Biomedical subjects
Publications and source records attributed to U Mintz.
A case of primary cardiac non-Hodgkin's B cell lymphoma is described in a patient presenting with obstructive right heart failure. Unlike the majority of cases, in this case the tumor was diagnosed ante mortem. THe patient's history combined with the aggressive use of noninvasive echocardiography are helpful in diagnosing this rare lesion.
Twenty patients with non-Hodgkin's lymphoma (NHL) had different histologic subtypes of NHL in multiple sites or in a single tumor mass either at the time of their initial biopsy and staging (13 patients) or in the course of their disease (seven patients). These 20 cases represent 3.7% of all patients with NHL seen at the University of Chicago between January 1968 and May 1979. The five-year actuarial survival rate for all 20 patients was 68%. For those 13 patients who had multiple histologic subtypes at the initial workup, the five-year survival rate was 45%; for the seven patients who developed a new histologic subtype later in the course of the disease, the five-year survival rate was 85%. In the latter group of patients, however, the initial biopsy specimens demonstrated better prognostic subtypes, and the median survival from the time of diagnosis of a new, less favorable histologic subtype averaged only four months. These findings indicate that the prognosis is related to the least favorable histologic subtype present, unless this is only a minor component of a composite lymphoma or is limited to one extranodal site.
In the past five years, we have treated 89 patients with small-cell carcinoma of the lung with radiotherapy plus one of three chemotherapy programs. The 24 patients with disease confined to the chest (Stage IIIMO) had an 87% response rate to the combined modalities (79% complete responses) and a median survival of 18 months; 13 patients with disease confined to the chest and ipsilateral supraclavicular nodes (Stage IIIMOSCN +) had an 84% response rate (69% complete responses) and 11-month median survival; the 52 patients with distant metastases (Stage IIIMI) had a 71% response rate (15% complete responses) and eight-month median survival. Survival was not affected by adding prophylactic cranial irradiation to the latest regimen, although the CNS relapse rate was reduced. We conclude that our three chemotherapy programs to date differ very little in their effect on survival of patients with metastatic disease. New and more vigorous approaches, possibly including surgery, need to be tested for the management of disease confined to the chest. The designation of patients as Stage IIIMOSCN + is valid because such patients have better survival rates than patients with distant metastatic disease.
Hairy cells from 5 patients with greater than 25% hairy cells in the peripheral blood (4 had greater than 45% hairy cells and white blood cell counts (WBC) greater than 10,000/mm3) were studied for surface immunoglobulin (SIg) presence and distribution by two methods, for lectin-induced cap formation, and for phagocytosis of zymosan. Hairy cells from all 5 cases were found to have distinct monoclonal patterns, 2 Gk, 1 MDk, 1 Dk, and 1 GMDk, as well as cap formation with SIg. All 5 cases showed distinct lectin-induced cap formation in a percentage of cells similar to the percentage of hairy cells, and 2 of the 5 patients had hairy cells which phagocytosed zymosan. These findings contrasted with the malignant cells from 4 patients with CLL, which had monoclonal SIg but no SIg cap formation and no significant percentage of lectin-induced cap formation. Cells from 2 cases of T cell lymphomas had no SIg and no lectin-induced cap formation as did cells from 2 cases of non-lymphocytic leukemia. Hairy cells not only appear to have SIg cap formation similar to some B-lymphocytes, which in some patients also phagocytose zymosan, but also demonstrate strong lectin-induced cap formation.
A program of combination sequential chemotherapy using cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (COMLA) was administered to 42 previously untreated patients with advanced diffuse histiocytic lymphoma. Twenty-three patients achieved a complete remission as determined by strict clinical restaging criteria. The observed median duration of survival for the complete responders is longer than 33 months. Eight patients achieved a partial response, with a median survival longer than 21 months. Eleven patients showed no response, with a median survival of 5 months. Toxicity was acceptable. None of the responders have shown central nervous system relapse. There was no difference in response rates between patients with stage III or IV lymphoma or between asymptomatic or symptomatic patients. The COMLA program produces a high rate of complete and durable remissions and should be considered as an initial form of management of patients with advanced diffuse histiocytic lymphoma.
Clinical and cytogenetic studies were done on 8 patients with dysmyelopoietic syndrome: 6 of these patients had refractory anemia with an excess of blasts (RAEB), and 2 patients had chronic myelomonocytic leukemia (CMML) according to the French-American-British classification. The ages of these 8 patients (3 female and 5 male) ranged from 45 to 70 yr (median, 61.5 yr). Seven of the 8 patients died 3-86 mo (median, 11 mo) after the onset of symptoms of hemorrhage or infections. Cytogenetic studies of bone marrow cells with the Q-banding technique showed clonal karyotypic abnormalities in 7 of the 8 patients (87.5%). Five of the 7 chromosomally abnormal patients had very complex karyotypes; all 7 patients, however, had at least 1 of 4 specific changes: -5 (or 5Q-), -7, +8, and +21. Three of the 7 patients with abnormal karyotypes had had some exposure to potential mutagenic/carcinogenic agents. Five of the 7 patients had serial cytogenetic analyses, 4 of which showed evolution of the karyotype to further complexity; in 2 cases, this coincided with the evolution of the disease into acute leukemia. The median survival time of patients whose initial cytogenetic samples showed both normal and abnormal metaphases was more than twice that of patients who had only abnormal metaphases initially (12 mo versus 4.5 mo).
