International open trial of uniform multi-drug therapy regimen for 6 months for all types of leprosy patients: rationale, design and preliminary results

Objective To describe the rationale, design and preliminary results of an open trial of 6 months uniform multi‐drug therapy (U‐MDT) for all types of leprosy patients assuming a cumulative relapse rate not exceeding 5% over 5 years of follow‐up. Methods We intended to recruit 2500 patients each in multi‐bacillary (MB) and pauci‐bacillary (PB) groups from India (five centres) and China (two centres). Standardized clinical criteria were used to assess skin lesions in the field. Results A total of 2912 patients enrolled from November 2003 to May 2007 (India, 2746; China, 166). MB patients constituted 39% and 3% had grade 2 disability. During follow‐up, 27 patients (0.9%) developed new lesions. Of these, 78% were on account of reactions. Six patients had clinically confirmed relapse. Clofazimine‐related skin pigmentation was short‐lived and was acceptable to patients. We analysed data for clinical status of skin lesions. About 2.9% of patients were lost to follow‐up; 85.9% completed treatment, of whom 19% had inactive skin lesions. PB patients responded better than MB patients (27%vs. 6%; P < 0.001). At the end of the first (n = 2013) and second year (n = 807) of follow‐up post‐U‐MDT, in 49% and 46% patients, lesions were inactive, respectively (59% and 57% in PB, 37% and 28% in MB; P < 0.001). Conclusion U‐MDT appears to be promising with respect to clinical status of skin lesions.     

Studies on risk of leprosy relapses in China: relapses after treatment with multidrug therapy

Based upon the data from the Chinese National System for Leprosy Surveillance, this paper reports on the relapses in 47,276 leprosy patients cured by or released from WHO-recommended multidrug therapy (WHO/MDT). The overall relapse rate was 0.73/1000 patient-years (PY). There was a statistically significant difference in the relapse rates of WHO/MDT-MB (0.61/1000 PY) and WHO/MDT-PB (1.04/1000 PY) (chi 2 = 15.7, p < 0.01) patients. For multibacillary (MB) patients, the relapse rate in patients treated with fixed-duration MDT (0.56/1000 PY) was comparable with that in patients treated with MDT until skin-smear negativity (0.73/1000 PY) (chi 2 = 2.20, p > 0.05). Our present study suggests that fixed-duration MDT is a cost-effective regimen for the treatment of leprosy in China. The present results also show that relapse of leprosy is acceptably low and has not yet become a serious clinical or public health problem but, based upon the incubation of relapse in MDT patients, it is necessary to encourage annual follow up for at least 5 years for paucibacillary (PB) and 10 years for MB patients after being released from WHO/MDT.     

Relapses among leprosy patients treated with multidrug therapy: experience in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia; practical difficulties with diagnosing relapses; operational procedures and criteria for diagnosing relapses.

Multidrug therapy (MDT), according to the recommendations of a WHO Study Group of 1982, was introduced in the leprosy control program of the All African Leprosy and Rehabilitation Training Center (ALERT), Ethiopia, in January 1983. Paucibacillary (PB) patients are treated with 6 months of MDT. Multibacillary (MB) patients are treated with at least 2 years of MDT and until skin-smear negativity. An analysis was made of the relapses which had been diagnosed among self-reporting patients in four rural districts and Addis Ababa. Among 3065 PB patients, 34 relapses (1.1%) were diagnosed during an average period of 6.1 years after stopping MDT (range 2 1/2 to 7 1/2 years). Among 2379 MB patients, 24 relapses (1.0%) were diagnosed during an average period of 4.7 years after stopping MDT (range 2 1/2 to 6 years). The estimated relapse rate per 1000 patient-years after release from MDT was 2.1 for PB patients and 2.4 for MB patients. From the analysis of the clinical, bacteriological, and histopathological findings, it was concluded that there was strong positive evidence for the diagnosis for 16 of the 34 relapses in the PB patients and for 0 of the 24 relapses in the MB patients. The main cause for overdiagnosis of MB relapses was that too much reliance had been put on skin-smear results, without a careful comparison of the results with those from before, during, and at completion of MDT; the diagnosis was based on the finding of positive smears in one set of smears only; insufficient attention was given to finding solid-staining bacilli; and findings in biopsies, if these were examined, did not confirm the diagnosis. The main cause of overdiagnosis of PB relapses was that too much reliance was put on histological findings, while these are often inconclusive for differentiating between a relapse and late reversal reaction. Recommendations are made on how to limit overdiagnosis of relapses. Operational procedures and criteria for making the diagnosis under conditions where facilities for back-up histological and mouse foot pad investigations are not available are proposed.     

