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Introduction Alors que le taux de lymphomes malins non-Hodgkiniens (LMNH) diagnostiques ne cesse d’augmenter dans le monde, le LMNH a localisation orbitaire est une tumeur relativement rare et de diagnostic difficile. Le but de cette etude est d’analyser les cas de LMNH a localisation conjonctivo-orbitaire examines, dans le service d’Ophtalmologie du CHU d’Amiens, au cours de ces 20 dernieres annees. Materiel et methodes Nous avons mene une etude retrospective des cas de lymphomes a localisation conjonctivo-orbitaire diagnostiques dans le Service d’Ophtalmologie d’Amiens entre 1982 et 2002. Les comptes rendus anatomopathologiques de 22 cas ont ete etudies, notamment le mode de survenue, la description clinique, radiologique, le mode diagnostique, les resultats anatomo-pathologiques et le type de traitement de ces tumeurs. Resultats Tous les LMNH etaient de type B. Ils etaient de bas grade de malignite dans 17 cas, isoles dans 22 cas, primitifs, de localisation orbitaire dans 9 cas et de type indolent. Discussion Le clinicien se heurte souvent a des lesions insidieuses dont l’acces a la biopsie est souvent difficile, retardant le diagnostic. Le premier diagnostic differentiel a evoquer est l’inflammation orbitaire chronique anciennement appelee pseudo-tumeur inflammatoire. Seule une biopsie orbitaire permet d’affirmer le diagnostic de LMNH. Conclusion Les nouveaux moyens diagnostiques tels que l’immunohistochimie et la genetique permettent de depister de plus en plus de LMNH, meme si leur histoire clinique peut encore faire errer le diagnostic De plus, des therapeutiques de plus en plus ciblees sur le type immunohistochimique du LMNH semblent donner des resultats tres prometteurs. Des etudes sont encore en cours.

Published data on transplantation in Waldenstrom's macroglobulinemia (WM) are still limited. We present a retrospective multicentric study of 27 WM patients who underwent 19 autologous (median age, 54 years) and 10 allogeneic (median age, 46 years) transplantations. Median time between diagnosis and transplantation was 36 months; 66% of patients had received three or more treatment lines and 72 % had chemosensitive disease. High-dose therapy (HDT) and autologous transplantation induced a 95% response rate (RR), including 10 major responses. With a median follow-up of 18 months, 12 patients are alive at 10 to 81 months and eight are free of disease progression at 10 to 34 months. The toxic mortality rate (TRM) was 6%. Allogeneic transplantation was preceded by HDT in nine patients and by a nonmyeloablative regimen in one patient. The RR was 80%, including seven major responses. With a median follow-up of 20.5 months, six patients are alive and free of progression at 3 to 76 months. Four patients died, all from toxicity, resulting in a TRM of 40%. HDT followed by autologous transplantation is feasible in WM, even in heavily pretreated patients, with some prolonged responses but a high relapse rate. Conversely, allogeneic transplantation is more toxic, but likely induces a graft-versus-WM effect and may, for some patients, result in long-term disease control.

Background. Primary bone lymphoma (PBL) is a rare entity that has only been reviewed in one prospective and small retrospective studies, from which it is difficult to establish treatment guidelines. We prospectively evaluated high-dose or conventional anthracycline-cyclophosphamide dose and radiotherapy for PBL.Patients and Methods. The GOELAMS prospective multicenter study (1986–1998) enrolled adults with localized high-grade PBL according to age and performance status (PS). Patients Results. Among the 26 patients included (VCAP: 19; VCEP-bleomycin: 7), 39% had poor PS ≥2. With a median follow-up of 8 years, overall survival, event-free survival, and relapse-free survival were 64%, 62%, and 65%, respectively, with no significant difference between treatment groups. Poor PS was significantly associated with shorter OS and EFS.Conclusions. Our results confirm the efficacy of our age-based therapeutic strategy. High-doses anthracycline-cyclophosphamide did not improve the outcome. VCEP-bleomycin is effective and well tolerated for old patients. The intensification must be considered for patients with PS ≥2, a poor prognostic factor.

Introduction Le lymphome malin non hodgkinien (LMNH) conjonctivo-orbitaire est une tumeur relativement rare de diagnostic difficile. L’attitude therapeutique face aux formes indolentes tend a se modifier, et le developpement de l’immunotherapie y contribue. Nous rapportons deux cas de patients traites par rituximab (anticorps anti-CD20). Observation Deux femmes, âgees respectivement de 50 ans et 59 ans, presenterent un LMNH indolent, isole et de bas grade de malignite : l’un, conjonctival de type MALT et l’autre, orbito-palpebral de type A selon la WFC, folliculaire a petites cellules. L’immunohistochimie montrait un marquage diffus pour l’anticorps anti-CD20. Les patientes recurent en 1 re intention une monotherapie de rituximab par voie intraveineuse, debutee en decembre 2000, a raison de 375 mg/m 2 , en 4 injections a 1 semaine d’intervalle. Aucun effet indesirable majeur ne fut constate. Les patientes sont en remission complete depuis la fin du traitement, soit un recul de 4 ans. Elles sont toujours sous suivi hematologique et ophtalmologique regulier. Conclusion Le rituximab (Mabthera ® ) offre une alternative non negligeable dans le traitement des LMNH orbitaires indolents. Son efficacite est surtout documentee dans les LMNH folliculaires ou chez les patients a rechutes. Celles-ci seraient un peu plus frequentes dans le type MALT. Par ailleurs, ce traitement presente une faible toxicite hematologique et est generalement bien tolere.

