High prevalence of syphilis in women, minors and precarious patients: a cross-sectional study in a Reunion Island sexually transmitted infection clinic, 2017-2020.

BACKGROUND: Syphilis is a sexually transmitted infection (STI) with a global prevalence estimated at 0.5% in 2012. Syphilis has been on the rise among men who have sex with men (MSM) in high-income countries and remains at endemic levels in low- and middle-income countries. This trend, however, has not been observed in Reunion Island. OBJECTIVES: To determine the prevalence, clinical characteristics and risk factors of syphilis in at-risk patients visiting the South Reunion STI clinic in Reunion Island. METHODS: This monocentric cross-sectional study included all patients who visited our STI clinic between 2017 and 2020. Syphilis serology was performed on all included patients, and data were collected using a standardized self-administered questionnaire. RESULTS: Over the 3-year study period, 2593 patients were enrolled. The prevalence of syphilis was 7.52% (n = 195, 95% CI, 6.50-8.65%) in the overall study population, 11.76% (n = 18, 95% CI, 6.97-18.59%) in minors (aged under 18 years) and 36.36% (n = 16, 95% CI, 21-59%) in pregnant women. The risk factors identified in multivariate analysis were being female [adjusted Prevalence Ratio (aPR) 1.85, 95% CI, 1.10-3.11], being MSM (aPR 2.87, 95% CI, 1.71-4.80), being aged under 18 years (aPR 3.54, 95% CI, 1.90-6.57), living in precarious conditions [aPR 3.12, 95% CI, 2.11-4.62] and being born in Reunion Island (aPR 2.43, 95% CI, 1.42-4.13). The clinical presentation was heterogeneous (plaques and papules, chancre, atypical ulcerations, multiple ulcerations, condyloma lata, etc.). CONCLUSIONS: These findings suggest a high prevalence of syphilis in at-risk patients visiting our STI clinic. Unlike the situation in other high-income countries, the people most at risk of syphilis in Reunion Island are local-born residents, minors, women and precarious patients. This is a source of concern, especially given the risk of resurgence of congenital syphilis on the island.

Prevalence of urogenital, anal, and pharyngeal infections with Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium: a cross-sectional study in Reunion island.

BACKGROUND: Recommendations for sexually transmitted infection (STI) screening vary significantly across countries. This study evaluated the prevalence of urogenital and extragenital infections with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Mycoplasma genitalium (MG) in patients visiting a French STI clinic in the Indian Ocean region to determine whether current STI screening practices should be updated. METHODS: This cross-sectional study examined all patients who visited the STI clinic between 2014 and 2015. Triplex polymerase chain reaction screening for CT, NG, and MG was performed on urine, vaginal, pharyngeal, and anal specimens (FTD Urethritis Basic Kit, Fast Track Diagnostics, Luxembourg). RESULTS: Of the 851 patients enrolled in the study, 367 were women (367/851, 43.2%) and 484 were men (484/851, 56.0%). Overall, 826 urogenital specimens (826/851, 97.1%), 606 pharyngeal specimens (606/851, 71.2%), and 127 anal specimens (127/851, 14.9%) were taken from enrolled patients. The prevalence of urogenital CT and MG was high in women ≤25 years (19/186, 10.21%; 5/186, 2.69%) and in men who have sex with women ≤30 years (16/212, 7.54%; 5/212, 2.36%). Among patients with urogenital CT infection, 13.7% (7/51) had urethritis. All patients with urogenital MG infection were asymptomatic. Men who have sex with men had a high prevalence of pharyngeal CT (2/45, 4.44%) and NG (3/44, 6.81%) and a high prevalence of anal CT (2/27, 7.41%), NG (2/27, 7.40%), and MG (1/27, 3.70%). After excluding patients with concomitant urogenital infection, extragenital infections with at least 1 of the 3 pathogens were found in 20 swabs (20/91, 21.9%) taken from 16 patients (16/81, 19.7%), all of them asymptomatic. CONCLUSIONS: Routine multisite screening for CT, NG, and MG should be performed to mitigate the transmission of STIs in high-risk sexually active populations.

Prospective validation of a new airway management algorithm and predictive features of intubation difficulty.

