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PubMed1982

Effect of age on therapeutic response and survival in advanced Hodgkin's disease.

Although age is a recognized prognostic factor in advanced Hodgkin's disease, there are few data concerning the use of combination chemotherapy in patients greater than 60 years. In two phase III trials of the Cancer and Leukemia Group B, 385 previously untreated patients with stage III or IV Hodgkin's disease received multidrug chemotherapy. All patients received a combination of either mechlorethamine or a nitrosourea, as well as a vinca alkaloid, procarbazine, and prednisone. Two hundred and five patients were less than 40 years of age, 107 were 40-59 years, and 73 were greater than or equal to 60 years. The overall response rates in these three age groups were 70%, 66%, and 40%, respectively. Age at the time of diagnosis was the predominant factor affecting response, and the response rate was not significantly higher in those older patients who received full doses of chemotherapy. Age was also associated with an increased frequency of serious leukopenia and thrombocytopenia. The group of patients greater than or equal to 60 years of age experienced the shortest median time to recurrence, 33 months. The intermediate age group also had a shorter time to recurrence (median, 44 months) than patients less than 40 years (median not yet reached). The low complete response rate and the short duration of response in the patients greater than or equal to 60 years of age resulted in a median survival time of 18 months. Even when the analysis of restricted to just the older patients who received greater than or equal to 90% of the projected drug doses, the complete remission rate, the median time to recurrence (20 months), and the duration of survival (27 months) are still much shorter than in younger patients.

Adult↗
PubMed1982

Long-term complications of MOPP chemotherapy in patients with Hodgkin's disease.

Two hundred and sixty-three patients in long-term remission from Hodgkin's disease were evaluated for complications of chemotherapy. All patients were interviewed by telephone conversation and reported complications were documented by chart review. Treatment consisted of mantle and para-aortic irradiation in 127 patients, total nodal irradiation (TNI) in 32, TNI and MOPP in 34, and mechlorethamine, vincristine, prednisone, and procarbazine (MOPP) chemotherapy alone or with lesser irradiation in 70. In this study, greater than 90% of the men who received MOPP remain infertile. In contrast, a substantial portion of female patients treated with MOPP chemotherapy have retained normal menses (58%) and only a small proportion have had persistent amenorrhea (9%). Five of eight female patients desiring families after MOPP chemotherapy have had normal children. The risk of developing a major infection requiring hospitalization was greatest in those patients who had received TNI and MOPP chemotherapy. The risk of developing a herpes zoster infection was greatest during or within the first year following therapy and was greatest in those patients receiving combined radiation therapy and chemotherapy. Nearly 100% of patients continue to lead normal lives following treatment for Hodgkin's disease. Only a small percent of patients (1.5%) have been totally disabled following treatment.

Adolescent↗
PubMed1981

Ethanol mustard cytotoxicity in vitro toward murine leukemia and bone marrow progenitor cells.

Ethanol mustard, 2-[bis(2-chloroethyl)amino]ethanol-picrate, was approximately one tenth as cytotoxic as mechlorethamine toward both murine bone marrow progenitor cells and L1210 leukemia cells. Choline protected cells against nitrogen mustard cytotoxicity, but increased their sensitivity toward ethanol mustard. 2-(di-n--butylamino)ethanol was the best protector of both bone marrow precursor cells and L1210 cells against ethanol mustard cytotoxicity. Both ethanol mustard and 2-(di-n-butylamino)ethanol showed non-competitive inhibition of choline transport.

Animals↗
PubMed1995

Peripheral T-cell non-Hodgkin's lymphoma following treatment of nodular lymphocyte predominance Hodgkin's disease.

