Search

Modern-day treatment for the malignant lymphomas has resulted in an improved remission rate and survival. However, in the longer run, many of these regimens are associated with a significant incidence of secondary haematologic malignancies. This study further defines this occurrence. The records from 2196 consecutive patients with lymphoreticular neoplasms were retrospectively reviewed. In each case management was on a standard chemotherapy or irradiation protocol, approved by institutional review committees, and based on histopathology coupled with clinical stage at presentation. Diagnosis of myelodysplasia or acute leukaemia was made according to the French-American-British (FAB) criteria. From 1970 to 1990, 475 individuals with Hodgkin's Disease, and a further 1721 with other malignant lymphomas, were treated. Myelodysplasia developed in 4, acute myeloblastic leukaemia in 6, possible acute lymphoblastic leukaemia in 1 and, in the remaining case, precise characterization was not possible. Of these twelve patients, comprising 0.5% of the study cohort, 5 (1.1%) had Hodgkin's Disease and seven (0.4%) other lymphoreticular tumours. The median age was sixty-eight (range 33 to 81) years; seven were male. The median latent period from therapy to onset of the secondary neoplasms was 5.6 years (range 1-15.6). Treatment was possible in four of the twelve: two achieved complete remission but relapsed, two had only partial response. None survived fourteen months. Although the incidence is small, it is again noteworthy that all but one of the patients had received alkylating agents and this re-emphasizes the need to develop effective regimens with Jess carcinogenic potential.

Hypochromic and microcytic erythrocytes, resulting from absolute iron deficiency, have a shortened survival due to ineffective production coupled with accelerated reticuloendothelial cell sequestration once released into the circulation. To explore the contribution of diminished deformability and increased fragility to these in vivo phenomena, iron status was correlated with the corresponding in vitro measurements using ektacytometry on whole erythrocytes or resealed ghost membranes. Compared to normal controls (Group 1: n = 15), those with iron deficiency of unknown origin (Group 2: n = 15), or when associated with primary proliferative polycythemia (Group 3: n = 20), were significantly less deformable and more fragile, whereas the latter category of patients, who were not anaemic (Group 4: n = 33), occupied an intermediate position. These observations support the contention that shortened intramedullary and extramedullary lifespan is contributed to by the altered physical characteristics of the red cell membrane. This observation is therapeutically important since the lesion can be readily corrected by oral iron supplementation which, at the same time, reverses the symptoms of the anaemia and prevents the development of paradoxical hyperviscosity. Additionally, it is speculated that the risk of thrombotic events in the polycythemic group may be reduced, since these appear to occur more frequently in the face of depleted body iron stores.

An unusual presentation of anaplastic large-cell (ALC) Ki-1 lymphoma is described, in which pulmonary involvement mimicked miliary tuberculosis. Lung involvement is uncommon in this type of lymphoma, and it is not clear from previous reports whether this was a presenting feature. Bone marrow involvement, rare in Ki-1 lymphoma, also was present in this case. Despite therapy skin involvement subsequently developed, and the patient died 3 months after presentation. Postmortem examination revealed lymphomatous involvement of the heart, liver, kidneys, stomach, and lymph nodes. This case highlights the need for awareness of ALC Ki-1 lymphoma particularly when it presents at uncommon extranodal sites.

Hypochromic and microcytic erythrocytes, resulting from absolute iron deficiency, have a shortened survival due to ineffective production coupled with accelerated reticuloendothelial cell sequestration once released into the circulation. To explore the contribution of diminished deformability and increased fragility to these in vivo phenomena, iron status was correlated with the corresponding in vitro measurements using ektacytometry on whole erythrocytes or resealed ghost membranes. Compared to normal controls (Group 1: n = 15), those with iron deficiency of unknown origin (Group 2: n = 15), or when associated with primary proliferative polycythemia (Group 3: n = 20), were significantly less deformable and more fragile, whereas the latter category of patients, who were not anaemic (Group 4: n = 33), occupied an intermediate position. These observations support the contention that shortened intramedullary and extramedullary lifespan is contributed to by the altered physical characteristics of the red cell membrane. This observation is therapeutically important since the lesion can be readily corrected by oral iron supplementation which, at the same time, reverses the symptoms of the anaemia and prevents the development of paradoxical hyperviscosity. Additionally, it is speculated that the risk of thrombotic events in the polycythemic group may be reduced, since these appear to occur more frequently in the face of depleted body iron stores.

In our experience, severe pulmonary tuberculosis (PTB) is often complicated by deep venous thrombosis (DVT). Because of the association between inflammation and haemostatic changes that can result in a hypercoagulable state, we have prospectively examined such predisposing factors in representative patients. Sequential analyses in a control group with active PTB showed anaemia, thrombocytosis, elevations in plasma fibrinogen, fibrin(ogen) degradation products (FDP), tissue plasminogen activator (t-PA) and inhibitor (PAI-1) with depressed antithrombin III levels. Age, sex and disease matched individuals with venographically proven DVT had higher FDP (15.8 +/- 14.3 v 3.2 +/- 1.7 micrograms/ml:P < 0.01), t-PA (19.4 +/- 14.9 v 11.3 +/- 0.8 ng/ml:P < 0.01), and functional PAI-1 activity (11.6 +/- 6.3 v 4.2 +/- 4.1:P < 0.01) with lower platelet counts (347 +/- 110 v 563 +/- 230 x 10(9)/1:P < 0.01). Fibrinogen levels in all patients rose during the first 2 weeks of therapy and, together with related disturbances, corrected within 12 weeks. In conclusion, elevated plasma fibrinogen with impaired fibrinolysis coupled with a decrease in antithrombin III and reactive thrombocytosis would appear to favour the development of DVT in PTB.

Bone marrow necrosis (BMN), defined morphologically by destruction of hematopoietic tissue, including the stroma, with preservation of the bone, is a rare syndrome. The conditions in which it is seen include sickle cell disease, acute leukemia, metastatic neoplasia, and bacterial infection, particularly when hypovolemia and septic shock are present. BMN is also associated with disseminated intravascular coagulation (DIC) following irradiation and antineoplastic therapy. The antiphospolipid syndrome (APS) is characterized by antibodies directed against the antiphospolipid substrate. Because this substrate is prominently involved in the coagulation cascade and widely distributed on cell walls, patients present with venous or arterial thromboses, recurrent abortion, thrombocytopenia, and Coombs' positive hemolytic anemia, typically with raised anticardiolipin antibodies or a diagnostic lupus anticoagulant test. BMN does not appear to have been previously recognized in this context. We report what we believe to be the first such case and suggest that the high titers of antibodies present may have played a central role in its pathogenesis.

In the presence of hepatic microsomes, vinyl chloride produces a ‘type I’ difference spectrum and stimulates carbon monoxide inhibitable NADPH consumption. A comparison of the binding and Michaelis parameters for the interaction of vinyl chloride with uninduced, phenobarbital and 3-methylcholanthrene induced microsomes indicates that the binding and metabolism of vinyl chloride is catalyzed by more than one type P-450 cytochrome, but predominantly by cytochrome P-450. Metabolites of vinyl chloride from this enzyme system decrease the levels of cytochrome P-450 and microsomal heme, but not cytochrome b5 or NADPH-cytochrome c reductase in vitro.