Immunocytochemical detection of tumor cells in bone marrow and peripheral blood stem cell collections from patients with ovarian cancer.

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.

Multicentric angiofollicular lymph node hyperplasia with peripheral neuropathy, pseudotumor cerebri, IgA dysproteinemia, and thrombocytosis in women. A distinct syndrome.

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.

Treatment of diffuse histiocytic lymphoma (DHL) with COMLA (cyclophosphamide, oncovin, methotrexate, leucovorin, cytosine arabinoside): a 10-year experience in a single institution.

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.

Treatment of metastatic colorectal carcinoma with cisplatin and 5-FU.

Twenty patients with measurable metastatic colorectal carcinoma were treated every 3 weeks with cisplatin (100 mg/m2 iv) on Day 1 and 5-FU (1000 mg/m2/day by iv infusion over 24 hours) on Days 1-5. Seven patients were previously treated with chemotherapy. The mean performance status for all of the patients was 1.5 (Eastern Cooperative Oncology Group). None of the patients had an objective response to the chemotherapy; 11 patients had stable disease and nine had no response. This study demonstrates that the combination of cisplatin and 5-FU, administered at this dose and schedule, has minimal activity in patients with metastatic colorectal cancer.

Angiolymphoid hyperplasia demonstrating extensive skin and mucosal lesions controlled with vinblastine therapy.

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.

Sinus histiocytosis with massive lymphadenopathy: response to cyclophosphamide therapy.

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.

Anticipatory nausea and vomiting associated with cancer chemotherapy.

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.

Absence of prolonged benefit of initial leukapheresis therapy for hairy cell leukemia.

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.

The treatment of lymphoblastic lymphoma with antithymocyte globulin.

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.

Response to 5-azacytidine in patients with refractory acute nonlymphocytic leukemia and association with chromosome findings.

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.

Prognostic significance of the Lukes and Collins classification in patient treated with COMLA.

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.

Survival of patients with localized diffuse histiocytic lymphoma.

Twenty-eight patients with previously untreated diffuse histiocytic lymphoma (DHL) were identified to be in pathologic stage (PS) I (11), IE (3), II (8), or IIE (6) by exploratory laparotomy and splenectomy. Six patients were treated with total nodal radiotherapy; 14 with an extended mantle; 5 with an inverted Y or whole abdomen; and 3 with an involved field. Twenty-six patients achieved a complete remission (93%) and 2 patients had persistent local disease. The median survival and disease-free survival and for the complete response group are 56 and 51.5 mo, respectively. Ten of the 11 stage I or IE patients had supradiaphragmatic lymph node disease. Patients with stage I or IE disease (n = 14) demonstrated a median survival of 72.5 mo and a median disease-free survival of 69.5 mo; there was 1 disease-related death. Patients with stage II or IIE disease (n = 14) demonstrated a median survival of 33 mo and median disease-free survival of 29.5 mo; there were 10 relapses or deaths. Patients in stages I, IE, II, or IIE with infradiaphragmatic disease (n = 7) had a median survival of 36 mo, while patients with supradiaphragmatic presentation (n = 21) demonstrated median survival of 68 mo (p = 0.37). The data indicate that patients with diffuse histiocytic lymphoma with stage I supradiaphragmatic lymph node disease are curable using radiotherapy alone, achieving a 93% 11-yr actuarial disease-free survival. Patients with stage II or IIE diseases are not readily curable with radiation therapy alone, achieving a 33% 11-yr actuarial disease-free survival; radiotherapy with adjuvant chemotherapy or chemotherapy alone should be considered for this group.

delta 9-Tetrahydrocannabinol as an antiemetic for patients receiving cancer chemotherapy. A pilot study.

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.

Diffuse histiocytic lymphoma with sclerosis: a clinicopathologic entity frequently causing superior venacaval obstruction.

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.

Late relapses in Hodgkin disease.

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).