BACKGROUND: Some patients have features that indicate possible difficulty with direct laryngoscopy for tracheal intubation. Prediction of the likely outcome and selection of patients for an enhanced management algorithm would reduce the possible harm from failed intubation attempts. METHODS: Adult elective patients were assessed for seven features associated with difficult direct laryngoscopy, ranked in difficulty from 0 to 3. For a patient with at least one Class 3 feature, or two or more features of class 1 or higher, the enhanced management used a channelled videolaryngoscope Airtraq™ instead of a Macintosh laryngoscope. A long flexible angulated stylet and a flexible fibrescope would be used as the second and third steps. For patients with lesser difficulty scores, a Macintosh laryngoscope was used. Outcomes of enhanced management were analysed. Logistic regression and Random Forest algorithm, using the ranks of the predictive features, were used to predict difficulty during enhanced management. RESULTS: We prospectively studied 16 695 patients. We selected 1501 (9%) for enhanced management, and tracheal intubation was successful in all of them. Of these, 73% were intubated in less than 30 s, and only 4.5% required more than 4 min for intubation. Progression to the second and third steps of enhanced management was predicted by restriction of mouth opening and reduced cervical spine mobility. CONCLUSIONS: An enhanced management algorithm allowed successful tracheal intubation of all patients with anticipated difficult laryngoscopy. The need to combine the use of a stylet and a fibrescope with the Airtraq™ could be predicted with a high degree of certainty.

From phaeohyphomycosis to disseminated chromoblastomycosis: A retrospective study of infections caused by dematiaceous fungi.

OBJECTIVE: Infections caused by dematiaceous fungi are more common in tropical and subtropical areas. We aimed to describe the clinical, microbiological and therapeutic aspects of case patients diagnosed at a University Hospital located on an Indian Ocean island. PATIENTS AND METHODS: We performed an observational retrospective study of infections caused by dematiaceous fungi diagnosed at the University Hospital of Saint-Pierre, Reunion, from 2000 to 2015. Mycological identifications were performed at the National Reference Center for Invasive Mycosis and Antifungal Agents (Paris). RESULTS: The review of clinical and microbiological data of 11 patients identified revealed that five were infected by dematiaceous fungi. Two had cutaneous phaeohyphomycosis, two had cerebral phaeohyphomycosis and one had cutaneous chromoblastomycosis with brain and potentially medullary dissemination. Skin lesions and cerebral abscesses were quite varied. CONCLUSION: Infections caused by dematiaceous fungi are rare. Medullary and brain localizations are extremely rare, especially for chromoblastomycosis. Cutaneous manifestations of phaeohyphomycosis are varied; diagnosis is thus more difficult. It is therefore important, when confronted with a chronic tumor-like lesion in endemic areas, to perform a biopsy for pathology and fungal culture. While surgical excision is not always sufficient, medical treatment of these infections is not standardized, but relies on an azole, which can be associated with another antifungal agent.

Rheumatism and chronic fatigue, the two facets of post-chikungunya disease: the TELECHIK cohort study on Reunion island.

Prolonged fatigue is increasingly reported among chikungunya virus (CHIKV)-infected populations. We investigated the relationships between CHIKV exposure, long-lasting rheumatic musculoskeletal pain (LRMSP) and chronic fatigue. 1094 participants (512 CHIKV seropositive and 582 seronegative) of the TELECHIK population-based cohort were analysed considering the duration of the manifestations throughout an average 2-year follow-up. Weighted prevalence rates and prevalence ratios for LRMSP, idiopathic chronic fatigue (ICF), and chronic fatigue syndrome (CFS)-like illness, both latter syndromes adapted from Centers for Disease Control (CDC)-1994/Fukuda criteria, were compared. Population attributable fractions (PAF) were estimated to assess the contribution of CHIKV infection to each of the three phenotypes. Among 362 adult subjects who had reported either rheumatic pain or fatigue at the onset of the infection, weighted prevalence rates of LRMSP, ICF and CFS-like illness were respectively of 32.9%, 38.7% and 23.9%, and of 8.7%, 8.5% and 7.4% among initially asymptomatic peers (P < 0.01, respectively). Each of the three outcomes was highly attributable to chikungunya (PAF of 43.2%, 36.2% and 41.0%, respectively). In the sub-cohort of CHIKV-infected subjects, LRMSP, ICF and CFS-like illness, which overlapped in 70%, accounted for 53% of the chronic manifestations. In addition to rheumatic disease, chronic fatigue could be considered in caring for patients with chronic chikungunya disease.

