on behalf of the Lyon BK virus Study group 5 BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age (P ¼ 0.028), unrelated donor (P ¼ 0.0178), stem cell source (P ¼ 0.0001), HLA mismatching (P ¼ 0.0022) and BU in conditioning regimen (P ¼ 0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) (P ¼ 0.0005) and peripheral blood stem cells (P ¼ 0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity (P ¼ 0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization (Po0.0001), more RBC (P ¼ 0.0003) and platelet transfusions (Po0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at h2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.

The purpose of this study is to describe the clinical and prognostic features and to evaluate the outcome of different therapeutic approaches among patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) who have been diagnosed and treated in different institutions. A total of 398 patients from 75 centers were included in the study. Treatment consisted of non-Hodgkin lymphoma (NHL)–like regimens in 129 (32.8%) patients and acute leukemia (AL)–like regimens in 113 (23.5%) patients. In 61 (15.5%) and 16 (4.1%) patients, chemotherapy was followed by allogeneic and autologous hematopoietic stem cell transplantation (HSCT), respectively. Twenty-seven (6.9%) patients received radiotherapy, 6 (1.5%) received new agents, and 62 (15.7%) received palliative care. After a median follow-up of 12 months, median overall survival (OS) was 18 months. Patients who received NHL/AL-like regimens, followed by allogeneic HSCT, had the best outcome; median OS was not reached. OS was 65 months for patients who underwent autologous HSCT; 18 months and 14 months, respectively, for those treated with AL-like and NHL-like regimens without consolidation; and 4 months for those receiving palliative care (P < .001). In BPDCN, chemotherapy with lymphoma- or AL-like regimens, followed by transplantation, represents the therapeutic strategy associated with the best outcome. Consolidation with allogeneic HSCT, when feasible, appears superior to autologous HSCT.

The aim of this retrospective study was to investigate the safety and efficacy of allogeneic hematopoietic cell transplantation (alloHCT) in patients pre-treated with ibrutinib. Eligible were patients aged >18 years allotransplanted for chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) after prior exposure to ibrutinib who were registered with the EBMT registry. Seventy patients (CLL 48, MCL 22) were included. At the time of alloHCT, 73% of the patients were ibrutinib responsive. All patients except one engrafted, and acute GVHD grade 2-4 (3-4) was observed in 49% (12%) of 68 evaluable patients. The cumulative incidence of chronic GVHD was 54% 1 year after transplant. In the CLL group, 12-month non-relapse mortality, relapse incidence (RI), progression-free survival (PFS), and overall survival (OS) were 10, 30, 60, and 72%, respectively, and in the MCL group 5, 19, 76, and 86%, respectively. Pre-transplant ibrutinib failure and poor performance status predicted inferior RI, PFS and OS in the CLL group. In conclusion, ibrutinib does not affect the safety of a subsequent alloHCT. While the relatively high post-transplant relapse risk in ibrutinib-exposed patients with CLL deserves further study, in patients with MCL consolidating disease responses to ibrutinib with alloHCT seems to be a promising option.

BackgroundThe study objectives were: 1) to report on invasive aspergillosis patients in a hematology department; and 2) to estimate its incidence according to the hematologic diagnosis. Design and MethodsA prospective survey of invasive aspergillosis cases was undertaken between January 2004 and December 2009 in the hematology department of a university hospital. Meetings with clinicians, mycologists and infection control practitioners were organized monthly to confirm suspected aspergillosis cases. Demographic characteristics, clinical and complementary examination results were recorded prospectively. Information on hospitalization was extracted from administrative databases. Invasive aspergillosis diagnosis followed the European Organization for Research and Treatment of Cancer criteria, and proven and probable IA cases were retained. A descriptive analysis was conducted with temporal trends of invasive aspergillosis incidence assessed by adjusted Poisson regression. ResultsOverall, 4,073 hospitalized patients (78,360 patient-days) were included in the study. In total, 127 (3.1%) patients presented invasive aspergillosis. The overall incidence was 1.6 per 1,000 patient-days (95% confidence interval: 1.4, 1.9) with a decrease of 16% per year (-1%, -28%). The incidence was 1.9 per 1,000 patient-days (1.5, 2.3) in acute myeloid leukemia patients with a decrease of 20% per year (-6%, -36%). Serum Aspergillus antigen was detected in 89 (71%) patients; 29 (23%) had positive cultures, and 118 (93%), abnormal lung CT scans. One-month mortality was 13%; 3-month mortality was 42%. Mortality tended to decrease between 2004 and 2009. ConclusionsInvasive aspergillosis incidence and mortality declined between 2004 and 2009. Knowledge of invasive aspergillosis characteristics and its clinical course should help to improve the management of these patients with severe disease.Key words: invasive aspergillosis, surveillance, hematologic disease, incidence, hospital. 2004 . Haematologica 2011 96(11):1685-1691. doi:10.3324/haematol.2011 Citation: Nicolle M-C, Bénet T, Thiebaut A, Bienvenu A-L, Voirin N, Duclos A, Sobh M, Cannas G, Thomas X, Nicolini F-E, De Monbrison F, Piens M-A, Picot S, Michallet M, and Vanhems P. Invasive aspergillosis in patients with hematologic malignancies: incidence and description of 127 cases enrolled in a single institution prospective survey from

