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High-dose chemotherapy (HDC) followed by autologous hematopoietic reconstitution is an experimental treatment option for patients with epithelial ovarian cancer. However, the incidence of occult ovarian tumor cell involvement in autologous bone marrow (BM) or peripheral blood stem cell (PBSC) autografts has not been widely investigated. We used a highly sensitive immunocytochemical (ICC) procedure that detects occult blood-borne tumor micrometastases. We analyzed 24 BM specimens (15 obtained during therapy and 9 harvest samples) and seven PBSC specimens from 22 patients with ovarian cancer. Overall, ICC analysis detected immunostained tumor cells in 10 of 23 evaluable BM specimens (43%) from 9 of 19 patients (47%). One of 9 (11%) harvest samples contained tumor cells. Only one of the 10 ICC-positive BM specimens had tumor cells detected by routine histopathological analysis. ICC-detectable tumor cells were cleared from the marrow of two patients during chemotherapy. None of the seven PBSC specimens contained tumor cells. We conclude that ovarian cancer micrometastases have the potential to contaminate BM, as is also the case in patients with other epithelial malignancies. In the limited number of specimens analyzed, PBSC harvests appeared to provide a less tumor-contaminated source of hematopoietic stem cells for autologous transplantation.

Four women with multicentric angiofollicular lymph node hyperplasia had a distinct clinical syndrome characterized by peripheral neuropathy, pseudotumor cerebri, IgA dysproteinemia, and thrombocytosis. The nodes displayed typical morphologic changes of the plasma cell variant of multicentric angiofollicular lymph node hyperplasia. The pathologic changes are morphologically distinct from angioimmunoblastic lymphadenopathy with dysproteinemia although clinical similarities do exist. In these four cases, the lymphadenopathy was usually bulky and multicentric. There was frequent splenic involvement. The neuropathies were severe and disabling. Clinical courses have been variable with some responses to therapy with steroids and alkylating agents. No neoplastic transformations have occurred. Multicentric angiofollicular lymph node hyperplasia may represent a reactive lesion in which the antigenic stimulus is unknown but results in follicular hyperplasia, angiogenesis, and the systemic manifestations of hyperimmune stimulation. We believe this clinical syndrome may represent a distinct variant of multicentric angiofollicular lymph node hyperplasia, and it requires close observation for neoplastic transformation and other complications of its multisystem nature.

Fifty adult oncology outpatients receiving chemotherapy were surveyed to assess their experiences with chemotherapy-associated nausea and vomiting. Of patients who noted post-chemotherapy nausea with or without vomiting, 46% reported anticipatory nausea. The anticipatory symptoms developed after the onset of post-chemotherapy neausea. Patients experiencing anticipatory symptoms had received chemotherapy over a significantly longer period of time than had the patients with post-treatment nausea only. Of these patients who had noted post-chemotherapy nausea with or without vomiting for two or more months, 50% reported pre-treatment nausea with or without vomiting. There was no tendency toward anticipatory symptoms according to age, sex, race, educational level, disease, or type of chemotherapy. Thoughts of chemotherapy, sights, specific odors and tastes evoked anticipatory symptoms. Pre-treatment or anticipatory nausea and vomiting are probably a manifestation of classical (Pavlovian) conditioning.

The consequences of radiation and antineoplastic therapy on the fetus are summarized. Animal and atom bomb studies clearly demonstrate the carcinogenic effects of radiation. Less information is available on neoplasia and neonatal malformations induced by chemotherapy, but there may be an increased risk. The delayed consequences of radiation and chemotherapy are not well known and require further study.

A 20-year-old man with previously treated lymphoblastic lymphoma, a known T-cell disorder, developed progressive disease despite intensive combination chemotherapy with doxorubicin, vincristine, and prednisone. He was subsequently treated with a 21-day course of intravenous antithymocyte globulin at a dose of approximately 15mg/kg per day. This resulted in a marked reduction in lymphadenopathy as determined by physical examination and chest x-ray. Toxicity was limited to minor pruritus which resolved with diphenyldramine and hydrocortisone premedication.