Helicobacter pylori resistance to clarithromycin in Reunion Island.

OBJECTIVE: The increasing resistance of Helicobacter pylori to clarithromycin led to developing new eradication treatment regimens. The objective of our observational study was to determine the proportion of H. pylori strains resistant to clarithromycin in infected patients in Reunion Island and to suggest a first-line treatment in agreement with the local ecology. PATIENTS AND METHODS: We included 200 patients who underwent esophagogastroduodenoscopy at the University Hospital of Saint-Pierre from February to July 2014. H. pylori was isolated from 73 patients. RESULTS: A wild-type susceptibility profile to clarithromycin was observed in 64 isolates (87.7%) and nine isolates (12.3%) had a resistant mutation profile. CONCLUSION: With a proportion of resistant strains below the critical threshold of 15%, physicians in Reunion Island may continue to prescribe the usual treatment regimen as a first-line option (clarithromycin, amoxicillin, and proton pump inhibitor for 14 days).

ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥ 4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial.

BACKGROUND: Treatment with escalated BEACOPP achieved a superior time to treatment failure over ABVD in patients with disseminated Hodgkin lymphoma. However, recent clinical trials have failed to confirm BEACOPP overall survival (OS) superiority over ABVD. In addition, the gain in low-risk patients is still a matter of debate. PATIENTS AND METHODS: We randomly compared ABVD (8 cycles) with BEACOPP (escalated 4 cycles ≥ baseline 4 cycles) in low-risk patients with an International Prognostic Score (IPS) of 0-2. The primary end point was event-free survival (EFS). This parallel group, open-label phase 3 trial was registered under #RECF0219 at French National Cancer Institute. RESULTS: One hundred and fifty patients were randomized in this trial (ABVD 80, BEACOPP 70): 28 years was the median age, 50% were male and IPS was 0-1 for 64%. Complete remission rate was 85% for ABVD and 90% for BEACOPP. Progression or relapses were more frequent in the ABVD patients than in the BEACOPP patients (17 versus 5 patients). With a median follow-up period of 5.5 years, seven patients died: six in the ABVD arm and one in the BEACOPP arm (HL 3 and 0, 2nd cancer 2 and 1, accident 1 and 0). The EFS at 5 years was estimated at 62% for ABVD versus 77%, for BEACOPP [hazards ratio (HR) = 0.6, P = 0.07]. The progression-free survival (PFS) at 5 years was 75% versus 93% (HR = 0.3, P = 0.007). The OS at 5 years was 92% versus 99% (HR = 0.18, P = 0.06). CONCLUSION: Fewer progressions/relapses were observed with BEACOPP, demonstrating the high efficacy of the more intensive regimen, even in low-risk patients. However, additional considerations, balancing treatment-related toxicity and late morbidity due to salvage may help with decision-making with regard to treatment with ABVD or BEACOPP.

Deletion of the 1p32 region is a major independent prognostic factor in young patients with myeloma: the IFM experience on 1195 patients.

Deletions of the 1p region appear as a pejorative prognostic factor in multiple myeloma patients (especially 1p22 and 1p32 deletions) but there is a lack of data on the real impact of 1p abnormalities on an important and homogeneous group of patients. To address this issue we studied by fluorescence in situ hybridization (FISH) the incidence and prognostic impact of 1p22 and 1p32 deletions in 1195 patients from the IFM (Institut Francophone du Myélome) cell collection. Chromosome 1p deletions were present in 23.3% of the patients (271): 15.1% (176) for 1p22 and 7.3% (85) for 1p32 regions. In univariate analyses, 1p22 and 1p32 appeared as negative prognostic factors for progression-free survival (PFS): 1p22: 19.8 months vs 33.6 months (P<0.001) and 1p32: 14.4 months vs 33.6 months (P<0.001); and overall survival (OS): 1p22: 44.2 months vs 96.8 months (P=0.002) and 1p32: 26.7 months vs 96.8 months (P<0.001). In multivariate analyses, 1p22 and 1p32 deletions still appear as independent negative prognostic factors for PFS and OS. In conclusion, our data show that 1p22 and 1p32 deletions are major negative prognostic factors for PFS and OS for patients with MM. We thus suggest that 1p32 deletion should be tested for all patients at diagnosis.

Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials.

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.

Clinical and pharmacokinetic phase II study of fotemustine in refractory and relapsing multiple myeloma patients.

BACKGROUND: Patients with relapsing or refractory multiple myeloma have poor prognosis. Few compounds are active in these patients and response duration remains short. We report the results of an open phase II trial evaluating the efficacy and safety of fotemustine monotherapy. PATIENTS AND METHODS: Twenty-one patients with relapsing (17) or refractory (four) multiple myeloma received fotemustine 100 mg/m(2) on an outpatient basis on days 1 and 8 of the induction cycle, followed after a 6-week rest period by fotemustine 100 mg/m(2) every 3 weeks until progression or unacceptable toxicity. Fotemustine pharmacokinetics during the first day of induction was compared between patients with normal or abnormal renal function. RESULTS: Five of 20 eligible patients had an objective response giving an intention-to-treat response rate of 25% [95% confidence interval (CI) 6% to 44%] and a 35.7% response rate (95% CI 11% to 61%) in the 14 patients having received at least four injections of fotemustine. The median time to objective response was 8.9 months. The median times to progression and survival were 13.8 and 23.1 months, respectively, with a 2-year survival rate of 49%. The main toxicity was myelosuppression with grade 3-4 neutropenia and thrombocytopenia in 66% and 71% of patients, respectively. There was one toxic death by sepsis after induction. The pharmacokinetic parameters in renal-impaired patients were not significantly different from those in patients with normal renal function with a similar incidence of grade 3-4 toxicity in both groups. CONCLUSIONS: Fotemustine as a single agent has definite activity in patients with relapsing or refractory multiple myeloma, with acceptable toxicity and can be administered at conventional doses in patients with mild or moderate renal impairment.

Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients.

To comparatively assess first-line treatment with fludarabine and 2 anthracycline-containing regimens, namely CAP (cyclophosphamide, doxorubicin plus prednisone) and ChOP (cyclophosphamide, vincristine, prednisone plus doxorubicin), in advanced stages of chronic lymphocytic leukemia (CLL), previously untreated patients with stage B or C CLL were randomly allocated to receive 6 monthly courses of either ChOP, CAP, or fludarabine (FAMP), stratified based on the Binet stages. End points were overall survival, treatment response, and tolerance. From June 1, 1990 to April 15, 1998, 938 patients (651 stage B and 287 stage C) were randomized in 73 centers. Compared to ChOP and FAMP, CAP induced lower overall remission rates (58.2%; ChOP, 71.5%; FAMP; 71.1%; P <.0001 for each), including lower clinical remission rates (CAP, 15.2%; ChOP, 29.6%; FAMP, 40.1%; P =.003). By contrast, median survival time did not differ significantly according to randomization (67, 70, and 69 months in the ChOP, CAP, and FAMP groups, respectively). Incidences of infections (< 5%) and autoimmune hemolytic anemia (< 2%) during the 6 courses were similar in the randomized groups, whereas fludarabine induced, compared to ChOP and CAP, more frequent protracted thrombocytopenia (P =.003) and less frequent nausea-vomiting (P =.003) and hair loss (P <.0001). For patients with stage B and C CLL first-line fludarabine and ChOP regimens both provided similar overall survival and close response rates, and better results than CAP. However, there was an increase in clinical remission rate and a trend toward a better tolerance of fludarabine over ChOP that may influence the choice between these regimens as front-line treatments in patients with CLL.

Response of a scleractinian coral, Stylophora pistillata, to iron and nitrate enrichment.

