Prognostic significance of a polymerase chain reaction-detectable dominant T-lymphocyte clone in cutaneous lesions of patients with mycosis fungoides.

Although mycosis fungoides (MF) is considered to be an indolent lymphoma, survival is highly influenced by TNM stage. At diagnosis, most MF patients present with early stage disease and a high probability of long-term survival. Treatment is generally directed towards skin lesions, and achievement and duration of complete responses are variable. A dominant T-cell clone is detectable in the cutaneous lesions of 60% of patients. The aim of this study was to determine whether the presence of a T-cell clonal population influences the clinical course of the disease after topical therapy. Cutaneous biopsies from 68 patients were histologically diagnosed as MF and T-cell clonality was analyzed by in vitro amplification of TCR-gamma chain gene rearrangements (polymerase chain reaction gamma [PCRgamma]). After a median follow-up of 48 months, response to treatment was clinically assessed. Age, sex, duration of symptoms before diagnosis, type of cutaneous lesions (T stage), TNM stage, and PCRgamma were evaluated as predictive factors of response to treatment in univariate and multivariate analyses. Univariate analysis demonstrated that T1 cutaneous lesions (P = .05) and PCRgamma negativity (P = .007) were associated with a higher complete remission rate. Using multivariate analysis, T stage (relative risk, 3.13; P = .06) and PCRgamma (relative risk, 4.4; P = .01) remained independent significant predictive parameters of response. In conclusion, T stage and cutaneous PCRgamma at diagnosis are the two predictive parameters of treatment response for MF. Therefore, the cutaneous PCRgamma findings should be considered in the analysis of future therapeutic trials.

Latent cochlear damage in personal stereo users: a study based on click-evoked otoacoustic emissions.

OBJECTIVE: To assess the effects of use of personal stereo systems (PS) on hearing by means of the objective measure of transient-evoked otoacoustic emissions. PARTICIPANTS AND SETTING: People aged between 10 and 59 years who had otoacoustic emissions recorded by the National Acoustic Laboratories between 1989 and 1997 were eligible for inclusion. Recordings from participants with hereditary disorders or any form of aural disease (e.g., otitis media, otosclerosis, fluctuant hearing loss, Meniere's syndrome, or exposure to ototoxic substances) were excluded. METHODS: Transient-evoked otoacoustic emission (TEOAE) records were obtained with a standard 260 repetitions of an 80 dB train of clicks used for recording outer hair cell activity. The measure of otoacoustic emission strength was the Otodynamics ILO88 variable Waverepro%. For each participant, all the key factors relating to their hearing history were assessed from patient referral information or from demographic information obtained in writing at the time of recording either in the form of a detailed questionnaire or verbal assessment. Otoacoustic emission data were analysed according to age, industrial noise exposure and personal stereo use. RESULTS: Usable otoacoustic emission records were obtained from 1724 people (1066 males and 658 females). Otoacoustic emission strength declined with age, and was significantly lower in males than females, lower in people exposed to industrial noise than those not exposed, and significantly lower in users of personal stereo systems than non-users. People with both kinds of noise exposure had values which were significantly lower again, indicating an additive effect. CONCLUSIONS: As only 39 people with PS exposure admitted any hearing problems, decline in otoacoustic emission strength forewarns premature hearing loss in personal stereo users.

Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d'Etude des Lymphomes Folliculaires. Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: To evaluate prospectively in patients with follicular lymphoma and a low tumor burden three therapeutic options: delay of any treatment until clinically meaningful progression, immediate treatment with an oral alkylating agent, or treatment with a biologic response modifier, interferon alfa-2b. PATIENTS AND METHODS: Newly diagnosed follicular lymphoma patients with a low tumor burden (n = 193) were randomly assigned to one of three arms: arm 1, no initial treatment (n = 66); arm 2, prednimustine 200 mg/m2/d for 5 days per month for 18 months (n = 64); or arm 3, interferon alfa 5 MU/d for 3 months then 5 MU three times per week for 15 months (n = 63). Clinical characteristics were similar in the three arms. RESULTS: Overall response rates with prednimustine and interferon alfa were 78% and 70%, respectively. The overall response to therapy, when deferred, was similar at 70%. With a median follow-up duration of 45 months after randomization, the median freedom-from-treatment (FFT) interval was 24 months in arm 1 and the interval of freedom from treatment failure (FFTF) was 40 months in arm 2 and 35 months in arm 3. The median overall survival time was not reached and the overall survival rate at 5 years was 78% in arm 1, 70% in arm 2, and 84% in arm 3. Therefore, deferred treatment does not adversely influence survival at 5 years. Patients who progressed within 1 year had a significantly shorter survival duration (median, 48 months). CONCLUSION: Delayed treatment is feasible in patients with follicular lymphoma and a low tumor burden. For patients with early progression, more intensive therapy should be considered. For others, because delay of treatment until significant clinical progression does not seem to hamper the prognosis or subsequent response to treatment, the long-term toxicity of alkylating agents can be reduced.

