Abnormal proliferation of T-colony-forming cells from peripheral blood of patients with T-cell acute lymphoblastic leukaemias and lymphomas in complete remission: potential prognostic value.

Peripheral blood T-colony-forming cells (T-CFC) from most patients with T-cell acute lymphoblastic leukaemias (T-ALL) and T-cell non-Hodgkin's lymphomas (T-NHL), can proliferate in vitro in methylcellulose in the absence of added growth factors or mitogens. We now report that spontaneous T-cell colonies could also be obtained during complete remission of 13 out of 21 patients with T-ALL and T-NHL, but none of eight patients with common (pre-B) ALL (cALL). Colony cells were mainly E+T3+, with a variable expression of other T cell markers. Spontaneous T-CFC did not possess self-renewal capacity in the absence of added growth factors. Moreover, incubation of spontaneous colonies with colchicine yielded mitoses in only two out of seven patients, with one normal and one abnormal karyotype. In five patients tested, recombinant interleukin 2 (IL2) could also induce the proliferation of some T-CFC. Both spontaneous and IL2-induced colonies were inhibited by an anti-IL2 receptor monoclonal antibody, suggesting that interaction of IL2 with its receptor may be involved in the proliferation of some T-CFC from these patients. A study of 14 T-ALL patients tested during their first remission indicated that patients who developed no or few spontaneous colonies during their first remission (less than 20 colonies/10(5) mononuclear cells) seemed to relapse later and to have a significantly longer survival than patients with a high number of spontaneous colonies. These data suggest that the spontaneous proliferation capacity of T-CFC might be of prognostic value in the clinical evaluation of T-ALL.

Regression of bronchial epidermoid metaplasia in heavy smokers with etretinate treatment.

Forty heavy-smoker (over 15 packets per year) volunteers were selected for and have completed a 6-month etretinate treatment on the basis of an index of metaplasia (IM) greater than 15% determined according to the following procedure: bronchoscopy with systematic biopsies in ten sites of the bronchial tree. Each biopsy was cut into ten sections and an IM was calculated: IM = number of sections with epidermoid metaplasia/number of sections examined X 100. Etretinate, a retinoid derivative, was given orally at the daily dose of 25 mg, at the end of which patients underwent a second fibroscopy protocol. A highly significant reduction of IM (P = 10(-5)) was observed after 6 months of treatment for those of the patients who maintained their smoking habits during treatment. Besides, the four patients who stopped smoking while under treatment and are excluded from the statistical analysis all had a complete regression of metaplasia at the second fibroscopy. No morbidity was due to etretinate or fibroscopy. Etretinate significantly reduces potentially precancerous bronchial epidermoid metaplasia in heavy smokers. Its association with smoking arrest may induce a rapid restoration of bronchial epithelium to normal.

Correlation of bronchial epidermoid metaplasia with level of tobacco consumption in heavy smokers.

One hundred forty-four heavy-smoker (125 males, 19 females) volunteers with at least 15 packet-year of smoking experience (number of daily packets of cigarettes X number of years of smoking) underwent bronchoscopy with systematic biopsies in ten sites of the bronchial tree. No morbidity was related to the fibroscopy procedure. Each biopsy was cut into ten sections and an index of metaplasia (IM) was calculated: IM = number of sections with epidermoid metaplasia/number of sections examined X 100. A highly significant statistical correlation was observed (P = 10(-4)) between the IM and the amount of cigarettes smoked (slope of the curve: 0.23). Sex appeared to play an important role in the incidence of metaplasia, since 84% of the examined females had an IM less than 15% versus 48% of the males (P adjusted for individual tobacco consumption in packet-years less than 0.01). Early study of HLA phenotype (locus A) failed to detect a link between HLA and risk of tobacco-induced epidermoid metaplasia.

Regression of bronchial epidermoid metaplasia in heavy smokers with etretinate treatment.

40 voluntary heavy smokers (over 15 packets-years) were selected for and have completed a six months etretinate treatment on the basis of an index of metaplasia (IM) greater than 15% determined according to the following procedure: bronchoscopy with systematic biopsies in 10 sites of the bronchial tree. Each biopsy was cut into 10 sections and an IM was calculated: (Formula: see text). Etretinate, a retinoid derivative, was given orally at the daily dose of 25 mg, at the end of which they underwent a second fibroscopy protocol. A highly significant reduction of IM (p = 10(-5)) was observed after 6 months of treatment for those of the patients who maintained their smoking habits during treatment. Besides, the 4 patients who stopped smoking while under treatment and are excluded from the statistical analysis, all had a complete regression of metaplasia at the second fibroscopy. No morbidity was due to etretinate or fibroscopy. Etretinate significantly reduces potentially precancerous bronchial epidermoid metaplasia in heavy smokers. Its association with smoking arrest may induce a rapid restoration of bronchial epithelium to normal.

The effect of zinc on normal and neoplastic T-lymphocyte proliferation.

After 24-72 h of PHA-stimulation, T-cells expressed the transferrin receptor. This receptor facilitates zinc uptake. Zinc transferrin stimulated DNA synthesis in pre-activated or activated, but not in resting T-cells. The regulatory nuclear protein matrix fraction increased from 5 to 40% of the total nuclear protein material in lymphocytes simultaneously with the initiation of DNA synthesis. In contrast, optimal concentration (0.1-0.4 mM) of zinc salts induced a mitogenic response in transferrin-receptor negative resting, but not in PHA-activated or leukemic T-cells. Higher concentrations were toxic. These findings can explain earlier reports on the effect of zinc on immunocompetence in zinc deficient mice and enteropathic acrodermatitis as well as present findings of a normalization of the T-suppressor-cell number in immunosuppressed patients.

