Search

A hundred and eight patients less than 60 years old with de novo acute myeloid leukemia were treated between 1982 and 1994 by protocols including final intensification with a transplant using autologous bone marrow purged by mafosfamide in first remission in the absence of an HLA-matched sibling donor available for allograft. From 1989, we attempted to improve tumor control by using high-dose anthracyclines in induction, by increasing from one to two the number of consolidation courses pre-transplant and by introducing intermediate doses of cytarabine in the first consolidation course. The CR rate was 77% (33/43) before 1989 and 90% (59/65) after 1989 (P = 0.06). Forty-five out of the 59 patients (76%) who achieved CR after 1989 could undergo bone marrow grafting in CR1 vs 16/33 (48%) before 1989 (P = 0.01). In spite of the higher proportion of patients above 50 years after 1989 (32%) toxicity was mild and an adequate graft was obtained more frequently after one collection. The principal factor relating to improvement in graft feasibility was the post-1989 modification of induction and consolidation regimens. This improvement in graft feasibility was associated with a better disease-free survival (DFS) (48 +/- 7% vs 32 +/- 8%, P = 0.04) and overall survival (OS) (53 +/- 6% vs 30 +/- 7%, P = 0.007) at 5 years. By multivariate analysis four factors were associated with overall survival (OS): karyotype, white blood cell count at diagnosis, treatment regimen and bone marrow grafting in CR1. This global approach should be prospectively compared with intensive chemotherapy.

We report a large family with a temporal partial epilepsy syndrome inherited in an autosomal dominant mode, with a penetrance of about 80%. This epilepsy syndrome is benign, with age of onset in the second or third decade of life. It is characterized by rare partial seizures, usually secondarily generalized, arising mostly during sleep, without postictal confusion. There is a good response to the antiepileptic therapy but often a recurrence of seizures after drug withdrawal. The partial component, visual (lights, colors, and simple figures) or auditory (buzzing or “humming like a machine”), the existence of temporo-occipital interictal electroencephalographic epileptiform abnormalities, and the hypoperfusion in the temporal lobe detected by interictal hexamethylpropyleneamine oxime–technetium 99m (HMPAO-Tc99m) single-photon emission computed tomography, strongly suggest a lateral temporal lobe origin. The genetic analysis found linkage to chromosome 10q, and localized a gene in a 15-cM interval that overlaps a previously found localization for partial epilepsy in a large three-generation family. This syndrome could be called autosomal dominant lateral temporal epilepsy. Ann Neurol 1999;45:182–188

PURPOSE To analyze retrospectively survival and prognostic factors of patients with non-Hodgkin's lymphoma (NHL) autografted from 1979 to 1995 in a single institution. PATIENTS AND METHODS A total of 120 patients, 64 with aggressive and 56 with low-grade NHL, were autografted. The carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) regimen was used in 104. The autograft was marrow in 101 patients. Marrow was purged in vitro by mafosfamide for 63 patients (adjusted dose [AD] in 32; unique dose [UD] in 31); 27 patients received a CD34+-selected graft. Following intensification, 45 patients received additional radiotherapy on previous sites of involvement. RESULTS Outcome at 5 years for patients transplanted with low-grade NHL in first complete remission (CR1), in first partial remission (PR1), and in second complete remission (CR2) or beyond showed an event-free survival (EFS) of 75% +/- 12%, 46% +/- 18%, and 57% +/- 24%, a relapse incidence (RI) of 21% +/- 12%, 49% +/- 19%, and 43% +/- 25%, and a transplant-related mortality (TRM) of 5% +/- 5%, 10% +/- 7%, and 0%, respectively. For patients with aggressive NHL transplanted in CR1, in PR1, in CR2 or beyond, and in resistant relapse or in primary refractory disease, the EFS was of 73% +/- 9%, 58% +/- 19%, 29% +/- 16%, and 10% +/- 9%, the RI 22% +/- 9%, 14% +/- 9%, 77% +/- 18%, and 66% +/- 20%, and the TRM 6% +/- 6%, 32% +/- 21%, 11% +/- 10%, and 71% +/- 22%, respectively. In patients autografted upfront in first remission, additional radiotherapy was associated with a higher EFS, in univariate (P = .03) and multivariate analysis (P = .02, relative risk [RR] = .021). The role of graft purging with mafosfamide on the outcome reflected by the dose of colony-forming unit-granulocyte-macrophage (CFU-GM) per kilogram infused postpurging was assessed by univariate analysis: patients in first remission who received lower doses of CFU-GM had a lower RI and a higher EFS. CONCLUSION This retrospective analysis suggests that marrow purging and posttransplant radiotherapy improve the outcome of patients with NHL autografted in first remission.

