Long-term outcome of patients receiving haematopoietic allogeneic stem cell transplantation as first transplant for high-risk Hodgkin lymphoma: a retrospective analysis from the Lymphoma Working Party-EBMT.

We analysed long-term outcome of patients receiving haematopoietic allogeneic stem cell transplantation (allo-HSCT) as a first transplant for high-risk Hodgkin lymphoma (HL). One hundred and ninety patients were included in this study, 63% of them had previously received brentuximab vedotin and/or checkpoint inhibitors. Seventy patients (37%) received an unrelated donor allo-HSCT, 99 (51%) had myeloablative conditioning (MAC) and 60% had in vivo T-cell/depleted grafts (TCD). The 100-day cumulative incidence (CI) of grade II-IV acute graft-versus-host disease (GVHD) was 25% and the 3-year CI of chronic GVHD was 38%. The 3-year CI of non-relapse mortality (NRM) and relapse rate were 21% and 38% respectively. After a median follow-up of 58 months, 3-year overall survival (OS) and progression-free survival (PFS) were 58% and 41% respectively. Multivariate analysis showed that, in comparison to reduced-intensity conditioning regimens with or without TCD, MAC using TCD had similar NRM and a lower risk of relapse leading to significantly better OS and PFS. MAC without TCD was associated with higher NRM and worse survival outcomes. These results suggest that in patients with high-risk HL and candidates of allo-HSCT, a MAC strategy with TCD might be the best option.

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.

Successful private-public funding of paediatric medicines research: lessons from the EU programme to fund research into off-patent medicines.

UNLABELLED: The European Paediatric Regulation mandated the European Commission to fund research on off-patent medicines with demonstrated therapeutic interest for children. Responding to this mandate, five FP7 project calls were launched and 20 projects were granted. This paper aims to detail the funded projects and their preliminary results. Publicly available sources have been consulted and a descriptive analysis has been performed. Twenty Research Consortia including 246 partners in 29 European and non-European countries were created (involving 129 universities or public-funded research organisations, 51 private companies with 40 SMEs, 7 patient associations). The funded projects investigate 24 medicines, covering 10 therapeutic areas in all paediatric age groups. In response to the Paediatric Regulation and to apply for a Paediatric Use Marketing Authorisation, 15 Paediatric Investigation Plans have been granted by the EMA-Paediatric Committee, including 71 studies of whom 29 paediatric clinical trials, leading to a total of 7,300 children to be recruited in more than 380 investigational centres. CONCLUSION: Notwithstanding the EU contribution for each study is lower than similar publicly funded projects, and also considering the complexity of paediatric research, these projects are performing high-quality research and are progressing towards the increase of new paediatric medicines on the market. Private-public partnerships have been effectively implemented, providing a good example for future collaborative actions. Since these projects cover a limited number of off-patent drugs and many unmet therapeutic needs in paediatrics remain, it is crucial foreseeing new similar initiatives in forthcoming European funding programmes.

OCCUPATION study (OCCUPationl asthma: a naTIONal based study): a survey on occupational asthma awareness among Italian allergists.

Occupational asthma (OA) is the most common work-related respiratory disease. Case identification still remains underperformed. The present survey aimed at investigating the awareness about OA among Italian allergists. 538 Italian Allergists completed a web anonymous questionnaire concerning: patient profile, occupational history, disease features, diagnostic work-up, causal agents, management after diagnosis. 80 cases were registered by 14 members (2.4%). Patients were mostly between 30 and 62 years old; noteworthy, 19% were between 18 and 30. All the patients had a concomitant rhinitis, usually preceding asthma onset. Bakers, hairdressers and healthcare workers were more frequently involved. Diagnostic process included: skin prick test (85%), stop/resume test (57%), specific IgE dosage for occupational allergens (52.5%), peak expiratory flow monitoring (32.5%). Noteworthy, only 27,5% of patients underwent specific challenge. After the diagnosis 50% of patients did not change job. One third of the subjects were not referred to the national Workers Compensation Authority. Our data show that OA is quite neglected by Italian allergists, despite they have a pivotal role both in early identification and in primary prevention of OA. Thus, it is worth increasing awareness concerning OA and creating an easy-access network involving allergists and referral centers for Occupational respiratory diseases.