Previous reports have suggested that nodular lymphocyte predominance Hodgkin's disease (NLPHD) is a germinal center-derived B-cell lymphoma that is distinct from other types of Hodgkin's Disease. A relationship between NLPHD and simultaneous or subsequent development of large-cell (LC) non-Hodgkin's lymphoma (NHL) has been established. Both Reed-Sternberg cell variants in NLPHD and NHL cells in these cases express B-cell-associated antigens, and in some cases the B-cell lineage of the NHL has been confirmed by immunoglobulin gene rearrangement studies. The B-cell phenotype and the indolent course of both lymphomas suggest histologic progression of NLPHD to B-cell NHL, rather than a de novo LCNHL unrelated to Hodgkin's Disease. We report a unique case of T-large-cell lymphoma (TLCL) following successful chemotherapy of NLPHD. A 54-year-old male was treated with seven cycles of mechlorethamine, vincristine, procarbazine, prednisone chemotherapy for NLPHD and 4 years later developed recurrent adenopathy. Lymph node biopsy showed a diffuse LCNHL. Frozen section immunotyping and gene rearrangement studies confirmed the diagnosis of TLCL. To our knowledge, this case represents only the second report of TLCL associated with NLPHD and is of significance in that: (1) it demonstrates that T-cell neoplasia can occur in the setting of NLPHD; (2) this case does not appear to represent histologic progression of NLPHD and most likely represents de novo disease that may be secondary to chemotherapy; and (3) the clinical course may differ from the favorable prognosis seen in NLPHD associated with B-cell NHL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Treatment of cutaneous T-cell lymphoma.

A review of current therapy for cutaneous T-cell lymphoma (CTCL) (mycosis fungoides and erythrodermic CTCL) is presented. Treatments for mycosis fungoides limited to the skin include topical steroids, mechlorethamine (nitrogen mustard) and carmustine (BCNU), electron beam radiation, low-dose methotrexate, and interferon-alpha (IFN). Treatments for erythrodermic CTCL include low-dose methotrexate, IFN, extracorporeal photopheresis, and single agent or combination chemotherapy. Treatment for systemic CTCL includes IFN, single or combination chemotherapy, and combined modalities. Newer therapies are reviewed. Whereas prognosis for patients with disease limited to the skin is generally good, that for those with nodal or visceral lymphoma is mostly unfavorable. Controversial issues relating to total skin versus local treatment, prolonged maintenance versus intermittent therapy, and aggressive versus conservative treatment of early stage disease are discussed. The UCSF approach to treatment of CTCL and lymphomatoid papulosis is presented.

Carmustine↗
PubMed1995

Topical treatment of early cutaneous T-cell lymphoma.

The two major topical treatment modalities for cutaneous T-cell lymphoma (CTCL) are mechlorethamine (nitrogen mustard) and topical carmustine (BCNU). Topical mechorethamine hydrochloride has been used since the late 1950s as therapy for CTCL. Topical BCNU solution is a highly effective treatment for early stage mycosis fungoides. This article describes these two modalities.

Administration, Topical↗
PubMed1996

Factors influencing the drug sensitization of human tumor cells for in situ lipofection.

The cisplatin induced enhancement of in situ lipofection was optimized by considering the factors that can increase the degree of sensitization. Two other anticancer drugs, mechlorethamine (nitrogen mustard) and taxol, enhanced CAT gene expression but the degree of sensitization was not as great as cisplatin. Besides human 2008 ovarian cancer cells we also found that human lung (A549) and head and neck cancer cells (SCC 25) were transiently sensitized by cisplatin. The transfectability of the two commercially available cationic liposomes, Lipofectin and LipofectAmine, was either weak or not consistent among tumors tested. In vivo transfection efficiency of 2008 cells was the highest at 1 microgram DNA per nmol or microgram liposome with all three cationic liposomes. In vitro transfection efficiency of 2008 cells at 1:1 (microgram of DNA:nmole of DC-chol/DOPE liposome) increased in a dose-dependent manner while at 1:10, an optimal ratio for in vitro lipofection, rapidly decreased with an increase in dose. This result indicated that there was a correlation between in vivo and in vitro lipofection at 1:1 ratio for delivering liposomal DNA. Most of the DNA injected into the tumor was concentrated in the tumor and in the skin above the tumor whether cisplatin was preinjected or liposomes were used as carriers.

Animals↗
PubMed1997

Comparison of nitrogen mustard, cytarabine and dacarbazine as pleural sclerosing agents in rabbits.