We report a large family with a temporal partial epilepsy syndrome inherited in an autosomal dominant mode, with a penetrance of about 80%. This epilepsy syndrome is benign, with age of onset in the second or third decade of life. It is characterized by rare partial seizures, usually secondarily generalized, arising mostly during sleep, without postictal confusion. There is a good response to the antiepileptic therapy but often a recurrence of seizures after drug withdrawal. The partial component, visual (lights, colors, and simple figures) or auditory (buzzing or "humming like a machine"), the existence of temporo-occipital interictal electroencephalographic epileptiform abnormalities, and the hypoperfusion in the temporal lobe detected by interictal hexamethylpropyleneamine oxime-technetium 99m (HMPAO-Tc99m) single-photon emission computed tomography, strongly suggest a lateral temporal lobe origin. The genetic analysis found linkage to chromosome 10q, and localized a gene in a 15-cM interval that overlaps a previously found localization for partial epilepsy in a large three-generation family. This syndrome could be called autosomal dominant lateral temporal epilepsy.

Treatment with interferon prolongs survival in chronic myelogenous leukemia. We conducted a clinical trial to assess the efficacy of treatment with a combination of interferon and cytarabine.Previously untreated patients with chronic myelogenous leukemia were randomly assigned to receive either hydroxyurea (50 mg per kilogram of body weight per day) and interferon alfa-2b (5 million units per square meter of body-surface area per day), or hydroxyurea and interferon in the same dosages plus monthly courses of cytarabine (20 mg per square meter per day, for 10 days). The end points were overall survival, complete hematologic remission at 6 months, and major cytogenetic response (less than 35 percent Philadelphia chromosome-positive cells in the bone marrow) at 12 months.The trial was stopped when a sequential analysis showed a benefit of interferon and cytarabine. A significant improvement in survival was observed in the interferon-cytarabine group (360 patients) as compared with the interferon group (361 patients) (P=0.02; relative risk of death, 0.64; 95 percent confidence interval, 0.44 to 0.93). After three years, the survival rate was 85.7 percent with interferon and cytarabine and 79.1 percent with interferon alone. The rate of hematologic response was higher in the interferon-cytarabine group than in the interferon group (P=0.003). Major cytogenetic responses were observed 12 months after randomization in 126 of 311 patients treated with interferon and cytarabine (41 percent) and in 75 of 314 patients treated with interferon only (24 percent, P0.001).The combination of interferon and cytarabine, as compared with interferon alone, increases the rate of major cytogenetic response and prolongs survival in patients with the chronic phase of chronic myelogenous leukemia.

Summary Background Relapsed or refractory Hodgkin’s disease (HD) patients were treated with an intensive salvage regimen (MINE) prior to high-dose therapy (HDT) with hematopoietic stem cell support. Patients and methods One hundred HD patients who either failed to respond to a front-line chemotherapy regimen (induction failure, n—41) or relapsed (untreated relapse, n—54; resistant relapse, n—5) were treated with the MINE regimen. Each course of MINE comprised mitoguazone 500 mg/m2 on days 1 and 5, ifosfamide 1500 mg/m2/d from day 1 to day 5, vinorelbine (Navelbine®) 15 mg/m2 on days 1 and 5, and etoposide 150 mg/m2/d from day 1 to day 3. At least two courses were given at 4-week intervals. Then, 72 patients received HDT followed by hematopoietic stem cell support. Results After MINE salvage, 34 patients achieved a complete response (CR) and 39 a partial response, yielding an overall response rate of 75%. Patients with untreated relapse had a 92.5% response rate and those with resistant relapse or induction failure a 53% response rate. A total of 58 patients reached a CR at the end of all treatments; 12 of them relapsed. Sixty-six patients were alive with a median follow-up of 26 months, including 46 patients in CR. The 2-year survival rate for the entire group was 59%. By univariate analysis, patients with an interval between their last treatment and salvage longer than 12 months, untreated relapse, or good performance status at salvage are shown to have longer survivals. The main toxic effects were neutropenia, thrombo-cytopenia, and infectious episodes. Three patients died of MINE-related complications and three after HDT. Conclusion Given early in the course of progressive HD, the MINE regimen reduced tumor burden in a high proportion of patients with relapsed or refractory disease. Responding patients further intensified with HDT have a better outcome than those who have not responded to salvage treatment.