Rhodotorula species are commensal yeasts of variable pathogenicity. The authors report the case histories of two patients presenting with febrile neutropenia. The first was a 3-year-old girl who had been treated with combination chemotherapy for a tumour of the posterior fossa. The second was a 46-year-old man who had received chemotherapy for lymphoplasmocytic lymphoma, followed by consolidation treatment with autologous bone marrow transplantation. Investigation revealed infection caused by Rhodotorula. The outcome was favourable after removal of the catheter in both patients. Rhodotorula species have been isolated during a variety of infectious complications. Almost all published cases of fungaemia concern patients with central venous catheters that have been in place over long periods, who have also been treated with broad spectrum antibiotics. Neoplasia represents the most frequent underlying disease. The pathogenicity of Rhodotorula species appears to be moderate in most cases; fungal therapy or the removal of infected catheters is generally effective. Nevertheless, Rhodotorula has been reported to provoke fatal endocarditis or meningitis and can probably cause septic shock.

We studied two cases of chronic myelogenous leukemia (CML) with unusual variant Philadelphia (Ph) translocation (22;22)(q11;q13). Southerr, blot analysis showed a chromosomal break in the BCR gene within the 5.8-kilobase (kb) breakpoint cluster region (bcr), between bcr exons 2 and 3 and between bcr exons 3 and 4, respectively. Chimeric bcr-abl mRNA was detected using polymerase chain reaction (PCR) which amplified, according to the respective bcr breakpoints, bcr exon 2- abl exon II and bcr exon 3- abl exon II junction products. These results further support the involvement, even when not cytogenetically detectable, of the 9q34 chromosomal region in all variant Ph translocations and that BCR-ABL gene fusion products are causally involved in the development of Ph positive CML.

From January 1979 to December 1987, 35 cases of primary central nervous system lymphoma (CNS-L) were treated. We recently reviewed these cases focusing on treatment results, treatment modalities, and radiotherapy (RT) or chemotherapy-radiotherapy (CT-RT). Variables such as age, risk factors, presenting symptoms, and histologic condition (all were high-grade or intermediate-grade non-Hodgkin's lymphomas [NHL]) and radiologic data were similar to those of series reported previously. The median survival time was 36 months (+/- 0.2 months) and the disease-free survival (DFS) time was 16 months (+/- 0.12 months). Twelve of 32 patients evaluable for treatment results experienced a recurrence (all but one occurred in the CNS). The DFS rate was 70% for the CT-RT group and 50% for the RT group (median follow-up time, 24 months). Therapeutic results in CNS-L are discussed with special emphasis on a putative role of CT in the management of this rare type of tumor.

Although the number of non-Hodgkin's lymphoma (NHL) cases continues to grow throughout the world, orbital NHL is still a rare tumor that is difficult to diagnose. The objective of our study was to analyze the different orbital NHLs diagnosed in our Ophthalmology Department during the last 20 years.[corrected] We conducted a retrospective study of conjunctive-orbital lymphomas diagnosed in the Amiens Ophthalmology Department between 1982 and 2002. The pathological reports of 22 cases were investigated, notably the mode of onset, the clinical and radiological description, the diagnostic mode, pathological results, and the type of treatment provided for these tumors.Every NHL was type B. They were for the most part low grade in terms of malignancy, isolated, primitive, orbital and inactive.Insidious, slow-growing lesions are often found, and biopsy can be difficult. This may explain delayed diagnosis. The first differential diagnosis is inflammatory pseudotumor. Only a good biopsy can confirm the diagnosis of NHL.New immunohistochemistry and genetic diagnostic methods make it increasingly possible to screen for NHL, even if the clinical history can be misleading. Moreover, treatments that are more and more precisely targeted to the immunohistochemical type of NHL seem to be giving very promising results. Several studies are ongoing.

Orbital non-Hodgkin's lymphoma is a rare tumor whose diagnosis is often difficult. Treatment of latent lymphoma have been changing because of progress in immunotherapy.We report two patients treated with rituximab (antibody anti-CD20). Two women, 50 and 59 years old, presented low-grade, IE-stage lymphoma. One was conjunctival MALToma, the other was orbitopalpebral, type A, of WFC classification, follicular, with small cells. Immunohistochemistry showed a diffused marking for Ac anti-CD20. Both patients received intravenous rituximab as a first treatment in December 2000, 375 mg/m2, four injections per week. We did not note any major undesirable effects. Both have been in complete remission for 4 years. These patients continue to be followed up.Rituximab's efficacy has been proved mainly in follicular LMNH or in recurrent forms. The recurrence may be more frequent in MALT lymphoma. This medical treatment has low hematologic toxicity.Rituximab offers an alternative for low-grade lymphoma treatment that is well tolerated by the patient.

