levoleucovorin and Acquired-Immunodeficiency-Syndrome

The usefulness of intensive chemotherapy with the MACOP-B protocol was evaluated in 8 patients with AIDS-related non-Hodgkin's lymphoma (NHL). Four patients had a prior AIDS diagnosis. The median CD4+ lymphocyte count was 0.079 cells x 10(9)/l (range 0.016-0.330). All patients responded to treatment. Four patients finished chemotherapy, all with complete remission, while another 3 patients deteriorated prior to finishing treatment and died. The median survival was 4 months (range 1 to 86 months). Major causes of the poor outcome were AIDS-related opportunistic infections and meningeal CNS involvement by NHL developing during or after chemotherapy. Patients with AIDS-related NHL usually do not appear to benefit from treatment with MACOP-B protocol. Advanced immunodeficiency is associated with poor tolerance to treatment and inability to finish this chemotherapy protocol. MACOP-B chemotherapy does not prevent meningeal spread of lymphoma in spite of using repeatedly systemic methotrexate crossing the blood-brain barrier. CNS prophylaxis with repeated application of intrathecal methotrexate may lower the risk of meningeal spread of lymphoma, which developed in 1 of 5 patients given CNS prophylaxis as compared to 2 of 3 patients without CNS prophylaxis.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Humans; Leucovorin; Lymphoma, AIDS-Related; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Prednisone; Survival Analysis; Vincristine

The scientific basis for using folinic acid in combination with the antiparasitic drugs prescribed to AIDS patients has been reviewed. In vitro and experimental data are unclear. On the basis of folinic acid metabolism and pharmacology and of clinical experience, we suggest that folinic acid should not be systematically added to the curative treatment of pneumocystosis with cotrimoxazole. Folinic acid may be added to prophylactic regimens using high-dose cotrimoxazole (i.e. 800 mg sulfamethoxazole twice a day) and in malnourished patients. It should be administered as soon as cytopenia occurs in the course of treatment. Concerning toxoplasmosis, the addition of folinic acid is recommended in doses of 10 to 20 mg/day in acute therapy and 5 to 10 mg/day in maintenance therapy. Dosage must be adjusted to the results of blood counts.

Topics: Acquired Immunodeficiency Syndrome; Drug Therapy, Combination; Folic Acid; Hematologic Diseases; Humans; Leucovorin; Opportunistic Infections; Pneumonia, Pneumocystis; Pyrimethamine; Sulfadiazine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

An increased frequency of toxoplasma encephalitis, caused by Toxoplasma gondii, has been reported in AIDS patients, especially in those with CD4+ T cell counts <100 cells/μL. Several guidelines recommend the combination of pyrimethamine, sulfadiazine, and leucovorin as the preferred regimen for AIDS-associated toxoplasma encephalitis. However, it is not commonly used in China due to limited access to pyrimethamine and sulfadiazine. The synergistic sulfonamides tablet formulation is a combination of trimethoprim (TMP), sulfadiazine and sulfamethoxazole (SMX), and is readily available in China. Considering its constituent components, we hypothesize that this drug may be used as a substitute for sulfadiazine and TMP-SMX. We have therefore designed the present trial, and propose to investigate the efficacy and safety of synergistic sulfonamides combined with clindamycin for the treatment of toxoplasma encephalitis.. This study will be an open-labeled, multi-center, prospective, randomized, and controlled trial. A total of 200 patients will be randomized into TMP-SMX plus azithromycin group, and synergistic sulfonamides plus clindamycin group at a ratio of 1:1. All participants will be invited to participate in a 48-week follow-up schedule once enrolled. The primary outcomes will be clinical response rate and all-cause mortality at 12 weeks. The secondary outcomes will be clinical response rate and all-cause mortality at 48 weeks, and adverse events at each visit during the follow-up period.. We hope that the results of this study will be able to provide reliable evidence for the efficacy and safety of synergistic sulfonamides for its use in AIDS patients with toxoplasma encephalitis.. This study was registered as one of 12 clinical trials under the name of a general project at chictr.gov on February 1, 2019, and the registration number of the general project is ChiCTR1900021195. This study is still recruiting now, and the first patient was screened on March 22, 2019.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiprotozoal Agents; China; Clindamycin; Drug Therapy, Combination; Female; HIV Infections; Humans; Leucovorin; Male; Prospective Studies; Pyrimethamine; Sulfadiazine; Sulfamethoxazole; Sulfonamides; T-Lymphocytopenia, Idiopathic CD4-Positive; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; Vitamin B Complex