The purpose of this study was to determine whether the addition of iron alone or in combination with nitrate affects growth and photosynthesis of the scleractinian coral, Stylophora pistillata, and its symbiotic dinoflagellates. For this purpose, we used three series of two tanks for a 3-week enrichment with iron (Fe), nitrate (N) and nitrate+iron (NFe). Two other tanks were kept as a control (C). Stock solutions of FeCl(3) and NaNO(3) were diluted to final concentrations of 6 nM Fe and 2 &mgr;M N and continuously pumped from batch tanks into the experimental tanks with a peristaltic pump. Results obtained showed that iron addition induced a significant increase in the areal density of zooxanthellae (ANOVA, p=0.0013; change from 6.3+/-0.7x10(5) in the control to 8.5+/-0.6x10(5) with iron). Maximal gross photosynthetic rates normalized per surface area also significantly increased following iron enrichment (ANOVA, p=0.02; change from 1.23+/-0.08 for the control colonies to 1.81+/-0.24 &mgr;mol O(2) cm(-2) h(-1) for the iron-enriched colonies). There was, however, no significant difference in the photosynthesis normalized on a per cell basis. Nitrate enrichment alone (2 &mgr;M) did not significantly change the zooxanthellae density or the rates of photosynthesis. Nutrient addition (both iron and nitrogen) increased the cell-specific density of the algae (CSD) compared to the control (G-test, p=0.3x10(-9)), with an increase in the number of doublets and triplets. CSD was equal to 1.70+/-0.04 in the Fe-enriched colonies, 1.54+/-0.12 in the N- and NFe-enriched colonies and 1.37+/-0.02 in the control. Growth rates measured after 3 weeks in colonies enriched with Fe, N and NFe were 23%, 34% and 40% lower than those obtained in control colonies (ANOVA, p=0.011).

[Hodgkin disease of the palatine tonsil. Clinical, histological, immunophenotype study and association with Epstein-Barr virus]. / Maladie de Hodgkin de l'amygdale palatine. Etude clinique, histologique, immunophénotypique et association avec le virus d'Epstein-Barr.

OBJECTIVE: To characterize clinical, histological and immuno-phenotypical features of a rare Hodgkin's disease presentation. METHODS: Retrospective analysis of three personal cases of Hodgkin's disease of the tonsil and a review of the literature. RESULTS: The clinical presentation was localized in the tonsil in all three cases. Age at onset was over 40 years in all patients. Symptoms were typical. A mixed cellularity histological type was found in all 3 instances. Reed-Sternberg cells stained positively with anti-CD30 and anti-CD15 monoclonal antibodies as well as with an anti-Epstein-Barr virus (EBV) specific monoclonal antibody. All 3 patients are currently in complete remission although for a short period of time (35, 20 and 15 months). CONCLUSION: This small series illustrates the main characteristics of this rare Hodgkin's disease presentation. Age at onset was older than the average for this disease which might explain the predominance of the mixed cellularity histologic subtype and the tighter linkage to EBV, although the rarity of such a presentation could raise some doubts about the EBV linkage. Prognosis of this unusual presentation does not appear to be different from that for more common presentations.

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.

Follicular large-cell lymphoma treated with intensive chemotherapy: an analysis of 89 cases included in the LNH87 trial and comparison with the outcome of diffuse large B-cell lymphoma. Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: The aims of this study were as follows: (1) to analyze clinical, histopathologic characteristics, treatment outcome, and prognostic factors of patients with follicular large-cell lymphoma (FLCL); and (2) to compare them with those of patients with diffuse large B-cell lymphoma (DLCL) treated in the same therapeutic trial. PATIENTS AND METHODS: Eighty-nine FLCL patients who were histologically reviewed and who received an intensive chemotherapy regimen according to the LNH 87 protocol were analyzed and compared with 1,096 B-cell DLCL patients included in the same protocol. RESULTS: After intensive induction treatment, 59 patients (67%) achieved a complete remission [CR]. Estimated 5-year survival was 59%, and estimated 5-year freedom from progression (FFP) was 39%. Prognostic factors associated with shorter FFP were age greater than 60 years (P = .02), advanced clinical stage (P = .01), abnormal lactic dehydrogenase (LDH) level (P = .02), abnormal beta-2 microglobulin (P = .02), B symptoms (P = .03), bone marrow involvement (P = .04), and high expression of bcl-2 protein (P = .05). When compared with B-cell DLCL patients, FLCL patients were younger (P = .02), had a better Eastern Cooperative Oncology Group (ECOG) status (P = .05), less bulky mass (P = .04), more advanced clinical stages (P < .001), and more bone marrow involvement (P = .02). No significant difference was observed between FLCL and DLCL patients for response to therapy (67% v 67% of CR), 5-year overall survival (58% v 51%), 5-year disease-free survival (53% v 57%), or FFP survival (39% v 43%). CONCLUSION: FLCL patients have a favorable response rate and survival when treated with intensive chemotherapy. Their outcome is similar to that of B-cell DLCL patients, and a long-term FFP is observed for a substantial number of patients. Some adverse prognostic factors (including those of the International Prognostic Index, bone marrow involvement, and beta-2 microglobulin) have been identified to define a subset of patients who require other therapeutic approach.

