AIDS-related malignant lymphoma: results of prospective treatment trials.

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.

Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi's sarcoma.

PURPOSE: To compare the safety and efficacy of liposomal daunorubicin (DaunoXome; NeXstar Pharmaceuticals, Inc, Boulder, CO) with a reference regimen of doxorubicin, bleomycin, and vincristine (ABV) in advanced AIDS-related Kaposi's sarcoma (KS). PATIENTS AND METHODS: In a prospective randomized phase III trial, 232 patients were randomized to receive DaunoXome 40 mg/m2 or a combination regimen of doxorubicin 10 mg/m2, bleomycin 15 U, and vincristine 1 mg, administered intravenously every 2 weeks. Treatment was continued until complete response (CR), disease progression, or unacceptable toxicity. RESULTS: Of 232 patients randomized, 227 were treated: 116 with DaunoXome and 111 with ABV. The overall response rate (CR or partial response [PR]) was 25% (three CRs and 26 PRs) for DaunoXome and 28% (one CR and 30 PRs) for ABV. The difference in response rates was not statistically significant. The median survival time was 369 days for DaunoXome patients and 342 days for ABV patients (P = .19). The median time to treatment failure was 115 days for DaunoXome and 99 days for ABV (P = .13). ABV patients experienced significantly more alopecia and neuropathy (P < .0001). DaunoXome patients experienced more grade 4 neutropenia (P = .021). Cardiac function remained stable, with no instances of congestive heart failure on either treatment arm. CONCLUSION: In this large phase III trial, the efficacy of DaunoXome was comparable to that of ABV. Response rates, time to treatment failure, and overall survival were similar on both treatment arms. DaunoXome is a safe and effective primary therapy for advanced AIDS-related KS.

Treatment of a unique anemia in patients with IDDM with epoetin alfa.

OBJECTIVE: To identify and treat a unique form of anemia in patients with long-term IDDM. RESEARCH DESIGN AND METHODS: Patients with IDDM, unexplained symptomatic anemia, and serum creatinine levels of < 177 mumol/l (2.0 mg/dl) were treated with epoetin alfa (Procrit, Ortho Biotech, Raritan, NJ), 50 U/kg three times weekly, subcutaneously, to reach a target hematocrit of 38-40%. Baseline serum erythropoietin titers were measured before drug therapy. RESULTS: Six patients were treated with epoetin alfa. Median age of the group was 74 years, with IDDM being diagnosed for a median of > 20 years. All patients had symptoms of anemia with a median hematocrit of 28.9% (range 27-31). Compared with iron deficiency control patients, the group had a limited erythropoietin (EPO) response to the degree of anemia. All patients showed increases in hematocrit, median peak of 40.9%, with median time-to-peak response of 12 weeks. Baseline symptoms of anemia resolved in all patients. No adverse effects were noted during the treatment period. CONCLUSIONS: There is a unique form of anemia in patients with long-term IDDM and clinically normal renal function who respond to low-dose epoetin alfa therapy. The rapid response to therapy and depressed baseline erythropoietin titers suggest the anemia is due to a lack of endogenous EPO release.

Seronegative disseminated coccidioidomycosis in patients with HIV infection.

Serologic testing for complement-fixing antibodies to Coccidioides immitis is commonly employed to assist in the diagnosis and management of this infection, but its usefulness in an HIV-coinfected population is unknown. In this study we reviewed all the mycologically or histologically proven cases of disseminated C. immitis infection after 1982. Disseminated C. immitis and proven HIV infection were present in eight patients. We performed serum complement-fixing antibody titers on all eight patients, six of whom gave positive tests, while two patients (25%) gave repeatedly negative results despite widely disseminated disease. We conclude that histopathology and culture remain the most reliable methods for the diagnosis of disseminated coccidioidomycosis in the HIV-infected host.

The long-term use of zidovudine in patients with severe immune-mediated thrombocytopenia secondary to infection with HIV.