Relapses in leprosy patients after release from dapsone monotherapy; experience in the leprosy control program of the all Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia.

Before implementation of multidrug therapy (MDT), leprosy patients who were clinically inactive, skin-smear negative and had been treated with dapsone monotherapy for at least 5 years (paucibacillary patients) or for at least 10 years (multibacillary patients) were released from treatment. An analysis was made of self-reporting relapses in 1081 paucibacillary (PB) patients and 1123 multibacillary (MB) patients who had been released in Addis Ababa and two rural districts of the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT). During an average period of 6.6 years after stopping dapsone, 44 relapses were diagnosed among the PB patients and 148 relapses among the MB patients. The overall relapse rate was 4.1% or 7.2 per 1000 patient-years after release from treatment for PB patients and 13.2% and 24.8, respectively, for MB patients. The annual relapse rate in PB patients did not differ significantly from year to year. However the relapse rate for MB patients was significantly lower during the fifth to seventh years after stopping treatment compared with the first 4 years. Based on clinical findings there was a strong suspicion of relapse with dapsone-resistant bacilli in 40.4% of MB relapses. It is concluded that the relapse rate for PB patients is acceptable. However, the relapse rate for MB patients is considered too high. It is strongly recommended to administer to all MB patients, including those who have been on long-term treatment with dapsone and have become clinically and bacteriologically inactive, a 2-year course of MDT.     

Stringent cessation criterion results in better durability of lamivudine treatment: a prospective clinical study in hepatitis B e antigen‐positive chronic hepatitis B patients

Summary. The cessation criteria for lamivudine treatment vary in published articles and their results are contradictory, especially factors predicting relapse. To clarify these contradictions, this long‐term follow‐up study of 125 Chinese hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B patients was designed with stringent cessation criterion. All patients received lamivudine and achieved HBeAg seroconversion (group A, n = 82) or loss (group B, n = 43) with undetectable hepatitis B virus (HBV) DNA by PCR assay during the treatment. Lamivudine was withdrawn ≥6 months after HBeAg seroconversion/loss occurred. The median treatment durations were 24 (12–54) months and 36 (18–89) months in group A and group B, respectively. Patients were followed up for median 24 (2–84) months. The cumulative relapse (defined as serum HBV DNA ≥10⁴ copies/mL) rates in the two groups at months 12, 24, 36 and 48 were 23.4%vs 35.0%, 25.0%vs 37.7%, 25.0%vs 41.1% and 29.4%vs 41.1%, respectively (log‐rank test, P = 0.119). For patients whose total treatment duration ≥18 months in group A, the cumulative relapse rates at months 12, 24, 36 and 48 were 18.3%, 20.1%, 20.1% and 25.1%, which was significantly lower than those with a shorter duration (log‐rank test, P = 0.002). The mean age and median total duration were statistically different between relapsers and nonrelapsers in group A (33.9 ± 13.6 vs 23.1 ± 11.0 years, P < 0.001 and 24 vs 26 months, P = 0.003). Cox regression revealed that age was the only predictive factor for relapse (RR, 1.069; 95% CI, 1.032–1.106, P < 0.001). Patients aged <30 years relapsed less frequently in 5 years (12.3%vs 53.5%, P = 0.001). In conclusion, for patients who maintained HBeAg seroconversion for ≥6 months and total duration for ≥18 months, lamivudine withdrawal is a reasonable option. Prolonged treatment may be required for patients aged greater than 30 years to reduce relapse.     