Component resolved diagnosis in real life: the risk assessment of food allergy using microarray-based immunoassay.

BACKGROUND: The development of component-resolved diagnostics constitutes a potential breakthrough in food allergy testing, as detection of specific IgE (sIgE) to individual allergens may make it possible to establish the risk of a mild versus severe reaction. OBJECTIVE: To compare allergists' risk assessment based on the current decision making process with that of virtual allergen-oriented risk assessment through microarray-based immunoassay. METHODS: An observational, real-life study was performed on 86 adults with food allergy. The prescription of epinephrine was the surrogate marker of a severe reaction. In the same patients, the prescription of epinephrine based on the current decision making of the allergist and the independently established allergen-oriented risk assessment determined by microarray-based immunoassay were compared. RESULTS: Fair degree of agreement between the specialists' risk assessment and that of the microarray-based immunoassay (k index 0.372 (95% CI: 0.185- 0.559) p < 0.001) was documented. Three causes of discrepancy emerged: the poor sensitivity of the allergen microarray-immunoassay (51.9%), the differences in risk assessment established by the specialist and the microarray-immunoassay (33.3%), the non-inclusion of the causative allergen in the microarray-immunoassay platform (14.8%). CONCLUSION: Improvement of the diagnostic accuracy of microarray-immunoassay, combined with marrying its results to clinical information, could one day soon lead to changes in clinical practice in food allergy.

Molecular diagnosis and the Italian Board for ISAC.

The Component Resolved Diagnostic (CRD) approach has been developed when highly purified or recombinant allergen molecules have become available. These molecules are the allergenic proteins toward which the specific and clinically relevant IgE immune response is directed. So, the identification of protein families and cross-reactivity patterns of importance in allergy have been possible. The Italian advisory BOARD for ISAC was born: to evaluate the advantages, disadvantages and placement in diagnosis of CRD studying its application in allergic patients; to facilitate the interpretation of molecular diagnostics for clinical allergists; to evaluate the effectiveness of CRD in improving diagnostic risk assessment and early preventive treatment of allergic diseases. In the last years, its fields of interest have been: the evaluation of the performance of CRD on multi-sensitized allergic patients with respiratory symptoms and on poly-sensitized athletes; the evolution of IgE repertoire directed to single allergenic components by evaluating allergic patients with different age at a molecular level; the relevance of results obtained using allergen microarray technique for describing the IgE repertoire in allergic patients by reviewing the main articles focused on CRD published in the last 2 years; the need for an educational program focused on this new diagnostic tool also through the creation of an exhaustive and interactive explanation of the laboratory report molecular allergy; the investigation of the performance and potential additional diagnostic values of the ISAC microarray in a real-life clinical setting, taking into account also the economic values.

The additional values of microarray allergen assay in the management of polysensitized patients with respiratory allergy.

BACKGROUND: The IgE response is directed against specific components from an allergenic source. The traditional diagnostic methods use whole extracts, containing allergenic, nonallergenic and cross-reactive molecules. This may pose diagnostic challenges in polysensitized patients. Microarray techniques detect specific IgE against multiple molecules, but their value in term of additional information and economic saving has not been yet defined. OBJECTIVE: We assessed the additional diagnostic information provided by an allergen microarray in a large population of polysensitized subjects. METHODS: In this multicentre study, allergists were required to carefully record diagnosis and treatment of consecutive patients referred for asthma/rhinitis, using the standard methodology (history, skin prick test, IgE assay). Then, a microarray allergen assay was carried out. Clinicians were required to review their diagnosis/treatment according to microarray results. RESULTS: 318 allergic patients (30% reporting also nonrespiratory symptoms) and 91 controls were enrolled. The clinicians reported at least one additional information from the microarray in about 60% of patients, this resulting in therapeutic adjustments. In 66% of patients IgE to pan-allergens were detectable, being this clinically relevant in 38% of patients with polysensitization to pollens. CONCLUSION: Microarray IgE assay represents an advancement in allergy diagnosis, as a third-level approach in polysensitized subjects, when the traditional diagnosis may be problematic.

