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Anaplastic lymphoma kinase–negative anaplastic large cell lymphoma (ALK– ALCL) is an aggressive neoplasm of T-cell/null-cell lineage. The T-Cell Project is a global prospective cohort study that consecutively enrolled patients newly diagnosed with peripheral T-cell lymphoma, registered through a centralized computer database between September 2006 and February 2018. Of 1553 validated cases from 74 sites in 13 countries worldwide, 235 were reported as ALK– ALCL. The median age at diagnosis was 54 years (range, 18-89 years), with a male predominance (62%). Stage III to IV disease was identified in 71% of patients, bulky disease and bone marrow involvement were uncommon, and 66% of patients presented with a low (0-1) International Prognostic Index score. Of all treated patients, 85% received multiagent initial chemotherapy, and 8% were consolidated with autologous hematopoietic cell transplantation. The initial overall and complete response rates were 77% and 63%, respectively. After a median follow-up of 52 months (95% confidence interval [CI], 41-63), the median progression-free survival (PFS) and overall survival (OS) were 41 months (95% CI, 17-62) and 55 months (95% CI, 36-75), respectively. The 3- and 5-year PFS rates were 52% and 43%, and the 3- and 5-year OS rates were 60% and 49%. Treatments containing both anthracycline and etoposide were associated with superior OS (P = .05) but not PFS (P = .18). In this large prospective cohort study, outcomes comparable to those previously reported in the retrospective International Peripheral T-Cell Lymphoma Project were observed. The study underscores the need for introducing novel platforms for ALK– ALCL and establishes a benchmark for future clinical trials. This trial was registered at www.clinicaltrials.gov as #NCT01142674.

PURPOSE: Rituximab maintenance therapy has been shown to improve progression free survival in patients with follicular lymphoma; however the optimal duration of maintenance treatment remains unknown. PATIENTS AND METHODS: Two hundred seventy patients with untreated relapsed stable or chemotherapy resistant follicular lymphoma were treated with four doses of rituximab monotherapy in weekly intervals (375 mg/m(2)). Patients achieving at least a partial response were randomly assigned to receive maintenance therapy with one infusion of rituximab every 2 months either on a short term schedule (four administrations) or a long term schedule (maximum of 5 years or until disease progression or unacceptable toxicity). The primary end point was event free survival (EFS). Progression free survival overall survival (OS) and toxicity were secondary end points. Comparisons between the two arms were performed using the log rank test for survival end points. RESULTS: One hundred sixty five patients were randomly assigned to the short term (n = 82) or long term (n = 83) maintenance arms. Because of the low event rate the final analysis was performed after 95 events had occurred which was before the targeted event number of 99 had been reached. At a median follow up period of 6.4 years the median EFS was 3.4 years (95 CI 2.1 to 5.3) in the short term arm and 5.3 years (95 CI 3.5 to not available) in the long term arm (P = .14). Patients in the long term arm experienced more adverse effects than did those in the short term arm with 76 v 50 of patients with at least one adverse event (P < .001) five versus one patient with grade 3 and 4 infections and three versus zero patients discontinuing treatment because of unacceptable toxicity respectively. There was no difference in OS between the two groups. CONCLUSION: Long term rituximab maintenance therapy does not improve EFS which was the primary end point of this trial or OS and was associated with increased toxicity.

Briefly presents research studies on efficacy of this method; discusses the teacher's role in inquiry; and provides guidelines for evaluation. A sample lesson plan on the Civil War concludes the article. (JB)

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.

Although the efficacy of plerixafor in peripheral blood stem cell (PBSC) mobilization has been explored in several studies, factors associated with successful plerixafor mobilization after administration of granulocyte-colony-stimulating factor (G-CSF), with or without chemotherapy, have not been investigated. We analyzed data on PBSC mobilization from a large Italian database of lymphoma and myeloma plerixafor-treated patients.Two endpoints were established to define successful mobilization: patients with at least 2 × 10(6) CD34+ cells/kg collected by three leukapheresis procedures and patients achieving a peak count of at least 20 × 10(6) CD34+ cells/L during mobilization.Plerixafor achieved successful mobilization in both predicted (n = 64) and proven poor mobilizers (PMs; n = 143), classified according to the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) criteria. Successful mobilization was independent of type of mobilization (steady state or chemotherapy); age; sex; disease; number or type of chemotherapy regimens preceding plerixafor; radiation therapy; prior treatment with melphalan, carmustine, lenalidomide, and radioimmune conjugates; and laboratory variables. Multivariate analysis identified previous fludarabine treatment and premobilization platelet count as predictors of successful mobilization.This large, prospective, nationwide study confirmed plerixafor efficacy for mobilizing PBSCs when added to G-CSF with or without chemotherapy. Plerixafor can overcome negative effects of most predictors of poor mobilization to achieve satisfactory harvest both in predicted and proven PM.

