[Epidemiology of monoclonal gammopathy in a general hospital and a university internal medicine department]. / Epidémiologie descriptive des gammapathies monoclonales. Expérience d'un centre hospitalier général et d'un service de médecine interne de centre hospitalier et universitaire.

PURPOSE: Monoclonal gammopathy are common in the general population. We describe biological features and etiology of monoclonal gammopathy diagnosed during more than a ten year period in the Internal Medicine Department of Rennes University Hospital and in all the medical departments of General Hospital of Blois. METHODS: Patients were identified by immunofixation registry of Biochemistry Laboratories in both hospital (from 1990 in Rennes and from 1980 in Blois). RESULTS: Internal Medicine Department of Rennes University Hospital: 1051 monoclonal gammapathies were identified: 514 men and 537 women. Median age was 71. Isotypes repartition was: IgG 42.8% (450 cases), IgM 31.9% (335), IgA 8.9% (94) biclonal gammopathy 9.8% (103). Sixty-nine monoclonal light chains (6.6%) were identified. Median concentration of monoclonal protein was 14 g/l (1.8-104.4). All department of General Hospital of Blois: 1282 monoclonal gammapathies were identified: 700 men and 582 women. Median age was 79. Isotypes repartition was: IgG 59.7% (765 cases), IgM 27.5% (329), IgA 11.8% (151). Thirty-four monoclonal light chains (2.7%) were identified. Median concentration of monoclonal protein was 5.6 g/l (0.5-96.6). Most frequent diagnosis were: monoclonal gammopathy of undetermined significance or MGUS (77.6% in Blois and 64.1% in Rennes), multiple myeloma (11.9% and 12.7%), Waldenström's macroglobulinemia (4.4% and 8.7%). CONCLUSION: Monoclonal gammopathy are common in clinical practice. MGUS account for more than 60% of monoclonal gammopathy. Given their frequency, diagnostic and follow-up strategies must be costless and simple.

[Follow-up of monoclonal gammopathy of undetermined significance in a population of 51 patients older than 70 years ]. / Gammapathie monoclonale de signification indéterminée: suivi évolutif de 51 patients âgés de plus de 70 ans.

UNLABELLED: Monoclonal gammopathy of undetermined significance (MGUS) are very frequent in the elderly. Its incidence is about 3% after 70 years. We have performed a retrospective study of patients aged of more than 70 years who were examined until 1995 for a MGUS. METHODS: The study included 51 patients: 24 men and 27 women. Information about evolution was obtained by medical file or by asking medical practitioner. We know the evolution of all patients until January 1st 2000. The median follow-up is 5.8 years (70 months). RESULTS: The MGUS remained stable for 34 patients (67%) with a median follow-up of 83 months (12 to 180 months). Nine patients (17%) developed malignant transformation of MGUS (6 multiple myeloma, 2 Waldenström macroglobulinemia, 1 malignant lymphoma). Eight (15%) developed a cancer. Twelve died without evidence of multiple myeloma or related disorder. The actuarial probability of malignant transformation at 5 years was 12%. CONCLUSION: The risk of malignant transformation of MGUS doesn't decrease in the elderly. A regular and prolonged follow-up is necessary.

[Cryptococcal meningitis associated with chronic lymphocytic leukemia: a case report. Review of the literature]. / Cryptococcose neuroméningée et leucémie lymphoïde chronique: à propos d'une observation. Revue de la littérature.

INTRODUCTION: The authors report the occurrence of a cryptococcal meningitis in a patient treated by corticosteroids and polychemotherapy for a chronic lymphocytic leukemia. EXEGESIS: A 63-year-old man with chronic lymphocytic leukemia was sent to hospital because of impaired condition with fever. Neurological disorders appeared. Cryptococcal meningitis was diagnosed. Under treatment, the outcome was favorable. CONCLUSION: This paper highlights the feature of this infection most likely underestimated in HIV-seronegative patients and the need to a priori consider this diagnosis.

[Gougerot-Sjögren syndrome and malignant lymphoproliferative syndromes]. / Syndrome de Gougerot-Sjögren et syndromes lymphoprolifératifs malins.