Various treatments for HIV-related thrombocytopenia have been reported. Since etiologies of the thrombocytopenia may differ with regard to risk group treatment outcomes may also vary. We have recently studied the long-term use of zidovudine in individuals with sexually transmitted HIV infection and severe thrombocytopenia. Twenty-five men, median age 34 years (range, 23-51 years), were treated with zidovudine (1000 mg/day) for a median duration of 12 months (range, 2.5- less than 26 months). Nineteen patients (76%) had had episodes of symptomatic bleeding secondary to thrombocytopenia prior to study entry. All patients bleeding symptoms resolved with therapy. Six (24%) achieved a complete response, with normalization of platelet counts, while 11 patients (44%) achieved a partial response, giving an overall response rate of 68%. The median time to partial or complete normalization of platelet counts was 12 weeks (range, 4-62 weeks). Toxicities were minimal during the study period. Only one patient developed an AIDS-defining diagnosis while on therapy. We conclude that patients with sexually transmitted HIV infection and immune thrombocytopenia may need a prolonged period of therapy with zidovudine to achieve a platelet response. Other treatment modalities may be required for the 30% of patients who do not respond to zidovudine.

The use of fine needle aspiration cytology in the management of human immunodeficiency virus-related non-Hodgkin's lymphoma and Hodgkin's disease.

We prospectively studied the utility of fine needle aspiration (FNA) to diagnose non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) in patients with human immunodeficiency virus (HIV) infection and lymphadenopathy. Twenty-one patients with a clinical evidence of lymphoma underwent 24 FNA and site-specific tissue biopsies. Twenty-two of the 24 biopsy results were consistent with a malignant lymphoproliferative neoplasm: NHL (19 cases), HD (two cases), and T-cell lymphoma (one case). Two biopsies showed reactive lymphoid hyperplasia consistent with a clinical diagnosis of persistent generalized lymphadenopathy. There was an 87% correlation (21 of 24) between FNA and biopsy diagnoses. Eighteen of the 19 biopsy-confirmed NHL cases were diagnosed with FNA. Both cases of HD and the one T-cell lymphoma were also diagnosed with aspirate material. In conclusion, the FNA in HIV-infected individuals with suspected malignant lymphadenopathy is highly sensitive (95%). The FNA, when used in conjunction with the clinical appearance, is a useful tool in the management of HIV infection and lymphadenopathy.

Serum erythropoietin titers in patients with human immunodeficiency virus (HIV) infection and anemia.

The pathophysiology of anemia in patients with human immunodeficiency virus (HIV) infection is multifactorial. In order to determine the role of erythropoietin (EPO) response as a cause of the anemia, serum levels were determined by direct radioimmunoassay in 110 symptomatic patients with various stages of HIV infection. Symptomatic patients (ARC and AIDS) not receiving zidovudine (ZDV) therapy demonstrated a strong inverse relationship between serum EPO and hemoglobin levels (p = 0.01 and p less than 0.001, respectively). Patients with AIDS who were anemic while receiving ZDV demonstrated serum EPO levels that ranged from normal to markedly elevated (9-3,390 mU/ml). The diversity of serum EPO levels in patients with HIV infection and anemia suggests that the etiology of anemia in these patients and their potential response to recombinant human EPO may not be uniform.

Bone marrow examination for the diagnosis of mycobacterial and fungal infections in the acquired immunodeficiency syndrome.

