Hodgkin's disease and non-Hodgkin's lymphomas.
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Biomedical subjects
Publications and source records attributed to L M Fuller.
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Fifty-eight laparotomy-staged I and II patients with upper torso presentations of Hodgkin's disease and 8 patients with lymphangiogram-staged lower torso disease were treated with radiotherapy alone or with 2 cycles of MOPP and radiotherapy. Patients with upper torso disease with either no mediastinal or only small mediastinal disease without hilar involvement and with no "B" symptoms were treated with mantle radiotherapy alone. Patients with large mediastinal masses or hilar disease were treated with 2 cycles of MOPP followed by definitive mantle irradiation and low dose lung irradiation. Those for whom "B" symptoms were the only adverse prognostic feature received 2 cycles of MOPP and mantle radiotherapy. Patients with lower torso disease were treated with radiotherapy alone if the disease was limited to the pelvis. Those with more extensive disease received 2 cycles of MOPP prior to radiotherapy. The 4-year survival for all 66 patients was 97%. The corresponding disease-free and freedom from second relapse figures were 77% and 92%. Survival for the patients with unfavorable presentations who received 2 cycles of MOPP and radiotherapy was 100%. It was 92% for the group with favorable presentations who were treated with radiotherapy only.
Thirst mechanisms in Brattleboro rats are activated because of a deficiency in circulating vasopressin. Plasma osmolality, renin, and angiotensin II (ANG II) are increased. We measured the responsiveness of Brattleboro rats and appropriate control strains to cellular and extracellular thirst stimuli taking the spontaneous base-line water intake into account. Brattleboro rats drank more in response to intraperitoneal hypertonic NaCl than controls, but when their fluid losses were prevented by nephrectomy they did not overdrink. Despite low urinary concentration, Brattleboro rats excreted the sodium load at least as rapidly as the controls. Brattleboro rats drank after intracranial injection of renin, renin substrate, and ANG I and II. The dose-response curves were similar to controls, although the Nottingham Long-Evans control strain drank significantly less in response to some doses of the peptides. Intracranial captopril inhibited renin- and ANG I-induced but not ANG II-induced drinking. Isoproterenol reduced spontaneous drinking of Brattleboro rats but increased drinking in controls. However, when urinary losses were prevented by ureteric ligation, isoproterenol caused markedly greater water intake in Brattleboro rats than in controls. Subcutaneous captopril in moderate, thirst-enhancing doses also caused a larger increase in water intake in Brattleboro rats than in controls. Therefore the renin-angiotensin system of Brattleboro rats is more responsive to renin-dependent thirst challenges than that of normal controls.
Changes in stimulated and non-stimulated whole saliva flow rates were measured in 11 Hodgkin's disease patients who received therapeutic doses of radiation to a mantle field at the M. D. Anderson Hospital in Houston, Texas. Salivary flow rates were examined before, during, and after radiotherapy. Mean flow rate reductions of 54% for non-stimulated saliva and 55.7% for paraffin-stimulated saliva were observed post-radiotherapy. Flow rates had not returned to pre-irradiation levels in any of the patients who were observed for two to three months after completion of therapy. Results obtained from this preliminary study indicate that most patients who receive therapeutic doses of radiation to a mantle field experience a significant reduction in salivary output which is manifest during the period of treatment and persists for a period of at least two to three months post-radiotherapy.