Long-term efficacy of 2 year WHO multiple drug therapy (MDT) in multibacillary (MB) leprosy patients

Relapse rate estimates after 2 year WHO multiple drug therapy (MDT) in multi-bacillary (MB) leprosy vary. Between 1987 and 1994, 500 MB leprosy patients completing 2 year MDT were enrolled in a prospective relapse study. The majority of patients (N = 316) were treated and followed at the physician-staffed Cebu Skin Clinic (CSC), whereas others (N = 184) received therapy from government clinics and were followed by CSC technicians in the field. Relapse definition was an increased bacteriologic index (BI) and new skin lesions, supplemented with mouse footpad inoculations. Through 2002, follow-up was 5368 person-years, with a mean of 10.8 years per patient. The absolute relapse rate was 3% (15/498; 0.28/100 person-years), with a cumulative risk estimate of 3.9% at 15 yrs. For a subset of 217 patients followed for >or=12 yrs or until relapse, relapses occurred in 9% (13/142) attending the CSC, versus 3% (2/75) assessed in the field (p = 0.09). The rate for patients followed at CSC for >or=12 yrs and a pre-treatment BI >or=2.7+ was 13% (13/98). All relapses were BL or LL, with pre-treatment BI's of >or=2.7+. Relapses occurred long after completion of therapy, between 3 and 11 yrs from the midpoint of the examination without relapse to detection, or between 6 to 13 yrs to the actual year of detection, 7 occurring at >or=10 yrs. Lesion material from all relapses contained M. leprae that was rifampin and clofazimine sensitive, whereas 3 showed partial or full dapsone resistance. [Follow-up rigor and time], medical expertise, and pre-treatment bacterial load influence relapse rates after 2 yr MDT.     

Relapses in paucibacillary leprosy after MDT--a clinical study

A study was undertaken in a field-based project to assess the incidence and clinical profile of relapses occurring in paucibacillary leprosy patients after adequate doses of multidrug therapy (MDT). Of the 1509 paucibacillary patients who had received not less than 6 doses of MDT (WHO regimen), 85 relapsed; a relapse rate of 5.63% (17.5/1000 person years at risk). These relapses included 12 cases with features of reversal reaction. Seventy-nine percent of the patients relapsed with skin lesions. The relapse rate was higher in borderline cases and in those with more lesions, and it was lower in those who had received dapsone for at least 6 months after cessation of MDT. Seventy-four percent of the relapses were detected between 7 and 24 months of follow up. We feel that uniform clinical criteria should be formulated for the diagnosis of relapse. Individualization of therapy, rather than adhering to a fixed duration of MDT, would be likely to achieve satisfactory cure rates and fewer relapses.     

Role of routine imaging in detecting recurrent lymphoma: A review of 258 patients with relapsed aggressive non‐Hodgkin and Hodgkin lymphoma

