[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Used in combination with antiretroviral therapy, subcutaneous recombinant interleukin-2 raises CD4+ cell counts more than does antiretroviral therapy alone. The clinical implication of these increases is not known.
We conducted two trials: the Subcutaneous Recombinant, Human Interleukin-2 in HIV-Infected Patients with Low CD4+ Counts under Active Antiretroviral Therapy (SILCAAT) study and the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT). In each, patients infected with the human immunodeficiency virus (HIV) who had CD4+ cell counts of either 50 to 299 per cubic millimeter (SILCAAT) or 300 or more per cubic millimeter (ESPRIT) were randomly assigned to receive interleukin-2 plus antiretroviral therapy or antiretroviral therapy alone. The interleukin-2 regimen consisted of cycles of 5 consecutive days each, administered at 8-week intervals. The SILCAAT study involved six cycles and a dose of 4.5 million IU of interleukin-2 twice daily; ESPRIT involved three cycles and a dose of 7.5 million IU twice daily. Additional cycles were recommended to maintain the CD4+ cell count above predefined target levels. The primary end point of both studies was opportunistic disease or death from any cause.
In the SILCAAT study, 1695 patients (849 receiving interleukin-2 plus antiretroviral therapy and 846 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 202 cells per cubic millimeter were enrolled; in ESPRIT, 4111 patients (2071 receiving interleukin-2 plus antiretroviral therapy and 2040 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 457 cells per cubic millimeter were enrolled. Over a median follow-up period of 7 to 8 years, the CD4+ cell count was higher in the interleukin-2 group than in the group receiving antiretroviral therapy alone--by 53 and 159 cells per cubic millimeter, on average, in the SILCAAT study and ESPRIT, respectively. Hazard ratios for opportunistic disease or death from any cause with interleukin-2 plus antiretroviral therapy (vs. antiretroviral therapy alone) were 0.91 (95% confidence interval [CI], 0.70 to 1.18; P=0.47) in the SILCAAT study and 0.94 (95% CI, 0.75 to 1.16; P=0.55) in ESPRIT. The hazard ratios for death from any cause and for grade 4 clinical events were 1.06 (P=0.73) and 1.10 (P=0.35), respectively, in the SILCAAT study and 0.90 (P=0.42) and 1.23 (P=0.003), respectively, in ESPRIT.
Despite a substantial and sustained increase in the CD4+ cell count, as compared with antiretroviral therapy alone, interleukin-2 plus antiretroviral therapy yielded no clinical benefit in either study. (ClinicalTrials.gov numbers, NCT00004978 [ESPRIT] and NCT00013611 [SILCAAT study].)
New England Journal of Medicine 10/2009; 361:1548-59. · 51.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: High dose chemotherapy with autologous stem cell transplantation (ASCT) is increasingly used in the treatment of patients with lymphoma. As previously shown with conventional treatments, second neoplasms are emerging as a long term complication of the procedure. In this study, we investigate the incidence of second neoplasm in a cohort of 171 patients treated with BEAM or BEAC regimens for Hodgkin's disease (n = 62) and non-Hodgkin's lymphomas (n = 109) followed up for a median of 52 months post ASCT. Six patients developed six second malignancies 12 to 105 months after ASCT: fibrolamellar carcinoma of the liver, malignant fibrous histiocytoma, pancreatic carcinoma, squamous cell carcinoma of the lung, invasive carcinoma of the vulva and acute myelogenous leukemia. The cumulative actuarial risk for developing second malignancy is 16.7 % (95% confidence interval: 5.9-39.3%) 13 years after transplant. The age-adjusted incidence of cancer in the study group is 4.1 times higher than that of primary cancer in the general population. These data confirm that ASCT recipients are at increased risk of later malignancies. This complication adds significant morbidity and mortality to the transplant process and therefore, needs to be taken into account in long term evaluation of new strategies which involve early intensification in the treatment of lymphomas.
Leukemia and Lymphoma 06/2009; 31(1-2):187-194. · 2.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We previously reported a beneficial effect of benfluorex (BFL) on oral glucose tolerance test (OGTT) and visceral fat mass in an open-label study conducted in 60 HIV-infected patients. The objective of this study was to assess whether administration of BFL compared to placebo (PBO) improves insulin resistance (IR) in HIV+ patients with HAART- induced lipodystrophy.
22 HIV-infected patients with IR or impaired glucose tolerance were double-blind randomly assigned to receive BFL 3 tablets/day or PBO for 24 weeks. Efficacy assessments included OGTT, abdominal computed tomography, and the measurement of fasting lipids.