We have previously shown that the intrapleural injection of mitozantrone but not bleomycin resulted in pleural fibrosis. Mechlorethamine hydrochloride (nitrogen mustard) was used extensively in the past to control malignant effusions, with relatively good success. The objective of this study was to determine if the intrapleural injection of nitrogen mustard would produce pleural sclerosis in our experimental model in rabbits. We therefore evaluated sclerosing capabilities of nitrogen mustard as well as those of cytarabine and dacarbazine. Nitrogen mustard (0.4 and 0.8 mg x kg(-1)), cytarabine (3, 6 and 20 mg x kg(-1)) and dacarbazine (4, 8 and 20 mg x kg(-1)) were instilled intrapleurally into anaesthetized rabbits. Twenty eight days after the instillation, the animals were killed, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The intrapleural injection of 0.8 mg x kg(-1) nitrogen mustard was effective in creating pleural fibrosis, either grossly or microscopically. The mean degree (scale 0-4) of gross pleurodesis in the rabbits that received 0.8 mg x kg(-1) nitrogen mustard was 3.2+/-1.0 and the mean degree of microscopic pleural fibrosis was 3.5+/-0.8. The intrapleural injection of 0.4 mg x kg(-1) nitrogen mustard and the different doses of cytarabine (3, 6 and 20 mg x kg(-1)) and dacarbazine (4, 8 and 20 mg x kg(-1)) were ineffective in producing pleurodesis. From this study, we conclude that the intrapleural injection of 0.8 mg x kg(-1) of nitrogen mustard produces clinically significant pleurodesis in rabbits. Consideration should be given to future clinical studies utilizing 0.6-0.8 mg x kg(-1) nitrogen mustard intrapleurally for the treatment of malignant pleural effusion.

Animals↗
PubMed1976

Study of in vivo tumor state and response to therapy by analysis of DNA distribution.

The growth characteristics of an in vivo tumor model were studied. This tumor offers an intermediate system useful for the study of tumor cells in the intact animal, but does not have the complexities of solid tumors. DNA distribution was correlated with macromolecular DNA synthesis. Mechlorethamine, BCNU, radiation, and hydroxyurea were studied and produced perturbation in stationary phase-cell kinetics. There was a redistribution of cell ages consistent with induced cycling activity with most, but not all, of the above agents. This indicated a recruitment from a stationary phase by cancer therapeutic agents, although subsequent cell-cycle traverse may also be greatly perturbed. A number of considerations important to the interpretation of this type of data are discussed.

Animals↗
PubMed1986

Histiocytosis X. Flow cytometric DNA-content and immunohistochemical and ultrastructural analysis.

A 76-year-old man developed a generalized orange-red nodular eruption associated with constitutional symptoms. A biopsy specimen of a nodule revealed an extensive infiltration of histiocytes with relatively abundant cytoplasm and folded nuclei. Electron microscopy showed Langerhans' cell granules, which confirmed the diagnosis of histiocytosis X. Results of immunohistochemical studies revealed a pattern of antigen expression usually found in histiocytosis X, including Ia, T6, and S100. Analysis of the DNA content of the cells with flow cytometry revealed an aneuploid peak. The patient responded partially to topical mechlorethamine hydrochloride therapy.

Adult↗
PubMed1980

Antiemetic effect of tetrahydrocannabinol. Compared with placebo and prochlorperazine in chemotherapy-associated nausea and emesis.

Fifty-five patients harboring a variety of neoplasms and previously found to have severe nausea or emesis from antitumor drugs were given antiemetic prophylaxis in a double-blind, randomized, crossover fashion. Tetrahydrocannabinol (THC), prochlorperazine, and placebo were compared. Nausea was absent in 40 of 55 patients receiving THC, eight of 55 patients receiving prochlorperazine, and five of 55 in the placebo group. The antiemetic effect of THC appeared to be more efficacious for cyclophosphamide, fluorouracil, and doxorubicin hydrochloride, and less so for mechlorethamine hydrochloride and the nitrosureas. Tetrahydrocannabinol appears to offer significant control of nausea in most patients and exceeding by far that provided by prochlorperazine.

Adult↗
PubMed1985

Humoral hypercalcemia in Hodgkin's disease. Association with elevated 1,25-dihydroxycholecalciferol levels and subperiosteal bone resorption.