In a series of 342 bone marrow examinations from 314 patients with human immunodeficiency virus infection, 70 examinations (20%) detected opportunistic mycobacterial or fungal infections. One hundred eleven of the 314 patients had such infections, and, hence, 63% (70/111) were detected by bone marrow examination. Special stains for microorganisms detected 16 (32%) of 50 Mycobacterium avium complex infections, 10 (22%) of 45 Mycobacterium tuberculosis infections, eight (73%) of 11 Histoplasma capsulatum infections, and five (83%) of six Cryptococcus neoformans infections. Bone marrow cultures detected 36 (72%) of the 50 M avium complex infections, 13 (29%) of the 45 M tuberculosis infections, and 63% of the fungal infections. Marrow examination revealed infection in only one of the 70 specimens (1%) collected to evaluate thrombocytopenia alone or hematologic malignancy, but in 69 (25%) of 274 with fever, neutropenia, anemia, or miscellaneous other indications for marrow examination. Granulomas were detected in 102 (30%) of the biopsy specimens, including 71 (64%) of those in cases with mycobacterial or fungal infection. The granulomas showed caseous necrosis in nine cases, all in patients with tuberculosis, and the 27 cases with tuberculosis-associated granulomas tended to show large, tightly cohesive granulomas. The presence of granulomas correlated with opportunistic infection in 82 (80%) of 102 cases. Without granulomas, special stains were positive in only eight (3%) of 240 specimens. These results suggest that (1) bone marrow granulomas are a common and valuable histologic clue to opportunistic infection; (2) without them, special stains may not be a cost-efficient way to diagnose such infection; and (3) bone marrow examination can be a useful method of diagnosing opportunistic mycobacterial and fungal infections in patients with fever, anemia or neutropenia, and underlying human immunodeficiency virus infection.

A review of the fine-needle aspiration cytology findings in human immunodeficiency virus infection.

Patients infected with the human immunodeficiency virus (HIV) are subject to infections and neoplasms, which frequently result in palpable or radiologically identified masses. Fine-needle aspiration (FNA) offers a rapid, simple, and cost effective approach for diagnosis of these masses. During a 2-yr period, 396 aspirates were performed on 362 HIV-infected patients within the LAC-USC Medical Center. Adequate material was obtained from 84% of the FNA, allowing the etiology of the mass to be determined in 90% of the cases by means of a combination of cytologic, microbiologic, and immunocytochemical procedures. Significant pathologic processes identified in these patients by means of FNA included reactive lymphoid proliferations (35%), abnormal lymphoid proliferations (12%), infections (12.5%), cystic (5.5%) and inflammatory processes (5%), nonlymphoid malignancies (4%), and salivary gland pathology (1%). We conclude that FNA is an appropriate initial diagnostic procedure in HIV positive patients presenting with mass lesions.

Thrombotic thrombocytopenic purpura in patients with human immunodeficiency virus infection: a report of three cases and review of the literature.

Three cases of thrombotic thrombocytopenic purpura (TTP) and coexistent human immunodeficiency virus (HIV) infection are presented with a review of 15 cases reported in the literature. Of the 18 total patients, one-half presented with no symptoms of HIV infection while nine patients presented with symptomatic HIV disease before or simultaneous to the diagnosis. The presenting symptoms were similar to those with classic TTP and included fever in 75% and 40% with neurologic symptoms. Laboratory parameters reflected the microangiopathic hemolytic anemia typically seen in patients with TTP. The median hematocrit was 19.4%, while the median platelet count was 16,000/mm3. As with classic TTP, patients with HIV-related TTP only had mild renal dysfunction (median creatinine of 1.2 mg/dl, range 0.8-4.8 mg/dl). Plasma exchange produced clinical remission in a majority of the patients. Importantly, approximately one-third of the patients died prior to the initiation of therapy. We conclude that TTP is a rare but treatable condition in patients with HIV infection. A TTP diagnosis should be considered in patients with HIV infection who present with severe anemia and thrombocytopenia. Plasma exchange should be considered as initial therapy. The role of both antiplatelet therapy and aspirin is unknown.

Advanced acquired immune deficiency syndrome-related Kaposi's sarcoma. Results of pilot studies using combination chemotherapy.