Use of multiagent chemotherapy has been associated with complete remission (CR) in approximately 50% of patients with newly diagnosed acquired immunodeficiency syndrome (AIDS)-lymphoma, although additional AIDS-related complications may occur. Both chemotherapy and antiretroviral therapy were employed in an attempt to ascertain if the combination was safe, and associated with changes in human immunodeficiency virus (HIV) p24 antigen levels during the course of treatment.. Low dose methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone(M-BACOD) chemotherapy and zalcitabine (ddC) were employed in 28 patients. Since both vincristine and zalcitabine may cause peripheral neuropathy, a Phase I/II study design was employed. Serum was analyzed for immune complex dissociated (ICD) HIV p24 antigen and interleukin (IL)-6 levels during therapy.. CR was achieved in 14 of 25 patients (56%), with partial response (PR) in 5 (20%). CRs were equivalent in patients with good or poor prognostic indicators, including a history of AIDS prior to lymphoma (CR = 60%); and/or CD4 lymphocytes < 200/mm3 (CR = 53%). Five patients with a CR subsequently relapsed (36%); median survival of CR patients was 29.2 months (4.1-61+), whereas that of all of the treated patients was 8.1 months. No significant peripheral neuropathy or other toxicity was observed. Serum ICD p24 antigen levels either fell (7/14) or remained consistently negative (2/14) in 9 of 14 patients (64%), whereas 36% experienced an increase. Elevated serum IL-6 levels at diagnosis were associated with systemic "B" symptoms (P = 0.023), whereas changes in IL-6 correlated with response to therapy over time (P = 0.006).. Combination antineoplastic and zalcitabine antiretroviral therapy may be safely administered to patients with AIDS-related lymphoma, resulting in CR in 56%, lack of significant neurotoxicity, and favorable effect on HIV p24 antigen in 50%. Elevation of serum IL-6 is associated with systemic "B" symptoms, whereas changes in serum IL-6 may correlate with response.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; HIV Core Protein p24; HIV-1; Humans; Interleukin-6; Leucovorin; Lymphoma, AIDS-Related; Male; Methotrexate; Middle Aged; Peripheral Nervous System Diseases; Remission Induction; Vincristine; Zalcitabine

Cerebral toxoplasmosis is the most frequent opportunistic infection in patients with acquired immune deficiency syndrome in France. We evaluated the effect of adding folic acid to the standard treatment (including pyrimethamine) on preventing induced cytopenia in order to determine the optimal dose.. From January to September 1990, pyrimethamine (50 mg 3 times per week) was given as primary prophylaxis against toxoplasmosis to 30 patients who were positive for human immunodeficiency virus (CDC classes II or II, CD4 counts < 200/mm3). The patients were randomly divided into three groups given 5, 25 and 0 mg folic acid 3 times per week. Associated treatments were the same in all patients (zidovudine 600 mg/d, pentamidine isethionate aerosol, 300 mg, once a month). Blood cell counts and lymphocyte subset counts were made on days 0, 30, 90 and 180.. Two patients were lost to follow-up and between day 90 and 180, 3 were excluded due to other opportunist infection and 1 due to zidovudine induced anaemia. Between the groups, there was no difference in haemoglobin level or cell counts on day 0. No haematologic toxicity was observed at day 90. Haemoglobin was significantly reduced in the control group (0 mg folic acid) on day 180 (mean haemoglobin on day 180, 13.8, 13.1 and 12.1 g/dl in groups 1, 2 and 3 respectively). No variation in polynuclear neutrophil counts was observed.. These findings suggest that folic acid has a moderate beneficial effect on preventing haematologic disease in patients treated with pyrimethamine. There was no observed dose effect.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Blood Cell Count; Hemoglobin A; Humans; Leucovorin; Prospective Studies; Pyrimethamine; Thrombocytopenia; Toxoplasmosis, Cerebral

