Biomedical subjects
Publications and source records attributed to H Messmore.
A 46-year-old white man had classic findings of scleredema; subsequently, a monoclonal immunoglobulin G lambda light chain was detected in his serum. Findings of a bone marrow biopsy specimen revealed that he had an increased percentage of plasma cells, some of which were atypical. A diagnosis of scleredema and smoldering myeloma was made.
Twenty patients with myelodysplastic syndromes were treated with daily subcutaneous injections of interferon alpha 2a, at the initial dose of 3 x 10(6) U/m2. Hemogram, chemistry profile, natural killer (NK) cell activity and lymphokine-activated killer (LAK) cell cytotoxicity were monitored serially. Bone marrow with cytogenetic analysis was done before therapy and every three months afterwards. Normalization to the complete blood count, and wherever applicable, decrease in blast count of 5% or less were defined as a complete response. Improvement in hemoglobin level to 12 g/dl, neutrophil count to 1000/mm3 and platelets to 100,000/mm3 was considered a partial response. The median age was 71 (range 59-83) years and 16 of the patients were males. Two patients withdrew from the treatment in the first week and were considered ineligible. Among the other 18, two had refractory anemia, two refractory anemia with ringed sideroblasts, four chronic myelomonocytic leukemia, eight refractory anemia with excess blasts, and two refractory anemia with excess blasts in transformation to acute leukemia. Twelve patients were treated for six months, the other six were taken off the treatment after six to eight weeks because of disease progression. Only one patient with chronic myelomonocytic leukemia had a partial response for two months. NK cell activity remained unchanged before (18.3 +/- 4.6 lytic units) and during interferon therapy (19.6 +/- 5.3 lytic units). LAK cytotoxicity was not detected in any patient before therapy and was seen in only one patient (not the responder) during therapy (5.7 lytic units). The toxicity of the interferon therapy was substantial. Seventeen patients required a dose reduction and fifteen lost greater than 10% of body weight. Eleven patients (61%) developed infections requiring antibiotic therapy, and eight (44%) required hospitalization. Seven patients developed neurologic toxicity. Interferon alpha 2a is an ineffective but toxic therapy in these elderly patients with myelodysplastic syndromes.
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Forty-eight patients with polycythemia vera (PV) were retrospectively studied for incidence of acute leukemia over a 12 year period. Initial clinical features, hemogram, RBC mass, B12 levels, neutrophil alkaline phosphatase (NAP), and therapy given were studied for association with development of acute leukemia. There were 25 males and mean age at diagnosis was 61.4 years. Initial Hg was 18.38 +/- 1.86 g/dl, WBC 16.44 +/- 12.92 (x 1,000/mm3), platelets 632.94 +/- 303.81 (x 1,000/mm3), B12 1,030.93 +/- 445.20 pg/ml, and neutrophil alkaline phosphatase (NAP) score 136.63 +/- 55.14. Twenty-three patients were treated with phlebotomy alone and 25 received additional myelosuppressive therapy as follows--2 received p32 alone, 4 alkylating agents alone, 8 hydroxyurea (HU) alone, and 11 received 2 or more (multiple) of these agents. None of those treated with phlebotomy alone but 6 of 25 (24%) patients given myelosuppressive therapy developed acute leukemia (P = .03) after a mean period of 46.8 months from start of myelosuppressive therapy. Four of the 11 patients (36%) receiving multiple agent therapy developed acute leukemia (P = .019). Initial hemoglobin levels, but not the other clinical parameters, were significantly higher in patients who developed acute leukemia (P = .002), and this difference persisted in various subgroups receiving myelosuppressive therapy. Thus, high initial hemoglobin and use of any myelosuppressive therapy are associated with an increased risk of leukemic transformation in polycythemia vera. This risk becomes substantial with the use of two or more myelosuppressive agents. Since myelosuppressive therapy does not prolong survival, its role in the management of polycythemia vera should be reexamined.
Hemostatic abnormalities are present in a majority of patients with metastatic cancer. These abnormalities can be categorized as 1) increased platelet aggregation and activation, 2) abnormal activation of coagulation cascade, 3) release of plasminogen activator, and 4) decreased hepatic synthesis of anticoagulant proteins like Protein C and antithrombin III. The abnormal activation of coagulation cascade is mediated through release of Tissue Factor, Factor X activators, and other miscellaneous procoagulants from the plasma membrane vesicles of tumor cells. Macrophages of a tumor-bearing host also produce increased amounts of Tissue Factor. Production of Factor X activators and macrophage Tissue Factor is decreased by warfarin. The ability of the tumor cells to produce platelet-aggregating activity and plasminogen activator parallels their metastatic potential in animal and experimental systems. These studies also show that antiplatelet agents and antibodies against plasminogen activator can suppress the metastatic process. One or more laboratory abnormalities of hemostasis can be shown in up to 95% of patients with metastatic cancer. These abnormalities, however, are unable to predict subsequent development of thromboembolic or hemorrhagic complications. Clinical complications occur in 9-15% of the patients in the form of thrombotic or hemorrhagic disorders. The therapy of tumor-related coagulopathy should be guided by its clinical expression. Subclinical DIC should not be treated. Coumadin is generally ineffective for therapy of thrombosis in cancer patients. There is no consensus regarding the use of heparin in acute promyelocytic leukemia (APL). The defibrination in APL may be from disseminated intravascular coagulation as well as systemic fibrinolysis, as shown by decreased alpha 2 antiplasmin levels. In such cases, epsilon aminocaproic acid plus heparin therapy may be of benefit.
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