To report on an uncommon association of agranulocytosis in primary Sjögren's syndrome (SS).The clinical, haematological, and immunological features of seven patients with primary SS associated with a chronic (6 months) agranulocytosis, and the outcome of the patients, were analysed.Patients were white women with an unexplained agranulocytosis. They all had non-erosive arthritis and three had a thrombocytopenia or Evan's syndrome. In three patients, transient or durable expansion of T lymphocytes was present in the peripheral blood or in the bone marrow, but evolved independently from neutrophil counts. There was no paroxysmal nocturnal haemoglobinuria clone or antibodies to neutrophil surface antigens. In vitro bone marrow culture was normal (four patients) or showed a decrease in colony forming unit-granulocyte monocyte (CFU-GM) and colony forming unit-erythroblast (CFU-E) (one patient). Serum levels of soluble Fas ligand (sFasL) were normal, and granulocyte-colony stimulating factor (G-CSF) concentrations were either normal or raised. One patient was treated with steroids associated with intravenous immunoglobulins and achieved a lasting response. Two other patients were treated with steroids and methotrexate, with poor efficacy. Short courses of subcutaneous G-CSF produced a transient and mild response in all three patients. Complete recovery of the neutrophils occurred temporarily during pregnancy in two patients. After a mean follow up of 34.8 months (range 6-139) all patients were alive and none developed serious infections.A subset of patients with primary SS and non-destructive arthritis may develop a chronic but well tolerated agranulocytosis that is usually poorly responsive to steroids and oral methotrexate.

Portal hypertension in chronic lymphocytic leukemia is rare. A 66 year-old man was admitted for splenomegaly, thrombopenia and cholestasis. Endoscopy showed esophageal varices. The hepatic venous pressure gradient was 15 mmHg. The liver biopsy showed dense leukemia cells in sinusoidal and portal sites. After splenectomy, the hepatic venous pressure gradient normalized, but esophageal varices and cholestasis persisted. The authors discuss the mechanisms of portal hypertension in chronic lymphocytic leukemia. Previously reported cases are summarized.

The authors report on the cases of two adult male patients presenting with autoimmune cytopenias associated with malignancies: a case of autoimmune haemolytic anemia occurring after remission of Hodgkin's disease and a case of autoimmune neutropenia in the setting of renal carcinoma. High-dose intravenous immune globulins (IIG) administered after failure of corticosteroid therapy produced a rapid and long-lasting response. These cases illustrate that intravenous immunoglobulins may be helpful in refractory cases of autoimmune cytopenias. The association of IIG and corticosteroid could be synergistic and effective independently of the outcome of the underlying disease. The pathophysiogenic mechanisms and literature are discussed briefly.

We designed a randomized trial of IC with or without quinine, an agent capable of reverting the multidrug resistance (mdr) phenotype, in patients agedor = 65 years with high risk MDS. Patients were randomized to receive Mitoxantrone 12 mg/m2/d d2-5 + AraC 1 g/m2/12 h d1-5, with (Q+) or without (Q-) quinine (30 mg/kg/day). 131 patients were included. PGP expression analysis was successfully made in 91 patients and 42 patients (46%) had positive PGP expression. In PGP positive cases, 13 of the 25 (52%) patients who received quinine achieved CR, as compared to 3 of the 17 (18%) patients treated with chemotherapy alone (p = 0.02). In PGP negative cases, the CR rate was 35% and 49%, respectively in patients who received quinine or chemotherapy alone (difference not significant). In the 42 PGP positive patients, median Kaplan-Meier (KM) survival was 13 months in patients allocated to the quinine group, and 8 months in patients treated with chemotherapy alone (p = 0.01). In PGP negative patients, median KM survival was 14 months in patients allocated to the quinine group, and 14 months in patients treated with chemotherapy alone. Side effects of quinine mainly included vertigo and tinnitus that generally disappeared with dose reduction. Mucositis was significantly more frequently observed in the quinine group. No life threatening cardiac toxicity was observed. In conclusion, results of this randomized study show that quinine increases the CR rate and survival in PGP positive MDS cases treated with IC. The fact that quinine had no effect on the response rate and survival of PGP negative MDS suggests a specific effect on PGP mediated drug resistance rather than, for instance, a simple effect on the metabolism of Mitoxantrone and/or AraC.

