Detection of Trypanosoma cruzi infection by PCR in Canis lupus familiaris and their ectoparasites in Chile.

Chronic Chagas disease affects humans and animals, involving rural and urban inhabitants. Dogs participate in the maintenance and transmission of Trypanosoma cruzi. The objective of this study was to evaluate the presence of T. cruzi in dogs and their ticks and fleas, in a rural area of Central Chile. Trypanosoma cruzi was detected by PCR both in dogs and ectoparasites. From the blood samples obtained, 57% were infected by T. cruzi, 5.4% of the ticks detected were positive, and all fleas were negative. Additionally, we performed electrocardiograms and found supraventricular arrhythmia in 44% of T. cruzi-positive dogs. Nevertheless, their risk for supraventricular arrhythmias was not higher in infected versus noninfected dogs. Considering the detected infection levels, dogs act as T. cruzi hosts in Central Chile, and ticks could be used as an indicator of infection when blood samples are not available. However, at this point, there is no indication that these ticks could pass on the parasite to another host. Periodic ectoparasitic treatment of pets should reduce the chance of vectorial transmission of T. cruzi and improve canine health; however, this is an uncommon practice among rural communities, so governmental programs are encouraged to tackle this problem.

What is the prognostic impact of FDG PET in locally advanced head and neck squamous cell carcinoma treated with concomitant chemo-radiotherapy? A systematic review and meta-analysis.

PURPOSE: Evidence is conflicting on the prognostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in head and neck squamous cell carcinoma. The aim of our study was to determine the impact of semiquantitative and qualitative metabolic parameters on the outcome in patients managed with standard treatment for locally advanced disease. METHODS: A systematic review of the literature was conducted. A meta-analysis was performed of studies providing estimates of relative risk (RR) for the association between semiquantitative metabolic parameters and efficacy outcome measures. RESULTS: The analysis included 25 studies, for a total of 2,223 subjects. The most frequent primary tumour site was the oropharynx (1,150/2,223 patients, 51.7%). According to the available data, the majority of patients had stage III/IV disease (1,709/1,799, 94.9%; no information available in four studies) and were treated with standard concurrent chemoradiotherapy (1,562/2,009 patients, 77.7%; only one study without available information). A total of 11, 8 and 4 independent studies provided RR estimates for the association between baseline FDG PET metrics and overall survival (OS), progression-free survival (PFS) and locoregional control (LRC), respectively. High pretreatment metabolic tumour volume (MTV) was significantly associated with a worse OS (summary RR 1.86, 95% CI 1.08-3.21), PFS (summary RR 1.81, 95% CI 1.14-2.89) and LRC (summary RR 3.49, 95% CI 1.65-7.35). Given the large heterogeneity (I2 > 50%) affecting the summary measures, no cumulative threshold for an unfavourable prognosis could be defined. No statistically significant association was found between SUVmax and any of the outcome measures. CONCLUSION: FDG PET has prognostic relevance in the context of locally advanced head and neck squamous cell carcinoma. Pretreatment MTV is the only metabolic variable with a significant impact on patient outcome. Because of the heterogeneity and the lack of standardized methodology, no definitive conclusions on optimal cut-off values can be drawn.

Myeloablative versus reduced intensity allogeneic stem cell transplantation for relapsed/refractory Hodgkin's lymphoma in recent years: a retrospective analysis of the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.

BACKGROUND: To evaluate long-term outcome of myeloablative allogeneic stem cell transplantation (allo-SCT) (MAC) versus reduced-intensity allo-SCT (RIC) in patients with relapsed/refractory Hodgkin's lymphoma (HL) in recent years. PATIENTS AND METHODS: A total of 312 patients (63 MAC and 249 RIC) with relapsed/refractory HL who received allo-SCT between 2006 and 2010 and were reported to the EBMT Database were included in the study. RESULTS: With a median follow-up for alive patients of 56 (26-73) months, there were no significant differences in non-relapse mortality (NRM) between MAC and RIC. Relapse rate (RR) was somewhat lower in the MAC group (41% versus 52% at 24 months, P = 0.16). This lower RR translated into a marginal improvement in event-free survival (EFS) for the MAC group (48% versus 36% at 24 months, P = 0.09) with no significant differences in overall survival (73% for MAC and 62% for RIC at 24 months, P = 0.13). Multivariate analysis after adjusting for disease status at the time of allo-SCT showed that the use of MAC was of borderline statistical significance for predicting a lower RR and EFS [HR 0.7, 95% CI (0.5-1.0), P = 0.1] and [HR 0.7, 95% CI (0.5-1.0), P = 0.07], respectively, after allo-SCT. CONCLUSIONS: With modern transplant practices, the NRM associated with MAC for HL has strongly decreased, resulting into non-significant improvement of EFS because of a somewhat better disease control compared with RIC transplants. The intensity of conditioning regimens should be considered when designing individual allo-SCT strategies or clinical trials in patients with relapsed/refractory HL.