We describe the use and outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for multiple myeloma (MM) in Europe between January 1990 and December 2012. We identified 7333 patients, median age at allo-HSCT was 51 years (range: 18-78), of whom 4539 (62%) were males. We distinguished three groups: (1) allo-HSCT upfront (n=1924), (2) tandem auto-allo-HSCT (n=2004) and (3) allo-HSCT as a second line treatment and beyond (n=3405). Overall, there is a steady increase in numbers of allo-HSCT over the years. Upfront allo-HSCT use increased up to year 2000, followed by a decrease thereafter and represented 12% of allo-HSCTs performed in 2012. Tandem auto-allo-HSCT peaked around year 2004 and contributed to 19% of allo-HSCTs in 2012. Allo-HSCT as salvage after one or two or three autografts was steadily increasing over the last years and represented 69% of allo-HSCTs in 2012. Remarkable heterogeneity in using allo-HSCT was observed among the different European countries. The 5-year survival probabilities from time of allo-HSCT for the three groups after year 2004 were 42%, 54% and 32%, respectively. These results show that the use of allo-HSCT is increasing in Europe, especially as second line treatment and beyond. There is an unmet need for well-designed prospective studies investigating allo-HSCT as salvage therapy for MM.

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We present results of a phase 3 randomized trial of autografting in chronic lymphocytic leukemia versus observation for responding patients after first-or secondline treatment. The primary objective was to demonstrate that autografting improves the 5-year event-free survival (EFS) from 30% to 50%. There were 223 enrolled patients, 72% men and 28% women, 83% after first and 17% after second-line treatment. Binet stages were progressive A 13%, B 67%, C 20%; at randomization, 59% were in complete remission, and 41% in less than complete remission. Patients were randomized between autografting (n ‫؍‬ 112) and observation (n ‫؍‬ 111). Median EFS was 24.4 months (range, 16.7-32 months) in the observation group and 51.2 months (39.8-62.5 months) in the autografting group; the 5-year EFS was 24% and 42%, respectively (P < .001). Accordingly, the 5-year relapse incidence was 76% versus 54% (P < .001). Median time to relapse requiring therapy or death was 40 months (25-56 months) in the observation arm and 65 months (59-71 months) after autografting (P ‫؍‬ .002). Cox modeling confirmed that autografting significantly improved EFS (hazard ratio 0.44, 95% confidence interval 0.30-0.65; P < .001). At 5 years, the probability of OS was 85.5% and 84.3% for autografting and observation, respectively (P ‫؍‬ .77). In chronic lymphocytic leukemia, consolidating autografting reduces the risk of progression by more than 50% but has no effect on overall survival. (Blood. 2011;117(5): 1516-1521)

We describe the results of 37 myeloma patients who received bortezomib following reduced intensity allogeneic stem cell transplantation (RIC-allo-SCT). Grade 1-2 peripheral neuropathy (35%), mild thrombocytopenia (24%) and fatigue (19%) were the most frequent adverse events, while there was no worsening of graft-vs-host disease symptoms. Twenty-seven patients (73%; 95% CI, 59-87%) achieved an objective response. With a median follow-up of 9 months from bortezomib initiation, the estimate of overall survival was 65% at 18 months while this was significantly higher (p=0.002) in the 27 patients achieving an objective response, suggesting that bortezomib is a safe and efficient option for myeloma patients after RIC-allo-SCT.Key words: bortezomib, allogeneic stem cell transplantation, multiple myeloma. Lavallade H, Nicolini FE, Shimoni A, Faucher C, Sobh M, Revesz D, Hardan I, Fürst S, Blaise D, and Citation: El-Cheikh J, Michallet M, Nagler A, de