Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in patients undergoing treatment for acute leukemia (AL). Antifungal prophylactic strategies are associated with significant toxicities and cost. We performed a retrospective study of the incidence and risk factors for IFD among patients newly diagnosed with and treated for AL between January 1, 2004 and July 1, 2006. Patient follow up concluded January 1, 2007. Among 231 patients with newly diagnosed AL, 31 (13.4%) developed IFD by the end of follow up, 24 (10.4%) of whom developed IFD within the first 100 days after diagnosis of AL. The cumulative probability of developing IFD was 5.9% by 30 days and 11.1% at 100 days after AL diagnosis. Patients who had persistent leukemia after an initial course of induction chemotherapy were significantly more likely to develop IFD than those who did not have evidence of persistent leukemia (14/65 (21.5%) vs. 15/148 (10.1%), P = 0.03). In a time‐dependent Cox model, the adjusted hazard ratio for developing IFD within the first 100 days of AL diagnosis based on the number of days of neutropenia in that period was 4.85 (95% confidence interval: 1.52, 15.4). Those patients with more days of neutropenia in the first 100 days after AL diagnosis, such as those who did not achieve remission after a first course of induction chemotherapy, were more likely to develop IFD. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.

Background Endogenous or iatrogenic antitumor immune responses can improve the course of follicular lymphoma (FL), but may be diminished by immune checkpoints in the tumor microenvironment. These may include effects of programmed death (PD)-1, a co-inhibitory receptor that impairs T-cell function and is highly expressed on intratumoral T cells. In a Phase II trial, we determined the activity of pidilizumab, a humanized anti-PD-1 monoclonal antibody, with rituximab in patients with relapsed FL. Methods FL patients with rituximab-sensitive disease relapsing after 1–4 prior therapies were eligible. Pidilizumab was administered at 3 mg/kg every 4 weeks for 4 infusions, plus 8 optional infusions every 4 weeks for patients with stable disease or better. Starting 2 weeks after the first infusion of pidilizumab, rituximab was given at 375 mg/m2 weekly for 4 weeks. The primary endpoint was to assess the overall response rate. Analysis was by intention to treat. Peripheral blood and tumor biopsies were studied to assess immunological effects of pidilizumab. This trial has been completed and was registered at www.clinicaltrials.gov as NCT00904722. Findings The combination was well-tolerated, with no autoimmune or therapy-related grade 3/4 toxicities. The most common grade 1 adverse events were anemia (14 patients) and fatigue (13 patients), and the most common grade 2 adverse event was respiratory infection (5 patients). Overall 19/29 (66%) and complete 15/29 (52%) response rates in 29 evaluable patients were high, with tumor regression in 25/29 (86%) of patients. Median progression-free survival was 18.8 months (95% CI: 14.7 months to not reached). The median response duration for the 19 responders was 20.2 months (95% CI: 13.9 months to not reached). Correlative studies of blood and tumor provided insights into predicting response and understanding mechanisms involved. Interpretation Pidilizumab with rituximab is well-tolerated and its activity compared favorably to historical retreatment with rituximab monotherapy in patients with relapsed FL. Our results establish that immune checkpoint blockade is worthy of further study in FL. Funding National Institutes of Health, Leukemia and Lymphoma Society, Cure Tech Ltd, and UT MD Anderson Cancer Center.

SummaryWe report our experience with 129 cases of double hit lymphoma (DHL), defined as B-cell lymphoma with translocations and/or extra signals involving MYC plus BCL2 and/or BCL6. All cases were reviewed for histopathological classification. Median age was 62 years (range, 18-85), 84% of patients had advanced-stage disease, and 87% had an International Prognostic Index score ≥2. Fourteen patients (11%) had a history of low-grade follicular lymphoma. MYC translocation was present in 81%, and extra signals of MYC in 25% of patients. IGH-BCL2 translocation was present in 84% and extra signals of BCL2 in 12% of patients. Two-year event-free survival (EFS) rates in all patients and patients who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), and R-HyperCVAD/MA (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, alternating with cytarabine plus methotrexate) were 33%, 25%, 67% and 32%, respectively. In patients achieving complete response with initial therapy (n = 71), 2-year EFS rates in patients who did (n = 23) or did not (n = 48) receive frontline stem cell transplantation were 68% and 53%, respectively (P = 0Á155). The cumulative incidence of central nervous system involvement was 13% at 3 years. Multivariate analysis identified performance status ≥2 and bone marrow involvement as independent adverse prognostic factors for EFS and OS. Further research is needed to identify predictive and/or targetable biological markers and novel therapeutic approaches for DHL patients.

Nonmyeloablative stem cell transplantation in patients with follicular lymphoma has been designed to exploit the graftversus-lymphoma immunity. The longterm effectiveness and toxicity of this strategy, however, is unknown. In this prospective study, we analyzed our 8-year experience. Patients received a conditioning regimen of fludarabine (30 mg/m 2 daily for 3 days), cyclophosphamide (750 mg/m 2 daily for 3 days), and rituximab (375 mg/m 2 for 1 day plus 1000 mg/m 2 for 3 days). They were then given an infusion of human leukocyte antigen-matched hematopoietic cells from related (n ‫؍‬ 45) or unrelated donors (n ‫؍‬ 2). Tacrolimus and methotrexate were used for graft-versushost disease (GVHD) prophylaxis. Fortyseven patients were included. All patients experienced complete remission, with only 2 relapses. With a median follow-up time of 60 months (range, 19-94), the estimated survival and progression-free survival rates were 85% and 83%, respectively. All 18 patients who were tested and had evidence of JH/bcl-2 fusion transcripts in the bone marrow at study entry experienced continuous molecular remission. The incidence of grade 2-IV acute GVHD was 11%. Only 5 patients were still undergoing immunosuppressive therapy at the time of last follow-up. We believe that the described results are a step forward toward developing a curative strategy for recurrent follicular lymphoma. (Blood. 2008;111:5530-5536)

ESHAP was found to be an active, tolerable chemotherapy regimen for relapsing and refractory lymphoma. Applying a prognostic model based on tumor burden and serum LDH level shows significant differences in survival in this patient population.