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Results for “CYCLOPHOSPHAMIDE”

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PubMed2001

Dose-intensive epirubicin-based chemotherapy is superior to an intensive intravenous cyclophosphamide, methotrexate, and fluorouracil regimen in metastatic breast cancer: a randomized multinational study.

PURPOSE: To determine the relative efficacy of a cyclophosphamide epirubicin and fluorouracil (CEF) regimen compared with an intravenous (IV) cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in metastatic breast cancer. PATIENTS AND METHODS: Patients were randomized to receive either CEF (cyclophosphamide 400 mg/m(2) IV, epirubicin 50 mg/m(2) IV, and fluorouracil 500 mg/m(2) IV on days 1 and 8), or CMF (cyclophosphamide 500 mg/m(2) IV, methotrexate 40 mg/m(2) IV, and fluorouracil 600 mg/m(2) IV on days 1 and 8). Treatment was given in 3- to 4-week cycles for a total of six to nine cycles. RESULTS: A total of 460 patients (223 CEF and 237 CMF) were randomized. Overall response rate was superior for CEF than CMF in all randomized patients (57% v 46%, respectively; P =.01) and in the assessable subset (66% v 52%, respectively; P =.005). With a median follow-up of more than 20 months, time to progression (TTP) was significantly longer with CEF than CMF (median 8.9 v 6.3 months, respectively; P =.0064), as was time to treatment failure (TTF) (median 6.2 v 5.0 months, respectively; P =.01). Significant survival differences were not observed between CEF and CMF (median 20.1 v 18.2 months, respectively; P =.23). Granulocytopenia and infections were similar in both arms. Grade 3/4 nausea/vomiting and alopecia were more frequent with CEF, whereas diarrhea was more frequent with CMF. Cardiac toxicity, primarily asymptomatic, required withdrawal from study of 15 patients on CEF (7%) and one patient on CMF. CONCLUSION: This CEF regimen safely provides significantly better tumor control than CMF, manifest as a higher response rate, and longer TTP and TTF, but not survival, when used as first-line chemotherapy for metastatic breast cancer.

Adult↗

PubMed2004

Efficacy of topotecan and cyclophosphamide given in a phase II window trial in children with newly diagnosed metastatic rhabdomyosarcoma: a Children's Oncology Group study.

PURPOSE: To determine the antitumor activity and toxicity of topotecan given immediately after cyclophosphamide as window therapy, then in combination with conventional agents in pediatric patients with newly diagnosed metastatic rhabdomyosarcoma (RMS). PATIENTS AND METHODS: Sixty-one patients younger than 21 years with newly diagnosed metastatic RMS or undifferentiated sarcoma were assigned window therapy (weeks 0 to 6) with topotecan (0.75 mg/m(2) daily x 5 every 21 days) immediately after cyclophosphamide (250 mg/m(2) daily x 5 every 21 days; TC). We continued to give these agents in combination with vincristine (VTC) to patients who showed objective improvement, partial response (PR), or complete response (CR) to TC and alternated courses of VTC with vincristine, dactinomycin and cyclophosphamide (VAC) during weeks 6 to 41 (VTC/VAC). Those who showed no response or progressive disease after TC received only VAC. All patients received radiotherapy to sites of unresected disease (weeks 15 to 21). RESULTS: The overall response rate (CR + PR) to TC was 47% (95% CI, 35% to 60%). Tumor size < or = 5 cm was associated with early response. Myelosuppression was the primary toxicity to TC. Overall 3-year disease-free survival and survival were estimated to be 10% (95% CI, 2% to 19%) and 20% (95% CI, 8% to 32%), respectively. Toxicity profiles for patients who received VTC/VAC or VAC alone were comparable. CONCLUSION: Topotecan after cyclophosphamide is a combination that is active against newly diagnosed RMS, with an acceptable toxicity profile. Disease-free survival and overall survival, however, remain disappointing for children with metastatic RMS at diagnosis.

Adolescent↗

PubMed1989

Differential effects of prednisone and cyclophosphamide on autoantibodies in human neuromuscular disorders.