After first‐line therapy, patients with Hodgkin lymphoma (HL) and aggressive non‐HL are followed up closely for early signs of relapse. The current follow‐up practice with frequent use of surveillance imaging is highly controversial and warrants a critical evaluation. Therefore, a retrospective multicenter study of relapsed HL and aggressive non‐HL (nodal T‐cell and diffuse large B‐cell lymphomas) was conducted. All included patients had been diagnosed during the period 2002–2011 and relapsed after achieving complete remission on first‐line therapy. Characteristics and outcome of imaging‐detected relapses were compared with other relapses. A total of 258 patients with recurrent lymphoma were included in the study. Relapse investigations were initiated outside preplanned visits in 52% of the patients. Relapse detection could be attributed to patient‐reported symptoms alone or in combination with abnormal blood tests or physical examination in 64% of the patients. Routine imaging prompted relapse investigations in 27% of the patients. The estimated number of routine scans per relapse was 91–255 depending on the lymphoma subtype. Patients with imaging‐detected relapse had lower disease burden (P = 0.045) and reduced risk of death following relapse (hazard ratio = 0.62, P = 0.02 in multivariate analysis). Patient‐reported symptoms are still the most common factor for detecting lymphoma relapse and the high number of scans per relapse calls for improved criteria for use of surveillance imaging. However, imaging‐detected relapse was associated with lower disease burden and a possible survival advantage. The future role of routine surveillance imaging should be defined in a randomized trial. Am. J. Hematol. 89:575–580, 2014. © 2014 Wiley Periodicals, Inc.     

Histological features associated with relapse after corticosteroid withdrawal in type 1 autoimmune hepatitis

Abstract: Relapse of type 1 autoimmune hepatitis after drug withdrawal may relate to incomplete histological improvement during corticosteroid therapy and/or persistence of pathogenic mechanisms. Aim: Determine the histological features prior to drug withdrawal that are associated with relapse in patients satisfying pre‐established clinical, laboratory, and histological criteria for remission and relapsing after corticosteroid withdrawal. Methods: One hundred liver tissue samples obtained immediately prior to corticosteroid withdrawal from 88 patients who had previously satisfied criteria for histological remission were reviewed retrospectively. Results: Histological findings in the patients who relapsed were similar to those in the patients who sustained remission in regard to histological activity index (1.7 ± 0.1 versus 1.6 ± 0.2, P = 0.6), fibrosis score (2.6 ± 0.3 versus 2.3 ± 0.4, P = 0.5), and frequencies of interface hepatitis (36% versus 20%, P = 0.2), cirrhosis (21% versus 17%, P = 0.8), and normal or near normal tissue (9% versus 7%, P > 0.9). Only the presence of portal plasma cells was associated with relapse (31% versus 7%, P = 0.01). The positive predictability of portal plasma cell infiltration for relapse was 92%, but its sensitivity was only 31%. Conclusions: Portal plasma cell infiltration is predictive of relapse after drug withdrawal in tissue specimens already satisfying criteria for remission. Portal plasma cell infiltration may be indicative of an active antibody‐dependent pathogenic mechanism. Its low sensitivity for relapse indicates the need for other complementary predictors of outcome.     

Relapse of aplastic anaemia after immunosuppressive treatment: a report from the European Bone Marrow Transplantation Group SAA Working Party

Summary This study was designed to determine the incidence of relapse and factors predictive for relapse in 719 patients with severe aplastic anaemia (SAA) after immunosuppressive treatment (IS). Patients developing myelodysplasia or acute leukaemia after IS, and patients receiving a transplant, were excluded from this analysis. Response was defined as reaching complete independence from transfusions, relapse was defined as becoming again transfusion dependent. This criteria was validated by similar figures when using other ‘relapse criteria’ such as drop in neutrophil or platelet counts. Of 358 patients responding to IS, 74 patients relapsed after a mean time of 778 d after treatment. The actuarial incidence of relapse is 35.2% at 14 years after IS. The risk for relapse was higher in patients responding within 120 d from IS (48%) compared to patients responding between 120 and 360 d (40%) and only 20% for slow responders (>360d from IS) (P<0.00001). In multivariate analysis this factor still proved significant (P<0.0001). The mean time between diagnosis and treatment was significantly longer in patients relapsing compared to patients who did not relapse (260 v 134 d, P=0.037). Relapse was not predicted by the severity of the disease, age, and sex. In 39 of the 74 relapsing patients a second response could be achieved. Responses after relapse were associated in univariate analysis with early response to previous IS and early occurrence of relapse. The actuarial survival of patients not relapsing is significantly better than survival of patients relapsing (79.8%v 67.1%, P = 0.0024). However, the actuarial survival of 39 relapsing patients who responded again to IS was similar to patients not relapsing (86%) and significantly better than in 35 patients not reaching a second response after relapse (49.3%, P=0.0015). This study indicates that relapse is a relevant problem in the treatment of aplastic anaemia, and does have an impact on overall survival. Prospective studies of immunosuppressive regimens, looking at responses, should also address this problem in the future.     