All transretinoic acid (ATRA) followed by daunorubicin (DNR)-AraC chemotherapy (CT) has improved the outcome of acute promyelocytic leukemia (APL) by comparison to CT alone. In a randomized trial, (1) we compared 2 induction schedules (ATRA followed by CT [ATRA--CT] and ATRA plus CT [ATRA+CT, with CT added on day 3 of ATRA treatment]) and (2) we assessed the role of maintenance treatment. Four hundred thirteen patients/=75 years of age and with newly diagnosed APL were included. Induction treatment was stratified on white blood cell (WBC) count and age: patients/=65 years of age and with an initial WBC count of/=5,000/microL (n = 208) were randomized between ATRA--CT and ATRA+CT (initially randomized patients); patients with a WBC count greater than (high WBC count group, n = 163) and patients 66 to 75 years of age with a WBC count greater than 5,000/microL (elderly group, n = 42) were not initially randomized and received ATRA+CT from day 1 and ATRA --CT, respectively. All patients achieving CR received 2 additional DNR-AraC courses (only 1 in patients 66 to 75 years of age) and were then randomized for maintenance between no treatment, intermittent ATRA (15 days every 3 months) for 2 years, continuous low-dose CT (6 mercaptopurine + methotrexate) for 2 years, or both, using a 2-by-2 factorial design. Overall, 381 (92%) of the patients achieved complete remission (CR), 31 (7%) suffered an early death, and only 1 patient had leukemic resistance. ATRA syndrome occurred in 64 patients (15%) and was fatal in 5 cases. The CR rate was similar in all induction treatment groups. Event-free survival (EFS) was significantly lower in the high WBC group (P =.0002) and close to significance in the elderly group (P =.086) as compared with initially randomized patients. Relapse at 2 years was estimated at 6% in the ATRA+CT group, versus 16% in the ATRA--CT group (P =.04, relative risk [RR] =.41). EFS at 2 years was estimated at 84% in the ATRA+CT group, versus 77% in the ATRA--CT group (P =.1, RR =.62). Two hundred eighty-nine patients were randomized for maintenance. The 2-year relapse rate was 11% in patients randomized to continuous maintenance CT and 27% in patients randomized to no CT (P =.0002) and 13% in patients randomized to intermittent ATRA and 25% in patients randomized to no ATRA (P =.02). An additive effect of continuous maintenance CT and intermittent ATRA was seen, and only 6 of the 74 patients who received both maintenance treatments had relapsed. Overall survival was improved in patients who received maintenance CT (P =.01), and there was a trend for better survival in patients who received maintenance ATRA (P =.22). Our findings strongly suggest that early addition of chemotherapy to ATRA and maintenance therapy combining continuous CT and intermittent ATRA can reduce the incidence of relapse in APL. This effect already translates into significantly better survival for maintenance treatment with continuous CT.

Anxiety can increase the risk of chemotherapy related emesis. We have studied the role of a benzodiazepine (alprazolam: A) in addition to granisetron for controlling emesis in patients treated with moderately emetogenic chemotherapy for malignant lymphomas according to an anxiety scale (Covi score). Two hundred twenty-five patients receiving at least 3 cycles of chemotherapy including adriamycin and/or cyclophosphamide and/or epirubicin and/or dacarbazine were randomized. Patients in arm G (n = 111) received 3 mg i.v. granisetron 10 min before chemotherapy at cycles (C) 1, 2 and 3 while in arm G+A (n = 114), alprazolam (A) was added per os 1 mg 1 hour before chemotherapy (H-1) and 0.5 mg at H+6 for C1. At C2 and C3, A was given 0.75 or 1.5 mg at H-48, H-24, H-1 and 0.5 mg at H+6. Patients characteristics were comparable between the 2 arms. Complete response rates (i.e. no emesis or at least slight nausea) were similar in both arms: G: 83, 94 and 93% versus G+A: 89, 93 and 97% in C1, C2 and C3 respectively. Nevertheless, the Covi score of the population was low rendering difficult the study of the factor "anxiety". Somnolence was significantly more frequent in the G+A arm (p0.0001).

We designed a randomized trial of IC with or without quinine, an agent capable of reverting the multidrug resistance (mdr) phenotype, in patients aged < 65 years with high risk MDS. Patients were randomized to receive Mitoxantrone 12mg/m2/d d2–5 + AraC 1g/m2/12h d1–5, with (Q+) or without (Q) quinine (30mg/kg/day). 131 patients were included. PGP expression analysis was successfully made in 91 patients and 42 patients (46%) had positive PGP expression. In PGP positive cases, 13 of the 25 (52%) patients who received quinine achieved CR, as compared to 3 of the 17 (18%) patients treated with chemotherapy alone (p=0.02). In PGP negative cases, the CR rate was 35% and 49%, respectively in patients who received quinine or chemotherapy alone (difference not significant). In the 42 PGP positive patients, median Kaplan-Meier (KM) survival was 13 months in patients allocated to the quinine group, and 8 months in patients treated with chemotherapy alone (p=0.01). In PGP negative patients, median KM survival was 14 months in patients allocated to the quinine group, and 14 months in patients treated with chemotherapy alone. Side effects of quinine mainly included vertigo and tinnitus that generally disappeared with dose reduction. Mucositis was significantly more frequently observed in the quinine group. No life threatening cardiac toxicity was observed. In conclusion, results of this randomized study show that quinine increases the CR rate and survival in PGP positive MDS cases treated with IC. The fact that quinine had no effect on the response rate and survival of PGP negative MDS suggests a specific effect on PGP mediated drug resistance rather than, for instance, a simple effect on the metabolism of Mitoxantrone and/or AraC.