Change of median insulin AUC was -53.0 microIU/mL (IQR, -126.0 to -12.7) in the BFL group vs. +33.6 microIU/mL (IQR, 7.0 to 115.6) (p = .01) in PBO group. Weight decreased significantly in the BFL group (-2 kg +/- 2.6; IQR, -6.8 to 2.0) compared to the PBO group (0.8 kg +/- 1.7; IQR, -2.0 to 0.5) (p = .02). No significant changes in visceral or subcutaneous fat mass and plasma lipid level were observed between the two groups.
Added to antiretroviral therapy, a 6-month therapy with BFL improved insulin sensitivity but is not sufficient to reduce significantly visceral fat mass.
HIV Clinical Trials 01/2009; 10(1):33-40. · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: IntroductionChronic lymphocytic leukemia (CLL) is the most common leukaemia in the Western world. Recent advancement in the aetiology, pathophysiology and the development of new therapeutics tools have significantly modified the current management of CLL.
Revue De Medecine Interne - REV MED INTERNE. 01/2008; 29(5):424-435.
[Show abstract][Hide abstract] ABSTRACT: or allogeneic 4 transplantation has been suggested. We report the first case of a woman with a non Hodgkin lymphoma (NHL) who developed PML after a combination of rituximab with chemotherapy as first line treatment. A 67-year-old woman suffered from a mantle cell lymphoma diagnosed on splenomegaly and hyperlym- phocytosis. Staging showed a stage IV with bone mar- row involvement. The patient was treated with a com- bination of rituximab (375 mg/m 2 ) and chemotherapy with standard CHOP: cyclophosphamide 750 mg/m 2 , doxorubicin 50 mg/m 2 , vincristin 2 mg, and oral predni- son 100 mg given in 3-week cycles. She received eight cycles of treatment. Evaluation after the eight cycles showed a complete remission. One month after the last chemotherapy, the patient rapidly presented psychiatric disturbances with speech dysfunction and paranoia delirium. PML was suspected on magnetic resonance imaging showing frontal and temporal leukoen- cephalopathy. JC viral DNA was detected in the cere- brospinal fluid. HIV serology was negative. Her total lymphocyte count was 470/∝L with 110/∝L CD4 + and 310/∝L CD8 + . Peripheral B cells were decreased with
[Show abstract][Hide abstract] ABSTRACT: The potential benefit of rituximab as adjuvant to high-dose therapy (HDT) has been investigated in patients under 60 years with poor-risk (age-adjusted international prognostic index at 2-3) CD20+ diffuse large B-cell lymphoma (DLBCL). The treatment consisted of four cycles of high-dose CEOP (cyclophosphamide, epirubicin, vincristine, prednisone), plus etoposide and cisplatin during the two last cycles. Peripheral blood stem cells were collected after cycle 1, and reinfused after cycles 3 and 4. Four weekly rituximab infusions were subsequently delivered. Among the 36 patients included, 30 could complete chemotherapy schedule, and 24/36 received rituximab. A complete response occured in 26/36 patients (72%). With a median follow-up of 30 months, the estimated 5-year overall survival (OS) and event-free survival (EFS) rates (mean +/- s.d.) were 65 +/- 16 and 63 +/- 15%, respectively. For the 24 patients who received both chemotherapy and rituximab, the estimated 5-year OS and EFS rates were 86 +/- 14 and 82 +/- 15%. These data suggest that rituximab after HDT is feasible. Both complete remission rate and survival curves compare favorably with the poor outcome usually observed in high-risk DLBCL patients managed with HDT without rituximab.
Bone Marrow Transplantation 09/2006; 38(3):217-22. · 3.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This retrospective and longitudinal study evaluated the long-term hepatic tolerance of a nelfinavir (NFV)-antiretroviral combined regimen in 82 patients of the HCV-HIV Cohort of CISIH-Sud of Marseilles. Follow-up data (liver enzyme levels, CD4 cell count, HIV viral load, and metabolic parameters) of patients treated with NFV on inclusion or during the follow-up of the cohort were analyzed under treatment over 24 months. Comparisons were performed with X2 or Kruskal-Wallis tests. At baseline (n = 82), the median exposure to NFV was 4.1 months; 58 patients received NFV combined with NRTI and 24 with NNRTI. The median CD4 cell count was 337/mm3 [interquartile range (IR): 216-480) and 39.7% had an undetectable HIV RNA level. Qualitative HCV PCR was positive in 91% of the patients and 19/51 patients with liver biopsy were F3-F4. Median alanine and aspartate aminotransferase (ALAT, ASAT), gamma-glutamyltransferase (GT), and alkaline phosphatase (ALP) were 46 UI/liter (IR: 36-76), 55 UI/liter (IR: 32-97), 97 UI/liter (IR: 50-194), and 88 UI/liter (IR: 72-104), respectively, with 76% of the patients with ALAT/ASAT grade <2. Median follow-up was 23 months (IR: 13.8-37). No significant difference was observed in the distribution of ALAT, ASAT, GT, and ALP as well as of ALAT/ASAT grades over the 24-month study period. Patients treated with NFV + NNRTI had significantly higher GT and ALP levels at baseline with no significant increase during follow-up. Cholesterol, triglyceride, and glycemia distributions remained stable over time. In conclusion, this study showed a good hepatic and metabolic tolerance of a long-term NFV-combined regimen in HIV-HCV coinfected patients.