Factors associated with risk of central nervous system relapse in patients with non‐core binding factor acute myeloid leukemia

Central nervous system (CNS) relapse is uncommon in patients with acute myeloid leukemia (AML) with the use of high‐dose cytarabine containing chemotherapy regimens. The clinical and molecular features associated with a higher risk of CNS relapse are not well defined. We assessed the incidence and outcome of CNS relapses among 1245 patients with relapsed/refractory AML referred to our institution between 2000 and 2014. CNS leukemia relapse was observed in 51 patients (4.1%). Using a multivariate regression model and after adjusting for age, FLT3‐ITD mutation (OR = 2.33; P = .02) and elevated LDH (>1000 IU/L, OR = 1.99; P = .04) were independent predictive factors for CNS relapse. Patients under 64 years of age with 0, 1, or 2 baseline adverse features had a probability of 3.8%, 7.0%‐8.0%, and 13.9% for developing CNS disease, respectively. Our study identifies patients with AML at higher risk for CNS relapse in whom prophylactic CNS therapy may be warranted.     

Increasing hematopoietic microchimerism is a reliable indicator of incipient AML relapse

Introduction: The reoccurrence or increase in autologous hematopoiesis after allogeneic transplantation has been linked to incipient leukemia relapse. However, the importance of such an emergency regarding microchimerism (i.e. mixed chimerism below 1% of autologous cells) still remains controversial, as fluctuating microchimerism can be observed for a very long time after transplantation. Methods: Using real‐time PCR (RQ‐PCR), we compare peripheral blood samples obtained from patients with acute myeloid leukemia (AML) before hematological relapse and those taken during complete remission (i.e. either complete cytogenetic remission or complete molecular remission where applicable). By comparison of these two groups, we describe microchimerism dynamics clearly connected with imminent AML relapse. Additionally, we compare applicability of RQ‐PCR and conventional PCR with fragment analysis. Results: Mere reappearance of autologous hematopoiesis within patients with complete donor chimerism is alarming, and another sample with further increase confirms ongoing relapse. In case of patients with continuous microchimerism, another two consecutive samples with increasing trend are required. RQ‐PCR predicted a significantly higher number of hematological relapses (87%vs. 39%) with a median anticipation period of 33 days, 26 days earlier than conventional PCR (P = 0.0002). Moreover, the outcome of microchimerism dynamics was in complete agreement with monitoring of minimal residual disease when analyzed from the same cell compartment. Conclusion: Within this paper, we emphasize the importance of microchimerism monitoring as a reliable indicator of incipient AML relapse, especially in patients where no other specific molecular marker is available.     

Effective Response Metric: a novel tool to predict relapse in childhood acute lymphoblastic leukaemia using time‐series gene expression profiling

Accurate risk assignment in childhood acute lymphoblastic leukaemia is essential to avoid under‐ or over‐treatment. We hypothesized that time‐series gene expression profiles (GEPs) of bone marrow samples during remission‐induction therapy can measure the response and be used for relapse prediction. We computed the time‐series changes from diagnosis to Day 8 of remission‐induction, termed Effective Response Metric (ERM‐D8) and tested its ability to predict relapse against contemporary risk assignment methods, including National Cancer Institutes (NCI) criteria, genetics and minimal residual disease (MRD). ERM‐D8 was trained on a set of 131 patients and validated on an independent set of 79 patients. In the independent blinded test set, unfavourable ERM‐D8 patients had >3‐fold increased risk of relapse compared to favourable ERM‐D8 (5‐year cumulative incidence of relapse 38·1% vs. 10·6%; P = 2·5 × 10⁻³). ERM‐D8 remained predictive of relapse [P = 0·05; Hazard ratio 4·09, 95% confidence interval (CI) 1·03–16·23] after adjusting for NCI criteria, genetics, Day 8 peripheral response and Day 33 MRD. ERM‐D8 improved risk stratification in favourable genetics subgroups (P = 0·01) and Day 33 MRD positive patients (P = 1·7 × 10⁻³). We conclude that our novel metric – ERM‐D8 – based on time‐series GEP after 8 days of remission‐induction therapy can independently predict relapse even after adjusting for NCI risk, genetics, Day 8 peripheral blood response and MRD.     