We reviewed 72 primary central nervous system lymphomas occurring in immunocompetent patients. The cases were reviewed for clinical data, histology, immunophenotype, bcl-2 and p53 expression, and Epstein-Barr virus association. Follow-up was available for 40 patients included in the Groupe Ouest Est d'étude des Leucénies et Autres Maladies du Sang (GOELAMS) lymphomes cérébraux primitifs (LCP 88) trial. Each diagnosis, requiring a consensus among at least 3 pathologists, was performed according to the recent Revised European-American Lymphoma classification and equivalents in the updated Kiel classification. Tumors were predominantly classified as diffuse large B-cell lymphomas. There were 3 T-cell lymphomas and 1 Hodgkin lymphoma. The proteins bcl-2 and p53 were expressed in 35% and 16% of the tested cases, respectively. Epstein-Barr virus was not found by in situ hybridization except in the case classfied as a cerebral localization of Hodgkin disease. No significant association was found between subtypes, bcl-2 or p53 expression, and patient survival. From the standpoint of their biologic characteristics, primary central nervous system lymphomas are very similar to systemic diffuse large B-cell lymphomas. In contrast to AIDS-related primary central nervous system lymphomas, primary central nervous system lymphomas are rarely associated with Epstein-Barr virus and in immunocompetent patients they express bcl-2 at a relatively low rate.

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.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.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.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.

The complete remission (CR) rate after intensive chemotherapy for acute myelogenous leukemia (AML) remains low in elderly patients, mainly because of a higher infectious mortality rate related to neutropenia and an increased incidence of adverse prognostic factors. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to potentially recruit leukemic blasts into cell cycle and improve cytotoxic effects when given during chemotherapy, and to shorten the duration of neutropenia when administered after chemotherapy. Two hundred forty patients aged 55 to 75 years who had newly diagnosed AML were randomly assigned to receive placebo or Escherichia coli-derived GM-CSF (5 micrograms/kg/d by 6-hour intravenous infusion) starting during induction chemotherapy on day 1 and continued through and after chemotherapy until recovery of neutrophils, or evidence of regrowth of leukemia, or up to day 28. Induction chemotherapy consisted of idarubicin (8 mg/m2/d on days 1 to 5) and cytarabine (100 mg/m2/d on days 1 to 7). The study drug was not administered subsequent to the induction course. Patients who achieved a CR received continuous maintenance therapy for 1 year with four quarterly reinduction courses; in the 55- to 64-year age subgroup, patients were randomly assigned to receive or not a consolidation course before maintenance therapy. The CR rate was similar in the GM-CSF and placebo groups (63% and 60.5%, respectively; P = .79). The mortality, rate of resistant disease, and rate of regrowth of leukemia were also similar in both groups. The time to neutrophil recovery was shorter in patients who received GM-CSF (24 v 29 days; P = .0001), but the incidence and characteristics of infectious events were not different. The 2-year disease-free survival (DFS) rate was significantly improved in the GM-CSF group (48% v 21% in the placebo group; P = .003). This effect was highly significant in the cohort of patients aged 55 to 64, but only marginal in patients/=65 years of age. There was a trend toward a longer overall survival (OS) in the GM-CSF group (P = .082). In summary, the administration of GM-CSF, concomitantly with chemotherapy and thereafter during induction course in AML, shortened the time to neutrophil recovery, but did not improve the CR rate in patients aged 55 to 75. Nonetheless, DFS and OS were significantly prolonged in patients aged 55 to 64 treated with GM-CSF. These results are promising and further evaluation of myeloid growth factors in AML is warranted.

Three intensive consolidation strategies are currently proposed to younger adults with acute myeloid leukemia (AML) in first complete remission (CR): allogeneic or autologous bone marrow transplantation (BMT) and intensive consolidation chemotherapy (ICC). Patients aged 15 to 50 years with de novo AML received an induction treatment with 7 days of cytarabine and either idarubicin or rubidazone. After achievement of a CR, patients up to the age of 40 and having an HLA-identical sibling were assigned to undergo an allogeneic BMT. All the other patients received a first course of ICC with high-dose cytarabine and the same anthracycline as for induction. They were then randomly assigned to either receive a second course of ICC with amsacrine and etoposide or a combination of busulfan and cyclosphosphamide followed by an unpurged autologous BMT. Of 517 eligible patients, 367 had a CR, but only 219 (59.5%) actually received the planned intensive postremission treatment (73 allogeneic BMT, 75 autologous BMT, and 71 ICC). With a median follow-up of 62 months, the 4-year disease-free survival (DFS) of the 367 patients in CR was 39.5%. The 4-year overall survival (OS) of the 517 eligible patients was 40.5%. In multivariate analysis, DFS and OS were influenced only by the initial white blood cell count and by the French-American-British classification. The type of postremission therapy had no significant impact on the outcome. There was no difference in the 4-year DFS and OS between 88 patients for whom an allogeneic BMT was scheduled (respectively, 44% and 53%) and 134 patients of the same age category and without an HLA-identical sibling (respectively, 38% and 53%). Similarly, there was no difference in the outcome between autologous BMT and ICC. The 4-year DFS was 44% for the 86 patients randomly assigned to autologous BMT and 40% for the 78 patients assigned to ICC (P = .41). The 4-year OS was similar in the two groups (50% v 54.5%, P = .72). The median duration of hospitalization and thrombocytopenia were longer after autologous BMT (39 v 32 days, P = .006, and 109.5 v 18.5 days, P = .0001, respectively). After a first course of ICC, a second course of chemotherapy is less myelotoxic than an unpurged autologous BMT but yields comparable DFS and OS rates.