Nasopharyngeal carcinoma in a low incidence European area : A prospective observational analysis from the Head and Neck Study Group of the Italian Society of Radiation Oncology (AIRO).

PURPOSE: To evaluate the outcomes with respect to long-term survival and toxicity in patients with nasopharyngeal carcinoma (NPC) treated in a European country with low incidence. MATERIALS AND METHODS: A prospective observational study carried out by the AIRO Head and Neck group in 12 Italian institutions included 136 consecutive patients treated with radiotherapy (RT) ± chemotherapy (CHT) for NPC (without distant metastasis) between January 1, 2008 and December 31, 2010. RESULTS: The disease-specific survival (DSS), overall survival (OS), and disease-free survival (DFS) at 5 years were 92 (±2), 91 (±3), and 69 % (±5 %), respectively. Distant failure was the most frequent modality of relapse. The local, regional, and locoregional control at 5 years were 89 (±3), 93 (±3), and 84 % (±4 %), respectively. The incidence of acute and late toxicity and the correlations with different clinical/technical variables were analyzed. Neoadjuvant CHT prolongs radiotherapy overall treatment time (OTT) and decreases treatment adherence during concomitant chemoradiotherapy. An adequate minimum dose coverage to PTV(T) is a predictive variable well related to outcome. CONCLUSION: Our data do not substantially differ in terms of survival and toxicity outcomes from those reported in larger series of patients treated in countries with higher incidences of NPC. The T stage (TNM 2002 UICC classification) is predictive of DSS and OS. The GTV volume (T ± N) and an adequate minimum PTV(T) coverage dose (D95 %) were also identified as potential predictive variables. Sophisticated technologies of dose delivery (IMRT) with image-guided radiotherapy could help to obtain better minimum PTV(T) coverage dose with increased DFS; distant metastasis after treatment still remains an unresolved issue.

Piperacillin/tazobactam (Tazocin™) seems to be no longer responsible for false-positive results of the galactomannan assay.

OBJECTIVES: Galactomannan (GM) testing is extremely useful for diagnosing invasive aspergillosis in high-risk patients, but false-positive results have been reported in patients treated with piperacillin/tazobactam. The aims of this study are to test if the recent piperacillin/tazobactam (Tazocin™; Pfizer) preparation still contains GM, and if serum GM positivity in haematopoietic stem cell transplant (HSCT) recipients receiving piperacillin/tazobactam can be attributed to this treatment. PATIENTS AND METHODS: Serum samples obtained from 1 October 2009 to 31 October 2010 from HSCT recipients for GM testing were analysed. The difference in the rate of positive results (defined as GM ≥ 0.5) in patients receiving and not receiving piperacillin/tazobactam was evaluated. Piperacillin/tazobactam vials from randomly selected batches were tested. RESULTS: Of 1606 samples drawn in the absence of piperacillin/tazobactam therapy, 25 (1.6%) tested positive for GM versus 10 of 394 samples (2.5%) drawn while on piperacillin/tazobactam (P = 0.18). The median GM result of samples drawn on piperacillin/tazobactam was slightly higher than that of samples drawn in the absence of piperacillin/tazobactam (0.141 versus 0.122; P < 0.001). All 90 piperacillin/tazobactam vials from 30 randomly selected batches tested negative for GM, with a median GM value of 0.057 (range: 0.011-0.320). CONCLUSIONS: Although some residual GM might still be present in piperacillin/tazobactam, currently available brand piperacillin/tazobactam preparations seem no longer responsible for false-positive GM results.