One hundred two adult patients with stage III1A (76 patients) and stage III1B (26 patients) Hodgkin's disease were treated with two cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and radiotherapy (XRT) between 1970 and 1984. Sixty-four of the patients were treated between 1970 and 1978 with two cycles of MOPP and XRT to the mantle, upper abdomen, and pelvis. The remaining 38 patients were treated from 1978 to 1984 with a modification of the protocol in which pelvic XRT was omitted and low-dose whole-lung XRT was administered to patients with unfavorable mediastinal disease. The 10-year actuarial freedom-from-progression (FFP) and determinate survival rates at a mean follow-up of 93 months were 84% and 86% for stage III1 disease, 86% and 84% for stage III1A disease, and 78% and 91% for stage III1B disease. Three patients died of treatment-related toxicities without evidence of Hodgkin's disease, two died of complications of myelosuppression and one of acute nonlymphocytic leukemia (ANLL). Neither FFP nor determinate survival rates were significantly influenced by B symptoms, unfavorable mediastinal disease, histologic subtype, extent of abdominal disease, the omission of pelvic XRT, the use of whole-lung XRT, or the number of splenic nodules. Patients 40 years of age or older had a 73% determinate survival rate at 10 years compared with 88% for patients younger than 40 years (P = .01). This survival difference was due to treatment-related toxicity in the older group. This study indicates that two cycles of MOPP and XRT to the mantle and upper abdomen is as effective as more intensive treatment for all patients with stage III1 Hodgkin's disease. This treatment program can preserve fertility and has had only a 1% actuarial incidence of ANLL at 15 years.
As part of the treatment for lymphoma, disease involving the supraclavicular region has been treated with megavoltage 60Co photons to a midline dose of 30 to 45 Gy through an anterior involved field and a supplementary posterior field when necessary. The spinal cord was shielded with a 5 cm lead block during treatment to the posterior field. A typical 40 Gy treatment results in a dose to the lower cervical and upper thoracic spinal cord in the range of 22 to 26 Gy, a level that could compromise subsequent mediastinal treatment in the event of a relapse. To reduce this cord dose, the midportion of the anterior supraclavicular 60Co To reduce this cord dose, the midportion of the anterior supraclavicular 60Co field was replaced with a high-energy (13 MeV) electron port, which reduces the dose to the cord to below 6 Gy in the average adult patient. This modification of the routine supraclavicular treatment allows greater flexibility in future treatment in the event of a mediastinal relapse.
Ninety-one patients with Hodgkin disease of the upper torso who had mediastinal masses were studied to determine the frequency of residual mass and the time required for resolution or stabilization of the mass. In 72 of these patients, radiographs from sufficient intervals were available for determination of the rate of regression. In 62 patients (86%), the mediastinum returned to normal width within 11 months, regardless of the size of the mass. The mediastinum returned to normal in all but one patient with small masses. The intrathoracic relapse rate did not correlate with the regression time of the masses, but relapse occurred more than twice as often in patients with residual mediastinal widening.
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From 1975 to 1982, 74 patients with stage III follicular lymphoma were treated with a combined modality protocol which included chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo), and radiotherapy to involved regions. This program resulted in a complete remission (CR) rate of 81%, a 5-year survival of 75%, and 5-year relapse-free survival (RFS) of 52% for all patients. Analysis of potential factors affecting treatment outcome revealed a significantly better CR rate for patients with small cleaved cell type (97%) than for patients with mixed (73%) or large-cell (57%) histologies. The 5-year survival was significantly better for patients with small cleaved (91%) and mixed (84%) cell types than for large cell (40%). In addition, bulky abdominal disease and elevated serum lactate dehydrogenase (LDH) were significant adverse prognostic factors for CR and for survival. Toxicity was moderate. No secondary leukemias have occurred. This combined modality regimen resulted in prolonged remission and potential cure for over half of patients who achieved CR, and is particularly encouraging for those with follicular small cleaved and mixed histologies.