Availability of HLA-allele-matched unrelated donors and registry size: Estimation from haplotype frequency in the Italian population.

In Italy, an HLA-matched unrelated donor is currently the primary donor when a HLA matched sibling is not found for allogeneic haematopoietic stem cell transplantation (HSCT). Better outcomes for transplantation require optimal matching between donor and recipient at least at the HLA-A, -B, -C, and -DRB1 loci; therefore, the availability of HLA-matched unrelated donors is important. The enormous HLA polymorphism has always necessitated registries with a large number of individuals in order to be able to provide well-matched donors to a substantial percentage of patients. In order to increase the efficiency of the Italian Bone Marrow Donor Registry (IBMDR) in providing Italian patients with a suitable donor, the probability of finding an HLA-A, -B, -C, and -DRB1 allele-matched (8/8) or a single mismatch unrelated donor (7/8) was estimated in this study according to IBMDR size. Using a biostatistical approach based on HLA haplotype frequencies of more than 100,000 Italian donors enrolled in the IBMDR and HLA-typed at high-resolution level, the probability of finding an 8/8 HLA-matched donor was 23.8%; 33.4%; and 41.4% in simulated registry sizes of 200,000; 500,000; and 1,000,000 donors; respectively. More than 2 million recruited donors are needed to increase the likelihood of identifying an HLA 8/8 matched donor for 50% of Italian patients. If one single mismatch at HLA I class loci was accepted, the probability of finding a 7/8 HLA-matched donor was 62.8%; 73.7%; and 80.3% in 200,000 donors; 500,000; and 1,000,000 donors; respectively. Using the regional haplotype frequencies of IBMDR donors, the probability of recruiting a donor with a new HLA phenotype, in the different Italian regions, was also calculated. Our findings are highly relevant in estimating the optimal size of the national registry, in planning a cost-effective strategy for donor recruitment in Italy, and determining the regional priority setting of recruitment activity in order to increase the phenotypic variability of IBMDR as well as its efficiency.

The Gene-Environment Interactions in Respiratory Diseases (GEIRD) Project.

The role of genetic and environmental factors, as well as their interaction, in the natural history of asthma, allergic rhinitis and chronic obstructive pulmonary disease (COPD) is largely unknown. This is mainly due to the lack of large-scale analytical epidemiological/genetic studies aimed at investigating these 3 respiratory conditions simultaneously. The GEIRD project is a collaborative initiative designed to collect information on biomarkers of inflammation and oxidative stress, individual and ecological exposures, diet, early-life factors, smoking habits, genetic traits and medication use in large and accurately defined series of asthma, allergic rhinitis and COPD phenotypes. It is a population-based multicase-control design, where cases and controls are identified through a 2-stage screening process (postal questionnaire and clinical examination) in pre-existing cohorts or new samples of subjects. It is aimed at elucidating the role that modifiable and genetic factors play in the occurrence, persistence, severity and control of inflammatory airway diseases, by way of the establishment of a historical multicentre standardized databank of phenotypes, contributed by and openly available to international epidemiologists. Researchers conducting population-based surveys with standardized methods may contribute to the public-domain case-control database, and use the resulting increased power to answer their own scientific questions.

Assessment of airborne soy-hull allergen (Gly m 1) in the Port of Ancona, Italy.

