Outcomes of active surveillance of EU-TIRADS 5 thyroid nodules.

OBJECTIVE: Active surveillance of cytologically proven microcarcinomas has been shown as a safe procedure. However, fine needle aspiration biopsy (FNAB) is not recommended by European Thyroid Association (ETA) and American Thyroid Association (ATA) guidelines for highly suspicious nodules ≤ 10 mm. The aim of the study was to assess the outcomes of active surveillance of EU-TIRADS 5 nodules ≤ 10 mm not initially submitted to FNAB. PATIENTS AND METHODS: 80 patients with at least one EU-TIRADS 5 nodule ≤ 10 mm and no suspicious lymph nodes, accepting active surveillance, were included. RESULTS: Mean baseline diameter and volume were 5.4 mm (±2.0) and 64.4 mm3 (±33.5), respectively. After a median follow-up of 36.1 months, a volumetric increase ≥ 50% occurred in 28 patients (35.0%) and a suspicious lymph node in 3 patients (3.8%). Twenty-four patients underwent an FNAB (30.0%) after at least a 1 year follow-up of which 45.8% were malignant, 8.3% benign, 33.3% undetermined and 8.3% nondiagnostic. Sixteen patients (20.0%) underwent conversion surgery after a median follow-up of 57.2 months, confirming the diagnosis of papillary carcinoma in 15/16 cases (not described in 1 histology report), all in remission at 6-12 months postoperative follow-up. CONCLUSION: Applying ETA and ATA guidelines to avoid FNA of EU-TIRADS 5 sub-centimeter nodules and proceeding to active surveillance of such nodules in selected patients is a safe procedure. Thus, US-FNAB could be postponed until the nodule shows signs of progression or a suspicious lymph node appears, with no added risk for the patient.

[Listeriosis in patients with malignant hemopathy. 3 cases in the same hospital ward]. / Listériose chez des malades ayant une hémopathie maligne. Trois observations dans un même service.

During the listeriosis epidemic which occurred in France in the summer 1992, three patients with malignant haematopathies hospitalized in our service contracted the disease. Although the retrospective investigations were hindered by the variable incubation period and the impossibility of examining the foods eaten at the time of infection, there was a high probability that two of the patients had been infected by cooked ham and dairy products at home. The third patient was apparently infected in hospital with well-cooked food found to be contaminated. The hypothesis of coinfection has been raised.

Role of chemoresistance prior to autologous bone marrow transplantation for Hodgkin's disease.

In the present study, the response to last salvage chemotherapy was analysed in a series of 30 patients with poor prognosis Hodgkin's disease having received high dose chemotherapy followed by autologous bone marrow transplantation. The probability of survival was 43% at 152 months for the 21 chemosensitive patients as compared to 11% at 36 months for the 9 chemoresistent patients. Two toxic deaths occurred, both in the group of chemoresistant subjects, while the probability of absence of disease progression was 65% at 152 months in the 21 chemosensitive cases. According to these results, the response to the last conventional therapy before grafting is an important prognostic factor for survival and absence of disease progression after transplantation. Patients with chemoresistant Hodgkin's disease should benefit from new therapeutic approaches in the context of phase I or II clinical trials.

Interleukin-2-induced increase of a monoclonal B-cell lymphocytosis. A novel in vivo interleukin-2 effect?

A 56-year-old man with refractory B-cell lymphocytic non-Hodgkin's lymphoma was treated in a Phase II study with interleukin-2 (IL-2) (Roussel-Uclaf, Romainville, France). The patient had involvement of multiple lymph nodes and medullary and peripheral blood (3.6 x 10(9) monoclonal CD19-positive [CD19+] B-lymphocytes/l). After a 5-day cycle of IL-2 treatment, an eightfold increase of the monoclonal CD19+ population was observed (27 x 10(9) monoclonal CD19+ cells). The lymphocytosis decreased dramatically during the second cycle (days 15 to 19) of IL-2 treatment, resulting in 6 x 10(9)/l peripheral lymphocytes, with 5.5 x 10(9) B-lymphocytes. As soon as day 20, peripheral B-cells again increased considerably, with 32 x 10(9) CD19+ cells/l at day 27. The CD19+ population remained monoclonal as assessed by kappa/lambda cell-surface phenotyping and kappa gene rearrangement evaluation. Kinetics of the monoclonal B-lymphocyte response to IL-2 paralleled the natural killer/lymphokine-activated killer and T-cell response, with a 4-day latency period, suggesting an indirect enhancing effect of IL-2. Before and during IL-2 treatment, peripheral B-lymphocytes never expressed detectable levels of the p55 IL-2 receptor. However, the p75 IL-2 receptor was expressed significantly in the IL-2-responsive monoclonal B-cell population. Tumor necrosis factor alpha, a known (in vitro) B-cell tumor growth factor, reached high serum levels during IL-2 treatment. Response evaluation at day 45 showed stability of the lymph node involvement and the marrow lymphocyte infiltrate. At day 45, peripheral B-cell lymphocytosis was 7.5 x 10(9)/l. To the knowledge of the authors, this is the first report of an in vivo IL-2-induced reversible increase of peripheral monoclonal B-cell lymphocytosis.