Among a cohort of 142 patients with Hodgkin disease (HD), pathologic stages (PS) IA through IVB, 84 remained in complete remission (CR) at least 3 years after the completion of initial protocol therapy. Eight of these patients subsequently developed a recurrence of HD and were defined as having a late relapse. The disease-free interval ranged from 37 to 76 months (median 53 months). Six of the relapse patterns were those of dissemination. All patients were salvaged and are in CR from 14 to 50 months after relapse. The actuarial survival, measured from the time of relapse, of the eight late-relapsing patients was superior to the actuarial survival of 38 patients with early relapse (disease-free interval less than 36 months), but as yet this difference is not statistically significant (P = 0.07, Gehan).

Chronic lymphocytic leukaemia is a disorder with variable clinical presentation, but with constant and easily recognizable morphological features. The majority of cases are of B-cell lineage, the cells being characterized by IgM and IgD surface markers. In occasional cases monoclonal gammopathies with idiotypes identical to those of the SIg are produced. Some cases of CLL may be confused with Waldenström's macroglobulinaemia. The clinical and morphological features of certain other lymphoproliferative disorders have been summarized. Finally, a progression of B-cell differentiation along an immunoexpressive spectrum has been described and the relative position of CLL defined. A correlation of cell morphology and function is possible in most cases. The possibility that CLL may terminate in an acute blastic crisis or histiocytic lymphoma is raised. It is emphasized that LPD include a wide range of diseases, some being non-malignant, others of questionable malignancy, and still others being frankly malignant. Clinical, morphological and immunological data are required for diagnosis in some cases.

We retrospectively reviewed the cases of eight patients with histiocytic lymphoma (reticulum-cell sarcoma) appearing as a primary bone lesion. Histological findings were classified according to the criteria of Rappaport. Lesions were staged as suggested by the Ann Arbor Conference. After thorough staging, four of the eight patients were shown to have more extensive disease than was initially thought, which altered the therapeutic approach used. Thorough staging is necessary for improved survival of patients with histiocytic lymphoma of bone. We suggest a diagnostic strategy for patients with histiocytic lymphoma presenting in bone that leads to appropriate therapy.

Four patients with malignant lymphoma who were treated with multiple courses of combination chemotherapy, consisting of cyclophosphamide, Oncovin, procarbazine, and prednisone (COPP), developed avascular necrosis of the femoral head(s). Disorders usually associated with the development of avascular necrosis were absent. The total prednisone dose received by each patient was small. Avascular necrosis of the femoral head should be considered in the differential diagnosis of bone pain in patients receiving multiple courses of combination chemotherapy.

Four patients with the leukemic phase of hairy cell leukemia were treated with leukapheresis. Two patients failed to respond, and the other two had only transient responses; hematologic improvement lasted one month in one case and four months in the second. The patient with a four-month response underwent a second series of leukapheresis resulting in a response lasting at least 8 months. Two of the four patients subsequently had an adequate trial of prolonged chlorambucil therapy and continued to have a clinical response. We conclude that leukapheresis has little to offer to the majority of hairy cell patients for the long-term management of post-splenectomy patients who develop the leukemic phase. However, an occasional patient can have a transient, and even, rarely, a prolonged response.

A patient with sinus histiocytosis with massive lymphadenopathy is described. After attempts to control lymph node size and constitutional symptoms with corticosteroids were unsuccessful with radiation therapy and nonsteroidal anti-inflammatory drugs, the patient was treated with two courses of low doses of oral cyclophosphamide therapy. He remains in complete remission 15 months after therapy was discontinued.