INTRODUCTION: This review is aimed at defining the frequency, anatomical and clinical presentation, pathogenesis, predictive factors and treatment of malignant lymphoproliferative diseases occurring in the course of Sjögren's syndrome. CURRENT KNOWLEDGE AND KEY POINTS: The frequency of non-Hodgkin's lymphoma (NHL) is estimated to be about 7%. Other malignant lymphoproliferative diseases (Waldenstrom's macroglobulinemia, multiple myeloma, Hodgkin's disease) are rarely observed. NHL is most frequently extranodal (affecting the salivary glands, stomach, lung, etc) in low grade malignancy (MALT lymphoma [mucosa associated lymphoid tissue]). The pathogenesis of NHL in Sjögren's syndrome is a multi-step process, including B cell monoclonal proliferation, oncogenic and/or infectious agents, and/or cytokines. Various predictive factors such as persistent enlargment of parotid glands, adenopathy, splenomegaly, mixed cryoglobulinemia, monoclonal gammopathy, suggest potential lymphoma evolution. The treatment of Sjögren's syndrome-associated NHL depends on the type of lymphoma. Moreover, in patients with low-grade lymphoma therapeutical strategies varies according to the stage and evolution of the disease. FUTURE PROSPECTS AND PROJECTS: Future prospective longitudinal studies should permit to define the best criteria for malignant transformation and to improve therapeutical strategies.

Chlorambucil in indolent chronic lymphocytic leukemia. French Cooperative Group on Chronic Lymphocytic Leukemia.

BACKGROUND: To determine whether chlorambucil treatment benefits patients with indolent chronic lymphocytic leukemia (CLL), we conducted two randomized trials in 1535 patients with previously untreated stage A CLL. METHODS: In the first trial, 609 patients were randomly assigned to receive either daily chlorambucil or no treatment; in the second trial, 926 patients were randomly assigned to receive either intermittent chlorambucil plus prednisone or no treatment. Median follow-up for the first and second trials exceeded 11 and 6 years, respectively. The end points were overall survival, response to treatment, and disease progression. RESULTS: Treatment of indolent CLL did not increase survival in either trial. In the treated group, as compared with the untreated group, the relative risk of death was 1.14 (95 percent confidence interval, 0.92 to 1.41; P=0.23) in the first trial and 0.96 (95 percent confidence interval, 0.75 to 1.23; P=0.74) in the second trial, with 76 percent and 69 percent of patients, respectively, having a response to therapy. Although chlorambucil slowed disease progression, there was no effect on overall survival. In the untreated group in the first trial, 49 percent of patients did not have progression to more advanced disease and did not need therapy after follow-up of more than 11 years; however, 27 percent of patients with stage A CLL died of causes related to the disease. CONCLUSIONS: Chlorambucil does not prolong survival in patients with stage A CLL. Since deferring therapy until the disease progresses to stage B or C does not compromise survival, treatment of indolent CLL is unnecessary.

[Triclonal gammopathy and malignant immunoproliferative syndrome]. / Gammapathie triclonale et syndrome immunoprolifératif malin.

Three distinct monoclonal gammopathies were identified in the serum of a 79 year-old man. In 1972 he presented with Waldenström's macroglobulinemia IgM Kappa. Twenty years later multiple myeloma was diagnoses. Serum protein electrophoresis performed at this time showed three monoclonal bands. Immunofixation identified these bands as monoclonal IgM kappa, IgG kappa and IgA kappa. Twenty-six cases of triclonal gammopathies were previously reported. Sixteen cases were associated with malignant immuno-proliferative diseases (non-hodgkin lymphoma, Waldenström's macroglobulinemia, multiple myeloma); five cases with non-hematologic diseases; three cases were of undetermined significance. The origin of three distinct monoclonal proteins may derive from three unrelated clones or alternatively from a single clone in which an isotype switch has occurred.

[Human babesiosis in 1997]. / La babésiose humaine en 1997.

Human babesiosis is a rare parasitic infection caused by an haemoprotozoan of genus Babesia, transmitted by tick bites. In Europe, the most severe cases are observed in asplenic patients infected by Babesia divergens. Acute intravascular haemolytic syndrome appears rapidly and is responsible for renal failure and is life threatening. Most of the cases have been reported in France. In contrast, Babesia microti babesiosis observed in the United States are less severe than Babesia divergens cases. The major problem raised by babesiosis is the rapidity of the clinical and biological diagnosis. The currently recommended treatment of severe cases consists of a blood exchange followed by clindamycine intraveine use, 25 mg/kg/d in three treatments, until disappearance of parasitemia. Prophylaxis against tick bites should be recommended for asplenic individuals.

[Epidermoid cyst of the spleen. 2 cases]. / Kystes épidermoïdes de la rate. Deux observations.