We compared the effects of treatment of patients with prednisone or cyclophosphamide on a series of different types of autoantibodies. Levels of antiacetylcholine receptor (anti-AChR) antibodies and of antibodies to GM1 and GD1a gangliosides were measured in patients with a variety of neuromuscular disorders before and after treatment. Most patients had several autoantibodies present. We showed that prednisone treatment resulted in a reduction in titers of anti-AChR but not antiganglioside antibodies. Cyclophosphamide treatment produced a reduction of antiganglioside antibody titers. An intravenous and oral regimen was more effective than a single intravenous course of cyclophosphamide. We conclude that an immunosuppressive medication such as prednisone may reduce levels of some autoantibodies while producing no change in others, even in an individual patient. In addition, cyclophosphamide can suppress autoantibodies that prednisone does not. These differences in immunopharmacologic responses suggest that there are several distinct mechanisms of autoantibody production in humans. The utility of immunosuppressive medications in specific disease processes may be related in part to the mechanism of production of pathogenic antibodies.

Autoantibodies↗

PubMed1990

Genetically engineered V79 Chinese hamster cells metabolically activate the cytostatic drugs cyclophosphamide and ifosfamide.

V79 cells, genetically engineered to express active cytochromes P450IIB1 and P450IA1, were used to study the cytotoxicity and mutagenicity of cyclophosphamide and ifosfamide. Cyclophosphamide, tested up to a concentration of 2 mM, was not cytotoxic in V79 nor in the P450IA1-expressing V79-derived cell line XEM2. Pronounced cytotoxicity was, however, observed in the P450IIB1-expressing V79-derived cell line SD1. Induction of gene mutations (acquisition of 6-thioguanine resistance) was observed in SD1 cells as well, but the effects were weak. Ifosfamide was inactive in V79 cells, but was cytotoxic in SD1 cells. Ifosfamide mustard, an active metabolite of ifosfamide, was equally cytotoxic and showed similar mutagenic effects in SD1 and parental V79 cells. The results indicate that cyclophosphamide and ifosfamide are metabolically activated by cytochrome P450IIB1. In contrast, cytochrome P450IA1 was not capable of activating cyclophosphamide. Thus, V79-derived cell lines defined for their expression of a specific form of cytochrome P-450 can be used as diagnostic tools to identify the cytochrome P-450 that is responsible for the metabolic activation of drugs.

Animals↗

PubMed1992

Treatment of life-threatening primary pulmonary hemosiderosis with cyclophosphamide.

This report describes a five-year-old boy with severe pulmonary hemorrhage caused by primary pulmonary hemosiderosis with cow's milk sensitivity. After failing to respond to corticosteroids and azathioprine, he dramatically improved after being given cyclophosphamide. He worsened after discontinuation of cyclophosphamide on two occasions and improved significantly with its reinstitution. Cyclophosphamide was continued for 14 months without further bleeding or adverse effects. The patient has remained in remission for nearly five years. Cyclophosphamide may be a life-saving alternative therapy for refractory pulmonary hemorrhage with pulmonary hemosiderosis.

Child, Preschool↗

PubMed1992

Use of intermittent, intravenous cyclophosphamide for idiopathic pulmonary fibrosis.

STUDY OBJECTIVE: To determine the safety and efficacy of intravenous cyclophosphamide for patients with idiopathic pulmonary fibrosis. DESIGN: Nonrandomized, open-labeled study of efficacy in symptomatic patients. SETTING: Patients were treated as outpatients in a referral clinic. PATIENTS: All patients had idiopathic pulmonary fibrosis with symptoms of dyspnea on exertion. Patients had either worsening disease or contraindication to corticosteroids. INTERVENTION: Thirty-three patients were treated with intravenous cyclophosphamide every two weeks. Initial dosage was 500 mg, and the dose was escalated provided the total white blood cell count remained > 3,000 cells per cubic millimeter. The maximum dose administered was 1,000 to 1,800 mg of cyclophosphamide. Corticosteroid therapy was tapered as tolerated by the patient. MEASUREMENTS AND RESULTS: Patients were treated for at least six months or until death. For the 33 patients, 18-month probability of survival was > 50 percent. For those patients surviving six months, there was a significant rise in the vital capacity (from 1.6 +/- .61 L [mean +/- SD] to 1.8 +/- .52 L, p < 0.01) which persisted for at least 18 months of treatment. This was associated with a significant fall in the average prednisone dosage from 32 +/- 13.0 mg/day to 4 +/- 10.4 mg/day (p < 0.01) by 12 months. Only one patient required hospitalization for possible drug-related toxic reaction. CONCLUSIONS: Intermittent, intravenous cyclophosphamide therapy was associated with improved pulmonary function and reduced corticosteroid dosage in patients with idiopathic pulmonary fibrosis who survived at least six months after institution of therapy.