From May 1992 to November 1994, 240 patients with de novo acute myeloid leukemia (AML) and aged 55–75 years (median 68 years) were enrolled in a multicenter, double-blind randomized study comparing placebo and granulocyte-macrophage colony-stimulating factor (GM-CSF) (Escherichia coli derived) (5/µg/kg per day 6-h infusion) during induction chemotherapy (idarubicin 8 mg/m2 per day i.v. on days 1–5 plus cytarabine, ara-C, 100 mg/m2 per day continuous infusion on days 1–7) and until recovery of a neutrophil count > 0.5 x 109/1. Post-remission therapy was identical in the two arms. The two groups were comparable regarding the following parameters: age, sex, performance status, fever, organomegaly, initial blood cell counts, French-American-British (FAB) classification, presence of myelodysplastic features, and incidence of karyotypic abnormalities. Of the 209 patients currently evaluable, 130 (62%) achieved complete remission (CR) with no significant difference between patients aged 55–64 (57/90 = 63%) and patients aged 65 to 75 years (73/119 = 61%). There were 17 (8%) early deaths, 18 (9%) deaths in aplasia, and 45 (21%) failures. No significant difference was observed between the GM-CSF group (n = 103) and the placebo group (n = 106) regarding the CR rate (63% vs. 61%), the incidence of early deaths (10% vs. 6%), of deaths in aplasia (8% vs. 9%), and of failures (19% vs. 24%). The duration of neutropenia was shorter in the GM-CSF group (median 22 days vs. 26 days, p = 0.002). However, the incidence of febrile episodes and of bacteriemias and the duration of hospitalization was similar in the two groups. With a median follow up of 19 months, the overall survival of all eligible patients was similar in both groups (39% actuarial survival at 2 years in the GM-CSF group vs. 33% in the placebo group, p = 0.45 log-rank test). Nonetheless, the disease-free survival was longer for patients who achieved CR in the GM-CSF group (44% continuous CR rate at 2 years vs. 19%, p = 0.024). The study medication was prematurely stopped due to toxicity in 17 patients (14 GM-CSF, three placebo; p = 0.003). We conclude that (a) the induction treatment with idarubicin and conventional doses of ara-C obtains a high CR rate in elderly patients (b) the administration of GM-CSF during and after induction chemotherapy results in a faster recovery of neutrophils but does not reduce infectious toxicity and increases neither the efficacy of this chemotherapy nor the overall survival. However, the disease-free survival was significantly longer for patients who received GM-CSF before achieving CR.

Low-dose chemotherapy in myelodysplastic syndromes (MDS) gives overall limited results in high-risk MDS [1–3]. Intensive chemotherapy in MDS and secondary leukemias (i.e., acute myeloid leukemia, AML, following de novo or therapy-related MDS) gives lower complete remission (CR) rates and shorter CR duration than in de novo AML [4–11]. This may be due in part to a higher incidence of mdr gene expression in MDS than in de novo AML as mdr gene expression is associated in our experience, with very low CR rates with intensive chemotherapy [12]. These recent results suggested that the use of agents capable of reverting mdr gene expression could improve the CR rate in MDS and secondary leukemias.

The International Prognostic Index (IPI) is widely used to predict outcome of patients with aggressive lymphomas. Our goal was to assess the prognostic value of this index for low-grade lymphoma.One hundred eighty-two patients with disseminated (stage III or IV) low-grade lymphoma were enrolled in a prospective multicenter trial. According to the initial features, treatment either was started immediately or was deferred until indicated by disease progression. Patients received the same polychemotherapy regimen, given monthly for six cycles. They were assigned to one of four risk groups according to the number of presenting risk factors: low-risk (0 or 1), low-intermediate-risk (2), high-intermediate-risk (3), high-risk groups (4).Survival curves (Kaplan-Meier method) demonstrated a high significant difference for the four groups (log-rank: P0.0001). Median survival for the low-risk group has yet to be reached, while that for the three other groups are, respectively, 65, 34, and 12 months.In this study, the IPI has been found to be an important prognostic tool in low-grade lymphoma and may be used in the selection of appropriate therapeutic approaches for individual patients.

