[Neuromeningeal sites of multiple myeloma: 3 cases and review of the literature]. / Localisations neuroméningées du myélome multiple: trois observations et revue de la littérature.

Neurologic manifestations are not unusual in multiple myeloma. Conversely meningeal and cerebral involvement have been very rarely reported. We report here on three patients with multiple myeloma and meningeal or cerebral involvement (two of them with autopsy study): one case of cerebellar involvement associated with secondary plasma cell leukemia and two cases of meningeal involvement. We reviewed the characteristics of 20 cases of meningeal involvement with demonstration of plasma cells at cerebrospinal fluid analysis (18 previously reported cases and our two patients). Meningeal involvement occurs in patients with initially stage III multiple myeloma in 85% of cases and is associated with the occurrence of plasma cell leukemia in 20% of cases. The most frequent neurologic signs are: confusion (60%), altered consciousness (25%), gait disorder (25%), cranial nerve palsy (25%). Meningismus is rarely present. Diagnosis is based on cerebrospinal fluid analysis after lumbar puncture which should be made after cranial magnetic resonance imaging. The diagnosis of intra-cranial haemorrhage and infectious meningitis have to be cautiously ruled out. Despite treatments (systemic and/or intrathecal chemotherapy, radiation therapy), prognosis is very poor: mean time of survival after the occurrence of neurologic signs is about 2 months.

IL-4 release by human leukemic and activated normal basophils.

Recently, authors have addressed the ability of human basophils to produce IL-4. We report here the detection of significant serum IL-4 levels in a case of acute transformation of chronic myelogenous leukemia with a predominant basophilic cell population. Leukemic basophils were isolated from patients' PBMC and assayed for their IL-4-mRNA expression and their ability to secrete this cytokine in vitro. Leukemic basophilic cells (> 90% toluidine blue positive) but not other PBMC expressed IL-4-mRNA, contained IL-4 protein, and secreted this cytokine. These cells had a spontaneous IL-4 secretion ability, without a need for an exogenous activator. Meanwhile, IL-4 release was significantly increased following leukemic cell activation through Fc epsilon RI-ligation or by Ca2+ ionophore. IL-4 and its mRNA were also detected in leukemic basophils from three other chronic myelogenous leukemia patients with moderate basophilia (13, 14, and 23% basophils in PBMC). To confirm these data in normal human cells, we have developed a method to obtain large numbers of purified basophils from human bone marrow cell cultures. In contrast to leukemic basophils, normal cells required in vitro activation through Fc epsilon RI ligation or by Ca2+ ionophore to express and secrete IL-4. Leukemic and normal basophils secreted histamine following in vitro activation, but were negative for tryptase. These data thus demonstrate the in vivo and in vitro ability of human basophils to produce IL-4.

[Allogenic bone marrow grafts in acute myeloid leukemias. A retrospective study in 111 grafted patients in first complete remission]. / Greffes de moelle allogéniques dans les leucémies aiguës myéloïdes. Etude rétrospective chez 111 malades greffés en première rémission complète.

Between 1978 and 1984, in 13 French Transplant Centers, 111 patients with acute myelogenous leukaemia underwent allogeneic bone marrow transplantation while in first complete remission. The conditioning regimen consisted of cytoxan 60 mg/kg X 2 and 10 Gy total body irradiation. To prevent graft-versus-host disease, 75% of the patients were given methotrexate and 25%, cyclosporine A. The probability of remaining in complete remission was 61% at 5 years. The probability of survival was 43% at 5 years, with a plateau between 2.5 and 6 years. The most frequent causes of death were interstitial pneumonia, relapses and graft-versus-host disease. Relapses were more frequent in cases with M 4-5 cytology than in those with M1 to M3 cytology (P less than 0.01). Transplant-related deaths were mainly consecutive to graft-versus-host disease and its facilitating effect on pneumonia (P less than 0.05). These results indicate that bone marrow transplantation can cure a large proportion of patients with acute myelogenous leukaemia, especially AML subtypes without monocytic differentiation. Improvements in conditioning regimens for the M 4-5 subtypes and in prevention of graft-versus-host reaction and cytomegalovirus infection should give rise to further developments in this field.

An application of mathematical morphology to analysis of the size and shape of nuclei in tissue sections of non-Hodgkin's lymphoma.

Using principles from the theory of mathematical morphology, a semiautomatic analysis of the size and shape of cell nuclei on tissue sections was carried out on a Leitz Texture Analysis System (Leitz-TAS). The four parameters proposed here are more discriminatory than conventional shape evaluation by the form factor (FF), which is based on the ratio of perimeter squared to area. The parameters quantified, respectively, nuclear elongation (ND), narrow (R1) and wide (R2) irregularities, and the distribution of R1 and R2 along the nuclear contour (ID). The properties of these parameters were tested nucleus-by-nucleus on 24 nuclear models. The methodology was then illustrated by a study of lymph node nuclei in non-Hodgkin's lymphoma (NHL). Prior to analysis, 45 lymphomas were classified into five categories of nuclear size and shape according to the International Working Formulation (IWF). Two hundred nuclei were measured on each lymph node section. Statistical interpretation was based upon an analysis of the nuclear surface area on sections and upon the mean values of R1, R2, and ND, the standard deviations of R1 and R2, and the percentage of cleaved nuclei detected by ID. The mean value of R2 discriminated best between the two sets of populations with regular and irregular nuclear contours, respectively. Parameters R1, ND, and ID permitted the distinction of certain NHL cases among populations with irregular nuclei. Nuclear invaginations decreased in depth as the nuclear area became greater. The median surface area was well correlated to the IWF, and the skewness coefficient (third statistical moment of the nuclear surface area distribution) was related to the number of nuclear size or shape subpopulations.