Mortality after bloodstream infections in allogeneic haematopoietic stem cell transplant (HSCT) recipients.

PURPOSE: Bloodstream infections (BSIs) are frequent after allogeneic haematopoietic stem cell transplantation (HSCT). The aim of this study was to identify predictors of mortality after BSI in patients who undergo HSCT. METHODS: Patients who underwent HSCT between 1 January 2004 and 31 January 2008 and developed BSI during the first year post-transplantation were included. Variables influencing overall mortality at 7 and 30 days after BSI were analysed. RESULTS: BSIs developed in 149 patients, within a median of 9 days after undergoing HSCT. Early and late mortality were 15 and 27%, respectively. Of the BSI, 54% were due to Gram-positive microorganisms, 33% were due to Gram-negative microogranisms, 10% were polymicrobial and 3% were fungal. The associated 7-and 30-day mortality was respectively 10 and 24% (Gram positive), 22 and 31% (Gram negative; Pseudomonas aeruginosa mortality 67%, all within 7 days), 13 and 27% (polymicrobial) and 40% (fungal, all within 7 days). Early mortality was higher in relapsed disease at HSCT (25.9%, p = 0.01), but lower in early (i.e. within 20 days of HSCT) BSI (11.7%, p = 0.03) and BSI due to Gram-positive infective agents (10%, p = 0.05). Multivariate analysis confirmed a higher mortality in late BSI [odds ratio (OR) 3.29, p = 0.03] and relapsed disease at HSCT (OR 2.2, p = 0.04). Late mortality was associated with the type of underlying disease (OR 0.44 for diseases other than acute leukaemia, p = 0.05) and its status (OR 6.04 for relapse at HSCT, p = 0.001). Appropriate empirical therapy was associated with lower early and late mortality in single Gram-negative BSI (16 vs. 45% for 7-day mortality, p = 0.09; 21 vs. 64% for 30-day mortality, p = 0.02). CONCLUSIONS: BSIs are frequent during the first year after HSCT and are associated with a high mortality rate. The aetiology influenced early mortality, while the type and phase of the underlying disease played a pivotal role in late mortality. Appropriate empirical therapy is crucial in BSI due to Gram-negative infective agents.

Chemo- immunotherapy and radiation in locally advanced head and neck cancer: Where do we stand?

Immunotherapy represents an effective therapeutic option in the management of recurrent/metastatic head and neck squamous cell carcinoma, along with chemotherapy in metastatic disease or radiotherapy/re-irradiation for (locoregionally confined) recurrent disease. On the other hand, concomitant chemo-radiation remains the primary treatment modality in many patients with locally advanced disease. In spite of promising preclinical, it is difficult to clearly establish the role of immunotherapy in the upfront management of locally advanced head and neck squamous cell carcinoma and its integration with the standard of care. In this paper, we discuss/review the main results thus far available and outline some unanswered questions that might help design future clinical trials.

Cisplatin-based chemoradiation plus cetuximab in locally advanced head and neck cancer: a phase II clinical study.

BACKGROUND: Intensification of chemoradiation for advanced head and neck squamous cell carcinoma (HNSCC) is unlikely due to toxicity. Cetuximab combined either with radiotherapy or with chemotherapy showed favourable toxic profile with positive results in both combinations. Therefore, cetuximab could intensify chemoradiation without worsening toxicity. We conducted a phase II study of chemoradiation and cetuximab. PATIENTS AND METHODS: Eligible patients had stage III-IV M0 HNSCC. Treatment consisted of three cycles of cisplatin (20 mg/m(2)/day × 5 days) and fluorouracil (200 mg/m(2)/day × 5 days) rapidly alternated to three split courses of radiotherapy up to 70 Gy and concurrent weekly cetuximab. The primary end point of the study was complete response (CR) rate. Secondary end points were toxicity, progression-free survival (PFS) and overall survival (OS). RESULTS: Fourty-five patients were enrolled: median age was 56 years, 38 had stage IV disease and 40 nodal involvement. CR occurred in 32 patients (71%). PFS and OS was 21+ months and 32.6+, respectively. Acute grade 3-4 toxic effects were in the expected range, but grade 3 radiodermatitis occurred in 33 patients. CONCLUSIONS: The combination of cetuximab, cisplatin, fluorouracil and radiotherapy leads to a very high proportion of CR and it is feasible with toxic effects similar to those expected by radiochemotherapy. The only unexpected toxicity was skin toxicity: grade 3 radiodermatitis occurred in 73% of the patients.