Intravenous immunoglobulin (IVIG) is currently used for an increasing number of indications where an immune-medicated disorder is suspected. It is considered as a safe and efficacious treatment but several cases of severe acute renal failure (ARF) have been described since 1987. We report four cases of IVIG-induced ARF and the literature on the subject is reviewed. The chronological and semiological characteristics of this rare adverse effect are analysed. A sudden and marked increase of serum creatinine within the 2 to 4 days following institution of IVIG therapy, especially when the patient becomes oligo-anuric, is very suggestive of IVIG renal toxicity. The recovery of renal function is often obtained in 10 to 15 days after discontinuation of the drug. Histological changes are characterized by osmotic nephrosis injuries. Patients generally presented numerous risk factors such as over 65 years, particularly in men, pre-existing renal disease, long-standing diabetes mellitus or hypertension, volume depletion, quick infusion rate, body-weight adjustment of IVIG doses in fat subjects. The mechanism of renal injury remains speculative but an oncotic overloading of kidney probably occurs. These results indicate the need for research and investigation of risk factors before starting IVIG therapy. Close monitoring of serum creatinine and diuresis should be carried out during and after treatment.

In this article clinical and neuroradiological features from a cohort of 48 immunocompetent patients who have a histologically proved primary cerebral lymphoma are considered. Our series consisted of 27 men and 21 women with an average age of 59. The clinical results gave 73% patients with a focal deficit, 46% with deterioration of vigilance, 35% intracranial hypertension, and only 8% with epilepsy, which was never revealing. We observed 4 uveitis of which 3 revealed, and preceded by several months, the neuroradiological manifestations. Histological classification using the criterias of the Working Formulation showed that 92% of our patients had a large cell lymphoma (class G or H). Precise analysis of computed tomography features of 40 patients revealed 46 lesions (most of them were isodense) before contrast medium administration. In all the cases, the lesion enhancement was intense and homogeneous. In 50% of the cases, there were multiple lesions. Sixty lesions were of the supra tentorial compartment, lobar in 32 cases, deep in 28 cases. Fifteen were infratentorial. From our experience, we can put forward the following suggestions: 1) Neuroradiological aspects suggesting primary cerebral lymphomas exist but none of them are specific. 2) Research of an uveitis is important, as this makes the histological diagnosis more simple. 3)The prescription of corticosteroids should be delayed until the histological diagnosis is certain because the primary cerebral lymphoma, which is very corticosensitive, is likely to disappear with this treatment and then change the biopsy results.

Haemophagocytic syndrome is a heterogenous disease characterized by disordered macrophage activation associated with viral, bacterial or parasitic infection. The few reports of haemophagocytosis occurring in the presence of mycobacterial infection show a high mortality rate and we present two further cases notable for their favourable issue. Rapidity of diagnosis and immediate treatment could explain the avoidance of a fatal outcome.

The first cases of Hodgkin's disease (HD) associated with HIV infection were reported in 1984. Since then, short series of seropositive patients suffering from HD have been published. In order to identify the characteristics, treatment response and outcome of HIV-associated Hodgkin's disease (HIV-HD), the data of HIV-HD patients recorded between 1987 and 1989 were analysed and compared with those of primary HD patient and with those of HIV-associated non-Hodgkin's lymphoma (HIV-NHL), registered during the same period.The 45 cases of HD collected by the French registry of HIV-associated tumors between January 1987 and December 1989 were included in this study. All patients were clinically staged according to the Ann Arbor system. To compare HIV-HD characteristics with those of primary HD, we used a cohort of 407 patients with clinical stages (CS) IA to IVB, who were enrolled between September 1981 and August 1988 in a multicentric clinical trial. To identify the relationship between HIV-HD and the course of HIV infection we studied, when available, the routes of infection, initial CD4 cell count at the moment of HD diagnostic as well as the CDC class of HIV infection and compared these data with the same parameters observed in 142 HIV-NHL enrolled in the registry during the same period.HIV-HD is characterized by an increase in mixed-cellularity histology (49%), with a predominance of advanced stages (75%) and B symptoms (80%). A unique observation is made regarding mediastinal involvement, present in only 13% of HIV-HD (71% in primary HD). The HIV-HD/HIV-NHL ratio was significantly higher in intravenous drug abusers than in male homosexuals. Median CD4 cell count was 306/microliters at HIV-HD diagnosis, and only 11% of the cases were preceded by an AIDS manifestation. With standard therapy, 79% of the patients achieved complete remission, but hematological and infectious complications were very frequent. The progression to AIDS rate was 94% at two years and opportunistic infections were the most frequent cause of death. Overall two-year survival was 41% with 71% for patients with initial CD 4 cell counts higher than 300/microliter and 0% for those with CD4 cell counts lower than 300/microliter (P0.01).HIV-HD has a particular clinico-pathological profile when compared to primary HD, with a predominance of mixed-cellularity type, a high frequency of advanced stages and a high proportion of patients without mediastinal involvement. Moreover, HIV-HD seems to occur preferentially in the group of subjects infected by needle sharing. Standard HD therapy seems to be efficient but excessively toxic.

the association of acute febrile neutrophilic dermatosis (Sweet's syndrome) with malignant haemopathies is well known and characterized by an usual lack of hyperleukocytosis: indeed, moderate neutropenia is often reported. However, cases of Sweet's syndrome in the agranulocytosis stage are exceptional (7 in the literature).We report the case of a woman with acute myeloblastic leukaemia who had presented with Sweet's syndrome in the phase of therapeutic aplasia during induction of treatment, in the absence of white blood cells transfusion or treatment with haematopoietic growth factor (GM CSF, GCSF).the physiopathology of Sweet's syndrome is unknown. Various mechanisms have been suggested, including immune reaction type III, increased interleukin-1 synthesis, increased chemotaxis of neutrophils, action of haematopoietic growth factors, iatrogenic effect of some drugs (e.g. cotrimoxazole, furosemide or minocycline). Yet none of these mechanisms involving circulating polymorphonuclears or their bone marrow precursors can explain the occurrence of Sweet's syndrome in the phase of agranulocytosis.the diagnosis of Sweet's syndrome must be considered in patients with agranulocytosis in order to avoid ineffective antibiotics and to initiate a corticosteroid therapy that will accelerate the cure of this benign dermatosis.

