Treatment with rituximab, dexamethasone, high-dose cytarabine, and oxaliplatin (R-DHAOx) produces a strong long-term antitumor effect in previously treated patients with follicular non-Hodgkin's lymphoma.

BACKGROUND: We explored the addition of rituximab to high-dose cytarabine (ara-C), oxaliplatin (L-OHP), and dexamethasone [R-DHAOx], in resistant and relapsed patients with CD20-positive follicular non-Hodgkin's lymphoma. METHODS: Twenty-two patients were included; they were treated previously with one to five chemotherapy regimens, including 13 patients who had also received rituximab. R-DHAOx consisted of rituximab, 375mg/m(2), day 1; dexamethasone, 40mg/d, days one to four; L-OHP, 130mg/m(2), day 1; and ara-C, 2000mg/m(2) every 12 h, day 2. Courses were repeated every 21 days for eight courses. RESULTS: Twenty-one patients (95%) achieved a complete response and one had a partial response. Responses were obtained in patients with and without resistance to prior treatment, either alone or combined with rituximab. The median follow-up time was 58.3 months (range, 8.7-92.6 months). Progression-free survival reached a plateau at 84% at 38.2 months. Only two of the 21 complete responders have relapsed. Tumor molecular markers disappeared in all 10 complete responders whose markers were found before treatment. Peripheral neuropathy related to the cumulative dose of L-OHP, and myelosuppression were the most prominent toxic effects. CONCLUSIONS: R-DHAOx is highly active for salvage treatment of patients with follicular non-Hodgkin's lymphoma, and it produces long-term antitumor efficacy.

Thrombotic microangiopathy: a new dose-limiting toxicity of high-dose sequential chemotherapy.

Ten patients with refractory (n = 8) or early relapsing (n = 2) aggressive non-Hodgkin's lymphoma were enrolled in a pilot study evaluating a high-dose sequential chemotherapy regimen with peripheral blood stem cell (PBSC) support. Five treatment phases were scheduled: phase I (cyclophosphamide + etoposide followed by lenograstim (G-CSF), and a PBSC harvest); phase II (cisplatinum + cytarabine + etoposide followed by lenograstim); phases III and IV (cyclophosphamide + cytarabine + etoposide followed by autologous PBSC infusion and lenograstim); and phase V (carmustine + cytarabine + etoposide + melphalan followed by autologous PBSC infusion and lenograstim). Ten, nine, eight, six and four of the 10 patients received one, two, three, four and five of the five scheduled phases of treatment, respectively. Four patients were withdrawn from the study due to progressive disease and two due to thrombotic microangiopathy (TM). Moreover, in the four patients who completed all treatment phases, an additional case of TM was seen. In all three patients with TM, laboratory studies showed evidence of Coombs negative hemolytic anemia, thrombocytopenia, renal dysfunction and in addition cardiac failure in two patients. TM may be a new dose-limiting toxicity of high-dose sequential chemotherapy followed by repeated PBSC transplantation.

Dexamethasone, high-dose cytarabine, and oxaliplatin (DHAOx) as salvage treatment for patients with initially refractory or relapsed non-Hodgkin's lymphoma.

BACKGROUND: Dexamethasone. cytarabine (ara-C), and cisplatin (DHAP) can be used effectively to treat patients with non-Hodgkin's lymphoma (NHL). We hypothesized that substitution of cisplatin by oxaliplatin (L-OHP) could result in less toxicity and greater efficacy. L-OHP is active in patients with lymphoma. It produces mild myelosuppression and is devoid of renal toxicity. We report on a phase II study of dexamethasone, high-dose ara-C, and L-OHP (DHAOx) used to treat patients with NHL who were previously treated with chemotherapy. PATIENTS AND METHODS: Fifteen patients were given DHAOx. They had failed to achieve a CR with initial chemotherapy or had recurrent disease. DHAOx consisted of dexamethasone, 40 mg/day (days 1 to 4): L-OHP, 130 mg/m2 (day 1); and ara-C, 2,000 mg/m2 every 12 h (day 2). Treatment was repeated every 21 days. RESULTS: Patients received a median of four courses of DHAOx. Myelosuppression and transient sensory peripheral neuropathy were the most prominent toxic effects. Serum creatinine levels did not increase in patients with normal renal function, nor in patients who had renal impairment before DHAOx. The median follow-up time from the start of DHAOx treatment was 17 months. Eight patients (53%) achieved a CR, and three patients (20%) had a PR. Responses were achieved by patients with lymphomas of various histologies that included mainly the follicular subtype, and by patients with and without resistance to prior chemotherapy. None of the eight responders have relapsed from CR at 4+. 6+, 14+, 15+, 19+, 20+, 24+, and 24+ months. They had various types of therapy after DHAOx. Disappearance of molecular markers was observed in all four patients who achieved a CR and whose tumor cells carried molecular abnormalities. CONCLUSION: DHAOx possesses characteristics of toxicity which compare favorably to those reported with DHAP, and it is useful as a salvage treatment for patients with NHL. Larger studies are required to establish the therapeutic potential of the regimen.