Evoked otoacoustic emissions and auditory selective attention.

The auditory system has an extensive peripheral efferent innervation. The question addressed in this paper is whether the olivocochlear bundle (OCB) efferent system innervating the outer hair cells (OHC) of the cochlea plays a role in selective attention. As evoked otoacoustic emissions (EOAE) provide a measure of the active micromechanical properties of OHCs, they can be used to assess the role of the efferent system in attention. Six experiments using tone-pip EOAEs are reported. In each experiment, EOAEs generated by 1 or 2 kHz tone pips when they were attended were compared with EOAEs to the same stimuli when they were unattended. In three experiments (1-4), a non-linear stimulus difference method was used to record a pure cochlear component of EOAEs. In Exps. 1-5, 1 and 2 kHz tone pips were delivered to the same ear and the difficulty of the subjects' task was manipulated in order to produce a more focussed attentional state or contralateral noise was presented to determine whether attention effects are dependent upon having an already activated efferent system. In Exp.6, the 1 and 2 kHz stimuli were delivered to opposite ears. A total of 70 subjects participated in the six experiments. There were no effects of attention on EOAEs in any of the experiments in the direction of previously reported effects. The results of these first six experiments employing simple attention switches between fixed auditory objects do not support active cochlear involvement in selective attention.

Autologous peripheral blood stem cell transplantation after high dose therapy in patients with advanced lymphomas.

Thirty-eight patients with refractory or relapsed non-Hodgkin's lymphoma (19 patients) or Hodgkin's disease (19 patients) were treated with salvage therapy. The peripheral stem cell collection was performed during hematologic recovery after myeloablative chemotherapy. In eight patients with Hodgkin's disease the number of CFU-GM collected was less than 0.5 x 10(4)/kg and these patients were excluded for stem cell transplantation. In the remaining 30 patients, a median of 4 x 10(4) CFU-GM/kg was collected (range 0.8-100 x 10(4)/kg) by three leukaphereses in 25 patients and six to 11 leukaphereses in five patients. Conditioning regimens were CBV (eight), BEAM (six), BEAC (10) and cyclophosphamide + total body irradiation (TBI) (six). Without TBI, the mean time for reaching a granulocyte count greater than 0.5 x 10(9)/l was 18 days and for a platelet count greater than 50 x 10(9)/l was 19 days in 23 out of 24 patients. With TBI, in five patients the mean time for reaching a granulocyte count greater tahn 0.5 x 10(9)/l was 37 days and for a platelet count greater than 50 x 10(9)/l was greater than 100 days. Complications were minor. There was only one toxic death. The outcome in these patients was similar to that observed in patients who received autologous bone marrow transplantation for advanced lymphomas. In conclusion, we observed good hematologic recovery except when TBI was used in the conditioning regimen.

Acute non-lymphocytic leukemia following FAM combination adjuvant chemotherapy for gastric and lung adenocarcinoma.

We report 2 cases of acute non-lymphocytic leukemia with distinct clinical and karyotypic features shared by therapy-related acute non-lymphocytic leukemia occurring after adjuvant chemotherapy including 5-fluorouracil, doxorubicin and mitomycin C. Our observation suggests a causal relationship between exposure to mitomycin C and the occurrence of acute non-lymphocytic leukemia.

[Autografts of blood cells at various stages]. / Autogreffes à partir des cellules souches sanguines.

Thirty-nine patients with acute myeloblastic or lymphoblastic leukaemia had peripheral blood mononuclear cells collected by 3 continuous-flow leukapheresis as they entered first remission after induction chemotherapy. CFU-GM were assayed as a measure of the number of haemopoietic stem cells in each collection. Numbers of CFU-GM harvested varied among the patients (for example 0.27 to 155.10(4)/kg for ANLL patients). Nineteen patients underwent peripheral blood stem cells autografts after a conditioning regimen with high dose cyclophosphamide and TBI. The patients were transfused with a median of 2.2.10(4)/kg CFU-GM cells (0.28 to 100.10(4) CFU-GM/kg). Only 1 patient had a graft failure. The rate of haemopoietic recovery was studied for our patients and those reported in the literature. A strong correlation exists between the numbers of CFU-GM transfused and the rate of granulocytes and platelets recovery. Very rapid recovery are regularly obtained when the number of CFU-GM transfused is superior to 5.10(4)/kg.