ET is in assessing prognosis. ET generally follows a chronic, indolent course. However, five of these six patients who had the Philadelphia chromosome underwent clinical transition to the accelerated phase of CML or blastic leukemia in 4-7 years.

Diminished interleukin 2 production and receptor generation characterize the acquired immunodeficiency syndrome.

The Acquired Immunodeficiency Syndrome (AIDS) is a disease found primarily in homosexual men, consisting of opportunistic infections and tumors, and is due to an acquired T-cell defect. In the present report, we studied various T-cell functions which might serve to distinguish homosexuals with a symptom complex including lymphadenopathy from those with AIDS. T lymphocytes from the lymphadenopathy and AIDS patients had markedly depressed proliferative responses in the autologous (auto) and allogeneic (allo) mixed lymphocyte reaction (MLR) compared to healthy homosexuals or heterosexual controls (P less than 0.001). Since proliferation in the MLR depends upon interleukin 2 (IL-2), a T-cell growth factor, we studied the production of and response to IL-2 in various groups of homosexuals and heterosexual controls. IL-2 production was markedly depressed in the lymphadenopathy and AIDS patients, 1.0 and 0.1 U/ml, respectively, compared to the healthy homosexual or heterosexual controls, both 5.0 U/ml (P less than 0.05 and P less than 0.01, respectively). Although the auto MLR of the lymphadenopathy patients rose to control values with the addition of exogenous IL-2, the auto MLR of the AIDS patients did not (P less than 0.01). This lack of responsiveness to IL-2 in the AIDS group was due to their inability to generate IL-2 receptors as shown by the absence of IL-2 absorption by activated cells and the absence of the Tac antigen (IL-2 receptor) on these same cells. The T4+ and T8+ T-cell subsets from the AIDS patients each demonstrated depressed IL-2 production and responsiveness following activation with autologous cells or mitogen, as well as the absence of Tac antigen. The diminished T-cell proliferation in the auto MLR in the lymphadenopathy group is associated with one defect, low IL-2 production, while the depressed proliferation in the AIDS group is associated with two defects, low IL-2 production and a lack of IL-2 receptor generation. These studies demonstrate that IL-2 receptor generation helps distinguish homosexuals with lymphadenopathy from those with AIDS, and that in addition to T-cell defects in the OKT4+ T-cell subset there are significant abnormalities in the OKT8+ T-cell subset in AIDS patients.

Hematologic toxicity of cisplatin and mitomycin in combination for squamous cell carcinoma of esophagus.

Seventy-six patients with squamous cell carcinoma of the esophagus (SCE) were treated with either cisplatin and mitomycin in combination or as single agents on ECOG protocol 2278. Sixty-six patients were evaluated for toxicity. Of 13 evaluable mitomycin and cisplatin treated patients, six (46%) experienced ECOG grade 4 thrombocytopenia and/or leukopenia. Of 28 evaluable patients treated with mitomycin alone, two (7%) experienced such toxicity; and of 25 evaluable patients treated with cisplatin alone, none experienced this toxicity. The average total dose prior to toxicity for those receiving mitomycin and cisplatin in combination was 51 mg and 131 mg, respectively, with average time to toxicity 3.6 weeks. For those two patients who received mitomycin alone, the average total dose was 68 mg and average time to toxicity 6.5 weeks. For those patients receiving cisplatin alone, the average total dose was 220 mg. The reasons for the enhanced hematologic toxicity of the agents together are not apparent, but it would be prudent to caution investigators using these agents in combination with potentially myelosuppressive drugs.

Association of subacute motor neuronopathy with thymoma.

A case of subacute motor neuronopathy in association with thymoma is described. Subacute motor neuronopathy is marked by a painless, progressive, and asymmetric muscle weakness that usually affects the lower extremities. It is a rare paraneoplastic effect of tumors that has been described with both Hodgkin's and non-Hodgkin's lymphoma. This is the first case report of its association with thymoma.

Further characterization of the erythrocyte membrane protein abnormality in megaloblastic anemia.

Erythrocyte membranes obtained from patients with severe megaloblastic anemia contain spectrin as indicated by double immunodiffusion against anti-spectrin raised in rabbits. These membranes have normal protein patterns determined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate after solubilization at 100 degrees C for 3 min in SDS. When incubation is carried out at 37 degrees C for 3 hours, however, the membrane protein patterns become grossly abnormal, lacking spectrin, band 3 and having several diffuse smaller bands. Cross-linking of these membranes with SH oxidizing agents, such as diamide prevented this dissociation phenomenon. The SH group content of megaloblastic membranes, both from severe and mild megaloblastic anemia, was significantly higher than that of control membranes. This was also confirmed by the greater incorporation of 3H-N-ethylmalemide into red cell membranes from mild and severe megaloblastic anemia than controls. Incorporation of this probe was greatest into the band 3 region. These findings indicate that the erythrocyte membrane proteins in megaloblastic anemia have an intrinsic abnormality which renders them more susceptible to degradation by their endogenous proteases.

Lentigo maligna in a woman with oculocutaneous albinism.

A 54-year-old black woman with oculocutaneous albinism was found to have a lentigo maligna and, subsequently, a pigmented compound nevus on non-sun-exposed areas of her body. The diagnosis for these lesions was confirmed by the results of histopathologic study. To our knowledge, this is the first such case reported in the literature. This patient reemphasizes the fact that melanoma development is dependent on the presence of melanocytes, but not necessarily on melanogenesis. We propose that the rarity of melanomas in these patients may be caused by the protective effect of unknown systemic factors.

Thrombocytopenia with decreased megakaryocytes. Evaluation and prognosis.

The presenting clinical pictures and courses of seven patients with thrombocytopenia, decreased megakaryocytes in the marrow, and minimal changes in other hematopoietic cell lines are described. Little information exists in the literature on such patients. Initial bone marrow aspiration and biopsy in all patients showed decreased megakaryocytes with an otherwise normal marrow. Erythrocyte mean corpuscular volume was elevated in five of seven patients. Bone marrow karyotypes of six of the seven patients were normal. Chromium-51 platelet survival studies with platelet sizing, done in five of the seven patients, showed normal results. In two patients the course progressed to aplastic anemia. One of these died 9 months after presentation, and one responded dramatically to lithium. One patient developed preleukemia and died. The other four patients have remained thrombocytopenic but clinically stable. No useful therapy was identified. The differential diagnosis of such patients should include idiopathic thrombocytopenic purpura with misinterpretation of morphologic findings, hereditary and acquired aplastic anemia, preleukemia, and systemic lupus erythematosus.