--To ascertain if low-dose multiagent chemotherapy, with central nervous system prophylaxis and antiretroviral therapy, might be associated with increased efficacy and decreased risk of intercurrent infection in patients with malignant lymphoma related to the acquired immunodeficiency syndrome (AIDS).. --A phase II prospective clinical trial, with median follow-up of 33 months.. --Eight university hospitals, within the context of the AIDS Clinical Trials Units, sponsored by the National Institute of Allergy and Infectious Diseases.. --Forty-two patients with AIDS-related malignant lymphoma. All were evaluable for toxicity assessment, and 35 for response.. --A low-dose modification of the M-BACOD regimen (day 1): cyclophosphamide, 300 mg/m2 intravenously (IV); doxorubicin, 25 mg/m2 IV; vincristine sulfate, 1.4 mg/m2 IV; bleomycin, 4 mg/m2 IV; dexamethasone, 3 mg/m2 orally on days 1 through 5; methotrexate, 500 mg/m2 IV on day 15, with leucovorin rescue. Intrathecal cytosine arabinoside (50 mg) to all on days 1, 8, 21, and 28, with radiation therapy to a helmet field to those with central nervous system involvement. Zidovudine for 12 months after completion of four to six cycles of chemotherapy.. --Response rate and number of opportunistic infections.. --Response rate was 51% with a complete response of 46%. Of 16 complete responses, relapse occurred in four, none isolated to the central nervous system. Opportunistic infections occurred in 21% of those receiving treatment. Median duration of survival among all 42 patients is 5.6 months, 6.5 months in 35 patients evaluable for response, and 15 months in patients with complete response. Lower concentration of CD4 cells, history of prior AIDS, bone marrow involvement, and stage IV disease were independently associated with decreased survival.. --Low-dose chemotherapy with central nervous system prophylaxis and zidovudine maintenance may be associated with durable remissions in AIDS-related lymphoma with fewer opportunistic infections than noted in prior reports.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Central Nervous System Diseases; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Follow-Up Studies; HIV Seropositivity; Humans; Leucovorin; Lymphoma; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Opportunistic Infections; Prospective Studies; Vincristine; Zidovudine

Toxoplasmosis is an important cause of enhancing brain lesions in patients with acquired immunodeficiency syndrome (AIDS), and it is typically associated with low CD4-lymphocyte counts. Extensive toxoplasma encephalitis when the CD4-lymphocyte count is above 100 cells/µl is unusual. Cavitary lung lesions are also not typically associated with toxoplasmosis. Here, we present a case of toxoplasmosis associated with extensive brain masses and cavitary lung lesions, both of which improved with directed toxoplasmosis therapy, in an AIDS patient with a CD4 cell count of 120 cells/µl.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antibodies, Protozoan; Antiprotozoal Agents; Brain; CD4 Lymphocyte Count; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Heterocyclic Compounds, 3-Ring; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Middle Aged; Oxazines; Piperazines; Polymerase Chain Reaction; Pyridones; Toxoplasma; Toxoplasmosis, Cerebral; Treatment Outcome

Short, intensive cycles of chemotherapy have resulted in improved survival in BurkittOs lymphoma/leukemia (BL) in adults. The prognosis of patients with immunodeficiency virus (HIV)-associated BL is considered to be poor, but these patients have seldom been treated with BL-specific protocols. However, a study (PETHEMA-LAL3/97) in which patients with BL were treated regardless of their HIV status failed to find differences between HIV-infected and immunocompetent individuals. Furthermore, patients who received highly active antiretroviral therapy (HAART) seemed to have a slightly better disease-free survival than those who did not (p=0.051). We extended the follow-up analysis to elucidate the role of HAART in the survival of HIV-infected patients included in the PETHEMA-LAL3/97 protocol.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Cyclophosphamide; Cytarabine; Dexamethasone; Disease-Free Survival; Etoposide; Female; Follow-Up Studies; Humans; Ifosfamide; Leucovorin; Leukemia; Lymphoma, AIDS-Related; Male; Methotrexate; Middle Aged; Prednisone; Treatment Outcome; Vincristine