Purpose Granulocyte colony-stimulating factors (G-CSFs), filgrastim and lenograstim, are recognised to be useful in accelerating engraftment after autologous stem cell transplantation. Several forms of biosimilar non-glycosylated G-CSF have been approved by the European Medicines Agency, with limited published data supporting the clinical equivalence in peripheral blood stem cell mobilisation and recovery after autologous stem cell transplantation. Method With the aim of comparing cost-effective strategies in the use of G-CSF after autologous stem cell transplantation, we retrospectively evaluated 32 patients consecutively treated with biosimilar filgrastim XM02 (Tevagrastim) and 26 with lenograstim. All patients received G-CSF (biosimilar or lenograstim) at a dosage of 5 mcg/kg/day subcutaneously from day 5 to absolute neutrophil count of 1500/mmc for three days. Results The median time to absolute neutrophil count engraftment was 11 days for the filgrastim XM02 group and 12 days for the lenograstim group. As for platelets recovery, the median time was 12 days in both groups. The median number of G-CSF vials used for patients was 9.5 for Tevagrastim and 10.5 for lenograstim, reflecting a mean estimated cost of about 556.1 euros for Tevagrastim versus 932.2 euros for lenograstim (p< 0.001). The median days of febrile neutropenia were 1.5 and 1 for filgrastim XM02 and lenograstim, respectively. No adverse event related to the use of XM02 filgrastim was recorded. Conclusion In our experience, filgrastim XM02 and lenograstim showed comparable efficacy in shortening the period of neutropenia after cytoreduction and autologous stem cell transplantation, with a favourable cost effect for filgrastim XM02.

Summary form only given. The well-known phenomenon of the formation of a Bose-Einstein condensate (BEC), a striking consequence of the Bose-Einstein statistics, has been traditionally linked to an ensemble of ultra-cold gas molecules. However, classical systems can also exhibit condensation effects; in the field of photonics, for example, signatures of this condensation in the mode dynamics (“light condensation”, LC) have been theoretically investigated and experimentally observed in various types of multimode lasers [1,2 and ref. therein]. In contrast to the previous efforts, we developed a novel theory for LC in the presence of disorder, which takes into account the overlapping mode structure and shows that light condensation is naturally sustained by the governing equations in such systems. We begin with the Maxwell equations in a generic, disordered medium with non-orthogonal eigenmodes and complex eigenfrequencies. By employing the Feshbach projection technique [3], we separate the resonator space and the channel space and for the modal amplitudes we obtain ∂an ∂t + n'n n'fn n' (1) where |an|2 represents the energy carried by the nth mode inside the resonator, Jn'n are the coupling amplitudes containing the interaction between the cavity and the environment and fn are the noise generators, calculated exactly in our model. We can show that the experimentally relevant dynamics can be described by the following Hamiltonian and noise generators, a rigorous reduction from the Maxwell eq. to a spherical 2-spin model: H = - 1 2 Jn'nan'an fn = 0 fn(t) fn'(t') = 2Tδnn'δ(t - t') n'n (2) where is the thermodynamic average and T is a dimensionless temperature. The contribution of disorder is contained in the noise generators and in the distribution of the eigenvalues of J. From here, we study the photon thermodynamics in the regime of strong localization of light, which corresponds to small fluctuations in the noise and, therefore, to low temperatures. We show that the photonic system experiences a phase transition, a condensation process - in good analogy with BEC systems - and, below the critical temperature, the energy of a single mode grows linearly as the temperature further decreases. For further investigation, we have also performed an ab initio, massively parallel 2D FDTD simulation campaign (reaching over 12 million core hours) on the IBM Blue Gene/P supercomputer “Shaheen”, using our custom code. We considered positional disorder of a photonic lattice, launched a Gaussian pulse and measured the local density of states inside the structure for decreasing localization length (increasing refractive index or disorder). One of our main observation is that the energy of a single, dominant mode (normalized by the total energy) had a substantial increase in the strongly localized regime.