We conducted a pilot study to ascertain the potential toxicity and possible efficacy of delta 9-tetrahydrocannabinol (THC) at the oral dose of 5 mg/m2. Over one third of the study population, which consisted of 25 patients, reported significant dysphoric reactions. Four patients (16 per cent) elected not to take THC rather than experience loss of motivation which interfered with their professional life. Paradoxically, on eight occasions nausea seemed to worsen with THC. After the first administration of THC, 18 patients (72 per cent) described less nausea and only two individuals (8 per cent) noted complete resolution of nausea. Two patients reported worsening of their nausea. Eighteen patients noted less vomiting (69 per cent) after the first administration of THC and four patients (15 per cent) reported completed resolution of their vomiting. By the third administration of THC, one of 14 patients (7 per cent) and two of 14 (14 per cent) noted complete alleviation of nausea and vomiting, respectively. Patients who scored high on the Brief Psychiatric Rating Scale, who reported euphoria, or who had psychogenic nausea and vomiting were most likely to have a favorable antiemetic response. The results of this pilot study suggest that orally administered THC is a toxic but transiently effective antiemetic when administered at 5 mg/m2.

Between March 1974 and December 1983, 83 patients with diffuse histiocytic lymphoma (DHL) were treated with COMLA (cyclophosphamide 1.5 g/m2 day 1; Oncovin (Lilly, Indianapolis) 1.4 mg/m2 days 1, 8, and 15; and cytosine arabinoside 300 mg/m2 and methotrexate 120 mg/m2 days 22, 29, 36, 43, 50, 57, 64, and 71; and leucovorin 25 mg/m2 every six hours X 4, beginning 24 hours after methotrexate). For the purpose of analysis, patients were divided into two groups. Group 1 (n = 54) included patients age 65 or under who had received no prior curative radiotherapy or chemotherapy. Group 2 (n = 29) included all patients over age 65 and patients who had received prior curative radiation therapy or prior minimal chemotherapy. The median time of follow-up for all patients was 28 months. Group 1 included 11 stage II, ten stage III, and 33 stage IV patients. Of 48 evaluable patients in this group, 21 (44%) achieved a complete remission (CR), eight (17%) achieved a partial remission (PR), and 19 (40%) showed no response (NR). Median survival of CR patients was 114+ months, PR patients, 42 months, and NR patients, 13 months. Six CR patients relapsed. The median disease-free survival of CR patients was 108+ months. Group 2 included nine stage II, seven stage III, and 13 stage IV patients. Of 24 patients evaluable for response, eight (33%) achieved a CR, six (25%) achieved a PR, and ten (42%) showed no response. The median survival of CR patients was 114+ months, that of PR patients was 17 months, and that of NR patients, 9 months. Two CR patients relapsed. The median disease-free survival of CR patients had not been reached at 102 months. The regimen was well tolerated in most patients and toxicity was acceptable. We conclude that COMLA is a well tolerated outpatient chemotherapy regimen capable of inducing durable CRs in some patients with DHL. Results achieved with COMLA, however, are inferior to those of more aggressive treatment programs; thus, the use of COMLA as first-line therapy in DHL should be limited to those patients unable to tolerate a more aggressive treatment program.

A patient with retroperitoneal and axillary lymphadenopathy and splenomegaly was demonstrated histologically to have the hyaline vascular type of giant lymph node hyperplasia, with plasma cell infiltrates in each region. The abdominal lesions were not surgically resectable and did not respond to radiotherapy. The clinical findings included polyclonal gammopathy, high cold agglutinin titers, neuropathy, and bilateral papilledema. All of these abnormalities have persisted three years since the initial diagnosis.