Modification of the Daily Activity Pattern of the Diurnal Triatomine Mepraia spinolai (Hemiptera: Reduviidae) Induced by Trypanosoma cruzi (Trypanosomatida: Trypanosomatidae) Infection.

Mepraia spinolai, (Porter) 1934, is a diurnal triatomine endemic to Chile and a wild vector of the protozoan Trypanosoma cruzi, (Chagas) 1909, which causes Chagas disease. Behavioral changes in M. spinolai induced by this parasite have been reported previously, which include detection of a potential host, defecation latency, and some life history traits. In this study we assessed changes in locomotor and daily activity due to infection with T. cruzi. No difference was detected in distance traveled between infected and uninfected individuals. However, the groups differed in their daily activity patterns; infected individuals showed significant reduction of movements during the light phase and concentrated their activity in the dark phase. Uninfected individuals showed no differences in locomotor activity between the phases. The results suggest that T. cruzi induces a displacement in the activity of M. spinolai toward the dark phase of the circadian cycle, which may improve its vector competence.

Risk factors for enterococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients.

Bacteremia is a well known cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients and enterococci are among the most frequently isolated pathogens. The aim of this study was to identify risk factors for enterococcal bacteremia during the first 30 days after allogeneic HSCT. A retrospective case-control study was performed; for each case, 3 controls were randomly selected among 306 patients transplanted during the study period (January 1, 2004 to December 31, 2007). Odds ratios (OR) with 95% confidence intervals (CI) were calculated for variables influencing the risk for bacteremia. Overall, 33 patients developed enterococcal bacteremia, within a median of 9 days after HSCT (range, 2-24). The cumulative incidence was 10.8%. Multivariate analysis identified the following variables as risk factors for enterococcal bacteremia: donor and transplant type (greater risk for mismatched related or cord blood) (OR=8.98, 95% CI, 1.65-48.99 and OR=7.52, 95% CI, 1.56-36.31, respectively, P=0.047); severe (grades 3-4) mucositis (OR=9.04, 95% CI, 1.97-41.52, P=0.018); pharyngeal enterococcal colonization (OR=4.48, 95% CI, 1.11-18.03, P=0.035); and previous empirical therapy with cephalosporins (OR=4.16, 95% CI, 0.93-18.66 for 1-7 days of therapy, and OR=7.31, 95% CI, 1.78-30.12 for 8-23 days, P=0.018). Higher Karnofsky score (≥50) and previous empirical therapy with glycopeptides were associated with a decreased risk (OR=0.25, 95% CI, 0.06-0.97, P=0.045 and OR=0.11, 95% CI, 0.02-0.59, P=0.010, respectively). The crude mortality at 7 and 30 days was 12% (4/33) and 24% (8/33), respectively. Enterococcal bacteremia is frequent after allogeneic HSCT. The factors associated with this infection are type of transplant, pharyngeal colonization, severe mucositis, and use of cephalosporins. Good general conditions and the use of vancomycin were associated with lower risk of enterococcal bacteremia.

Does a 6-point scale approach to post-treatment 18F-FDG PET-CT allow to improve response assessment in head and neck squamous cell carcinoma? A multicenter study.