Treatment of acute myeloid leukemia with a combination of intensive induction chemotherapy, early consolidation, splenectomy and long-term maintenance chemotherapy.

The authors developed a therapeutic regimen in which 33 patients aged 11 to 61 years (mean +/- SE, 35.9 +/- 2.3 years) with acute myeloid leukemia (AML) were given intensive induction chemotherapy with Adriamycin (doxorubicin) (ADM), vincristine (VCR) and cytosine arabinoside (ARA-C). Twenty-nine of these patients (88%) attained a complete remission (CR) after 1, 2, or 3 courses and were then subjected to an early consolidation course of chemotherapy, identical to that for induction. After consolidation, all patients in CR received a long-term continuous maintenance therapy in which 6-mercaptopurine (6-MP) and methotrexate (MTX) were alternated, associated with periodic reinforcements with daunorubicin (DNR) and VCR. Twenty-five of the 29 patients who achieved a CR were splenectomized soon after the consolidation course. Histologic sections of the spleens, liver biopsy specimens, and lymph nodes, stained routinely and with the naphthol AS-D chloroacetate esterase (NCA) method, showed mature granulocytes and a few NCA positive mononuclear cells, but no proved leukemic infiltrates. For the 25 splenectomized patients, the probability of remaining in CR at 36 and 54 months was 75% and 66%, respectively; the probability of survival at 36 and 54 months was 85% and 75%, respectively. Age older than 40 years and evidence of extramedullary involvement at presentation appeared to carry a bad prognosis for disease-free survival.

Doxorubicin, vincristine, bleomycin, cytembena and cisplatin as combination chemotherapy for squamous cell lung cancer.

Thirty-nine evaluable patients with squamous cell lung carcinoma were treated with combination chemotherapy consisting of doxorubicin, oncovin, bleomycin, cytembena and cis-platin. Objective responses were seen in 46 per cent of the patients. Patients with limited disease had a response rate of 56 per cent. Two of the four complete responses were endoscopically and histologically verified. The median survival time was 37.6 and 26.3 weeks for patients with limited and extensive disease, respectively (p less than 0.05), and 29.9 weeks for the whole group. Hematologic and gastrointestinal toxicities were moderate. There was one drug-related death due to septicemia and 2 reversible acute renal failures. The chemotherapeutic combination appears to be relatively effective. It causes some tumor regression and may extend the survival of responding patients with acceptable quality of life. Maintenance chemotherapy with CCNU, cyclophosphamide, methotrexate, procarbazine alternating with vinblastine, nitrogen-mustard, methotrexate, procarbazine, frequently had to be discontinued because of severe toxicity.

[Treatment of acute myeloid leukemia with a protocol combining intensive induction chemotherapy, early consolidation treatment, splenectomy and long-term maintenance chemotherapy. Preliminary study]. / Traitement des leucémies aiguës myéloïdes par un protocole associant une chimiothérapie d'induction intensive, un traitement précoce de consolidation, une splénectomie et une chimiothérapie de maintien au long cours. Etude préliminaire.

Twenty-seven patients aged from 10 to 60 years (mean 34.4 +/- 13 years) in the first perceptible phase of acute myeloid leukemia were subjected to intensive induction chemotherapy consisting of adriamycin (ADM), vincristin (VCR) and cytosine arabinoside (ARA-C). Twenty-four patients (89%) attained complete remission (CR) after 1 to 3 cycles and were then given an early consolidation treatment with one of the previous cycles. This was followed by long-term continuous maintenance chemotherapy with 6-mercaptopurine (6-MP) and methotrexate (MTX) alternatively and 3-monthly reinforcement courses of donaurubicin (DNR) and VCR. Twenty of these 24 patients were splenectomized soon after the consolidation treatment. None of the spleens were enlarged, and histological sections of the spleens, liver biopsies and mesenteric lymph-nodes stained with routine dyes and by the naphthol AS-D chloroacetate esterase method revealed mature granulocytes but no demonstrable leukaemic cells. In the group of splenectomized patients, the probabilities of staying in complete remission at 27 and 44 months were 70 +/- 12.6% and 52 +/- 18.5% respectively, and the probabilities of remaining alive at 32 and 55 months were 79 +/- 11% and 57 +/- 19% respectively. Age over 40 and evidence of extramedullary infiltration at presentation appeared to leave little hope of disease-free survival. The rationale for the present therapeutic study is discussed.

Correlation between precancerous bronchial metaplasia and cigarette consumption, and preliminary results of retinoid treatment.

Vitamin A and its derivatives, so-called retinoids, can prevent squamous metaplasia induced not only by vitamin A deficiency but also by carcinogenic hydrocarbons. An aromatic retinoid, such as ET1, has been shown to prevent chemically induced papillomas in mice and to amplify certain immunologic reactions. Heavy smokers, 106 volunteers, were submitted to fibrobronchoscopy with bronchial biopsies. An index of metaplasia (IM) was calculated on the basis of microscopical examination of a total of 9,633 sections of 1,010 biopsies. Despite the subjectivity of the estimates of cigarette consumption, this was significantly (P less than 0.02) and positively correlated to the IM. Eighty-five percent of the women had a low IM as compared to only 42% of the men (P less than 0.01), although there was no significant difference in the reported cigarette consumption. Fifty-two subjects had an IM greater than 15% and were given 25 mg ET1 orally daily for 6 months. The bronchoscopy was repeated in 30 patients following completion of the 6-month treatment. The IM was significantly (P less than 0.01) reduced after treatment.