BACKGROUND: Epidemic asthma outbreaks are potentially a very high-risk medical situation in seaport towns where large volumes of soybean are loaded and unloaded Airborne allergen assessment plays a pivotal role in evaluating the resulting environmental pollution. OBJECTIVE: The aim of this study was to measure the airborne Gly m 1 allergen level in the seaport of Ancona in order assess the soybean-specific allergenic risk for the city. METHODS: Allergen and PM10 were evaluated at progressive distances from the port area. Allergen analysis was performed by monoclonal antibody-based immunoassay on the sampled filters. Daily meteorological data were obtained from the local meteorological station. For estimating the assimilative capacity of the atmosphere, an approach based on dispersive ventilation coefficient was tried. RESULTS: The allergen concentrations detected were low (range = 0.4-171 ng/m3). A decreasing gradient of the airborne allergen from the unloading area (22.1 +/- 41.2 ng/m3) to the control area (0.6 +/- 0.7 ng/m3) was detected. The concentration of the airborne Gly m 1 was not coupled with the presence of the soy-carrying ships in the port. A statistically significant relationship between airborne allergen, PM10 and local meteorological parameters quantifies the association with the atmospheric condition. CONCLUSION: Airborne Gly m 1 is part of the atmospheric dust of Ancona. The low level of this allergen seems consistent with the absence of asthma epidemic outbreak.

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.

The natural history and epidemiology of insect venom allergy: clinical implications.

Hymenoptera stings can cause severe systemic allergic reactions and occasionally fatal anaphylaxis, which contribute significantly to morbidity and deterioration in health-related quality of life. The latest epidemiological data confirm the importance of insect sting allergy as a cause of anaphylaxis. Despite the high prevalence of asymptomatic sensitization, the prevalence of sting-induced systemic reactions (SRs) is low. However, to date, no parameter has been identified that can predict who will have a future reaction and whether it will be a large local reaction or anaphylactic. The combination of several concomitant factors, which include environmental, genetics and individual factors, may account for the occurrence of a system reaction in individual patients. Several not completely known factors may be associated with the severity of systemic re-stings. As about 50% of subjects with fatal sting reactions had no documented history of a previous SR, greater insight of the natural history and risk factors is required, especially in asymptomatic sensitized subjects. For patients with SRs, prevention of future severe allergic reactions starts with referral to an emergency department, correct administration of epinephrine by medical staff, referral to an allergist and coaching for the self-administration of epinephrine. However, most insect sting victims failed to seek medical advice and hospital attendance does not always correlate with the severity of the allergic reaction. Moreover, only about one-third of patients received a prescription for self-injectable epinephrine and were officially referred to an allergist after being discharged, causing the non- or delayed prescription of specific immunotherapy. Significantly, this means that at least half of the sting fatalities in patients with a positive history could have been avoided through the timely administration of specific immunotherapy. These findings indicate the urgent need to educate the general population and doctors on the management of venom-allergic patients.

Allergic rhinitis and associated pathologies: the rationale for steroid options.

The aim of this review article is to provide greater insight into the relationship between allergic rhinitis and the three most frequently diagnosed conditions of exacerbating viral infections, chronic rhinosinusitis with polyps and obstructive sleep apnoea syndrome. The alleged physiopathological effects of steroids are also investigated within the scope of this paper. Regarding the exacerbating viral infections, seems to establish a dynamic and counter relationship between the load and nature of the viral infection on one hand and widespread and pre-existing allergic inflammation on the other. If chronic rhinosinusitis with polyps and allergic rhinitis present overlapping picture of inflammatory cell and cytokine, the etyiological relationship between the two conditions appears to be influenced by the type of antigenic stimulus. Allergic rhinitis can influence the presence of OSAS through both obstructive and inflammatory mechanical factors. Topical corticosteroid therapy is a promising candidate as a new therapeutic tool able to improve symptoms and quality of life in patient with chronic rhinosinusitis with polyps and obstructive sleep apnoea syndrome. Other study are necessary to elucidate relationship between corticosteroids therapy and hypothetical benefit effect on viral infection when concomitant atopy inpatient.

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.

'Real-life' report on the management of chronic GvHD in the Gruppo Italiano Trapianto Midollo Osseo (GITMO).