PURPOSE: Response assessment to definitive non-surgical treatment for head and neck squamous cell carcinoma (HNSCC) is centered on the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET-CT) 12 weeks after treatment. The 5-point Hopkins score is the only qualitative system available for standardized reporting, albeit limited by suboptimal positive predictive value (PPV). The aim of our study was to explore the feasibility and assess the diagnostic accuracy of an experimental 6-point scale ("Cuneo score"). METHODS: We performed a retrospective, multicenter study on HNSCC patients who received a curatively-intended, radiation-based treatment. A centralized, independent qualitative evaluation of post-treatment FDG-PET/CT scans was undertaken by 3 experienced nuclear medicine physicians who were blinded to patients' information, clinical data, and all other imaging examinations. Response to treatment was evaluated according to Hopkins, Cuneo, and Deauville criteria. The primary endpoint of the study was to evaluate the PPV of Cuneo score in assessing locoregional control (LRC). We also correlated semi-quantitative metabolic factors as included in PERCIST and EORTC criteria with disease outcome. RESULTS: Out of a total sample of 350 patients from 11 centers, 119 subjects (oropharynx, 57.1%; HPV negative, 73.1%) had baseline and post-treatment FDG-PET/CT scans fully compliant with EANM 1.0 guidelines and were therefore included in our analysis. At a median follow-up of 42 months (range 5-98), the median locoregional control was 35 months (95% CI, 32-43), with a 74.5% 3-year rate. Cuneo score had the highest diagnostic accuracy (76.5%), with a positive predictive value for primary tumor (Tref), nodal disease (Nref), and composite TNref of 42.9%, 100%, and 50%, respectively. A Cuneo score of 5-6 (indicative of residual disease) was associated with poor overall survival at multivariate analysis (HR 6.0; 95% CI, 1.88-19.18; p = 0.002). In addition, nodal progressive disease according to PERCIST criteria was associated with worse LRC (OR for LR failure, 5.65; 95% CI, 1.26-25.46; p = 0.024) and overall survival (OR for death, 4.81; 1.07-21.53; p = 0.04). CONCLUSIONS: In the frame of a strictly blinded methodology for response assessment, the feasibility of Cuneo score was preliminarily validated. Prospective investigations are warranted to further evaluate its reproducibility and diagnostic accuracy.

Nilotinib in steroid-refractory cGVHD: prospective parallel evaluation of response, according to NIH criteria and exploratory response criteria (GITMO criteria).

We conducted a phase I-II study to evaluate Nilotinib (NIL) safety and pharmacokinetics in 22 SR-cGVHD patients; we also evaluated ORR by using in parallel NIH criteria and an exploratory approach, combining objective improvement (OI) without failure criteria (GITMO criteria). Results: 22 patients were enrolled. After dose escalation up to 600 mg/day, MTD was not reached. Main toxicities were asthenia, headache, nausea, pruritus, cramps, and mild anemia. Mean and median plasma concentrations of NIL (C-NIL) were 817 (SD ± 450) and 773 ng/ml. ORR at 6 months, according to 2005 and 2014 NIH and GITMO criteria were 27.8%, 22.2%, and 55.6% respectively; close correspondence has been observed for ORR, according to 2014 NIH criteria, both assessed in a conventional way and assisted by dedicated software (CROSY). At 48 months OS was 75% while FFS, according to NIH and GITMO criteria, was 30 and 25%. In conclusion the safety profile of NIL and long-term outcome makes NIL an attractive option in SR-cGVHD. Exploratory GITMO criteria could represent an alternative tool for easy response evaluation in patients with prevalent skin and lung involvement, but require validation in a larger population; CROSY software showed excellent reliability in capturing ORR according to the 2014 NIH criteria.

Intensity modulated radiation therapy and oral mucosa sparing in Head and neck cancer patients: A systematic review on behalf of Italian Association of Radiation Oncology - Head and neck working group.

Oral mucositis is a common dose-limiting toxicity during radiotherapy with or without chemotherapy in head and neck cancer patients. This potentially severe complication globally worsens quality of life and negatively impacts local control and survival's outcomes. Several studies have been published on feasibility and/or clinical benefit of intensity modulated radiotherapy (IMRT) mucosa-sparing technique. In 2017, the Italian Association of Radiation Oncology Head and Neck Cancer Working Group organized a study group to perform a systematic review. The aim was to verify if practical indications, including dose-constraints and demonstrated clinical benefit, could be proposed for oral mucosa (OM)-sparing IMRT in order to reduce the incidence of severe acute mucositis. Although dose to OM should be reduced as much as possible without compromising target volumes coverage, it is still tricky to firmly state that OM-sparing procedure should be considered the standard of care, especially due to high subjective variability in OM contour.