[Follow-up of allogenic bone marrow graft with DNA polymorphisms. Use of two minisatellite MS31 and MS43 probes. Comparison with data of chromosomal polymorphisms]. / Suivi de greffe allogénique de moelle osseuse par les polymorphismes de l'ADN. Utilisation de deux sondes minisatellites MS 31 et MS 43. Comparaison avec les données des polymorphismes chromosomiques.

OBJECTIVES: Allogenic bone marrow transplantation is widely used to treat many diseases of the haemopoietic system as well as metabolic disorders. Follow-up is essential to assess acceptance, rejection or post-graft relapse. This study was undertaken to evaluate the usefulness of the minisatellite probes MS31 and MS43 used as a routine follow-up test after bone marrow transplantation. METHODS: Twenty receivers of allogenic bone marrow transplants were followed-up. Two monoclonal minisatellite probes, MS31 and MS43, were used for comparison with the classical polymorphism methods. RESULTS: Fourteen cases of total chimeras, 3 cases of rejections and 3 cases of mixed chimeras were observed with the molecular probe techniques. In 19 of the 20 cases, this technique gave results compatible with classical polymorphism results. CONCLUSIONS: The minisatellite probes MS31 and MS43 were found to be sensitive, effective tests for bone marrow transplants which can be used in routine follow-up.

Timed sequential chemotherapy for previously treated patients with acute myeloid leukemia: long-term follow-up of the etoposide, mitoxantrone, and cytarabine-86 trial.

PURPOSE: To confirm and extend encouraging preliminary results of timed sequential chemotherapy (TSC) in patients with previously treated acute myelogenous leukemia (AML). PATIENTS AND METHODS: We report the results of the regimen of mitoxantrone on days 1 to 3, etoposide on days 8 to 10, and cytarabine on days 1 to 3 and 8 to 10 (EMA) in 133 patients, with a median follow-up of 40 months. RESULTS: Sixty percent of patients, with a 95% confidence interval (CI) ranging from 51% to 68%, achieved complete remission (CR), including 44% (CI, 32% to 57%) of refractory patients and 76% (CI, 64% to 86%) of late first-relapse patients (P = .0002). Twenty-nine percent of patients did not respond to therapy, and 11% died from toxicity. Median duration of neutropenia and thrombocytopenia was 31 days and 29 days, respectively. Severe nonhematologic toxicity included sepsis in 54% of patients and mucositis in 23%. Postinduction therapy included a second course of EMA in 27 patients, maintenance in 10, autologous bone marrow transplantation (BMT) in 12, and allogeneic BMT in 13. Median survival of patients who did not have transplantation performed is 7 months, with 11% (CI, 4% to 18%) survival at 5 years. Median disease-free survival (DFS) is 8 months with 20% (CI, 8% to 32%) DFS at 5 years. Twenty-eight percent (CI, 15% to 44%) of nontransplanted patients who achieved CR had an inversion of CR duration. Previous refractoriness was the main factor associated with poor prognosis for CR achievement, DFS, and survival. CONCLUSION: These results confirm initial reports on TSC and show that approximately 20% of patients with first relapse after therapy can enjoy prolonged DFS using chemotherapy only.

Prospective genetically randomized comparison between intensive postinduction chemotherapy and bone marrow transplantation in adults with newly diagnosed acute myeloid leukemia.