Surveillance of Aspergillus galactomannan antigenemia for invasive aspergillosis by enzyme-linked immunosorbent assay in neutropenic patients treated for hematological malignancies.

INTRODUCTION: The incidence of invasive fungal infections is increasing in patients with hematological malignancies. Invasive aspergillosis is one of the most frequently encountered infections with a high mortality rate. New diagnostic tests for invasive aspergillosis such as the detection of Aspergillus galactomannan antigen by a sandwich enzyme-linked immunosorbent assay (ELISA) have recently been described. The objective of this study was to evaluate this assay as a potential surrogate for invasive procedures used to diagnose IA. MATERIALS AND METHODS: We analyzed the performance of a commercially available ELISA test which we routinely use for the surveillance of galactomannan antigenemia in patients with hematological malignancies experiencing chemotherapy-induced prolonged neutropenia (ANC < 500/mm(3) for more than 7 days). Serum samples were collected on a weekly basis. Test positivity was defined in accordance with the manufacturer's recommendations. RESULTS: Over the 2 year study period, we analyzed 507 samples obtained during 193 neutropenic episodes from 135 patients. Ten, six and two patients were considered to have proven, probable or possible invasive aspergillosis, respectively, based on clinical, radiological or microbiological data. Forty-four positive (Index>1.5) and 26 'undetermined' (1.5 > Index > 1.0) test results were observed in 17 and ten patients respectively. All invasive aspergillosis cases had at least a positive or an undetermined test result. Only one positive and one undetermined result were found in two patients before the onset of clinical or radiological signs suggesting invasive aspergillosis. Sensitivity was 69% and specificity 96% if only positive results are considered; when 'undetermined' test results were combined with positive results, sensitivity attained 100% and specificity 92% suggesting that the cutoff value for positivity can be lowered from 1.5 to 1.0. CONCLUSIONS: Although the ELISA test did not appear to play a role in the early diagnosis of invasive aspergillosis and in the anticipation of antifungal therapy in our experience, it clarifies the diagnosis of infection in probable or possible invasive aspergillosis especially when the cutoff value is lowered and is useful for monitoring patients receiving specific therapy.

Extraskeletal osteosarcoma of the mediastinum after treatment of a mediastinal germ-cell tumor.

Three years after four cycles of bleomycin, etoposide, and cisplatin (BEP) chemotherapy for a nonseminomatous germ-cell tumor of the mediastinum followed by complete resection of residual teratoma in a 21-year-old man, a mediastinal recurrence was diagnosed as an extraskeletal osteosarcoma. After unsuccessful chemotherapy and removal of the tumor, the patient died of cerebral metastases. Histologic transformation of the teratomatous components of nonseminomatous germ-cell tumors is an uncommon phenomenon showing a particular aspect of germ-cell tumor biology. We review the literature and discuss the pathogenesis concerning this subject.

Gallium scan in the evaluation of post chemotherapy mediastinal residual masses of aggressive non-Hodgkin's lymphoma.

Optimal evaluation of residual masses of non Hodgkin's lymphomas (NHL) after chemotherapy is of major importance, and gallium scan (GS) is routinely used for this purpose, particularly for mediastinal sites. However, sensitivity and specificity of GS in this setting has been diversely appreciated and needs to be more accurately defined especially if radiotherapy is not planned. A retrospective analysis selected all the patients treated in a single institution for aggressive NHL who presented a residual mass in the mediastinum after chemotherapy and who were evaluated by GS. The value of GS for distinguishing true complete responses (CR) from partial responses (PR) was analyzed in patients who were either submitted to resection of their residual mass or followed up without further treatment after GS. A residual mass with mean perpendicular diameters measuring 4.1 cm x 2.8 cm was found in 42 patients and was GS positive in 8 cases and negative in 34 cases. After GS, radiotherapy was delivered to 10 patients, but 12 patients underwent resection of their residual mass and 20 were followed up without further treatment. In the patients who did not receive radiotherapy, 3 false positive and 6 false negative GS results were disclosed. The specificity and the sensitivity of GS were 88% and 25%, and its positive predictive value and negative predictive value 40% and 78%, respectively. GS was not sufficiently reliable to evaluate post chemotherapy residual masses. Surgical resection of residual masses should be considered particularly in young patients. Patients in true CR should be spared pointless radiotherapy and its late side effects, while patients in PR may benefit from further intensified chemotherapy followed by radiotherapy.