Two large epidermoid cysts of the spleen have been accidentally discovered in two young men. These cysts are uncommon and represent about 10% of the non parasitic benign cysts of the spleen. From these cases, the authors reviewed the literature. These cysts, which are caused by an abnormal development during the seventh week of the intra-uterine life, are often asymptomatic but the occurrence of a complication may enable the diagnosis. This diagnosis relies on the surgical ablation of the cyst and the histopathologic examination. The surgery should be as conservative as possible.

Primary malignant tumors (lymphoma excluded) in patients with chronic lymphocytic leukemia. A series of 22 cases from a retrospective study of 248 patients.

This retrospective study was conducted to evaluate the incidence of primary malignant tumors in patients with chronic lymphocytic leukemia (CLL). Between 1974 and 1994, 313 patients were hospitalized for CLL. Patients lost to follow-up were excluded (n = 65). Among the remaining 248 patients (167 men and 81 women), 22 patients (8.8%) developed primary malignant tumors (17 males, 5 females; age range 48 to 90 years); those who developed Richter's lymphoma (n = 9) or basal cell epithelioma (n = 5) were excluded from the cohort of the cancer patient. There were 18 epithelial tumors (3 lung adenocarcinoma) and 4 parenchymal tumors. We observed only one cancer of the prostate, and no breast cancer. The malignant tumor occurred at the same time as CLL in 8 cases and after a delay of 3 to 11 years in the 14 other cases. There was no particular features in the stage of duration of CLL before diagnosis of cancer. Outcome was particularly unfavorable, 20 deaths, compared with mortality in the other 226 patients (53.5%). These findings, together with the data in the literature, emphasize the importance of careful follow-up in patients with CLL.

Sequential induction chemotherapy with vincristine, daunorubicin, cyclophosphamide, and prednisone in adult acute lymphoblastic leukemia.

Sequential chemotherapy with vincristine, daunorubicin, cyclophosphamide, and prednisone doses was administered to 57 adult patients with acute lymphoblastic leukemia (ALL). Complete remission (CR) was achieved in 51 (89%, 95% confidence intervals, [CI] 78-96%). Among patients achieving CR, 62% were in CR after one sequence of chemotherapy, 23% after two sequences, and 5% after three sequences. Six patients (11%) had resistant disease. All patients experienced profound myelosuppression. Median time to recovery of neutrophils > 0.5 x 10(9)/1 was 22 days (range: 5-89 days), and of platelets > 100 x 10(9)/1 21 days (range: 0-45 days). Nonhematologic WHO grade 3 or more side effects consisted predominantly of hyperbilirubinemia (7%), mucositis (5%), nausea and vomiting (2%), and cutaneous toxicity (1%). Severe infectious complications occurred in only 14% of cases. One patient (2%, 95% CI 0-9%) died of therapy-related toxicity while in early CR. We concluded that sequential use of prednisone seemed at least as effective as continuous administration at the expense of a few adverse side effects.

[Pleural involvement of myeloma. Apropos of 2 cases]. / Atteinte pleurale du myélome. A propos de deux observations.

The authors report two cases of myelomatosis localised to the pleura, one of which was associated with an adenocarcinoma. Pleural effusions are relatively rare during the course of multiple myeloma and most often occur with non-specific disorders of the disease. The myelomatous origin of a pleural effusion can only be made by analysis of the pleural fluid and should be recognised early enough to enable aggressive treatment to be instituted even if the prognosis associated with such a localisation is very poor.

Expression of the multidrug resistance-associated P-glycoprotein (P-170) in 59 cases of de novo acute lymphoblastic leukemia: prognostic implications.

Immunocytochemical detection of the multidrug resistance (MDR)-associated membrane protein (P-170) was performed at time of diagnosis in a series of 36 children and 23 adults with acute lymphoblastic leukemia (ALL) using two monoclonal antibodies JSB1 and C219. Immunophenotypes were obtained in all cases and karyotypes were analyzed in 37 cases. Detection with JSB1 or with C219 led to similar results in terms of positive cells and cases, but the intensity of staining was higher with JSB1. In the populations studied, the rate of first complete remission differed between MDR-positive and MDR-negative in adult patients only (56% v 93%, respectively, P = .05). Of the 16 MDR-positive patients who had presented a first complete remission, 13 (81%) relapsed, compared with 13 of 35 (37%) MDR-negative (P = .008) patients. A higher rate of relapse among MDR-positive compared with MDR-negative patients was observed in adults and in children taken separately (adults 100% v 46%; children 73% v 32%, respectively). The survival rates (Kaplan-Meier method) were significantly higher in MDR-negative compared with MDR-positive populations as a whole (P = .002) and among children (P = .05) and adults (P = .03) taken separately. Event-free survival curves followed this trend. The percentage of second complete remission was very low in the MDR-positive group (15%) compared with 38% for the MDR-negative group. These results were shown by multivariate analysis to be independent of age, immunophenotypes, and karyotypes and clearly show the importance of MDR phenotype detection in ALL.