Ten of 55 patients with chronic myelogenous leukemia (CML) diagnosed between 1972 and 1977 were found to lack the Philadelphia (Ph1) chromosome. Serial clinical, morphologic, and cytogenetic studies of patients with Ph1-negative CML showed that 30% of them had chromosomal abnormalities. Two had an extra chromosome No. 8 at the time of blast crisis, with a morphological picture of myeloblasts in the bone marrow. A third patient had a 6:14 translocation initially Abnormalities of chromosome No. 14 are frequently seen in lymphoproliferative disorders, and the bone marrow and peripheral blood contained a significant population of lymphoblasts as well as myeloblasts. The median survival for the 10 patients was 19 months. The exact nature of Ph1-negative CML is not yet clear; disease appears to be a distinct entity among the myeloproliferative disorders.
Sixty-seven previously untreated patients with Hodgkin's disease, pathologic stages I and II, seen during a 7-year period were evaluted with respect to initial staging and treatment, as well as relapse and retreatment results. The initial treatment consisted of radiation therapy (RT) to an involved field (IF) or an extended field (EF) for patients with stages IA and IIA, or RT and, in recent cases, combination chemotherapy [cyclophosphamide, Oncovin, procarbazine, and prednisone (COPP)] for patients with stages IB and IIB. Nineteen of the 67 patients relapsed (28%), including 11 of 56 patients with stages IA and IIA (20%) and 8 of 11 patients with stages IB and IIB (73%). Seventeen of the 19 relapses occurred within 24 months after completion of the initial therapy (89%). The relapse-free survival at 5 years was 75% for the A patients and 25% for the B patients. The actuarial survival of stage IA and stage IIA patients at 5 years was 91%; there was no significant difference between patients treated initially with either IF or EF. The actuarial survival at 5 years for the patients with stages IB and IIB was 88%, as most responded to a second program of induction therapy. No correlation could be found between the pattern of relapse and the initial pathologic stage or the mode of treatment.
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The eosinophils of a patient with eosinophilic leukaemia were studied with 13 different cytochemical methods using light and electron microscopy. Apart from the 'left shift' of the eosinophils in bone marrow and peripheral blood, the following morphological changes were noted: uncoordinated maturation of the nucleus and cytoplasm, changes in size of the specific granules, and hypogranulation to such an extent that some of the cells bore only very few granules. The cytochemical studies showed a strongly positive periodic acid Schiff reaction in the eosinophils, caused by a high content of glycogen, and a relatively strong positive acid-phosphatase reaction. These cells were also tested for aryl sulphatase and coenzyme Q. Electron microscopy confirmed the presence of a high-content glycogen and a strong acid phosphatase response in the cells. Peroxidase reaction, detected in electron microscopy as well, enabled us to trace the maturation of the eosinophil cell line.
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Four postsplenectomy patients with progressive hairy cell leukemia were treated with daily low doses of an alkylating agent (chlorambucil, 4 mg). An objective response, measured by improvement in blood counts in four patients as well as decreased bone marrow involvement on core biopsy in three patients, could be documented within 6 mo. It is important to identify the postsplenectomy patient with progressive disease as early as possible in order to initiate low-dose single agent chemotherapy and have the time necessary to effect an objective response.
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We observed chromosome-banding abnormalities in leukemic cells of 46 of 90 (51 per cent) adults with acute nonlymphocytic leukemia at initial hospital admission. The difference in survival between 37 treated patients with an initially normal karyotype (10 months) and 43 with an initially abnormal karyotype (four months) was significant (P less than 0.01). When patients were classified as having acute myelogenous leukemia or acute myelomonocytic leukemia, this difference in survival was even more pronounced. Of 16 treated patients with acute myelogenous leukemia and a normal karyotype, 11 (69 per cent) had a complete remission and a median survival of 13 months. Of eight patients with acute myelogenous leukemia in whom only abnormal metaphases were observed, none had a complete remission, and the median survival was only two months (P approximately 0.50). Remission rate and median survival were not significantly different in patients with acute myelomonocytic leukemia grouped according to initial karyotypes.
Four patients with advanced diffuse histiocytic lymphoma who developed lactic acidosis are described. All four patients demonstrated disturbed liver function tests. In two of the patients, the lactic acidosis was unresponsive to treatment. The third patient responded successfully to the early initiation of combination chemotherapy with achievement of a clinical remission and correction of the lactic acidosis. The fourth patient responded to the initiation of chemotherapy with abatement of his lactic acidosis, but expired probably as the result of a pulmonary embolus. It seems likely that extensive hepatic infiltration may be one of the factors contributing to lactic acidosis in patients with diffuse histiocytic lymphoma. The early initiation of antineoplastic therapy may be important in the management of patients with histiocytic lymphoma and lactic acidosis.
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