Pilot studies were conducted to evaluate the toxicity and efficacy of two relatively marrow-sparing chemotherapy regimens in the treatment of advanced or progressive epidemic Kaposi's sarcoma. Chemotherapy regimens consisted of bleomycin (10 mg/m2), vincristine (1.4 mg/m2, 2 mg maximum) and Adriamycin (doxorubicin) at either 10 mg/m2 (Group I) or 20 mg/m2 (Group II). The therapy was given intravenously, every 2 weeks, until intolerable toxicity or maximum antitumor response. Thirty-three patients were treated. Although the patient populations were similar regarding pretreatment prognostic factors, the patients were not assigned randomly to these two treatment regimens. Major responses (complete or partial remission) were attained in 79% of the cases. The treatment-related toxicities consisted of mild to moderate nausea, hair loss, and peripheral sensory neuropathy. Bone marrow suppression consisted primarily of neutropenia (less than 1000/mm3) which occurred in a third of the patients. Variables significantly associated with shorter survival included hemoglobin (less than 10 g/dl), low Karnofsky performance status (less than 70%), and weight loss. Opportunistic infections occurred in the majority of cases during administration of chemotherapy, and were most likely related to severe cell-mediated immune dysfunction and low CD4-positive lymphocyte counts.

Intravenous immune globulin use in patients with human immunodeficiency virus-related thrombocytopenia who require dental extraction.

Five patients with human immunodeficiency virus (HIV)-related immune thrombocytopenia who were undergoing dental extraction were treated with intravenous immune globulin (IVIG). All patients received IVIG, 1 gram per kg, the day before the dental extraction and again the day of the dental extraction. Four patients had a previous history of minor clinical bleeding. The median baseline platelet count before extraction was 20 X 10(9) per liter (range 13 to 44). The median peak platelet count was 100 X 10(9) per liter (range 56 to 528) following infusion. This peak response was achieved by day 2 in 3 patients and by days 5 and 7 in 1 patient each. No patients had complications or toxicity from the infusions or perioperative bleeding. No patients required blood product transfusions for the surgical procedure. In conclusion, IVIG infusion should be considered in patients with HIV-related immune thrombocytopenia requiring surgical procedures when a prompt rise in platelet count is desired.

Autopsy findings in AIDS-related lymphoma.

Autopsies in 20 patients with the acquired immune deficiency syndrome (AIDS)-related lymphoma were studied retrospectively to ascertain the precise cause of death and the extent of lymphomatous disease. Eight patients had primary central nervous system (CNS) lymphoma: two of them were diagnosed antemortem; CNS lymphoma was suspected in three others by computerized tomographic (CT) scan and was confirmed at autopsy. The remaining three were diagnosed incidentally at autopsy. All had concurrent infections at autopsy, including opportunistic infection in six and pyogenic infections in two. Opportunistic infections at autopsy in these patients outnumbered those diagnosed clinically. Twelve patients had systemic lymphoma. Three were diagnosed only at autopsy, two of whom had extensive Kaposi's sarcoma (KS) as well. Eight patients were treated with chemotherapy, but died with disseminated disease. Opportunistic infections were found at autopsy in five patients. Secondary involvement of the CNS by lymphoma was frequent (66%) and was not related to previous bone marrow involvement. The authors conclude that the incidence of lymphoma occurring in AIDS may be more frequent than diagnosed clinically. Similarly, multiple opportunistic infections occur in these patients which are not diagnosed premortem and may contribute to early death.

Treatment of epidemic Kaposi's sarcoma with combination chemotherapy (vincristine and bleomycin) and zidovudine.

Advanced AIDS-associated Kaposi's sarcoma often requires systemic cytotoxic chemotherapy. Despite high response rates, the majority of the patients die of opportunistic infections (OIs). Effective anti-retroviral agents in combination with cytotoxic chemotherapy may be useful in preventing the development of OIs in addition to increasing the tumor response. Twelve patients with extensive EKS were treated with a non-myelosuppressive drug regimen consisting of bleomycin and vincristine (BV) in combination with the anti-retroviral agent, zidovudine (ZDV). The dose of ZDV was 200 mg orally every four hours (full dose) in eight patients (Group I) or 100 mg orally every four hours (half dose) in four patients (Group II). Toxicity was acceptable with only 3 patients (all from Group I) requiring blood transfusions. ZDV dose reduction due to granulocytopenia was required in 6 patients (5 in Group I and 1 in Group II). Only two patients developed OIs during 27.5 cumulative months of therapy. The overall response rate was 83% in both groups with 4 patients achieving complete remission (CR) and 6 patients acheiving a partial remission (PR). We conclude that a combination of (BV) chemotherapy and ZDV can be used safely with high response rates. Prospective studies of such combination regimens are currently in progress.