Marrow transplantation from HLA non-identical family donors for the treatment of leukaemia: a pilot study of 15 patients using additional immunosuppression and T-cell depletion.

Fifteen patients with high-risk leukaemia were given T-cell depleted marrow transplants from HLA non-identical related donors. They were treated with a combination of total body irradiation (TBI), high-dose cytosine arabinoside (Ara-C) and high-dose melphalan in an attempt to prevent a host-versus-graft reaction. Antilymphocyte globulins were given prior to transplantation for additional immunosuppression to 13 patients and in-vivo monoclonal antibody anti-human LFA1 to two. Engraftment and chimaerism assessed by HLA typing were achieved in 14 patients. Seven developed acute graft-versus-host disease (two fatal), one failed to engraft. Six patients died in complete remission from cytomegalovirus (CMV) interstitial pneumonitis and three remain alive in complete remission 2, 3 and 13 months after transplant. We conclude that aggressive immunosuppression allows for sustained engraftment of T-cell depleted HLA non-identical marrow. The incidence and severity of GVHD are acceptable and CMV pneumonitis remains the major problem.

Neuroblastoma-like epidural localization in non-Hodgkin's lymphoma.

We report a case of non-Hodgkin's lymphoma with CNS involvement confined to the epidural space causing cranial suture diastasis. Cerebrospinal fluid and bone marrow were normal. Two cases only of cranial epidural lymphoma have been reported in the literature; in both cases, the leptomeninges were also involved but without suture diastasis.

[Primary cerebral lymphoma. Diagnostic and therapeutic values. Apropos of 4 cases]. / Lymphomes primitifs cérébraux. Intérêts diagnostique et thérapeutique. A propos de 4 observations.

The authors report four recent cases, of primary cerebral Lymphoma discovered since the use of the C.T. scan. Even though rare, the incidence of this tumor seems to be in slowly increase. The lesions on the C.T. scan are too variables and the surgical biopsy is necessary for the diagnosis. The primary cerebral Lymphoma should be considered more and more like the others Lymphomas. For this reason, they have started the treatment after surgical biopsy, with chemotherapy followed by radiotherapy associated with corticotherapy. The two last patients, are still alive with a follow up of 36 months for one of them. The prognosis seems to us, better as much as the diagnosis and the treatment was started early.

[Acute myeloblastic leukemias and myelodysplasias: treatment with low doses of aracytine]. / Leucémies aiguës myéloblastiques et myélodysplasies: traitement par aracytine à faible dose.

The anti-leukaemic effect of low-dose cytosine arabinoside was assessed in 36 patients; 15 patients presented with an acute myeloblastic leukaemia and were treated in first induction because of age or preexisting disease and clinical and biological stabilization was obtained in 7 cases, with a mean duration of 8.7 months. In 4 relapsed patients 2 complete remissions were obtained, 1 of which after several courses of cytosine arabinoside. In all cases an important haematopoietic and extra-haematopoietic toxicity was noticed. In 15 patients treated for a myelodysplastic syndrome terminating in acute myeloblastic leukaemia stabilization was obtained in 8 cases, but final conclusions were difficult. The cytotoxic effect of cytosine arabinoside even at low dosage remains important. The optimal modalities in the administration, and the actual advantages of this treatment compared with conventional chemotherapy have still to be defined.

Removal of marrow T cells with OKT3-OKT11 monoclonal antibodies and complement to prevent acute graft-versus-host disease. A pilot study in ten patients.

We studied the feasibility of T cell depletion of bone marrow for transplantation in preventing acute graft-versus-host disease GVHD in patients having a high risk of acute GVHD. We report our preliminary clinical experience of the ex-vivo treatment of allogeneic marrow using a pan-T monoclonal antibody combination (OKT3-OKT11) plus baby rabbit complement. Ten patients received allografts from HLA-identical sibling donors. All patients had malignant hematological disease with poor prognosis (6 acute leukemia, 3 chronic granulocytic leukemia, and 1 multiple myeloma). Nine patients were at high risk of acute GVHD (older than 30 years for 4 patients, chronic granulocytic leukemia in acute or accelerated phase for 3, and acute leukemia in relapse for 2). Posttransplant management with methotrexate was maintained until day 100 in the first four patients and stopped at day 11 for the six others. The ex-vivo treatment with the OKT combination and complement removed 88.3% +/- 11.8 of the T lymphocytes. The myeloid progenitors recovered at the end of the procedure showed a moderate effect of monoclonal antibodies and complement (75.8% +/- 12.2). Engraftment was achieved in all patients: 23.3 days +/- 5.10 to reach 0.5 X 10(9) granulocytes per liter and 31.5 days +/- 12.2 to reach 50 X 10(9) platelets per liter. No acute GVHD was observed in this group of patients. Of the 10 patients, 7 are alive and well and have been in continuous remission from 2-10 months. Three patients have relapsed.