Cyclophosphamide↗

PubMed2003

Treatment of corticosteroid-resistant neurosarcoidosis with a short-course cyclophosphamide regimen.

BACKGROUND/OBJECTIVES: Many patients with neurosarcoidosis have disease that is refractory to corticosteroids or they are unable to tolerate high-dose corticosteroids because of detrimental side effects. We examined a short-course, pulse-dose regimen using cyclophosphamide to treat such patients. METHODS: We identified a population of patients with neurosarcoidosis refractory to standard therapy with corticosteroids. Patients who were unable to tolerate corticosteroid therapy due to side effects were also included. Alternative therapy for these patients was initiated using i.v. cyclophosphamide. RESULTS: Seven patients were identified for treatment with our cyclophosphamide regimen. The mean duration of therapy was 5.4 months. Four of the seven patients reported symptomatic improvement on therapy, and all seven patients demonstrated objective improvement in either MRI or cerebrospinal fluid abnormalities. Mean corticosteroid dose of the group was reduced from 42 mg/d before therapy to 18 mg/d after therapy. Relapse of neurologic symptoms was noted in one patient after the completion of therapy. One patient acquired an opportunistic infection, and a second patient required hospitalization for a central venous catheter infection. CONCLUSION: Short-course cyclophosphamide appears to be a reasonable, steroid-sparing treatment option for patients with corticosteroid-refractory neurosarcoidosis.

Adult↗

PubMed2005

Phase I trial of infusional cyclophosphamide, doxorubicin, and etoposide plus granulocyte-macrophage colony stimulating factor (GM-CSF) in non-Hodgkin's lymphoma.

PURPOSE: To determine the recommended phase II dose (RPTD) of a 96-h continuous intravenous infusion (CIVI) of cyclophosphamide (200, 300, or 400 mg/m2/d) and etoposide (60 or 90 mg/m2/d) when used in conjunction with doxorubicin (12.5 mg/m2/d) (CDE) given every 28 d plus granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with poor prognosis non-Hodgkin's lymphoma (Group A), and the same regimen given every 21 d (Group B). METHODS: In Group A, infusional CDE was repeated every 28 d, GM-CSF (250 microg/m2) was given subcutaneously from d 6 until neutrophil recovery, with dose escalation in cohorts of three to six evaluable patients. The RPTD of cyclophosphamide and etoposide established in Group A was then used with CDE given every 3 wk (Group B) with GM-CSF given on d 6-20, and dose escalation was attempted again. RESULTS: In Group A, the RPTD of cyclophosphamide and etoposide were 300 mg/m2/d and 90 mg/m2/d, respectively; prolonged neutropenia was the dose-limiting toxicity. In Group B, use of GM-CSF on d 6-20 did not facilitate dose escalation above the RPTD established in Group A. Complete response occurred in 13/26 patients (50%) with no prior chemotherapy, and in 4/16 patients (25%) who had relapsed after prior chemotherapy. CONCLUSIONS: Because of the increase in dose and dose-density afforded by the administration of GM-CSF, the relative dose intensity was increased by twofold for cyclophosphamide (400 vs 200 mg/m2/wk) and etoposide (120 vs 60 mg/m2/wk), and by 1.3-fold for doxorubicin (16.7 vs 12.5 mg/m2/wk).

Adult↗

PubMed1999

Lethal encephalitozoonosis in cyclophosphamide-treated rabbits.

Encephalitozoonosis is an opportunistic infection in animals and humans. Its clinical form is observed in immunosuppressed hosts. We studied the occurrence of the manifest form of rabbit microsporidiosis under cyclophosphamide immunomodulation in 40 New Zealand rabbits. The experimental animals were intraperitoneally infected with 5 x 10(7) Encephalitozoon cuniculi spores. Two weeks after infection the animals were treated intraperitoneally with cyclophosphamide, first with 50 mg/kg and then with 15 mg/kg weekly during the 12-week experimental period. Positive controls were either E. cuniculi-infected or cyclophosphamide-immunosuppressed animals. The negative control rabbits remained untreated. Both clinical signs of encephalitozoonosis and depression of peripheral blood cell count developed between weeks 4 and 6 in the experimental animals which died during week 6 of the experiment. No clinical signs compatible with encephalitozoonosis were observed in any of the controls. The results suggest that immunosuppression induced by cyclophosphamide can give rise to a lethal form of encephalitozoonosis.