Several guidelines have been published about management of chronic GvHD (cGvHD), but the clinical practice still remains demanding. The Gruppo Italiano Trapianto di Midollo Osseo (GITMO) has planned a prospective observational study on cGvHD, supported by a dedicated software, including the updated recommendations. In view of this study, two surveys have been conducted, focusing the management of cGvHD and ancillary therapy in cGvHD, to address the current 'real life' situation. The two surveys were sent to all 57 GITMO centers, performing allografting in Italy; the response rate was 57% and 66% of the interviewed centers, respectively. The first survey showed a great disparity especially regarding steroid-refractory cGvHD, although extracorporeal photo-apheresis resulted as the most indicated treatment in this setting. Another challenging issue was the strategy for tapering steroid: our survey showed a great variance, and this disagreement could be a real bias in evaluating outcomes in prospective studies. As for the second survey, the results suggest that the ancillary treatments are not standardized in many centers. All responding centers reported a strong need to standardize management of cGvHD and to participate in prospective trials. Before starting observational and/or interventional studies, a detailed knowledge of current practice should be encouraged.

Cryotherapy in the prevention of oral mucositis in patients receiving low-dose methotrexate following myeloablative allogeneic stem cell transplantation: a prospective randomized study of the Gruppo Italiano Trapianto di Midollo Osseo nurses group.

Severe oral mucositis is a major cause of morbidity following allogeneic hematopoietic stem cell transplantation (AHSCT). Cryotherapy, that is, the application of ice chips on the mucosa of the oral cavity during the administration of antineoplastic agents, may reduce the incidence and severity of chemotherapy-related oral mucositis. In this multicenter randomized study, we addressed whether cryotherapy during MTX administration is effective in the prevention of severe oral mucositis in patients undergoing myeloablative AHSCT. One hundred and thirty patients undergoing myeloablative AHSCT and MTX-containing GVHD prophylaxis were enrolled and randomized to receive or not receive cryotherapy during MTX administration. The incidence of severe (grade 3-4) oral mucositis, the primary end point of the study, was comparable in patients receiving or not cryotherapy. Moreover, no difference was observed in the incidence of oral mucositis grade 2-4 and the duration of oral mucositis grade 3-4 or 2-4, or in the kinetics of mucositis over time. In univariate and multivariate analysis, severe oral mucositis correlated with TBI in the conditioning regimen and lack of folinic acid rescue following MTX administration. Thus, cryotherapy during MTX administration does not reduce severe oral mucositis in patients undergoing myeloablative allogeneic HSCT. Future studies will assess cryotherapy before allogeneic HSCT.

Treatment of refractory chronic GVHD with rituximab: a GITMO study.

The anti-CD20 chimaeric monoclonal antibody Rituximab has recently been shown to induce significant clinical response in a proportion of patients with refractory chronic graft-versus-host disease (cGVHD). We now report 38 patients, median age 48 years (22-61), receiving Rituximab for refractory cGVHD, assessed for clinical response and survival. Median duration of cGVHD before Rituximab was 23 months (range 2-116), the median number of failed treatment lines was 3 (range 1 to > or =6) and the median follow-up after Rituximab was 11 months (1-88). Overall response rate was 65%: skin 17/20 (63%), mouth 10/21 (48%), eyes 6/14 (43%), liver 3/12 (25%), lung 3/8 (37.5%), joints 4/5, gut 3/4, thrombocytopaenia 2/3, vagina 0/2, pure red cell aplasia 0/1 and, myasthenia gravis 1/1. During the study period 8/38 died: causes of death were cGVHD progression (n=3), disease relapse (n=1), infection (n=3), sudden death (n=1). The actuarial 2 year survival is currently 76%. We confirm that Rituximab is effective in over 50% of patients with refractory cGVHD and may have a beneficial impact on survival.

Ocular surface analysis in hematological patients before and after allogeneic hematopoietic stem cell transplantation: implication for daily clinical practice.