From May 1987 to July 1990, 45 cases of Hodgkin's disease (HD) were recorded by the French Registry of HIV-associated tumors. Thirty-nine patients were male and median age was 30 years. Twenty-two cases had mixed cellularity type (MC), 18 nodular sclerosis, two lymphocyte depletion and three were not classified. Thirty-four patients had advanced HD clinical stages (CS III and IV). Thirty-six patients (80%) presented with B symptoms. Bone marrow involvement was diagnosed in 12 patients. Mediastinal involvement was present in only 4/30 patients (12%). Risk groups for AIDS were homosexuality in 18 cases, intravenous drug abuse in 17, both in one, and other in nine cases. In 40 cases (89%), HD occurred before any AIDS-related episode. Median CD4 cell count at HD diagnosis was 304 cells/microliters. Seventy-nine percent of the patients achieved complete remission with standard therapy, but hematological and infectious complications were very frequent. The rate of progression to AIDS was 71% at three years and opportunistic infections (mainly pneumocystis carinii pneumonia) were the most frequent cause of death. Overall two-year survival was 41% (78% for patients with initial CD4 cell count higher than 300 cell/microliters and 0% for those with CD4 cell count lower than 300/microliters). HD-HIV has a specific clinical profile as compared to primary HD, with a predominance of MC type and advanced clinical stage, without mediastinal involvement (88%). This study provides a basis for future clinical trials on HD-HIV: intensity of chemotherapy should be adapted to CD4 cell count; pneumocystis carinii prophylaxis is mandatory in all cases. Zidovudine should be included during and after HD treatment; the potential role of hematological growth factors has still to be evaluated.

Primary CNS lymphoma is a rare entity. In the last few years, increasing numbers of reports have focused on the clinical, radiological and biological aspects of this tumor. The problem of the therapy of this particular localisation of lymphoma remains mostly unsolved. Radiotherapy still remains the standard approach. However, recent trials combining chemo and radiotherapy have shed promising light on a dark prognosis. These aspects are reviewed based on recent reports in the literature.

The authors report the case of a 66 year old man with a Boden stage I adenocarcinoma of the rete testis treated by orchiectomy and adjuvant chemotherapy. Lung metastases developed 46 months later and were responsible for death despite further chemotherapy. Adenocarcinoma of the rete testis is an exceptional tumour, as only 23 cases satisfying the criteria defined by Feek and Hunter have been reported in the literature. The prognosis is poor even in the apparently localized forms (5 year survival less than 25%) and local recurrences and lung and/or hepatic metastases are frequent. Radiotherapy and chemotherapy appear to have little value.

Primitive chondrosarcoma of the foot is rare. About 50 cases have been reported. It often poses diagnostic problems, and the confirmation of malignancy necessitates a broad resection. The tumor is radioresistant and chemotherapy is minimally effective, as illustrated by the present report.

We studied two cases of chronic myelogenous leukemia (CML) with unusual variant Philadelphia (Ph) translocation (22;22)(q11;q13). Southern blot analysis showed a chromosomal break in the BCR gene within the 5.8-kilobase (kb) breakpoint cluster region (bcr), between bcr exons 2 and 3 and between bcr exons 3 and 4, respectively. Chimeric bcr-abl mRNA was detected using polymerase chain reaction (PCR) which amplified, according to the respective bcr breakpoints, bcr exon 2-abl exon II and bcr exon 3-abl exon II junction products. These results further support the involvement, even when not cytogenetically detectable, of the 9q34 chromosomal region in all variant Ph translocations and that BCR-ABL gene fusion products are causally involved in the development of Ph positive CML.

We report a case history of a woman of 66 years of age who had a granulocytic sarcoma of the cervix which presented as metrorrhagia and which at first was thought to be an anaplastic cancer. The poor general state of the patient made it impossible to start any anti-leukaemic treatment and the patient died two months after the diagnosis was made. A review of the literature shows that 62 cases of granulocytic sarcoma have been reported of which 22 were in the breast, 19 in the ovary, 13 in the cervix or the uterus, 6 in the vagina and 2 in the vulva. The cells seem to invade the blood and the bone marrow in all occasions by the time of diagnosis or at the most a few weeks later and cases of granulocytic solitary sarcoma are very rare. It blood has not been attacked it is difficult to make a histological diagnosis unless immunological marking and Giemsa staining is carried out together with Leder's reaction. The treatment should be similar to those used for acute myeloid leukaemia.