A 58-year-old man was initially seen with fatigue and weight loss. Laboratory examination detected hypercalcemia, elevated 1,25-dihydroxycholecalciferol levels, low parathyroid hormone (PTH) concentrations, and subperiosteal bone resorption. The patient underwent subtotal parathyroidectomy for presumed hyperparathyroidism, but serum calcium and 1,25-dihydroxycholecalciferol levels remained elevated following surgery. Search for another cause of the hypercalcemia disclosed enlarged para-aortic lymph nodes, biopsy specimens of which demonstrated Hodgkin's disease. After treatment of the patient with two cycles of chemotherapy with mechlorethamine hydrochloride, vincristine sulfate, procarbazine hydrochloride, and prednisone, serum calcium, 1,25-dihydroxycholecalciferol, and PTH levels normalized. We speculate that the humoral hypercalcemia in this patient resulted from tumor production of 1,25-dihydroxycholecalciferol.

Bone Resorption↗
PubMed1966

Coexistence of chronic lymphocytic leukemia and Hodgkin's disease. A case report.

In the present case there was coexistence of chronic lymphocytic leukemia and Hodgkin's disease. The leukocyte count of 213,000/cu mm, being among the highest reported in association with Hodgkin's disease, is unusual. The patient was treated for chronic lymphocytic leukemia with an unfavorable response to triethylenemelamine, and short-lived response to mechlorethamine and prednisone. The autopsy confirmed the existence of Hodgkin's disease and chronic lymphocytic leukemia. The coexistence of these two diseases does not imply that one is necessarily related to the other. In view of the continued controversy about the relationships of lymphoproliferative disorders to each other, this case should stimulate interest.

Fatal Outcome↗
PubMed1985

Erythrocyte mean corpuscular volume during cytotoxic therapy and the risk of secondary leukemia.

Erythrocyte mean corpuscular volume (MCV) evolution during cytotoxic therapy of Hodgkin's disease, lymphoma, multiple myeloma, ovarian cancer, and breast cancer was studied. The fastest and the highest MCV increases were observed in the diseases and with the therapies the most frequently involved in secondary leukemia: Hodgkin's disease treated with MOPP (mechlorethamine, vincristine, procarbazine, prednisone), and multiple myeloma and ovarian cancer treated with melphalan. On the contrary, with cytotoxic regimens not linked to a high frequency of secondary leukemia such as CMF (cyclophosphamide, methotrexate, 5-fluorouracil) used in ovarian or breast cancer, MCV increase was moderate. As the MCV increase reflects the bone marrow reaction to cytotoxic therapy, an unusually high increase could indicate bone marrow damages which could lead to secondary leukemia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Acute T-cell leukemia/lymphoma mimicking Hodgkin's disease with secondary HTLV I seroconversion.

The authors observed a pleiomorphic lymphoma mimicking Hodgkin's lymphoma in a French Guyana black woman lacking antibodies for human T-cell lymphoma/leukemia virus type I (HTLV I). After two courses of chemotherapy with either mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or doxorubicin, bleomycin, vincaleukoblastine, and dacarbazine (ABVD), a typical acute T-cell leukemia/lymphoma developed with HTLV I seroconversion. Specific HTLV I DNA sequences were detected using the polymerase chain reaction (PCR) on a lymph node biopsy obtained before chemotherapy. The mechanisms of the seroconversion are discussed.

Adult↗
PubMed1991

Gallium-67 scans as an adjunct to computed tomography scans for the assessment of a residual mediastinal mass in pediatric patients with Hodgkin's disease. A Pediatric Oncology Group study.

This study determines the utility of gallium-67 (Ga-67) scintigraphs as an adjunct to computed tomography (CT) scans for the assessment of residual mediastinal masses in children and adolescents with advanced-stage Hodgkin's disease. At diagnosis 42 patients with CT scan-documented mediastinal disease had a Ga-67 scan performed. Thirty-four of 42 patients (81%) had gallium-avid mediastinal lesions, whereas in eight (19%), the Ga-67 scan was negative. At the completion of eight cycles of therapy of Mustargen (mechlorethamine), Oncovin (vincristine), procarbazine, prednisone (MOPP) alternating with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD), 21 of 34 patients with initially positive Ga-67 scans had them repeated; 18 of 21 converted to negative results, and three remained positive. In 11 of 18 patients, the loss of gallium avidity was consistent with a negative mediastinal CT scan. In seven, although the gallium scan was negative, the CT scan remained positive; all seven patients had a mediastinal biopsy of suspected residual disease and in all seven the biopsy results were negative for Hodgkin's disease. These preliminary results in a small cohort of patients demonstrate that Ga-67 scans may be of benefit in evaluating residual mediastinal masses in patients with Hodgkin's disease.