Animals↗

PubMed2002

Sialic acid changes in Dalton's lymphoma-bearing mice after cyclophosphamide and cisplatin treatment.

Sialic acid changes in Dalton's lymphoma cells and other tissues of 10-12-week-old Swiss albino mice were investigated in relation to tumour growth in vivo and following cyclophosphamide (ip, 200 mg/kg body weight) or cisplatin (ip, 8 mg/kg body weight) treatment. Three to four animals of both sexes were used in each experimental group. The sialic acid level of tumour cells (0.88 micromol/g) increased with tumour progression (1.44-1.59 micromol/g; P < or =0.05) in mice. Sialic acid concentration in other tissues (liver, kidney, testes and brain) also increased (approximately 40, 10, 30 and 58%, respectively) in the tumour-bearing hosts as compared with that in the respective tissues of normal mice. In vivo cyclophosphamide or cisplatin treatment resulted in an overall decrease of sialic acid contents in the tissues. Cyclophosphamide was more efficient in lowering tissue sialic acid than cisplatin (P < or =0.01, ANOVA). It is suggested that sialic acid residues could be an important factor contributing to the manifestation of malignant properties in cancer cells in general and Dalton's lymphoma cells in particular. A significant decrease in the sialic acid content of Dalton's lymphoma cells after cisplatin or cyclophosphamide treatment may bring about specific changes in tumour cells which could be associated with tumour regression.

Animals↗

PubMedDate not supplied

Treatment of immune-mediated hemolytic anemia in dogs with cyclophosphamide.

A review of 60 cases of immune-mediated hemolytic anemia (IMHA) in the dog was performed in order to characterize the disease and to identify potential prognostic indicators. Dogs ranged in age from 1 to 13 years, with a mean age of 6.5 years. The 2 most commonly affected breeds were Cocker Spaniels and Labrador Retrievers. Fifty-two of the 60 dogs tested (87%) were autoagglutination positive and spherocytes were present in 45 (75%). Forty-one (89%) of 46 patients tested positive for the presence of immunoglobulin on the red blood cell surface (Coombs assay). The most common clinical signs at presentation were lethargy, weakness, pale mucous membranes, icterus, hemoglobinuria, and anorexia. PCV less than 25% was present in 59 (98%) dogs. At the time of presentation, 35 dogs (58%) had a nonregenerative anemia, whereas 25 patients (42%) had a regenerative response. Thrombocytopenia was seen in 41 (68%) dogs. Nine of 34 dogs (26%) had a prolonged prothrombin time, 19 of 34 (56%) had a prolonged activated partial thromboplastin clotting time, and 12 of 34 (35%) had abnormal fibrinogen concentrations. All dogs received prednisone at immunosuppressive doses (2.2-4.4 mg/kg PO as a single or divided dose every 24 hours) and cyclophosphamide as primary therapy. Forty-one dogs (63%) received cyclophosphamide at 50 mg/m2 q24h for 4 days, whereas 9 dogs (15%) received an initial high dose (200 mg/m2) followed by 3 days of a lower dose (50 mg/m2 q24h). No statistical difference in survival times was found for either protocol. Thirteen dogs were treated with azathioprine in addition to cyclophosphamide and prednisone. The median survival time of dogs that received all 3 drugs was 370 days as compared to 9 days for those dogs that were treated with cyclophosphamide and prednisone alone. Thirty-one (52%) dogs died from the disease, 13 (22%) dogs were alive, and 15 (25%) dogs were lost to follow-up. The median length of survival for all dogs was 21 days. Eight dogs that were discharged from the hospital suffered a relapse (PCV < 25%).

Anemia, Hemolytic, Autoimmune↗

PubMed2005

Compatibility of palonosetron with cyclophosphamide and with ifosfamide during simulated Y-site administration.

PURPOSE: The physical and chemical compatibility of palonosetron with cyclophosphamide and with ifosfamide during simulated Y-site administration was studied. METHODS: Test samples were prepared in triplicate by mixing 7.5 mL of palonosetron hydrochloride 50 microg (of palonosetron) per milliliter with 7.5 mL of cyclophosphamide 10 mg/mL and with ifosfamide 20 mg/mL. Physical stability was assessed by turbidimetry, particle sizing, and visual inspection. Chemical stability was assessed by stability-indicating high-performance liquid chromatography. Evaluations were performed immediately and one and four hours after mixing. RESULTS: The samples were clear and colorless when viewed in normal fluorescent room light and when viewed with a high-intensity monodirectional light. Turbidity remained unchanged, and particulate content was low and exhibited little change. Palonosetron, cyclophosphamide, and ifosfamide remained chemically stable throughout the four-hour test period. CONCLUSION: Palonosetron hydrochloride was physically compatible with cyclophosphamide or ifosfamide during simulated Y-site administration.