P-glycoprotein is a product of the multidrug resistance (MDR-1) gene. In non-Hodgkin's lymphoma, less than 20% of untreated de novo lymphomas express MDR-1 compared with approximately 50% after failure of chemotherapy. We wished to study the expression of MDR-1 in AIDS-related non-Hodgkin's lymphoma (AIDS-NHL). Tissue biopsies from 50 patients with newly diagnosed AIDS-NHL were studied by immunohistochemical analysis using C494, a monoclonal antibody specific for the MDR-1 isoform of P-gp. MDR-1 expression was correlated with patient demographics, lymphoma characteristics, response to chemotherapy, and survival. Forty-six males and four females with a median age of 38 years (range 26-63) were studied. A prior AIDS-defining opportunistic infection was reported in 35 patients (70%). The median CD4+ lymphocyte count was 69/mm(3) (range 0-920). Thirty-two patients (63%) had received prior anti-HIV therapy, including a protease inhibitor in five (10%). Pathologic types consisted of diffuse large cell in 13 (26%), immunoblastic in 13 (26%), small non-cleaved in 22 (44%), and high grade not otherwise specified in two (4%). The majority of patients (76%) had stage III/IV disease. Pre-treatment lymphoma tissues from 33 patients (66%) stained positively for MDR-1. MDR-1 positive patients had a significantly lower complete remission rate compared to MDR-1 negative patients (33 versus 65%, P=0.042). Duration of complete response was significantly longer in MDR-1 negative patients compared with MDR-1 positive patients (not reached versus 9.9 months, P=0.003). Strategies to overcome MDR-1 expression may be important for initial treatment in patients with AIDS-NHL.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-HIV Agents; Antineoplastic Combined Chemotherapy Protocols; ATP Binding Cassette Transporter, Subfamily B, Member 1; Bleomycin; Cyclophosphamide; Dexamethasone; Disease-Free Survival; Doxorubicin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Gene Expression Regulation, Leukemic; Humans; Leucovorin; Lymphoma, AIDS-Related; Male; Methotrexate; Middle Aged; Neoplasm Proteins; Prednisone; Remission Induction; Retrospective Studies; Survival Analysis; Vincristine

Life-threatening conditions requiring urgent medical treatment rarely present to the ophthalmologist. This case report describes a patient with precipitious visual loss as the primary complaint and which subsequently led to the diagnosis of Toxoplasmic papillitis and life-threatening cerebral involvement as an initial manifestation of AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Bacterial Agents; Anti-Infective Agents; Drug Therapy, Combination; Humans; Leucovorin; Male; Optic Disk; Optic Neuritis; Pyrimethamine; Sulfadiazine; Tomography, X-Ray Computed; Toxoplasmosis, Cerebral; Toxoplasmosis, Ocular; Vision Disorders

Recent studies showed that patients with non-Hodgkin's lymphoma (NHL) with human immunodeficiency virus type 1 (HIV-1) infection may benefit from an intensive chemotherapeutic regimen. We report on our experience in the treatment of NHL-associated HIV-1 infection, with excellent prognostic factors, with MACOP-B regimen.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; HIV-1; Humans; Leucovorin; Lymphoma, AIDS-Related; Methotrexate; Middle Aged; Prednisone; Prognosis; Remission Induction; Survival Rate; Vincristine