Human immunodeficiency virus-related lymphoma. Prognostic factors predictive of survival.

In an attempt to determine factors predictive of survival in patients seropositive for human immunodeficiency virus (HIV) with acquired immune deficiency syndrome (AIDS)-related lymphoma, the authors studied 60 such patients, all of whom were treated with curative intent. Eleven patients presented with lymphoma primary to the brain (P-CNS); the remaining 49 had systemic AIDS-related lymphoma. Patients with P-CNS lymphoma had more severe underlying HIV-related disease than did patients with systemic lymphoma as evidenced by a higher incidence of AIDS before the diagnosis of lymphoma (73% versus 37%; P = 0.04), and lower median number of CD-4-positive lymphocytes in peripheral blood at diagnosis of lymphoma (30/dl versus 189/dl; P = 0.005). Median survival of such patients was 2.5 months versus 6.0 months for patients with systemic lymphoma (P = 0.04). Forty patients with systemic AIDS-related lymphoma have died; three factors were strongly associated with shorter survival: (1) Karnofsky performance status (KPS) of less than 70% (multivariate relative survival risk [RSR] = 3.1); (2) history of AIDS before the diagnosis of lymphoma (multivariate RSR = 3.0 for opportunistic infection plus Kaposi's sarcoma); and (3) bone marrow involvement (RSR = 3.1)). All three factors (KPS of less than 70%, prior AIDS diagnosis, and marrow involvement) were associated with early demise attributed to AIDS, whereas death attributed to lymphoma per se was associated with only two factors (KPS of less than 70% and marrow involvement). In the absence of all three risk factors, a "good prognosis" group of 17 patients was defined, with a median survival of 11.3 months; the median survival of the remaining patients ("poor prognosis") was 4.0 months (P = 0.0002). Attainment of complete response to therapy (CR) was strongly related to prolonged survival in the patients in the good prognosis group (17.8 months in patients with CR versus 5.0 months in those with less than CR); however, such meaningful prolongation of survival was not seen in patients with poor prognosis who attained CR (6.3 months versus 3.4 months). The patients with poor prognosis may be unable to tolerate the insult of multiagent chemotherapy, experiencing low CR rates (25%) and death caused by lymphoma and AIDS. However, patients in either prognostic category who attained CR remained at risk for dying of AIDS while the lymphoma was in remission. Thus, it is apparent that meaningful prolongation of survival in the patient with AIDS-related lymphoma will require not only effective antineoplastic intervention, but also control of the underlying HIV infection. In addition, future therapeutic trials should stratify patients based upon the prognostic factors defined here in an attempt to clarify the results obtained.

Interferon-alpha maintenance therapy after cytotoxic chemotherapy for treatment of acquired immunodeficiency syndrome-related Kaposi's sarcoma.

A prospective phase I clinical trial with recombinant interferon-alpha-2b as maintenance therapy after cytotoxic chemotherapy was conducted. Twenty-one homosexual and bisexual males with extensive mucocutaneous or visceral epidemic acquired immunodeficiency syndrome (AIDS)-Kaposi's sarcoma (KS) were studied. After a complete response (6 patients) or partial response (15 patients) from chemotherapy consisting of Adriamycin (20 mg/m2), bleomycin (10 U/m2), and vincristine (1.4 mg/m2; 2 mg maximum), patients were given interferon-alpha (IFN-alpha) in an attempt to prolong disease-free survival. Three dose levels of daily IFN-alpha were tested: 5, 10, and 15 million U. The maximum tolerated dose was 10 million units. Dose-limiting toxicities included recurrent grade 3 fatigue, diarrhea, and fever, which resulted in the termination of therapy in eight patients (38%). Hematologic toxicities were infrequent (four patients; 19%). Responses were observed in two patients on IFN-alpha, both at the 10-million-U dose level. The median duration of response on IFN-alpha therapy following chemotherapy was 8 weeks (range, 3-11). We conclude that the duration of IFN-alpha maintenance response following cytotoxic chemotherapy is short with response to residual disease observed in a minority of cases at this dose and schedule. Additional trials of maintenance therapy in patients with advanced AIDS-KS combining antiretroviral agents are in progress.