Relapses in multibacillary patients treated with multi-drug therapy until smear negativity: findings after twenty years

The Schieffelin Leprosy Research and Training Center at Karigiri, India participated in several of the World Health Organization (WHO) trials. The first trial on combined therapy in multi-bacillary leprosy was initiated in 1981. The main objectives of this field trial were to evaluate the efficacy of WHO recommended regimens in preventing relapses, especially drug resistance relapses. This paper reports on the relapses twenty years after patients were inducted into the WHO field trial.Between 1981 and 1982, 1067 borderline lepromatous and lepromatous patients were inducted into the WHO field trial for combined therapy in multi-bacillary leprosy trial. Among them, 357 patients were skin smear positive. During the follow-up in 2002, only 173 of them could be traced and assessed. The mean duration of follow-up was 16.4 +/- 1.83 years. Two patients relapsed 14 and 15 years after being released from treatment, the relapse rate being 0.07 per 100 person years follow-up. Drug susceptibility tests done on one of the relapsed patients revealed drug sensitive organisms to all multi-drug therapy drugs.     

Late relapse in patients with diffuse large B-cell lymphoma: impact of rituximab on their incidence and outcome

Diffuse large B-cell lymphoma (DLBCL) constitutes 25–35% of all non-Hodgkin lymphomas in Western countries. Approximately two thirds of the patients can be cured with standard immuno-chemotherapy. Most relapses occur within 1–2 years from diagnosis, however, the occurrence of relapses after 5 years or more has been described. We aimed at defining the incidence and clinical features of late relapses. Data of 1113 DLBCL patients were analysed. Among the 196 patients relapsing after a first complete remission, 36 (18% of relapses and 3% of all DLBCLs) experienced a recurrence more than 5 years from diagnosis. Late relapsing patients, in comparison with those relapsing earlier, showed a more favourable risk profile at presentation: normal lactate dehydrogenase levels (P = 0·002), early Ann Arbor stage (P = 0·006) and low International Prognostic Index (P = 0·003). The risk of late relapse was lowered by the introduction of rituximab as part of the front-line treatment (P < 0·001). Cause-specific survival (CSS) from the time of relapse was significantly better for late relapsing patients compared to those relapsing early: 5-year CSS rates were 53% and 31%, respectively (P = 0·033). A trend toward a better overall survival was also observed, with 5-year rates after relapse of 47% and 25%, respectively (P = 0·054).     