A presumptive diagnosis of toxoplasmic encephalitis was made in 73 of the 428 AIDS patients followed in the Bordeaux Regional Hospital between 1985 and 1990. The sex ratio (M:F) was 2.8:1. The mean age was 36.2 years. Forty-three percent were homosexuals, 30 percent intravenous drug abusers. The encephalitis revealed the HIV infection in 10 percent of the cases; it was the first opportunistic infection in 27 percent. The clinical manifestations were: focal neurologic deficit (62 percent), fever (58 percent), headaches (47 percent), altered consciousness (45 percent), seizures (18 percent). The CT scan findings were focal lesions with (60 percent) or without (40 percent) ring enhancement. Oedema was present in 58 percent of the lesions, and multiple lesions in 59 percent. At the time of diagnosis, the mean CD4 lymphocyte count was 72 per mm3. The initial therapeutic regimens were: pyrimethamine (P) plus sulfadiazine (n = 57), P plus clindamycin (n = 11) and P plus clarithromycin (n = 5). Following acute therapy the patients had a complete (64 percent) or partial (18 percent) response, and 18 percent died. Adverse reactions were noticed in 53 percent. Sixty patients received a maintenance therapy; after a mean follow-up of 8 months, 12 relapsed and died of toxoplasmic encephalitis; 17 died of another cause. The median survival after toxoplasmosis was diagnosed was 7.5 months.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Clarithromycin; Clindamycin; Drug Therapy, Combination; Female; France; Humans; Leucovorin; Male; Middle Aged; Pyrimethamine; Recurrence; Retrospective Studies; Sulfadiazine; Tomography, X-Ray Computed; Toxoplasmosis, Cerebral

The clinical efficacy of trimetrexate, a dihydrofolate reductase inhibitor with potent in vitro antitoxoplasma activity, was assessed in 9 sulfonamide-intolerant patients with AIDS and biopsy-proven cerebral toxoplasmosis. The 9 patients were treated for 28-149 days with trimetrexate (30-280 mg/m2/day) plus leucovorin (20-90 mg/m2 every 6 h). Radiographic responses were documented in 8 patients, and clinical responses in 5 patients. Despite continued therapy, all patients deteriorated clinically and radiographically within 13-109 days of their initial improvement. Trimetrexate at very high doses for extended periods was not associated with serious toxicity. Trimetrexate alone had dramatic but transient activity in sulfonamide-intolerant patients and thus is not adequate as single-agent therapy for AIDS-associated toxoplasmosis.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Drug Evaluation; Female; Humans; Leucovorin; Male; Tomography, X-Ray Computed; Toxoplasmosis, Cerebral; Trimetrexate

Topics: Acquired Immunodeficiency Syndrome; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Lymphoma, Non-Hodgkin; Male; Methotrexate; Prednisone; Vincristine

Cerebral toxoplasmosis related to AIDS was treated with a combination regimen of pyrimethamine, clindamycin, and spiramycin, and in a second trial with a combination of pyrimethamine and clindamycin. Both regimens proved to be equally effective. The experience with the second trial shows that spiramycin does not provide additional benefit. Myelosuppressive side-effects due to pyrimethamine were prevented in most cases by addition of folinic acid to the regimen at the start of the antitoxoplasmic therapy. These data suggest that the combination of pyrimethamine and clindamycin is an effective alternative to the commonly used regimen consisting of pyrimethamine and sulfonamides.

Topics: Acquired Immunodeficiency Syndrome; Acute Disease; Brain Diseases; Clindamycin; Drug Therapy, Combination; Humans; Leucovorin; Pyrimethamine; Spiramycin; Toxoplasmosis

To determine the maximal tolerable dosage of trimetrexate for treatment of pneumocystis pneumonia, 25 patients were treated each day with 45 mg/m2 of trimetrexate and 80 mg/m2 of leucovorin; 10 received 60 mg/m2 and 80 mg/m2; 12 received 60 mg/m2 and 160 mg/m2; and 6 received 90 mg/m2 and 160 mg/m2, respectively. Leucovorin was increased twofold and trimetrexate reduced by 50% or suspended briefly for various levels of neutropenia and thrombocytopenia until blood counts increased. Dosage-modifying hematologic toxicity occurred in 12 (46%), 8 (80%), 9 (75%), and 4 (67%) patients with the respective groups. Cytopenias were in each case reversible and other toxicities were well tolerated. All survivors but one were able to receive a full 21 doses of trimetrexate. Twenty-four (92%), 10 (100%), 7 (58%), and 4 (80%) of patients in the respective groups survived. Thus, the 45 mg/m2/day dosage of trimetrexate with 80 mg/m2/day of leucovorin resulted in the least dosage-modifying toxicity and excellent efficacy. This combination should be selected for studies to compare trimetrexate with other therapies for pneumocystis pneumonia.