Adolescent↗
PubMed1993

Treatment of human immunodeficiency virus-associated Hodgkin disease. Is there a clue regarding the cause of Hodgkin disease?

BACKGROUND: The occurrence of human immunodeficiency virus (HIV)-associated Hodgkin disease (HD) offers a unique opportunity to study the cause of HD and compare HIV-HD with the well-characterized HIV-non-Hodgkin lymphoma (NHL). METHODS: Eight patients with HIV-HD and 17 with HIV-NHL were treated. RESULTS: The complete remission (CR) rate in HIV-HD was 100% with mechlorethamine, vincristine, procarbazine, and prednisone or doxorubicin, bleomycin, vinblastine, and dacarbazine (median survival, > 38.0 months). HIV-NHL patients were treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CR, 80%; median survival, 13.0 +/- 1.3 months). Durable CR was achieved with one to six cycles of chemotherapy (median, 4). There were no late relapses. The difference between the survival rate associated with chemotherapy-treated HIV-HD and chemotherapy-treated HIV-NHL approached statistical significance (P = 0.06). Analysis indicated that all patients with HIV-HD (n = 8) may have acquired HIV through intravenous drug abuse (IVDA) compared with 1 of 17 patients with HIV-NHL (P = 0.0001). A combined analysis (metaanalysis) of 157 patients with chemotherapy-treated HIV-NHL and 51 with chemotherapy-treated HIV-HD confirmed the significantly better survival of those with HIV-HD (P < 0.0001). CONCLUSIONS: Standard combination chemotherapy, truncated as necessary, offers survival outcomes that are at least equivalent and, perhaps, superior to previously published experimental approaches for HIV-NHL and HIV-HD. HIV-HD has a significantly better prognosis than HIV-NHL and is associated with IVDA. These data suggest that the etiologic agents of HIV-HD and HIV-NHL may be transmissible, identifiable, and unique.

Adult↗
PubMed1994

Continuous infusion ABDIC therapy for relapsed or refractory Hodgkin's disease.

BACKGROUND: Patients whose Hodgkin's disease is refractory to standard combination chemotherapy usually have a poor prognosis. These patients are generally considered for bone marrow transplantation if the disease is still sensitive to chemotherapy. METHODS: Between May 1988 and January 1992, 19 patients with refractory or relapsed Hodgkin's disease were treated with a regimen of doxorubicin, bleomycin, dacarbazine, lomustine, and prednisone (ABDIC). The ABDIC regimen as modified for continuous infusion by Hagemeister consisted of doxorubicin 25 mg/m2 by continuous infusion daily for 2 days, dacarbazine 200 mg/m2 by continuous infusion daily for 5 days, bleomycin 5 U/m2 intravenously on days 1 and 5, CCNU 40 mg/m2 on day 1, and prednisone 40 mg/m2 daily on days 1-5. Treatment was repeated every 28 days. RESULTS: At the time of treatment, mean age was 30.5 years (range 19-70), and time to ABDIC from initial diagnosis was 5.6 years (range 1-14). The mean number of prior chemotherapy regimens was 2.7 (range 1-5), and three of the patients had had autologous bone marrow transplantation before ABDIC: All patients had earlier received either mechlorethamine, vincristine, procarbazine, and prednisone or a regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine, and 16 had received both. The mean number of ABDIC cycles was 3.9 (range 2-12). Total response rate was 63%, with 10 patients having partial response and 2 having complete response of 12 and 27 months' duration. Seven patients subsequently underwent bone marrow transplantation; two of these are free of disease at 35 and 41 months. The treatment was well tolerated; major toxicities were nausea and bone marrow suppression. CONCLUSION: ABDIC is an active and well tolerated therapy in patients with relapsed or refractory Hodgkin's disease, including those previously treated with ABVD. More importantly, perhaps, ABDIC as cytoreductive therapy followed by bone marrow transplantation offers the possibility of long term disease free survival in this heavily pretreated patient population.

Adult↗