Changes in lung volumes and airway responsiveness following haematopoietic stem cell transplantation.

Changes in lung volume occur following haematopoietic stem cell transplantation (HSCT); airway hyperresponsiveness was occasionally reported, without mechanistic explanation. The present authors studied 17 patients by standard methacholine (MCh) challenge before and then 3 and 12 months after HSCT (n = 16 and n = 13, respectively). Another 6 patients were challenged before and 3 months after HSCT using a modified challenge to investigate the effect of deep inhalations. No patient developed bronchiolitis obliterans or bronchiolitis obliterans organising pneumonia. At 3 months, forced vital capacity (FVC) was significantly reduced by 0.33+/-0.55 L, forced expiratory volume in one second (FEV(1)) by 0.31+/-0.50 L, total lung capacity (TLC) by 0.39+/-0.37 L and single-breath diffusing capacity of the lung for carbon monoxide (D(L,CO)) by 15+/-12%. At 12 months, TLC decreased by 0.43+/-0.36 L and D(L,CO )by 8+/-8%. With standard challenge, no significant changes in FEV(1) response to MCh were observed after HSCT but FVC decreased significantly less after HSCT compared with prior to HSCT, suggesting less air trapping. With modified challenge, deep inhalations reversed the MCh-induced decrease in partial expiratory flow more after HSCT compared with before HSCT and this correlated with TLC decrements. In conclusion, an increase in airway responsiveness is unlikely after haematopoietic stem cell transplantation, at least in patients without pulmonary complications, and mechanisms opposing airway narrowing may blunt the bronchoconstrictor response.

Treatment strategies for patients with severe aplastic anemia.

Treatment strategies for patients with severe aplastic anemia (SAA), depend on the severity of the disease, the age of the patient and the availability of a family donor. Progress in the past has included the early use of combined immunosuppressive therapy (IST) and better matching strategies to select unrelated donors. Currently, the actuarial 10-year survival in 2479 patients registered within the European Group for Blood and Marrow Transplantation (EBMT), is 73 and 68% for patients receiving first-line BMT or IST. The outcome of BMT has significantly improved since 1996, and this is true for both matched sibling donor BMT as well as for alternative donor BMT. Survival is significantly better in children (<16 years) as compared with adults (79 vs 68%, P<0.0001). In contrast, there has been no significant improvement over time for patients receiving IST. Again, results were significantly better in children compared with adults (81 versus 70%, P=0.001), especially in very severe aplasia (83 versus 62%, P=0.0002). This report outlines some of these results as a basis for treatment strategies in SAA.

Lymphocyte subsets recovery following allogeneic bone marrow transplantation (BMT): CD4+ cell count and transplant-related mortality.

To assess the kinetics of lymphocyte subset recovery, 758 allografted patients were monitored by surface markers (CD3, CD4, CD8, CD56), with a 5-year follow-up. The donor was a matched sibling donor (MSD) (n=502) or an alternative donor (family mismatched or unrelated, AD) (n=256). The stem cell source was bone marrow for all patients. CD4+ cell recovery was influenced -- in univariate analysis -- by three factors: donor type, patient age and GvHD. This was not the case for CD8+ and CD56+ cells. The median CD4+ cell count on day +35 after HSCT was 86/mul. Patients achieving this CD4+ cell count had significantly lower transplant-related mortality (TRM) compared to patients who did not achieve this CD4+ cell count (20 vs 39%, P=0.00001), due to a lower risk of lethal infections (24 vs 47%, P=0.0003). In multivariate analysis MSD (RR 3.45, P=0.0001) and recipient age less than 16 years (RR 3.23, P=0.003) were significantly associated with a better CD4+ cell recovery. CD4+ counts on day +35 was predicted TRM (RR=1.97, P=0.0017) together with acute GvHD grade II-IV (RR 1.59, P=0.0097). No difference of TRM was observed for CD8+ and CD56+ cell counts.

Recent improvement in outcome of unrelated donor transplantation for aplastic anemia.