Topics: Acquired Immunodeficiency Syndrome; Adult; Dose-Response Relationship, Drug; Drug Evaluation; Drug Therapy, Combination; Humans; Leucovorin; Male; Pneumonia, Pneumocystis; Quinazolines; Trimetrexate

Topics: Acquired Immunodeficiency Syndrome; Anemia, Macrocytic; Anemia, Megaloblastic; Dapsone; Humans; Leucovorin; Pneumonia, Pneumocystis; Trimethoprim; Vitamin B 12 Deficiency

An AIDS patient with cerebral toxoplasmosis had a folate deficiency-induced acute pancytopenia, which was rapidly reversed by the administration of folic acid. This observation is particularly important as a possible preventive therapy to be given to all HIV-infected patients because of the anti-folic activity of the majority of anti-infectious agents used during the course of this disease and the many potential sites of hematopoietic involvement. The patient's condition is stressed because the undernourished subject is at greater risk for this type of manifestation.

Topics: Acquired Immunodeficiency Syndrome; Acute Disease; Adult; Brain Diseases; Folic Acid Antagonists; Folic Acid Deficiency; HIV-1; Humans; Leucovorin; Male; Pancytopenia; Pyrimethamine; Toxoplasmosis

Topics: Acquired Immunodeficiency Syndrome; Adult; Brain Diseases; Diagnosis, Differential; False Negative Reactions; Female; HIV Seropositivity; Humans; Infant, Newborn; Kidney Transplantation; Leucovorin; Magnetic Resonance Imaging; Pregnancy; Pyrimethamine; Sulfisoxazole; Tomography, X-Ray Computed; Toxoplasmosis

Topics: Acquired Immunodeficiency Syndrome; Drug Therapy, Combination; Humans; Leucovorin; Leukopenia; Pneumonia, Pneumocystis; Quinazolines; Trimetrexate

A retrospective study was made of the cases of cerebral toxoplasmosis (CT) diagnosed since 1985 in patients with AIDS. In the period studied, out of a total of 70 patients with AIDS, 13 (18.5%) were diagnosed with CT. In eight cases (11%) CT was the first illness indicating AIDS. The clinical, neuro-radiological and serological findings were analyzed. Also the response to treatment with pyrimethamine and sulfadiazine. Although the rate of mortality from CT has been very low among our patients, relapses have been frequent, even in patients who were on maintenance treatment with pyrimethamine, and in the medium term the prognosis is made more gloomy by the appearance of other opportunistic infections.

Topics: Acquired Immunodeficiency Syndrome; Adult; Brain Diseases; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Leucovorin; Male; Pyrimethamine; Retrospective Studies; Sulfadiazine; Toxoplasmosis

A case of pulmonary T-cell lymphoma in an Acquired Immune Deficiency Syndrome (AIDS) patient is presented. Morphologically, it belonged to the large cell, immunoblastic category of the Working Formulation and demonstrated a helper/inducer phenotype. Clinically there was no association with manifestations of human T-lymphotropic virus (HTLV)-I related lymphoma and the patient was seronegative for HTLV-I and HTLV-II antibodies. High-grade B-cell lymphomas occur with an increased frequency in patients with AIDS but the occurrence of a peripheral T-cell lymphoma in AIDS has not been documented before. The case is discussed in the context of current concepts of AIDS-related lymphomagenesis.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; HIV; Humans; Immunohistochemistry; Leucovorin; Lung Neoplasms; Lymphoma; Male; Methotrexate; T-Lymphocytes; Vincristine