Antiemetics↗

PubMed2002

Nonspecific interstitial pneumonia/fibrosis completely recovered by adding cyclophosphamide to corticosteroids.

Nonspecific interstitial pneumonia/fibrosis (NSIP) was first described by Katzenstein and Fiorelli in 1994 (Am J Surg Pathol 18: 136-147). Many reports have described that corticosteroids are effective for NSIP. We describe a case of group II idiopathic NSIP in whom cyclophosphamide was administered since the initial response to corticosteroids had been insufficient. Lung biopsy was performed by video-assisted thoracoscopic surgery and NSIP was diagnosed pathologically, clinically and radiologically. Although the initial response to corticosteroids was insufficient, interstitial infiltrates on chest computed tomography improved dramatically after adding intravenous cyclophosphamide followed by oral cyclophosphamide. This case demonstrates that the addition of cyclophosphamide to corticosteroids might be a useful treatment for patients with NSIP.

Cyclophosphamide↗

PubMed1983

Respiratory infection of cyclophosphamide-treated mice with Pseudomonas aeruginosa.

The dose of cyclophosphamide that permits the colonization of the nasopharynx with Pseudomonas aeruginosa and the survival of the animal was determined in mice. This dose, 100 mg/kg of cyclophosphamide, allowed P aeruginosa to colonize but not invade mouse nasal epithelium. Mice treated with 100 mg/kg cyclophosphamide were exposed to aerosol of 35S-labeled P aeruginosa to study clearance. Results indicated that this dose of cyclophosphamide suppressed both the pulmonary clearance of viable P aeruginosa (in situ killing) and the clearance of radiolabeled P aeruginosa (mechanical clearance).

Animals↗

PubMed1994

Remission of lupus nephritis with cyclophosphamide and late relapses following therapy withdrawal.

We describe the long-term follow-up of severe lupus nephritis treated with cyclophosphamide, with emphasis on the incidence of relapses after therapy withdrawal. From a cohort of SLE patients followed over a period of twelve years, we review the charts of the eleven with histologic evidence of class IV nephritis who reached complete remission with cyclophosphamide and who were followed for more than four years after the discontinuation. In all patients, cyclophosphamide was maintained for longer than two years after complete remission. Four patients relapsed following therapy withdrawal (36%). Sequential biopsies were taken in eight patients after remission or relapse and show a good histologic correlation with clinical renal data. Clinical remission with re-induction therapy could not be achieved in two patients after relapse. We conclude that relapse is frequently observed following cyclophosphamide withdrawal in lupus patients with diffuse proliferative glomerulonephritis initially responsive to this therapy. Studies are needed to determine the influence of different regimes of maintenance therapy on the rate of relapses.

Cyclophosphamide↗

PubMed1988

Active immunotherapy of human melanoma exploiting the immunopotentiating effects of cyclophosphamide.

Malignant tumors may escape rejection by the immune system because they induce a state of immunological tolerance mediated by tumor antigen-specific suppressor T cells. In animal systems, cyclophosphamide can reverse the tolerance and thereby facilitate immunologically mediated tumor destruction. We have applied these concepts to the immunotherapy of human malignant melanoma. Forty-three patients with metastatic disease were treated with a whole cell vaccine 3 days after intravenous administration of cyclophosphamide, 300 mg/m2. The vaccine consisted of cryopreserved, irradiated autologous melanoma cells, obtained from metastatic masses by dissociation with collagenase and DNAse, mixed with bacillus Calmette-Guerin (BCG) and injected intradermally. The cyclophosphamide (CY) + vaccine combination was repeated every 28 days. Delayed-type hypersensitivity (DTH) was tested by injecting 1 x 10(6) melanoma cells intradermally and measuring the diameter of induration at 48 h. Most patients had minimal pretreatment DTH responses to melanoma cells (mean +/- SE, mm = 2.4 +/- 0.5). After two vaccine treatments, the responses increased significantly (mean increase +/- SE = 12.1 +/- 1.6 p less than .001) and that level of response was maintained after 4, 6, and 8 treatments. The patients were also skin-tested with a mixture of the enzymes used to dissociate the tumors. No patients exhibited DTH to collagenase + DNAse prior to vaccine injection, but every patient developed DTH to the mixture following two treatments (mean, mm = 26.4 +/- 3.9). Although extracting viable cells from tumor tissue without the use of enzymes proved difficult, we were able to test DTH to mechanically dissociated tumor cells in 23 patients. After two vaccine treatments, there was a significant increase in DTH to enzyme-free autologous melanoma cells (mean DTH +/- SE, mm: 5.4 +/- 1.0, p less than .01). Whereas 5 of 23 patients had positive DTH responses (5 mm induration or greater) before treatment, 11 of 23 were positive after two treatments. Further significant increases in DTH enzyme-free cells were observed after 6 and 8 treatments. Thus, it appears that patients receiving CY + vaccine developed DTH to tumor-associated antigens as well as to residual collagenase and DNAse on the cell surface. Thirty-three patients could be evaluated for antitumor effects of cyclophosphamide + vaccine. There were 3 complete remissions, 1 partial remission, and 2 minor responses. Two complete responders remain alive and free of disease after 57 and 12 months, respectively, and the third died after 39 months. The partial remission consisted of 75% regression of a pulmonary metastasis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1993