Low-dose chemotherapy with central nervous system prophylaxis and zidovudine maintenance in AIDS-related lymphoma. A prospective multi-institutional trial.

OBJECTIVE: --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). DESIGN: --A phase II prospective clinical trial, with median follow-up of 33 months. SETTING: --Eight university hospitals, within the context of the AIDS Clinical Trials Units, sponsored by the National Institute of Allergy and Infectious Diseases. PATIENTS: --Forty-two patients with AIDS-related malignant lymphoma. All were evaluable for toxicity assessment, and 35 for response. INTERVENTION: --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. MAIN OUTCOME MEASURES: --Response rate and number of opportunistic infections. RESULTS: --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. CONCLUSIONS: --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.

Intravenous immunoglobulin in the treatment of human immunodeficiency virus-related thrombocytopenia.

Fourteen patients with sexually transmitted human immunodeficiency virus (HIV)-related immune thrombocytopenia were treated with intravenous gammaglobulin (IVIG). The patients were treated with a uniform program consisting of 1 g/kg of IVIG on day 1 and day 2, followed by 1 g/kg on day 15. Most patients had pretreatment bleeding symptoms, which included petechiae, spontaneous and traumatic ecchymoses, gum bleeding, and epistaxis. Median baseline platelet count was 17,000/mm3 (range 3-61,000/mm3). After the infusion of the IGIV, all patients had a resolution of their bleeding by day 8. The median maximum platelet count achieved with the IGIV was 220,000/mm3 (range 76-426,000/mm3). No patient achieved either a sustained complete or partial remission after the conclusion of the IVIG therapy. Toxicities were minimal with the majority being headache and nausea. In conclusion, patients with sexually transmitted HIV infection and immune thrombocytopenia respond favorably to IVIG. This treatment should be considered as first-line therapy for patients with HIV-related immune thrombocytopenia who require immediate but temporary increase in their platelet count, attributable to symptoms or signs of clinical bleeding or because of the need for an invasive procedure.

Liposomal daunorubicin in the treatment of relapsed or refractory non-Hodgkin's lymphoma.

PURPOSE: To assess the efficacy and toxicity of liposomal daunorubicin administered as a two-hour intravenous infusion to patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Eligible patients had relapsed or refractory NHL with measurable or evaluable disease, and low grade, select intermediate grade, or mantle cell pathologic types. Prior exposure to an anthracycline or anthracenedione was allowed. Liposomal daunorubicin at a dose of 100 mg/m2 was given intravenously over a minimum of 120 minutes every 3 weeks. as a single agent. RESULTS: Thirty-three patients were accrued: twenty-three (70%) had low-grade histologies; six (18%) had intermediate-grade histologies (follicular large-cell and diffuse small cleaved); and four (12%) patients had mantle-cell lymphoma. Eighteen (55%) had received two or more prior regimens; fourteen (42%) received a prior anthracycline. A median of six cycles of liposomal daunorubicin were administered (range 1-15). Of 31 patients evaluable for response, 2 complete and 10 partial remissions were documented for a major response rate of 39% (95% confidence interval (CI): 22%-58%). The median duration of response was 19.5 months (range 4.3-41.1+). Six responders (50%) had received a prior anthracycline; one responder had mantle-cell histology. The major toxicities were grade 3 or 4 neutropenia in 26 patients (79%), mild to moderate nausea in 22 (67%), and fatigue in 16 (48%). CONCLUSIONS: Liposomal daunorubicin at 100 mg/m2 every three weeks has activity in patients with relapsed or refractory NHL, including patients with prior exposure to an anthracycline. Further studies of liposomal daunorubicin in combination with other agents are warranted.