The aim was to determine whether outcome of unrelated donor transplantation for severe aplastic anemia has improved in recent years and whether this is due to patient selection or better transplant technology. We analyzed 498 patients transplanted during 1990-2005. By running univariate regression models dichotomizing year of transplantation we defined 1998 as the year of the most significant change in survival. Five-year survival increased from 32+/-8% before 1998 to 57+/-8% after 1998 (P<0.0001). When comparing the cohort before (n=149) and after 1998 (n=349), there were no differences except for older age, and more frequent use of PBSCs, after 1998. High-resolution HLA typing data were unavailable. After 1998, there was less graft failure (11 vs 26%, P<0.0001), less acute GvHD (cumulative incidence 28 vs 37%, P=0.02) and less chronic GvHD (22 vs 38%, P=0.004). In multivariate analyses adjusting for differences in age, HLA-mismatch, performance score and time to transplantation, there was no change in the year of transplant effect (relative risk of death in transplants after 1998: 0.44 (95% confidence interval 0.33-0.59)). There is no evidence for patient selection to explain significantly improved survival in patients transplanted after 1998. We speculate that this is due to better donor matching.

Low IPSS score and bone marrow hypocellularity in MDS patients predict hematological responses to antithymocyte globulin.

Immunosuppressive therapy has been shown to induce sustained hematological responses in a subset of patients with myelodysplastic syndromes (MDS). In particular, antithymocyte globulin (ATG), a polyclonal immunoglobulin induces hematological responses in up to 60% of MDS patients. We report herein on the results of a retrospective multicenter study on the use of ATG in the treatment of 96 patients with MDS. Patients were evaluated for duration of response to ATG, as well as survival after administration of ATG. The median age of the cohort was 54.7 years (range: 19-75 years), with a median follow-up of 33.8 months (range: 0.8-133 months). A total of 40 patients (42%) achieved a hematological response, of which 30 patients (75%) had a durable hematological response lasting a median duration of 31.5 months (range: 6-92 months). On multivariate analysis, both low International Prognostic Scoring System (IPSS) and bone marrow (BM) hypocellularity were independent predictive factors for improved response to ATG (IPSS Int-2/high: odds ratio (OR) 0.08, P=0.018 and BM normo/hypercellularity: OR 0.49, P=0.012). In addition, IPSS was the sole predictor of overall survival, with Int-2/high risk patients having a significantly poorer survival outcome (OR 0.08, P<0.01). In conclusion, this study identifies BM hypocellularity and a low IPSS as important factors predicting response to ATG.

Allogeneic stem cell transplantation following reduced-intensity conditioning can induce durable clinical and molecular remissions in relapsed lymphomas: pre-transplant disease status and histotype heavily influence outcome.

The safety and efficacy of reduced-intensity conditioning (RIC) followed by allogeneic stem cell transplantation (SCT) for relapsed lymphomas remains unresolved. We conducted a prospective, multicentered, phase II trial. A total of 170 relapsed/refractory lymphomas received a RIC regimen followed by SCT from sibling donors. The primary study end point was non-relapse mortality (NRM). Histologies were non-Hodgkin's lymphomas (NHL) (indolent (LG-NHL), n=63; aggressive (HG-NHL), n=61; mantle cell lymphoma (MCL), n=14) and Hodgkin's disease (HD, n=32). Median follow-up was 33 months (range, 12-82). The results show that frequencies were as follows: cumulative NRM at 3 years, 14%; acute and chronic graft-versus-host disease (GVHD) 35 and 52%, respectively; 3-year overall survival (OS), 69% for LG-NHL, 69% for HG-NHL, 45% for MCL and 32% for HD (P=0.058); and 3-year relapse incidence, 29, 31, 35 and 81%, respectively (P<0.001). Relapse risk differed significantly at 3 years between follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL) (14 versus 46%, P=0.04). Molecular remission occurred in 94 and 40% (P=0.002) of patients with FL and CLL, respectively. On multivariate analysis, OS was influenced by chemorefractory disease (hazard ratio (HR)=3.6), diagnosis of HD (HR=3.5), and acute GVHD (HR=5.9). RIC allogeneic SCT is a feasible and effective salvage strategy in both indolent and aggressive NHL.