Circadian rhythms in cortisol and testosterone in both blood and cerebrospinal fluid (CSF) were studied in four groups of male and female talapoin monkeys. Samples were taken 4 h apart under two conditions: whilst the sexes were kept separate (isosexual) and again after 24 h of interaction (heterosexual). There were similar rhythms in cortisol in males and females during the isosexual condition, though in blood (but not in CSF) mean levels were higher in females. Heterosexual interaction increased cortisol levels in both sexes (though more so in males), and also altered the shape of the rhythm, acrophase being delayed by 4 h in males and by 2 h in females. The amplitude of the rhythm was not altered. Cortisol levels were positively correlated in both males and females with the amount of aggression received from other males, but not from females nor with the animal's social rank. Circadian rhythms in serum testosterone in males were also altered by heterosexual interaction. Access to females delayed acrophase by 2 h, but had no effect on mean levels (unlike the effect on cortisol). As for cortisol, the amplitude of the testosterone rhythm remained unchanged. Serum testosterone was negatively correlated with aggression from males, but not from females nor with sexual interaction. This was associated with a pronounced decrease in the levels of testosterone during the night, not observed in males receiving no aggression from others. There was a non-significant trend towards a positive correlation between social rank and serum testosterone.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical features and treatment results are analyzed for 76 patients with Stage I-II follicular lymphoma seen between 1974 and 1981. During this period, 66% of the patients received involved-field radiotherapy (XRT) alone, and 34% received chemotherapy with or without XRT. At 5 years, the overall survival was 67%, the cause-specific survival was 73%, and the relapse-free survival (RFS) was 48%, with no relapses to date among nine patients followed beyond 60 months. Adverse prognostic features for survival included extranodal disease and elevated serum lactate dehydrogenase. For RFS, adverse features included extranodal disease and bulky abdominal disease. The RFS was significantly better for patients receiving chemotherapy with or without XRT than for XRT alone (64% versus 37% at 5 years, P = 0.02), despite a higher frequency of adverse prognostic features in the chemotherapy-treated group. About 50% of Stage I-II follicular lymphoma patients may be curable, and the inclusion of chemotherapy in the initial treatment may increase the potentially curable fraction.
This study was undertaken to ascertain the influence of both more precise staging and more intensive treatment on results in 38 patients with Stage IE and IIE lymphomas of the thyroid. These patients were admitted between 1947 and 1984. Using the modified Rappaport system, the disease was classified as diffuse large cell in 32 patients. The initial investigation included lymphangiography in 25 patients, five of which had a staging laparotomy. The assigned stages were IEA--11, IEB--1, and IIEA--26. Treatment consisted of definitive radiotherapy alone in 15; combination chemotherapy and radiotherapy in 14; and chemotherapy alone in 6 patients. The remaining three patients were treated with surgery alone. In general, combination chemotherapy consisted of cyclophosphamide, Adriamycin, vincristine, and prednisone, with or without bleomycin (CHOP +/- Bleo). The overall 5-year survival and disease-free survival were 72 and 64%, respectively. For patients treated with radiotherapy only, results depended on stage. For Stage IE, the survival and disease-free survival were 100 and 83%, respectively. The corresponding Stage IIE results were 88 and 75%. Within this group, results were better for a subset of patients where disease did not involve the mediastinum. Survival and disease-free survival for combined modality treatment were both 77% (10 of these 17 patients had Stage IIE disease). Survival and disease-free survival for combination chemotherapy were 53 and 30% (all had Stage IIE disease). In conclusion, radiotherapy alone is excellent treatment for disease limited to the thyroid with or without cervical adenopathy. Results for patients with mediastinal extensions was unsatisfactory and the addition of combination chemotherapy is indicated.
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Previously untreated adult patients who presented with advanced diffuse large-cell lymphoma (DLCL) at diagnosis were studied to identify possible prognostic factors. One hundred five patients were seen between 1974 and 1981; 45 patients were stage III and 60 patients were stage IV. All patients received cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo). Stage III patients also received radiation therapy alternated with chemotherapy. Overall survival was 50% at 5 years and 43% at 8 years. Seventy-four patients achieved a complete remission (CR) and 37 are alive and disease-free with a median follow-up of 72 months. There was no difference in clinical outcome between stage III and stage IV. However, a proportional hazards model identified lactic dehydrogenase (LDH) level and tumor burden, among all clinical factors studied, as independent risk factors for survival. These two factors were also important for achievement of remission and relapse-free survival. Three distinct patient risk groups were identified with 5-year survival rates of 87%, 48%, and 20%, respectively. The measure of tumor burden proposed herein, along with LDH level, can be used for developing treatment programs, and for meaningful comparison of different treatment regimens, as well as assessment of prognosis.