PURPOSE: To compare intensive chemotherapy and HLA-identical allogeneic bone marrow transplantation (BMT) as postinduction therapy in young adults with acute myeloid leukemia (AML). PATIENTS AND METHODS: Seventy-eight consecutive AML patients younger than 40 years of age were treated according to a prospective protocol in which every patient in complete remission (CR) with an HLA-identical sibling was scheduled to receive BMT rather than intensive chemotherapy consolidation. To minimize comparison biases, the availability or not of an HLA-identical sibling donor was considered to be the equivalent of genetic randomization to the BMT or chemotherapy arm, respectively. RESULTS: Fifty-eight patients (74%) achieved a CR. A donor was found for 27 patients (BMT arm), and 20 of these patients were actually transplanted in first CR. The 31 patients without a donor were allocated to the chemotherapy arm. Patients in the two arms had similar disease characteristics at diagnosis and previous responses to induction therapy. The cumulative risk of relapse was 43% +/- 24% in the BMT arm and 67% +/- 19% in the chemotherapy arm (P = .01). The 7-year leukemia-free survival (LFS) rate was 41% +/- 20% in the BMT arm and 27% +/- 16% in the chemotherapy arm, a difference that is not statistically significant between the two arms. The overall survival rates were 41% +/- 20% and 46% +/- 19%, respectively. CONCLUSION: In this study, the availability of an HLA-identical sibling donor was not associated with a better survival rate because of both the impossibility of some patients with a donor to receive BMT and the more efficient salvage treatment of patients who relapsed after intensive consolidation chemotherapy than of patients who relapsed after BMT.

Trisomy 12 in B-cell chronic lymphocytic leukemia: interphase study by in situ hybridization in 75 patients.

Trisomy 12 is the most common cytogenetic abnormality in chronic lymphocytic leukaemia (CLL) and may be a prognostic indicator. In the present study, fluorescence in situ hybridization (FISH) is shown to be a method of choice for detection of trisomy 12 in interphase cells. Seventy-five cases of B-cell CLL were analysed with a chromosome 12 specific alpha satellite DNA probe and results compared with those from cytogenetic analysis. FISH showed the three hybridization spots characteristic of trisomy 12 in 32/75 patients (42.6%). Sixty-three patients were also studied by conventional cytogenetics: failure in 7 cases, normal karyotype in 28, trisomy 12 in 9 (14.3%) and in 19 cases abnormalities other than trisomy 12. In these same 63 patients, trisomy 12 was detected on 29 occasions by FISH (46%): in one case of failure by cytogenetic analysis, in 9 cases thought to have a normal karyotype, in 10 cases carrying abnormalities other than trisomy 12 and in all 9 cases showing trisomy 12 by conventional cytogenetic investigation. Correlation between trisomy 12 and the three stages of the Binet classification indicated an increasing proportion of trisomy 12 from stage A to stage C. It is concluded that fluorescence in situ hybridization is a powerful and sensitive technique for detection of trisomy 12 in CLL and although more cases will be required to confirm a correlation between the incidence of trisomy 12 and the stage of the disease, this link could be important from a prognostic point of view.

[Acquired hypogammaglobulinemia and multifocal granulomatosis]. / Hypogammaglobulinémie acquise et granulomatose multifocale.

In adult acquired hypogammaglobulinaemia multi focal granulomas have often been described and have regularly led to the hypothesis of an association with sarcoidosis. We present a case of this type in a man aged 29 who was a smoker with a hypoglobulinaemia involving IgG, IgA and IgM and which was discovered following pneumococcal pneumonias. He presented with a significant hepatosplenomegaly and absent cutaneous reactions to T dependent antigens with an elevated ACE activity. Histological examination of the splenectomy specimen and of the liver biopsy showed an infiltration by epithelioid follicles and confluent giant cells without necrosis. The pulmonary studies showed a normal chest radiograph but the bronchial biopsy again found a granulomatous infiltration. The broncho-alveolar lavage was cytologically normal and a very slight and paradoxical reduction of the alveolar immunoglobulins was noted implying either an active intra-alveolar concentration of immunoglobulins or a local synthesis. In the light of the few reported cases it seems that the diagnosis of sarcoidosis should be dismissed here in favour of multi focal granulomatosis with hypogammaglobulinaemia. In hypogammaglobulinaemia there is no clinical or biological method (IDR tuberculin, ACE, Kveim, histology) to confirm a superadded diagnosis of sarcoidosis.