Low‐dose rituximab in adult patients with primary immune thrombocytopenia

Backgrounds: Rituximab 375 mg/m² weekly for 4 wks has significant activity in adults with primary immune thrombocytopenia (ITP). In this setting, several evidences support the possible use of lower doses of rituximab. Objectives: To investigate the activity of low‐dose rituximab as salvage therapy in previously treated symptomatic ITP. Methods: Forty‐eight adult patients were treated prospectively with rituximab 100 mg weekly for 4 wks. Results: Overall and complete responses (CR) (platelet level ≥ 50 and 100 × 10⁹/L) were 60.5% and 39.5%, respectively. In responders, the median time to response was 35 d (range: 7–112 d). The median time of observation was 18 months (range 3–49 months). Sixteen of 29 responding patients (55%) relapsed and 14 needed further treatments. The 12‐ and 24‐month cumulative relapse‐free survival was 61% and 45%, respectively. In univariate analysis, CR rate was in inverse relation with weight OR = 0.95, CI_95% [0.91; 0.99] (P = 0.019) and age OR=0.96, CI_95% [0.93; 0.99] (P = 0.047). Cox regression model showed that relapse probability increases as weight (HR = 1.06, CI_95% [1.0031; 1.111]) and period between diagnosis and rituximab therapy (HR = 1.01, CI_95% [1.002; 1.017]) increase. One patient developed an interstitial pneumonia 1 month after the end of rituximab treatment. No other infectious, hematologic or extra‐hematologic complications were documented during follow‐up. Conclusions: Low‐dose rituximab is active in ITP but has moderate long‐term effect. A comparative study with standard dose is warranted.     

Prognostic scoring systems for myelodysplastic syndromes (MDS) in a population‐based setting: a report from the Swedish MDS register

The myelodysplastic syndromes (MDS) have highly variable outcomes and prognostic scoring systems are important tools for risk assessment and to guide therapeutic decisions. However, few population‐based studies have compared the value of the different scoring systems. With data from the nationwide Swedish population‐based MDS register we validated the International Prognostic Scoring System (IPSS), revised IPSS (IPSS‐R) and the World Health Organization (WHO) Classification‐based Prognostic Scoring System (WPSS). We also present population‐based data on incidence, clinical characteristics including detailed cytogenetics and outcome from the register. The study encompassed 1329 patients reported to the register between 2009 and 2013, 14% of these had therapy‐related MDS (t‐MDS). Based on the MDS register, the yearly crude incidence of MDS in Sweden was 2·9 per 100 000 inhabitants. IPSS‐R had a significantly better prognostic power than IPSS (P < 0·001). There was a trend for better prognostic power of IPSS‐R compared to WPSS (P = 0·05) and for WPSS compared to IPSS (P = 0·07). IPSS‐R was superior to both IPSS and WPSS for patients aged ≤70 years. Patients with t‐MDS had a worse outcome compared to de novo MDS (d‐MDS), however, the validity of the prognostic scoring systems was comparable for d‐MDS and t‐MDS. In conclusion, population‐based studies are important to validate prognostic scores in a ‘real‐world’ setting. In our nationwide cohort, the IPSS‐R showed the best predictive power.     

Clinical features,management and prognosis of multifocal primary bone lymphoma: a retrospective study of the international extranodal lymphoma study group (the IELSG 14 study)

‘Multifocal bone lymphoma’ or ‘polyostotic lymphoma’ is a neoplasm with exclusive multifocal involvement of the skeleton, without affecting lymph nodes or other soft tissues. Knowledge on this uncommon condition is limited because the related literature is sparse and fragmentary. We reviewed cases of multifocal bone diffuse large B‐cell lymphoma (MB‐DLBCL) registered in a clinico‐pathological database of the International Extranodal Lymphoma Study Group that includes 499 cases of bone lymphoma. Clinical features, management and prognosis of 37 MB‐DLBCL patients and 63 ‘controls’ (stage‐IV DLBCL and skeletal involvement) were analysed. Presentation and treatment of MB‐DLBCL and controls were identical. At a median follow‐up of 52 months (10–189), MB‐DLBCL patients exhibited a significantly better response rate (92% vs. 65%; P = 0·002), progression‐free survival (5‐year: 56 ± 9% vs. 34 ± 6%; P = 0·003) and overall survival (5‐year: 74 ± 8% vs. 36 ± 7%; P = 0·002). Among MB‐DLBCL patients, the use of post‐chemo radiotherapy was associated with better overall survival (5‐year: 83 ± 12% vs. 55 ± 16%; P = 0·003). Two MB‐DLBCL patients (5·4%) with spine and skull involvement experienced central nervous system (CNS) relapse. Thus, MB‐DLBCL patients exhibit a significantly better prognosis compared to patients with advanced‐stage DLBCL, and should be treated with conventional anthracycline‐based chemotherapy, keeping intensified treatment for relapsing cases, considering involved‐field radiotherapy, and CNS prophylaxis in high‐risk patients.     