PurposeTo evaluate ocular surface parameters before and after hematopoietic stem cell transplantation (HSCT) and to correlate them with clinical and transplant variables.MethodsThis is a retrospective analysis of data from 93 patients affected by hematological malignancies undergoing HSCT. Values from Ocular Surface Disease Index, Schirmer test, Break-up Time, ocular surface staining, and Meibomian Gland Dysfunction score obtained before HSCT and 3-6 months after were retrieved from charts. Diagnosis and staging of dry eye (DE) disease was performed according to Dry Eye WorkShop criteria. Graft-versus-host-disease (GVHD) was classified according to the NIH criteria. Odds ratios for DE onset after HSCT were estimated for demographic, ocular, hematological and transplant variables.ResultsDE was diagnosed before HSCT in 50 (53%) of the patients, mostly of hyperevaporative profile. After HSCT, all ocular parameters significantly worsened with no change in DE profile. A 51% incident cases (22 of the 43 non-DE subjects) were reported. Increasing recipient age and female sex, higher CD34+ cells infused, donor-recipient sex mismatch (males receiving from females), related donors, and peripheral blood cells as stem cell source were associated with a significant higher incidence of DE after HSCT. Systemic chronic GVHD was diagnosed in 42% while ocular GVHD in 35.5% of the patients, which decreased to 12% when taking into account only incident cases.ConclusionsHigh DE prevalence was shown already before HSCT. A pre-HSCT ocular surface assessment is recommended for early DE diagnosis and treatment. This new protocol also influences the prevalence of ocular GVHD.

Factors predicting outcome after allogeneic transplant in refractory acute myeloid leukemia: a retrospective analysis of Gruppo Italiano Trapianto di Midollo Osseo (GITMO).

The clinical outcome of primary refractory (PRF) AML patients is poor and only a minor proportion of patients is rescued by allogenic hematopoietic stem cell transplantation (HSCT). The identification of pre-HSCT variables may help to determine PRF AML patients who can most likely benefit from HSCT. We analyzed PRF AML patients transplanted between 1999 and 2012 from a sibling, unrelated donor or a cord blood unit. Overall, 227 patients from 26 Gruppo Italiano Trapianto di Midollo Osseo e Terapia cellulare centers were included in the analysis. At 3 years, the overall survival was 14%. By multivariate analysis, the number of chemotherapy cycles, (hazard ratio (HR): 1.87; 95% confidence interval (CI): 1.24-2.85; P=0.0028), the percentage of bone marrow or peripheral blood blasts (HR: 1.75; 95% CI: 1.16-2.64; P=0.0078), the adverse cytogenetic (HR: 1.44; 95% CI: 1.00-2.07; P=0.0508) and the age of patients (HR: 1.77; 95% CI: 1.08-2.88; P=0.0223) remained significantly associated with survival. Thus, we set up a new score predicting at 3 years after transplantation, an overall survival probability of 32% for patients with score 0 (no or 1 prognostic factor), 10% for patients with score 1 (2 prognostic factors) and 3% for patients with score 2 (3 or 4 prognostic factors).

Radioimmunotherapy-augmented BEAM chemotherapy vs BEAM alone as the high-dose regimen for autologous stem cell transplantation (ASCT) in relapsed follicular lymphoma (FL): a retrospective study of the EBMT Lymphoma Working Party.

Relapse remains the most common cause of treatment failure in patients receiving autologous stem cell transplantation (ASCT) for follicular lymphoma (FL). The aim of this study was to evaluate the effect of adding radioimmunotherapy or rituximab (R) to BEAM (carmustine, etoposide, ara-c, melphalan) high-dose therapy for ASCT in patients with relapsed FL. Using the European Society for Blood and Marrow Transplantation registry, we conducted a cohort comparison of BEAM (n=1973), Zevalin-BEAM (Z-BEAM) (n=207) and R-BEAM (n=179) and also a matched-cohort analysis of BEAM vs Z-BEAM including 282 and 154 patients, respectively. BEAM, Z-BEAM and R-BEAM groups were well balanced for age, time from diagnosis to ASCT and disease status at ASCT. The cumulative incidences of relapse (IR) at 2 years were 34, 34 and 32% for Z-BEAM, R-BEAM and BEAM, respectively. By multivariate analysis, there were no significant differences with Z-BEAM or R-BEAM compared with BEAM for IR, non-relapse mortality, event-free survival or overall survival. With the caveat that the limitations of registry analyses have to be taken into account, this study does not support adding radioimmunotherapy or R to BEAM in ASCT for relapsed FL. However, we cannot rule out the existence a particular subset of patients who could benefit from Z-BEAM conditioning that cannot be identified in our series, and this should be tested in a randomized trial.