Comparison of lymphangiography and computed tomography scanning in evaluating abdominal disease in stages III and IV Hodgkin's disease. A Southwest Oncology Group study.

The authors reviewed the records of 139 patients who had laparotomy plus computed tomography (CT) and/or lymphangiograms (LAG) as part of a their staging workup for Hodgkin's disease, in accordance with Southwest Oncology Group (SWOG) protocol 7808. They evaluated the relative ability of CT and LAG to detect disease in the abdomen. Two regions of the abdomen were designated, the upper and the lower, to further examine the capabilities of CT and LAG in the lower abdomen and CT in the upper abdomen. A LAG was more sensitive (P less than 0.05) than CT in detecting positive lower abdominal nodes. In the upper abdomen, CT scan had low sensitivity for detecting positive nodes, liver, or spleen. This study suggests that LAG of the lower abdomen provided more information than CT, and therefore should not be abandoned as a valid method for detecting nodal disease.

Osteomyelosclerosis with granulocytic sarcoma of chest wall. Morphological, ultrastructural, immunologic, and cytogenetic study.

A case of granulocytic sarcoma presenting as a soft-tissue tumor in the chest wall in a patient with osteomyelosclerosis is reported. The tumor mass was detected by a computed tomographic scan during an investigation of the cause of chest pain in a 58-year-old man. Biopsy of the mass showed findings compatible with either a large-cell lymphoma or a granulocytic sarcoma. The latter was confirmed by naphthol-ASD-chloracetate esterase stain and electron microscopic examination. Immunologic study of the tumor mass showed expressions of membrane/cytoplasmic CD 13 and CD 15 antigens. In addition, the tumor cells coexpressed CD 19, although all other T- and B-cell-associated antigens were absent. Cytogenetic study showed translocation t(1;7)(q11;q11) with a net deletion of the entire long arm of chromosome 7 and duplication of the long arm of chromosome 1. Peripheral blood examination showed typical leukoerythroblastosis with teardrop poikilocytosis, large hypogranular platelets, and 0.11 myeloblasts. A bilateral iliac bone marrow biopsy at this time showed osteomyelosclerosis. The patient was treated with hydroxyurea followed by local irradiation, resulting in marked reduction in the size of the tumor and in the pain. He was asymptomatic without any progression in hematologic parameters 10 months after the initial diagnosis.

Platelet function and structure in myeloproliferative disease, myelodysplastic syndrome, and secondary thrombocytosis.

Platelet function and morphologic characteristics were evaluated in 43 patients with myeloproliferative disease (MPD), 5 patients with myelodysplastic syndrome (MDS), and 7 patients with secondary thrombocytosis (ST). Platelet Factor IV (PF4) and B-thromboglobulin (BTG) showed slight elevation in ST but significant elevation in all MPDs. They were either normal or slightly elevated in MDS. Defective platelet aggregation with one or more inducers was seen in 62% of all patients. An epinephrine-induced defect was the most consistent aggregation abnormality. Hyperaggregation and spontaneous aggregation were seen in 15% of patients. Of the eight patients who showed increased bleeding tendency, all eight showed defective aggregation with two or more inducers, five showed decreased surface activation response, as well as decreased or abnormal granules and dense tubular disarray in the transmission electron microscope (TEM) study. Seven patients had clinical evidence of recurrent arterial and venous thromboses. Five of these patients showed hyperaggregation response to adenosine diphosphate and collagen and abnormal Wu and Hoak platelet aggregate ratio. Four patients showed spontaneous aggregation on aggregometer. Surface activation response was significantly increased in five patients, and an increase in platelet granules by TEM study was seen in four patients. Primary thrombocythemia could be differentiated from secondary thrombocytosis (ST) by the presence of abnormal aggregation response and significantly increased PF4 and BTG in the former, and greatly elevated plasma fibrinogen and Factor VIII, as part of acute phase reactant response, in the latter.

Primary fibrinolysis in acute monocytic leukemia.

We present the case of a young man with acute monocytic leukemia (French-American-British classification:M5) and systemic hyperfibrinolysis with severe bleeding. Although fibrinolysis is usually mild and secondary to disseminated intravascular coagulation, its role as a primary and dominant factor in rare cases of leukemia warrants that its presence be sought as a cause of abnormal bleeding. Decreased serum plasminogen and increased serum plasmin determined by synthetic substrate assay and a negative protamine paracoagulation test are crucial findings. Use of high-dose epsilon-aminocaproic acid was effective in treating this complication. A transient increase in fibrinolytic activity coincident with the early effect of antileukemic treatment suggested that plasminogen activator and/or fibrinolytic protease substances were released from leukemic cells. Fibrinolytic activity subsequently disappeared with reduction in the population of leukemic cells.