The preferred histopathological classification of Hodgkin's disease (HD) is that suggested by Lukes and Butler as modified at the Rye Symposium; the histologic subtypes are highly reproducible and correlate well with the anatomic sites of involvement, clinical stage, and survival. The accuracy of the bipedal lymphangiogram, 67gallium scan, and ultrasonography in predicting abdominal involvement by HD is 90% , 50%, and 88%, respectively. Staging laparotomy remains the most accurate method of detecting intra-abdominal disease and has added immensely to new concepts in the management of HD. These concepts suggest that patients with nodal disease limited to the celiac axis or upper para-aortic areas (substage III1) or pathologic stage (PS) IIIS+N-A, when treated with extended field radiotherapy alone have survival rates comparable to PS IIA patients. In contrast, patients in PS IIIA with lower abdominal nodal disease (substage III2), regardless of splenic involvement, have a prognosis comparable to PS IV disease. Thus, there may only be two stages of HD, those curable with extended mantle or smaller radiotherapy fields alone, and those requiring chemotherapy with or without supplemental radiotherapy.

The Lukes and Collins classification was applied to 47 patients who received COMLA (cyclophosphamide, vincristine, methotrexate, leucovorin, and cytarabine) as initial treatment for diffuse histiocytic lymphoma (DHL). Pathologic staging was complete in 39 of 47 patients; two patients had stage IIE disease, 17 had stage III, and 28 had stage IV. Complete remission, which was documented by extensive clinical restaging, was achieved in 25 (64%) of 39 patients with morphologic B-cell lymphomas and in only three of eight patients with non-B-cell lymphomas. The medial duration of complete remission is significantly longer in patients with B-cell lymphomas than in those with non-B-cell lymphomas (45 + versus 13 months, P less than 0.01). Among patients with DHL, median survival is significantly longer for those with B-cell lymphomas than for those with lymphoma of T-cell or in determinate origin (60 + versus 6 months, P less than 0.01). While DHL is regarded as a curable disease, patients not achieving complete remission are rarely salvaged; median survival for these patients was 10 months. The Lukes and Collins classification allows us to identify patients with DHL in whom newer therapies are needed for initial treatment. Further study may enable us to identify additional unfavorable subsets in the B-cell category.

Since Kimura's original description of an unusual subcutaneous disorder with distinctive histologic features of vascular and lymphoid proliferation, numerous descriptions of diseases with similar features have been reported. A variety of descriptive labels, including Kimura's disease, angiolymphoid hyperplasia (ALH) with eosinophilia, atypical pyogenic granuloma, papular angioplasia, and histiocytoid hemangioma, have been applied to these diseases. Although this information has broadened our understanding of the clinical and pathologic spectrum of ALH, the etiology and/or pathogenesis remains unknown. Our case report illustrates the wide range of clinical features of ALH, demonstrating extensive lesions on skin and mucosa. The extreme histologic variability with regard to eosinophils, lymphoid infiltrates, and vascular alterations is also illustrated. Dramatic response to vinblastine sulfate treatment has not been previously reported and may provide a viable treatment alternative in selected patients.

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.

Patients with malignant lymphoma, diffuse type, have an unfavorable prognosis when compared to those patients with modular patterns. Prior to the introduction of combination chemotherapy, 50% survival rates for MC-D or PDL-D were about 2 years, HL-D about 1 year. Aggressive combination chemotherapy for advanced MC-D or PDL-D results in complete remission rates of 22-82%, with median survivals of 1-2 years. Patients with localized HL-D are probably curable with radiotherapy alone in 75% of cases. Patients with advanced disease are best treated with intensive combination chemotherapy, achieving a long-lasting complete remission in over one-half of cases, with median survivals now at 1-3 years. Many of these patients are probably cured, central nervous system relapse may now be a concern. The results of treatment of advanced histiocytic lymphoma are now approaching the results reported for advanced Hodgkin disease.

Twenty of 65 patients with diffuse histiocytic lymphoma were identified by staging laparotomy as being in pathologic stages (PS) I, I(E), II, II(E). Six of the 20 patients were treated with total nodal, 10 with extended mantle, and four with involved-field radiotherapy. The survival rate and relapse-free survival at five years were 71% and 78%, respectively. All relapses occurred within the first year and were confined to patients with PS II disease and four or more sites of involvement. Accurate pathologic staging identifies patients who are potentially curable with radiotherapy. Further studies are required to determine the treatment necessary to achieve cure in PS II patients with more than four sites of involvement.