Extranodal lymphomas which present in the nasal cavity and/or the paranasal sinuses are rare. Thirty-eight patients with disease that was clinically limited to the head and neck (Ann Arbor Stages IE-IIE) were admitted between 1947 and 1983. Twenty-eight patients were treated with radiotherapy alone and 10 received combination chemotherapy in addition. The overall 5-year survival figure was 56%. The corresponding result for Stage IE was 67%. No patient with Stage IIE disease survived 5 years. Extent of the extranodal disease also influenced results for Stage IE patients who were treated with radiotherapy only. When the extranodal disease was staged using the American Joint Committee TNM system, the 5-year disease-free survival for T1 and T2 patients was 78% as compared with 19% for patients with T3 and T4 disease. The addition of combination chemotherapy improved results for patients with T3 and T4 lesions.
Gastric lymphoma can be treated effectively by a combination of chemotherapy and radiotherapy of the intact stomach; this often eliminates the need for gastrectomy. This article presents 21 patients with gastric lymphoma and compares the radiographic appearance of the intact stomach before and after treatment. There was a variable decrease in lymphomatous involvement of the stomach during the first several months after radiotherapy alone or in combination with chemotherapy. Gastric atrophy with diminished distensibility and constrictive changes was observed, but most remarkable was the appearance of linitis plastica.
In adrenalectomized, deoxycorticosterone-treated and normal rats, injection of angiotensin II through a cannula implanted in the preoptic region caused increased intakes of hypertonic NaCl and water when both fluids were available, whereas injection of carbachol through the same cannula only caused increased water intake. Carbachol depressed NaCl intake of adrenalectomized rats that were allowed access to hypertonic NaCl after being deprived of it for 24 h. Angiotensin-stimulated rats were more likely to go into positive sodium balance than controls, whereas carbachol-stimulated animals were more likely to go into negative balance. After angiotensin, adrenalectomized or deoxycorticosterone-treated rats drank a larger proportion of their total fluid intake as hypertonic NaCl than did normal rats. Angiotensin caused significant increases in sodium excretion in normal, isotonic saline-loaded and deoxycorticosterone-treated rats, but not in adrenalectomized rats, although angiotensin caused increased intakes of NaCl in all groups. On the other hand, carbachol caused a significant increase in sodium excretion at 1 h in all groups despite the absence of an increase in NaCl intake. After angiotensin, only normal rats showed a significant kaliuresis at 1 h, whereas all carbachol-injected rats showed increased potassium excretion. Therefore, angiotensin is a primary stimulus to increased sodium appetite, normally acting in conjunction with other stimuli which enhance its effect, whereas carbachol is a central inhibitor of sodium appetite.
A long-term analysis of the clinical outcome of previously untreated adult patients who presented with stage IV diffuse large-cell lymphoma at diagnosis was performed to identify possible prognostic factors. Sixty-one patients were seen between 1974 and 1981; all were treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin followed by cyclophosphamide, vincristine, prednisone, and bleomycin for a total of one year. Overall five-year survival was 48.5%, with a median follow-up of 53 months. Of the 56 patients evaluable for remission status, 41 achieved a complete remission, and 27 are alive and disease free. Clinical factors of prognostic importance for survival included age, constitutional symptoms, lactate dehydrogenase (LDH) level, presence of mediastinal disease, large-cell infiltration of bone marrow, and number of extranodal sites of disease. The proportional hazards model then identified age, number of extranodal sites, and, to a lesser extent, serum LDH level as independent risk factors for survival. Four distinct patient risk groups were identified using these three factors. Younger patients with only one extranodal site of disease and normal LDH levels responded well on this therapy, with 100% alive at five years. In contrast, survival was less than 30% at five years for patients in the lowest risk group. There were 11 relapses; LDH level, constitutional symptoms, and mediastinal disease predicted for relapse. Knowledge of these risk factors permits individualization of treatment planning and allows more meaningful comparisons with the results of treatment studies using other intensive regimens.