Phase II evaluation of aclarubicin in refractory adult acute leukemia: a Southwest Oncology Group Study.

Aclarubicin, a new anthracycline antibiotic, was used to treat 24 adult patients with refractory adult leukemia, using a total dose of 300 mg/m2 (75 mg/m2/day X 4). There were 20 patients with acute myelogenous and four with acute lymphoblastic leukemia. Approximately two-thirds of the patients had a Karnofsky score of less than or equal to 2, and two-thirds had received two or more previous induction programs. Interim bone marrow evaluation was obtained in 18 of 30 remission induction courses and revealed marked hypocellularity in 14, inadequate specimens in three, and persistent disease in one. Seven patients received more than one course. Two patients refused further therapy. In patients with myelogenous leukemia, there were two complete remissions lasting 10 and 16 months and one partial remission lasting 4 1/2 months. There were no responders in patients with lymphoblastic leukemia. Toxicity included profound leukopenia and thrombocytopenia, moderate nausea and vomiting, diarrhea, and mucositis. There were no cardiac symptoms associated with the drug infusion, but there were three late events possibly associated with anthracycline cardiotoxicity. Used in this dosage schedule, aclarubicin is an active, but toxic, agent in the acute myelogenous leukemias.

Nonsecretory multiple myeloma with osteoporosis: immunocytologic and bone resorptive studies.

Two patients, ultimately found to have advanced nonsecretory multiple myeloma, presented with skeletal pain, diffuse skeletal demineralization, and fractures. The correct diagnosis was initially obscured by the absence of typical hematologic findings and discrete lytic bone lesions. Bone marrow examination was diagnostic. Intracytoplasmic IgA or IgD kappa was demonstrated in the myeloma cells of each case. Decreased quantitative polyclonal serum immunoglobulins and hypercalcemia were important clinical clues. The demonstration of increased osteoclast activating factor (OAF) derived from the cultured myeloma cells from each case suggests that the secretion of OAF and immunoglobulin are unrelated.

Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone alone or with levamisole or with levamisole plus BCG for malignant lymphoma: a Southwest Oncology Group Study.

Between 1977 and 1983 the Southwest Oncology Group (SWOG) evaluated chemotherapy alone (cyclophosphamide, doxorubicin, vincristine, prednisone; CHOP) or chemoimmunotherapy (CHOP-levamisole or CHOP-levamisole-BCG) in a randomized prospective clinical trial involving 715 eligible patients with all types of malignant lymphoma (ML). Of 281 evaluable patients with favorable histologic types of ML, 171 (61%) achieved complete remission (CR) and there was no difference in CR rate, CR duration, or survival according to the type of initial treatment. Of 388 evaluable patients with unfavorable histologic types of ML, 194 (50%) achieved CR. Levamisole appeared to adversely affect CR rates in nodular mixed and nodular large-cell lymphoma and CR duration in patients with unfavorable histology ML. Chemoimmunotherapy with levamisole or levamisole-BCG offers no advantage in terms of CR rates, CR duration, or survival compared to CHOP chemotherapy alone, and levamisole may have had an adverse impact on outcome in certain subtypes of ML.

The Sézary syndrome with rapid pulmonary dissemination.

The authors report the case of a patient with long-standing Sézary syndrome who developed the acute onset of bilateral pulmonary infiltration, severe hypoxemia, and hypotension. Initial diagnostic considerations centered around infection, but an open-lung biopsy revealed "mycosis fungoides" without evidence of an infectious process. The patient showed striking improvement when given vincristine and cyclophosphamide, but ultimately died 3 months later of a nonpulmonary catheter-related infection. This rare clinical association stresses the value of open lung biopsy as a diagnostic measure even in desperately ill individuals.

High incidence of monoclonal proteins in the serum and urine of chronic lymphocytic leukemia patients.

Chronic lymphocytic leukemia (CLL) is generally considered a nonsecretory B cell immunoproliferative disorder. Conventional electrophoretic and immunoelectrophoretic methods have revealed serum monoclonal proteins in less than 10% of these patients. However, there is increasing experimental evidence from in vitro studies demonstrating that CLL cells may secrete immunoglobulins, particularly free light chains. We examined the serum and urine of 36 consecutive CLL patients for monoclonal proteins using sensitive immunochemical methods (high resolution agarose gel electrophoresis combined with immunofixation). The results obtained were correlated with the Rai stage, quantitative immunoglobulin levels, and lymphocyte membrane immunoglobulin phenotype of the leukemic cells. Twenty-three monoclonal proteins were identified in the serum or urine of 22 patients, an incidence of 61%. Six patients had serum monoclonal proteins, seven had only urinary monoclonal proteins, and nine had monoclonal proteins in serum and urine. In every instance the monoclonal protein was the same light chain type as expressed on the leukemic cells. Our findings suggest that the monoclonal proteins observed in the serum or urine of CLL patients are secretory products of the tumor cells and that their discovery is a function of the sensitivity of the method used for their detection.