Of 107 patients with diffuse histiocytic lymphoma (DHL) seen at the University of Chicago, 14 (13%) were classified as having moderate to marked sclerosis. Three of the 14 (21%) had predominantly retroperitoneal masses. Fifty percent of our group, however, had bulky disease seen predominantly or exclusively in the mediastinum, and all of these individuals had superior venacaval (SVC) obstruction. Of the seven patients with SVC syndrome, three were in Pathologic Stage IIA, three were in Clinical Stage II, and only one was in Clinical Stage IIIA. No other patients with DHL displayed SVC obstruction or predominantly mediastinal disease. Five of seven patients with SVC syndrome had large cleaved cell histology. In spite of an apparently favorable histopathologic subtype and a tendency to localized involvement, patients with DHL and sclerosis who have bulky or disseminated disease appear to be resistant to megavoltage radiotherapy alone and relatively resistant to combination chemotherapy.

The first documented case of primary histiocytic lymphoma of the epididymis is presented. The tumor showed distinct nodularity, which is unusual for extranodal lymphomas, and marked sclerosis. Extensive staging work-up showed no evidence of extraepididymal spread. Unusual features included the youth of the patient at presentation and the severe diffuse atrophy of the adjacent testicular parenchyma. Following orchiectomy and radiotherapy, there has been no subsequent clinical evidence of systemic disease.

Twenty-one patients with grade III or IV astrocytomas were assigned randomly to receive either BCNU alone or BCNU and VM-26 after surgery and radiation therapy. Patients surviving radiation therapy and receiving single-agent chemotherapy had a median survival of 14 months while those receiving combination chemotherapy had a median survival of 22 months (P greater than 0.05). None of the patients who failed BCNU-only therapy responded to VM-26. Performance status was not affected by either regimen. Computerized tomographic scanning of the brain was useful only in confirming tumor progression. Two patients died from BCNU-related interstitial pulmonary fibrosis.

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.

The malignant lymphomas are reviewed, and involvement of urogenital-ridge derivatives, including the reproductive organs, is summarized. Implications of therapy for pelvic lymphoma are discussed. It is shown by a retrospective analysis that Hodgkin's disease has little effect on fertility, the course of gestation, delivery or fetal wastage and that maternal death is not increased. No adverse effect of pregnancy on the symptoms or longevity of women with Hodgkin's disease can be demonstrated. Women diagnosed in pregnancy as having lymphoma should undergo therapeutic abortion so that proper staging and therapy may be given. Pregnancies over 32 to 34 weeks should be induced. Women previously treated for lymphoma may become infertile as a result of therapy. Those not infertile after therapy should avoid pregnancies since there is a potential risk of malformations and malignancies in the offspring.

Fifteen patients with acute nonlymphocytic leukemia (ANLL) who either had a relapse after a previous complete remission (nine patients) or progressive disease after initial induction attempts with combination chemotherapy (six patients) were treated with 5-azacytidine. Five patients (33%) achieved a complete remission (CR); of these, three had a relapse and died 30, 35, and 38 weeks after 5-azacytidine therapy was begun. Two patients are still alive at 39 and 138 weeks. Chromosomes were analyzed at the time of diagnosis; ten patients had a normal karyotype and five had an abnormal karyotype. Three of the five CR patients had an abnormal karyotype initially. Two of these individuals had a translocation of chromosomal material from a No. 8 chromosome to a No. 21 chromosome, t(8;21); this particular translocation has been associated with a better prognosis than have other types of chromosomal abnormalities in patients with ANLL. Even when abnormal chromosomes are present, 5-azacytidine can induce complete remission in patients with previously treated ANLL.

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.