Between 1981 and 1986, we treated 179 newly diagnosed patients with advanced-stage malignant lymphoma or related conditions with methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin (MACOP-B). Experience with 12 different histologic subtypes indicates that MACOP-B is acceptably tolerated and effective for diffuse large cleaved cell, diffuse large noncleaved cell, diffuse mixed large and small cleaved cell, immunoblastic, and discordant lymphomas but not for angioimmunoblastic lymphadenopathy or for diffuse small cleaved cell, follicular large cell, follicular mixed large and small cleaved cell, acquired immune deficiency syndrome (AIDS)-related, unclassifiable, or small noncleaved cell lymphomas. Pooled long-term results for the 126 patients with variants of diffuse large cell lymphoma (cleaved, noncleaved, immunoblastic, and mixed) show an actuarial relapse-free survival of 67% for the 86% of patients who had a complete response and an overall survival for all patients of 65% at 78 months of follow-up. Analysis of toxicity reveals a substantially higher risk of lethal toxicity in patients over 59 years of age. MACOP-B should only be used for patients with one of the diagnoses for which it is effective; meticulous care should be taken to prevent severe toxicity in older patients.

Topics: Acquired Immunodeficiency Syndrome; Adult; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Drug Evaluation; Humans; Leucovorin; Lymphoma, Non-Hodgkin; Methotrexate; Middle Aged; Prednisone; Vincristine

Eleven patients with non-Hodgkin's lymphoma and three patients with Hodgkin's disease were observed among 876 anti-HIV-positive subjects attending the AIDS clinic at the University Hospital, Zurich, Switzerland. Compared to the general population this represents a 50-fold (95% confidence limits: 25-90) increased risk of non-Hodgkin's lymphoma and an 11.4-fold (2.3-33) increased risk for Hodgkin's disease in anti-HIV-positive men. High malignancy, advanced stage of disease at the time of diagnosis, and extranodal localization are characteristic of non-Hodgkin's lymphoma in AIDS patients, which carries a poor prognosis. However, remissions and prolonged disease-free survival are possible in individual cases. Only one opportunistic infection was observed during 92 months of treatment and observation using a mild chemotherapeutic regimen (m-BACOD). Less myelosuppressive chemotherapeutic schedules appear to be more beneficial than aggressive regimens in anti-HIV-positive patients due to the lower incidence of opportunistic infections.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; Hodgkin Disease; Humans; Leucovorin; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Opportunistic Infections; Prognosis; Risk Factors; Vincristine

12 AIDS/ARC patients with or suspected of Pneumocystis carinii pneumonia were treated with co-trimoxazole and received supplementary folic or folinic acid to avoid peripheral blood cytopenia. Most patients developed decreased numbers of neutrophils and hemoglobin while receiving co-trimoxazole. Supplementary folate/folinate could not abolish the drug-induced cytopenia. Routine prescription of folinic acid is not recommended. Folic acid is cheap and may be beneficial and should be prescribed.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Anemia; Drug Combinations; Folic Acid; Hematologic Diseases; Humans; Leucovorin; Leukopenia; Pneumonia, Pneumocystis; Prospective Studies; Sulfamethoxazole; Thrombocytopenia; Time Factors; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Twenty-two consecutive patients with high-grade, B-cell lymphomas related to the acquired immunodeficiency syndrome (AIDS) were accrued onto two sequential phase II studies, consisting of a standard regimen (M-BACOD, group no. 1, N = 13), or a novel, intensive regimen (group no. 2, N = 9), which included high-dose cytosine arabinoside (HD-Ara-C), and high-dose methotrexate (HD-MTX), in an attempt to prevent CNS relapse and improve response rates. Stage IV disease was present in 82%. Complete remission (CR) was achieved in seven of 13 patients (54%) in group no. 1, and in three of nine (33%) group no. 2 (P = NS). By multivariate analysis, the most significant factor in predicting response was a Karnofsky performance score (KPS) greater than 60 (P = .04). Three of the ten patients who achieved CR on either regimen have relapsed; in all, five of 13 patients (31%) in group no. 1 have achieved disease-free survival for more than 1 year, compared with one of nine (11%) in group no. 2. CNS progression occurred in six patients in group no. 2, and in two patients in group no. 1. Hematologic toxicity was significantly greater in group no. 2, and these patients had an increased risk of opportunistic infection (one in group no. 1 v seven in group no. 2; P less than .01). Survival was similar, with a median of 11 months in group no. 1 and 6 months in group no. 2. We conclude that the intensive regimen of combination chemotherapy described here is associated with significant risk of early death due to opportunistic infection in patients with AIDS-related lymphoma, and that progression in the CNS remains a major problem. Trials of combination chemotherapy of a less intensive nature, perhaps in combination with immunomodulators or antiretroviral agents should be explored.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; B-Lymphocytes; Bleomycin; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Prednisone; Prospective Studies; Vincristine

