Martha González

Retracted: Adjuvant Radiotherapy in Stage IV Diffuse Large Cell Lymphoma Improve Outcome

RETRACTED

Pegylated liposomal doxorubicin in combination chemotherapy in the treatment of previously untreated aggressive diffuse large-B-cell lymphoma

Anthracyclines remain as the best drugs in the treatment of patients with aggressive malignant lymphoma in combination with other cytotoxic drugs. However, dose escalation is poorly tolerated and acute and late cardiac toxicity has limited the use of these compounds. Pegylated liposomal doxorubicin has been proven to be useful in some malignancies, without the presence of acute cardiac toxicity and with a good response rate in patients with relapsed/refractory lymphomas. We report the first study of this drug in combination chemotherapy in patients with previously untreated aggressive malignant lymphoma.Twenty consecutive patients with diagnosis of diffuse large-B-cell lymphoma, age <18 yr to <70 yr, without previous treatment, HIV-negative high and high-intermediate clinical risks were treated with the CHOP-Bleo regimen at standard doses, using pegylated-liposomal doxorubicin instead of doxorubicin, at 25 mg/m2 (3 patients), 30 mg/m2 (3 patients), and 35 mg/m2 (14 patients).Complete response was achieved in 17 cases (85%), with failure in 3 patients (15%). At a median followup of 18.1 mo, relapse has not been observed. Two patients died secondary to tumor progression. Toxicity was mild, only three episodes of granulocytopenia grade I were observed, and no mucositis, thrombocytopenia, or granulocitopenia grade >2 was observed. Erythrodisestesias grade II was observed in one case and grade I in two cases. Cardiac function was normal before and 12 mo after chemotherapy. Pegylated liposomal doxorubicin appear as an promising drug in the treatment of patients with aggressive malignant lymphoma.

Dose dense (CEOP-14) vs dose dense and rituximab (CEOP-14 +R) in high-risk diffuse large cell lymphoma.

To assess efficacy and toxicity of rituximab and dose chemotherapy in high-risk diffuse large cell lymphoma, we conducted a controlled clinical trial to assess efficacy and toxicity of a dose-dense regimen CEOP-14 (cyclophosphamide, epirubicin, vincristine, and prednisone every 14 d) compared to CEOP-14 plus rituximab. One hundred and ninety-six patients were randomized to received CEOP-rituximab (cyclophosphamide 1500mg/m2, epirubicin 120 mg/m2, vincristine, and prednisone at standard dose and rituximab at 375 mg/m2) compared with the same chemotherapy administered every 14 d (CEOP-14). In an intent-to-treat analysis all patients were available for efficacy and toxicity. Complete response in CEOP-14 was observed in 73 cases (74%) and in 75 patients (76%) in the CEOP-R regimen (76%) (p=0.8). With a median follow-up of 53.4 mo, median has not been reached in time to tumor-progression (TTP) and overall survival (OS). Actuarial curves at 5 yr showed that TTP and OS in patients treated with CEOP-R were 74% and 67%, respectively, that were not statistical different when compared to CEOP-14, 72% and 65%, respectively (p=0.8). Acute toxicity was mild and well tolerated. The use of a dense-dose regimen is useful and well tolerated in patients with very high risk diffuse large cell lymphoma. The addition of rituximab did not improve outcome in these setting of patients.

Novel therapy in multiple myeloma

Treatment in patients with multiple myeloma remain to be defined. Younger patients (defined as a cut-off level < 65 years old) will be treated with chemotherapy and transplant procedures. However, most patients > 65 years old are not candidates for this therapeutic approach and the use of intensive chemotherapy could be associated to severe toxicity. We developed an new, not-cytotoxic regimen with dexamethasone 30 mg/m2, iv, days 1 to 4, all trans retinoic acid 45 mg/m2, po, days 5 to 14 and interferon alfa 2a 4.5 MU, sc, daily, days 5 to 14 (DAI regimen) administered every 28 days in number of 6 cycles, at this point patients were restaging, if they showed complete response, objective response or partial response they were conducted to received thalidomide 100–200 mg po, daily and dexamethasone 10 mg/2, po days 1 to 4 at monthly intervals, for 18 months. Forty one patients were enrolled in an Phase II study. In an intent to treat analysis all patients were evaluable. Complete response was observed in 18 cases (43%), objective response in 10 patients (24%) and partial response in 5 patients (12%), overall response rate was 80%. Eight patients were considered failures. At an median of 36 months, no relapse of progression disease has been observed, thus actuarial curves at 3-years showed that event free survival is 100% and overall survival is 91%. Toxicity was mild, all patients received the planned dose in time. This regimen appear to be useful in older patients with multiple myeloma, the response rate is higher and toxicity was mild. Controlled clinical trials comparing with conventional chemotherapy will be conducted to define the role of this therapeutic approach.

Treatment of Advanced Hodgkin's Disease: EBVD versus Intensive Brief Chemotherapy

We start a controlled clinical trial to assess efficacy and toxicity of EBVD (epirubicin, bleomycin, vinblastine and dacarbazine) with an intensive and brief program of seven drugs administered weekly for 12 weeks in previously untreated patients with advanced Hodgkins disease. Two hundred and sixty four patients were randomized to receive EBVD chemotherapy (134 cases) or intensive chemotherapy (130 cases). Eligible patients were either previously untreated stages III or IV. Patients with bulky disease received adjuvant radiotherapy. In an intent to treat analysis, all patients were evaluable for efficacy and toxicity. Complete response rate to the two regimens were similar (88 and 84%, respectively). However, actuarial 5 years overall survival rates were 87% (95% confidence interval (CI): 78-94%) for the EBVD regimen, which is statistically different to 59% (95% CI: 48-66%) for the intensive program <formula>(<italic>p</italic><0.01).</formula> Event-free survival were 83% (95% CI: 74-89%) for EBVD and 65% (95% CI: 58-71%) for the intensive program <formula>(<italic>p</italic><0.01).</formula> Significantly, more episodes of granulocytopenia grade III-IV, infection-related granulocytopenia, death-related infection even early hematological support with granulocyte colony stimulating factor were seen with the intensive, program. In the present single center trial, intensive chemotherapy did not appear to have better results when compared with standard chemotherapy in patients with advanced Hodgkins disease.

25. Neurophysiological tests in the diagnostic strategy of a NARP syndrome

Coeliac disease is a gastrointestinal disorder caused by intolerance to cereals due to an immunological mechanism. It is the most common cause of poor absorption in the developed countries. It has heterogeneous clinical and pathological features. Neurological and psychiatric disorders have been reported, such as epilepsy, occipital calcifications epilepsy (Goby’s syndrome), axonal polyneuropathy, cerebella syndromes, brain atrophy and dementia, schizophrenia, autism and depression. The pathogenic mechanism of these disorders is not completely clear although biochemical factors such as low serum concentrations of vitamin E and vitamin B6 may be a cause. The most frequent symptom of epilepsy in celiac patients is sudden, brief loss of consciousness. We present a 16-year-old girl with celiac disease who suffered from loss of consciousness. CT scan was normal. Neurophysiological studies showed normal EEG, PESS, PEAT and ENG. However, PEV showed a marked delay in P100 wave latency, with greater involvement of the left eye. An exhaustive review of the literature showed only a few papers discussing the neurophysiological changes seen in celiac disease.