Splenectomy for splenomegaly exceeding 1000 grams: analysis of 47 patients.

Forty-seven patients who underwent splenectomy for splenomegaly > or = 1000 g were studied retrospectively. There were 29 men and 18 women of mean age 56 (range 19-87) years. Haematological malignancy was the most common disorder (42 patients). The main indications for splenectomy were cytopenia (20 patients), diagnosis (14), initial treatment of leukaemia (eight), pain (four) and spontaneous rupture (one). Thirteen patients underwent an associated surgical procedure. One patient died (mortality rate 2 per cent) and 12 (26 per cent) had postoperative complications. The advantages of splenectomy included histopathological diagnosis in 13 of 14 patients with splenomegaly of unknown origin, effective initial treatment in prolymphocytic and hairy cell leukaemia, definitive relief of pain in all affected patients, and long-term improvement of cytopenia in most.

[Felty's syndrome: retrospective study of 12 cases]. / Syndrome de Felty: étude rétrospective de 12 cas.

A retrospective study of twelve cases of Felty's syndrome was performed. The main points of this syndrome (clinical presentation, physiopathology, complications, treatment) are described.

A randomized trial of amsacrine and rubidazone in 39 patients with acute promyelocytic leukemia.

Thirty-nine patients with untreated acute promyelocytic leukemia (APL) were randomly allocated to receive rubidazone (zorubicin) 200 mg/m2/d, days 1 to 4 plus cytarabine (Ara C) 200 mg/m2/d, days 1 to 7 (arm A, 21 patients), or amsacrine (Amsa) 150 mg/m2/d, days 1 to 4 plus Ara C 200 mg/m2/d, days 1 to 7 (arm B, 18 patients). Prophylaxis of disseminated intravascular coagulation was made by platelet transfusions and heparin. In case of leukemic resistance, patients received a second course with 2 days of rubidazone (arm A) or Amsa (arm B) and 3 days of Ara C. Patients who achieved complete remission (CR) received three consolidation courses with the two drugs used for induction and maintenance therapy for 3 years. Two patients in arm A and one in arm B were allografted in first CR. Initial characteristics were similar in both arms. In arm A, 18 patients (86%) reached CR, two had hypoplastic death, and one had leukemic resistance after two courses. In arm B, 12 patients (66%) achieved CR, two had early death (CNS bleeding, one case; ventricular fibrillation, one case), and four had resistant leukemia after two courses. The difference in CR rate between the two arms was not significant. In arm A, disease-free survival (DFS) showed a plateau at 54.3% after 34 months (95% confidence interval [CI], 32.1% to 74.9%), with eight CRs longer than 34 months. In arm B, DFS was significantly shorter (P less than .03), showing a plateau at 16.7% after 38 months (95% confidence interval, 4.7% to 44.6%), and only two prolonged CRs were seen. The difference in DFS remained significant after censoring allografted patients and patients who died in CR (one in arm A, two in arm B). Our results suggest that Amsa-Ara C combinations may be inferior to anthracycline-Ara C combinations in the treatment of APL, because they seem to provide shorter DFS and, possibly, a higher incidence of initial leukemic resistance. However, studies with larger numbers of patients are required.

[Splenectomy for massive splenomegaly. Apropos of 36 cases]. / Splénectomie pour splénomégalie massive. A propos de 36 observations.

Thirty-six splenectomies for splenomegaly exceeding 1000 grams are reported. The enlargement of the spleen most often was related with a malignant disease (n = 32). Cytopenia was the main indication in 14 cases, and splenectomy was contemplated for diagnosis (n = 12), initial treatment (n = 6), or due to pain (n = 3) or spontaneous rupture (n = 1). Ten patients (27.8%) had an associated surgical treatment. One patient died postoperatively (2.8%) and 12 patients presented with 14 complications (33%) usually with a rapidly favorable evolution. In 11 of 12 cases (91.6%), the operation allowed establishing the diagnosis in cases of splenomegaly with an unknown origin. Lastly, it was always effective to relieve pain and in most cases improved cytopenia. The authors conclude that the patients with massive splenomegaly are improved by splenectomy, although it most often is merely a palliative treatment in cases of malignant hemopathy.