[Venous occlusive disease of the liver and autologous bone marrow transplantation. Preventive role for heparin?]. / Maladie veino-occlusive du foie et autogreffe de moelle osseuse. Rôle préventif de l'héparine?

The pathogenesis of veno-occlusive disease (VOD) of the liver remains unclear. In a retrospective study we reviewed 63 patients treated with high dose conditioning regimens followed by autologous bone marrow transplant. All patients were given low dose heparin (1 mg/kg). Only one patient developed VOD when heparin was stopped. We think that low dose heparin seems an interesting proposal for an randomized study to prevent VOD.

Intensive cytoreductive regimen and autologous bone marrow transplantation in leukemia. Present status and the future. A review.

High-dose cytoreductive treatment followed by ABMT represents a new approach to the treatment of acute leukemia as an alternative when leukemic patients do not have HLA-identical donors. ABMT protocol seems to be a valuable treatment for AML if it is immediately employed after the remission obtained to consolidate the remission. For ALL adult patients, and so for poor prognosis ALL in children, intensive therapy with ABMT represents a new approach when conventional therapy has failed or failed to consolidate the remission. The results of ABMT in CML in the literature have been disappointing; the bone marrow could be collected during the course of the first chronic phase after hydroxyurea therapy or other treatment programs. In leukemia the ABMT approach will be more credible if the protocol includes in vitro immunologic or pharmacologic means to eliminate residual leukemic cells.

Autologous bone marrow transplantation in acute myeloid leukemia in relapse or in complete remission.

We report ten cases of acute myeloid leukemia treated by intensive therapy followed by autologous bone marrow transplantation. Seven patients were in first relapse, and three were in complete remission. The conditioning regimen consisted of either chemotherapy alone (6-thioguanine, cytarabine, lomustine, and cyclophosphamide [TACC; eight patients]) or cyclophosphamide and total-body irradiation (two patients). All the patients in first relapse achieved complete remission (CR). The median remission duration was 9.9 months (range, 5-14), and the median survival was 14.4 months (range, 9-23.8). Of the three patients autografted during CR, one relapsed at Month 5 and two others remain in CR and are well at 18+ and 18.3+ months. High-dose chemotherapy followed by autologous bone marrow transplantation seems to be a valuable treatment for acute myeloid leukemia, if it is used immediately after the CR to consolidate the remission.

[Prognosis of adult non-Hodgkin's lymphomas. Retrospective study of sixty-six patients (author's transl)]. / Pronostic des lymphomes non-hodgkiniens de l'adulte. Etude rétrospective de soixante-six malades.

The authors studied the prognosis of 66 adults NHL according to: histological, clinical, biological and evolution criteria. The patients were treated by polychemotherapy or polychemo-and radiotherapy. Three years actuarial survival compared by the X2 test permits to consider only two independent prognostic factors: histologic type and complete remission due to treatment.

[Autologous haematopoietic stem cell transplantation. Preliminary results of a regional multicentric study (author's transl)]. / Greffe de cellules-souches hématopoïétiques autologues. Premiers résultats d'un protocole régional (author's transl)]

Autologous bone marrow transplantation represents a new approach to the treatment of malignant diseases when conventional therapy has failed. For this reason, the authors have collected bone marrow from 46 patients, including 24 with acute leukaemia, 7 with chronic myeloid leukaemia, 10 with lymphosarcoma and 5 with solid tumours. The mean of total cryopreserved CFU-c was 8.5 X 10(6) (range: 0.2-25). Ten cases of autologous bone marrow transplantation are reported. Seven patients had been prepared with high dosage chemotherapy alone (TACC) and three with chemotherapy combined with total body irradiation. Haematopoiesis restarted within 9 to 15 days in 5 patients and within 22 to 34 days in the other 5. Complete remission was obtained in all 5 patients with acute myeloid leukaemia grafted during their first relapse, the longest remission up to now being 390 days. One patient with chronic granulocytic leukaemia is still in second chronic phase after 360 days. Stem cells were transplanted early in the course of a T-lymphosarcoma, during complete remission; maintenance chemotherapy was withdrawn, and the chances of success of this treatment alone are being evaluated. The kinetics of blood and bone marrow CFU-c populations after transplantation were studied in 4 cases and were found to correlate closely with haematopoietic recovery following ablative bone marrow therapy. Stem cell transplantation can only be justified in acute leukaemia if it is carried out immediately after complete remission to consolidate the results and, hopefully, to prolong the remission.