AIDS Research and Human Retroviruses 11/2005; 21(10):841-4. · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: T-cell lymphoma is an aggressive lymphoma that cannot be cured despite aggressive therapy, including autologous stem cell transplantation. Thalidomide is an immunomodulatory drug with numerous properties that has proven effective in relapsed multiple myeloma and, to a lesser extent, in other hematologic diseases. We report three cases of relapsed refractory T-cell lymphoma treated with thalidomide with a good tumor response.
European Journal Of Haematology 03/2005; 74(2):169-71. · 2.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Extramedullary (EM) localizations at diagnosis or during the course of multiple myeloma (MM) are rare. We conducted a large retrospective study to more accurately describe the clinical and laboratory features of this entity, and the outcome of these manifestations. The charts of 19 eligible patients out of 432 patients with MM were retrieved from the hematology department of the Institut Paoli-Calmettes Cancer Center. Median age was 61 (range: 39-79) with a female/male sex ratio of 8/11. Ten patients were found to have EM and extraosseous tumor at the time of MM diagnosis, and nine patients developed EM tumor during the course of the disease. Neither the stage of the disease, the LDH level, or the type of immunoglobulin (Ig) was found to be associated with the development of EM disease. Patients who developed EM tumor during the course of MM had a lower serum Ig and a higher monoclonal Bence-Jones proteinuria at the diagnosis of MM than patients who presented with EM tumor at diagnosis. Multiple sites were usually involved. Resistance to chemotherapy was frequent and response to thalidomide was poor. Eight out of the 19 patients responded to high-dose chemotherapy. The remaining 11 patients progressed while on therapy. With a median follow-up of 13 months (range: 2-65), six patients are alive, four patients are in partial remission and two patients in present progressive disease. In conclusion, EM tumors are a rare manifestation of MM, with a cumulative incidence of 4.6% of MM. Multiple sites are usually involved. The response to chemotherapy is very poor with a very low response rate to thalidomide. The prognosis is very poor, especially when the diagnosis of EM tumor is concurrent with the diagnosis of MM.
European Journal Of Haematology 01/2005; 73(6):402-6. · 2.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In all, 41 multiple myeloma (MM) patients received an antithymocyte globulin (ATG), fludarabine, and busulfan-based reduced intensity conditioning (RIC) for allogeneic stem cell transplantation (allo-SCT) from HLA-identical siblings. In total, 29 patients (70%) were in partial remission, one patient in complete remission, and 11 (27%) with progressive disease at the time of allo-SCT. Median time between diagnosis and allo-SCT was 24 months. The cumulative incidences of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) were 36% (95% CI, 21-51%) and 7% (95% CI, 2-20%), respectively. Overall, 10 patients developed limited chronic GVHD, whereas seven developed an extensive form (cumulative incidence, 41% (95% CI, 26-56%) at 2 years). With a median follow-up of 389 days, the overall cumulative incidence of transplant-related mortality (TRM) was 17% (95% CI, 6-28%). In all, 11 patients (27%) are in continuous complete remission, and the Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) at 2 years were 62% (95% CI, 47-76%) and 41% (95% CI, 23-62%), respectively. PFS and OS were significantly higher in patients with chronic GVHD as compared to patients without chronic GVHD (P=0.006 for PFS and P=0.01 for OS). Collectively, these data demonstrate that RIC allo-SCT can mediate a potentially curative graft-versus-myeloma effect with an acceptable incidence of toxicity and TRM.
Bone Marrow Transplantation 08/2004; 34(1):77-84. · 3.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 57-year-old man with acute myeloid leukemia (AML) French-American-British (FAB) 4 developed disseminated invasive cerebral and pulmonary aspergillosis during postinduction aplasia. According to international consensus, infection was categorized as probable (two host factors: deep neutropenia for >10 days and refractory fever for >96 h; major clinical criteria of lower respiratory tract and CNS invasive fungal infection; positive results for galactomannan antigen in three blood samples). After the failure of standard amphotericin-based therapy, the spectacular regression of multifocal brain and lung lesions was rapidly achieved under a caspofungin acetate/voriconazole combination. Further permanent caspofungin maintenance with voriconazole added during aplasia periods permitted two consolidation courses and autograft-based intensification without any delay.
Annals of Hematology 07/2004; 83(6):390-3. · 2.87 Impact Factor