Methylprednisolone and cyclophosphamide pulse therapy in crescentic glomerulonephritis: safety and effectiveness.

In a previous study, we found that aggressive immunosuppressive therapy with continuous high-dose oral steroid and cyclophosphamide combined with plasma exchanges for extracapillary crescentic glomerulonephritis gave controversial results since, although disease activity was controlled, iatrogenic complications had led to death in some aged patients. We then modified our therapeutic regimen, and we analyze here the evolution of 30 consecutive patients who were admitted for biopsy-proven crescentic glomerulonephritis between 1989 and 1991. The mean plasma creatinine level at admission was 393 +/- 59 mumol/L (range 70 to 1100), and 15 patients had crescent formation in more than 50% of glomeruli on initial renal biopsy. Ten patients did not receive any immunosuppressive treatment since they either had a normal renal function or they had terminal renal failure and no severe extrarenal manifestation. The 20 other patients received initial steroid pulses 500 mg x3 (n = 17), low oral steroid treatment (n = 20), cyclophosphamide pulses (n = 13), or oral cyclophosphamide (n = 3). In 4 cases plasma exchanges were also used. As a whole, 10 patients (33%) were discharged with a normal renal function, and 18 patients (60%) had chronic renal failure, 7 of them requiring dialysis or transplantation; only 2 patients died of pulmonary hemorrhage. No severe iatrogenic complication was observed. These results indicate that reduction in oral steroid dosage, cyclophosphamide pulse therapy rather than continuous oral treatment, and plasma exchanges do not induce overimmunosuppression and iatrogenic complication. It can be safe, well tolerated, and as effective as a more intensive immunosuppressive regimen for the treatment of crescentic extracapillary glomerulonephritis.

Actuarial Analysis↗

PubMed1979

The effects of cyclophosphamide on mitogen-induced and antibody-dependent cellular cytotoxicity in guinea pigs.

Lymph node cells from normal guinea pigs, when stimulated with the non-specific mitogen PHA, were transformed to activated killer cells, capable of lysing 51Cr labeled mouse fibroblasts. Similarly, these lymphoid cells effected lysis of antibody coated chicken red cells in an antibody-dependent cellular cytotoxicity assay. Following cyclophosphamide, 150 mg/kg IP, the reactivity of an aliquot of lymph node cells to effect either cytotoxic reaction was not diminished. These results indicate that this immunosuppressant does not promote a selective decrease in either lymphoid effector. Rather, they are diminished in parallel with the generalized lympholysis resulting from drug administratioin. During the recovery phase, lymph node cells showed increased ability to lyse target cells, suggesting a rebound phase of heightened activity. Thymic cells from normal and cyclophosphamide treated animals were poor effectors in either cytotoxic assay. The addition of an equal number of thymocytes to lymph node cells resulted in decreased mitogen-induced cytotoxicity. Thymic inhibitory activity was mediated only by viable cells and the phenomenon did not represent an altered shift in PHA sensitivity. This suppressive activity persisted when thymic cells from cyclophosphamide treated-animals were employed, indicating that inhibitory cells were also not selectively depleted by this drug. In antibody-dependent cellular cytotoxicity assays, thymocytes from normal or cyclophosphamide-treated animals did not alter the cytotoxicity capacity of lymph node cells.

Animals↗