Nature of intracytoplasmic crystalline inclusions in myeloma cells (morphologic, cytochemical, ultrastructural, and immunofluorescent studies).

The authors describe a 70-year-old woman with multiple myeloma and adult Fanconi syndrome. A monoclonal protein of IgA heavy-chain class and kappa light-chain class was demonstrable in the serum. Urine immunoelectrophoresis showed the presence of kappa light chains. Bone marrow aspirate showed increased plasma cells with large bundles of pink-staining Auer-rod-like crystals in their cytoplasm. These crystals failed to stain with Sudan black B, peroxidase, esterase, and PAS, but showed strong acid phosphatase and beta-glucuronidase positivity. Ultrastructural studies showed them to have a fibrillar and an unusual cross-striated pattern. Immunofluorescent studies showed strong IgA and kappa activity in the cytoplasm of the tumor cells, but the fluorescence was absent in the region of the crystals, which were identified easily by their negative birefringence. The authors interpret these observations to indicate that the intracytoplasmic crystals in this case are of lysosomal origin.

Smoldering acute granulocytic leukemia. Observations on its natural history and morphologic characteristics.

In this prospective study, 24 patients with smoldering acute granulocytic leukemia received no specific treatment. Median survival duration from diagnosis was 9.29 months. Fourteen patients died of infection, four died of hemorrhage, two (8%) progressed to aggressive acute leukemia, and three remain alive at 36, 32, and 10 months. No survival predictions could be made from the severity of leukopenia, thrombocytopenia, or both. Neither sepsis nor hemorrhage, as causes of death, segregated into short- or long-term survivors (9.0 and 8.75 months' median survival, respectively). Thirteen patients (59%) had French, American, and British M2 subclassification of acute granulocytic leukemia. The following marrow findings distinguished this entity from preleukemia and other dysplastic states: clustering of stem cells; percentage usually between 20% and 40%; and Auer rods. The use of aggressive chemotherapy v only supportive measures in this condition remains unsolved.

Colchicine in refractory chronic lymphocytic leukemia. A Southwest Oncology Group study.

Fourteen patients with active chronic lymphocytic leukemia who had failed prior therapy were treated with progressive doses of weekly intravenous colchicine beginning at 2 mg and escalating as high as 7 mg in a single injection. Responses were seen in two of 14, with a lessening of adenopathy and splenomegaly. Toxicity was characterized by gastrointestinal intolerance in eight and thrombocytopenia in 12. There is activity of the drug in chronic lymphocytic leukemia but, as administered in this study, high dose therapy is not ideal and it may be more beneficial if the drug were given as low dose daily or weekly therapy.

Long survival in acute myelogenous leukaemia: an international collaborative study.

A group of 82 adult patients with acute myelogenous leukaemia had survived in continuous first remission for more than three years was studied. These long-surviving patients were being treated at 12 referral centres in Europe and the USA, and they were compared with other patients with acute myelogenous leukaemia from 10 of these centres. There was no clear difference in the amount of induction chemotherapy or the time taken to achieve remission. Immunotherapy was not found to improve chances of long-term survival. The 82 patients were also compared with a group of 115 patients who had no appreciable difference in the number of blood or marrow myeloblasts between these two groups at presentation, but the long survivors had significantly higher initial platelet counts and were slightly younger. The long survivors also tended to have a lower total white cell count at presentation and lower granulocyte counts; there was no obvious explanation for these differences. Eight of the 82 patients relapsed from three to four years after remission and two (of 69 patients) after four to five year. Thereafter relapse was rare, and it seems likely that some of the 40 patients who have survived for five years or more are cured.

Essential thrombocythemia with transition into acute leukemia.

A 57-year-old black man with sustained platelet count of 2 million/mm3 and evidence of intermittent gastrointestinal bleeding was diagnosed as having essential thrombocythemia. Studies of bone marrow morphology, platelet aggregation, and other variables were confirmatory of the disease. The patient was treated briefly with low doses of Myleran for less than three weeks. He was then lost to follow-up study. Approximately 16 months later he reappeared complaining of recurrent nose bleeds. He was found to be pancytopenic and diagnosis of acute leukemia was made on the basis of bone marrow aspiration.