Dipstick assay to identify leprosy patients who have an increased risk of relapse

Classification of leprosy patients into paucibacillary (PB) and multibacillary (MB) determines the duration of treatment; misclassification increases the risk of relapse because of insufficient treatment if an MB patient is classified as PB. We explored the possibility of using a simple dipstick assay based on the detection of antibodies to the Mycobacterium leprae-specific phenolic glycolipid-I (PGL-I) as a tool for classification of patients into PB and MB for treatment purposes. The sensitivity of the dipstick test for detection of MB patients was 85.1%, the specificity 77.7%. We found that of the 71 dipstick negative PB patients 25 (35.2%) were clinically cured at the end of treatment, compared with only two (9.5%) of the 21 dipstick positive PB patients. Of 170 patients in the study population, nine (5.3%) relapsed within the 5-year follow-up period. Seven were MB patients, all dipstick positive. Two PB patients relapsed, one was dipstick negative and one was dipstick positive. Dipstick positivity is a risk factor for the future development of relapses, especially in those groups of patients who had received a shorter-than-usual course of treatment and the dipstick can be used as an additional, simple tool for classification of patients and for identification of those patients who have an increased risk of relapse.     

Eosinophilic granulomatosis with polyangiitis (Churg‐Strauss): Clinical characteristics and long‐term followup of the 383 patients enrolled in the French Vasculitis Study Group cohort

Objective

Earlier studies of eosinophilic granulomatosis with polyangiitis (Churg‐Strauss) (EGPA), with limited patient numbers and followup durations, demonstrated that clinical presentation at diagnosis, but not outcome, differed according to antineutrophil cytoplasmic antibody (ANCA) status. This study was undertaken to describe the main characteristics of a larger patient cohort and their long‐term outcomes.

Methods

A retrospective study of EGPA patients in the French Vasculitis Study Group cohort who satisfied the American College of Rheumatology criteria and/or Chapel Hill definitions was conducted. Patient characteristics and outcomes were compared according to ANCA status and year of diagnosis.

Results

We identified 383 patients diagnosed between 1957 and June 2009 (128 [33.4%] before 1997 or earlier) and followed up for a mean ± SD of 66.8 ± 62.5 months. At diagnosis, their mean ± SD age was 50.3 ± 15.7 years, and 91.1% had asthma (duration 9.3 ± 10.8 years). Main manifestations included peripheral neuropathy (51.4%); ear, nose, and throat (ENT) signs (48.0%); skin lesions (39.7%); lung infiltrates (38.6%); and cardiomyopathy (16.4%). Among the 348 patients tested at diagnosis for ANCA, the 108 ANCA‐positive patients (31.0%) had significantly more frequent ENT manifestations, peripheral neuropathy, and/or renal involvement, but less frequent cardiac manifestations, than the ANCA‐negative patients. Vasculitis relapses occurred in 35.2% of the ANCA‐positive versus 22.5% of the ANCA‐negative patients (P = 0.01), and 5.6% versus 12.5%, respectively, died (P < 0.05). The 5‐year relapse‐free survival rate was 58.1% (95% confidence interval [95% CI] 45.6–68.6) for ANCA‐positive and 67.8% (95% CI 59.8–74.5) for ANCA‐negative patients (P = 0.35). Multivariable analysis identified cardiomyopathy, older age, and diagnosis during or prior to 1996 as independent risk factors for death and lower eosinophil count at diagnosis as predictive of relapse.

Conclusion

The characteristics and long‐term outcomes of EGPA patients differ according to their ANCA status. Although EGPA relapses remain frequent, mortality has declined, at least since 1996.