Topics: Acquired Immunodeficiency Syndrome; Drug Therapy, Combination; Humans; Leucovorin; Pneumonia, Pneumocystis; Quinazolines; Trimetrexate

Preclinical studies have demonstrated that trimetrexate is a potent inhibitor of dihydrofolate reductase from Pneumocystis carinii. On the basis of this evidence, this lipid-soluble antifolate was used as an antipneumocystis agent in 49 patients with the acquired immunodeficiency syndrome (AIDS) and pneumocystis pneumonia. Simultaneous treatment with the reduced folate leucovorin was used as a specific antidote to protect host tissues from the toxic effects of the antifolate without affecting the antipneumocystis action of trimetrexate. Patients were assigned to three groups and treated for 21 days: in Group I, trimetrexate with leucovorin was used as salvage therapy in patients in whom standard treatments (both pentamidine isethionate and trimethoprim-sulfamethoxazole) could not be tolerated or had failed (16 patients); in Group II, trimetrexate with leucovorin was used as initial therapy in patients with a history of sulfonamide inefficacy or intolerance (16 patients); and in Group III, trimetrexate with leucovorin plus sulfadiazine was used as initial therapy (17 patients). The response and survival rates were, respectively, 69 percent and 69 percent in Group I; 63 percent and 88 percent in Group II; and 71 percent and 77 percent in Group III. Trimetrexate therapy had minimal toxicity; transient neutropenia or thrombocytopenia occurred in 12 patients and mild elevation of serum aminotransferases in 4. We conclude that the combination of trimetrexate and leucovorin is safe and effective for the initial treatment of pneumocystis pneumonia in patients with AIDS and for the treatment of patients with intolerance or lack of response to standard therapies.

Topics: Acquired Immunodeficiency Syndrome; Adult; Drug Evaluation; Drug Therapy, Combination; Female; Folic Acid Antagonists; Humans; Leucovorin; Male; Middle Aged; Pneumonia, Pneumocystis; Quinazolines; Sulfadiazine; Trimetrexate

Although Toxoplasma gondii is the most commonly recognized cause of central nervous system mass lesions in patients with acquired immune deficiency syndrome, published investigations have provided little information about criteria for diagnosis of toxoplasmosis or the response to therapy. In this series the method of diagnosis and response to therapy were assessed in 14 patients who had evidence for toxoplasmosis based on routine histopathology, immunoperoxidase staining, or mouse inoculation. These patients presented with clinical and radiologic findings that did not clearly distinguish them from patients with other infectious or neoplastic processes. Excisional biopsies usually showed tachyzoites on routine histology, but needle biopsies were usually negative unless mouse inoculation or immunoperoxidase staining was employed. Response to pyrimethamine and sulfadiazine therapy was often prompt, but therapy had to be continued for long periods of time to maintain a clinical response, and no alternative regimen of one or more drugs appeared to be effective in patients unable to tolerate both pyrimethamine and sulfadiazine.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antibodies; Drug Therapy, Combination; Encephalitis; Humans; Leucovorin; Male; Middle Aged; Pyrimethamine; Sulfadiazine; Tomography, X-Ray Computed; Toxoplasma; Toxoplasmosis

Topics: Acquired Immunodeficiency Syndrome; Drug Combinations; Humans; Leucovorin; Leukopenia; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination