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Purpose Patients undergoing a hematopoietic stem cell transplantation (HCT) have varied symptoms during their hospitalization. This study examined whether daily symptom reporting (with electronic patient-reported outcomes [PROs]) in an inpatient bone marrow transplant clinic reduced symptom burden on post-transplant days +7, +10, and +14. Methods A prospective, single-institution 1:1 pilot randomized, two-arm study recruited HCT patients. HCT inpatients ( N  = 76) reported daily on 16 common symptoms using the PRO version of the Common Terminology for Adverse Events (PRO-CTCAE). Fisher’s exact test was used to examine differences in the proportion of patients reporting individual symptoms. Multivariable linear regression modeling was used to examine group differences in peak symptom burden, while controlling for symptom burden at baseline, age, comorbidity, and transplantation type (autologous or allogeneic). Results HCT patients receiving the PRO intervention also experienced lower peak symptom burden (average of 16 symptoms) at days +7, +10, and +14 (10.4 vs 14.5, p  = 0.03). Conclusions Daily use of electronic symptom reporting to nurses in an inpatient bone marrow transplant clinic reduced peak symptom burden and improved individual symptoms during the 2 weeks post-transplant. A multi-site trial is warranted to demonstrate the generalizability, efficacy, and value of this intervention. Trial registration ClinicalTrials.gov identifier: NCT 02574897

There are no prospective studies of aggressive non-Hodgkin lymphoma (NHL) treated with CHOP in sub-Saharan Africa. We enrolled adults with aggressive NHL in Malawi between June 2013 and May 2015. Chemotherapy and supportive care were standardized, and HIV+ patients received antiretroviral therapy (ART). Thirty-seven of 58 patients (64%) were HIV+. Median age was 47 years (IQR 39-56), and 35 (60%) were male. Thirty-five patients (60%) had stage III/IV, 43 (74%) B symptoms, and 28 (48%) performance status ≥ 2. B-cell NHL predominated among HIV+ patients, and all T-cell NHL occurred among HIV- individuals. Thirty-one HIV+ patients (84%) were on ART for a median 9.9 months (IQR 1.1-31.7) before NHL diagnosis, median CD4 was 121 cells/μL (IQR 61-244), and 43% had suppressed HIV RNA. HIV+ patients received a similar number of CHOP cycles compared to HIV- patients, but more frequently developed grade 3/4 neutropenia (84% vs 31%, p = 0.001), resulting in modestly lower cyclophosphamide and doxorubicin doses with longer intervals between cycles. Twelve-month overall survival (OS) was 45% (95% CI 31-57%). T-cell NHL (HR 3.90, p = 0.017), hemoglobin (HR 0.82 per g/dL, p = 0.017), albumin (HR 0.57 per g/dL, p = 0.019), and IPI (HR 2.02 per unit, p<0.001) were associated with mortality. HIV was not associated with mortality, and findings were similar among patients with diffuse large B-cell lymphoma. Twenty-three deaths were from NHL (12 HIV+, 11 HIV-), and 12 from CHOP (9 HIV+, 3 HIV-). CHOP can be safe, effective, and feasible for aggressive NHL in Malawi with and without HIV.

Aims We evaluated pedometry as a novel patient-cen-tered outcome because it enables passive continuous assessment of activity and may provide information about the consequences of symptomatic toxicity complementary to self-report. Methods Adult patients undergoing hematopoietic cell transplant (HCT) wore pedometers and completed PRO assessments during transplant hospitalization (4 weeks) and 4 weeks post-discharge. Patient reports of symptomatic treatment toxicities (single items from PROCTCAE, http://healthcaredelivery. cancer.gov/pro-ctcae) and symptoms, physical health, mental health, and quality of life (PROMIS® Global-10, http://nih.promis.org), assessed weekly with 7-day recall on Likert scales, were compared individually with pedometry data, summarized as average daily steps per week, using linear mixed models. Results Thirty-two patients [mean age 55 (SD = 14), 63 % male, 84 % white, 56 % autologous, 43 % allogeneic] completed a mean 4.6 (SD = 1.5, range 1-8) evaluable assessments. Regression model coefficients (β) indicated within-person decrements in average daily steps were associated with increases in pain (β = –852; 852 fewer steps per unit increase in pain score, p < 0.001), fatigue (β = –886, p < 0.001), vomiting (β = –518, p < 0.01), shaking/chills (β = –587, p < 0.01), diarrhea (β = –719, p < 0.001), shortness of breath (β = –1018, p < 0.05), reduction in carrying out social activities (β = 705, p < 0.01) or physical activities (β = 618, p < 0.01), and global physical health (β = 101, p < 0.001), but not global mental health or quality of life. Conclusions In this small sample of HCT recipients, more severe symptoms, impaired physical health, and restrictions in the performance of usual daily activities were associated with statistically significant decrements in objectively measured daily steps. Pedometry may be a valuable outcome measure and validation anchor in clinical research.

Case reports of treatment failure with standard-dose daptomycin (6 mg/kg) have recently surfaced in vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI) episodes with daptomycin MICs of 3 to 4 mg/L. The clinical implications of daptomycin MICs of 3 to 4 mg/L in VRE BSIs have not been elucidated. We performed a single institutional retrospective analysis of adult stem cell transplant recipients and patients with hematologic malignancies diagnosed with VRE BSI from 2006 to 2014 and compared outcomes between those with daptomycin MICs of 3 to 4 mg/L those with 2 mg/L, as determined by Etest. Forty-two daptomycin-treated VRE BSI episodes, all due to Enterococcus faecium were identified; 19 episodes with daptomycin MICs of 3 to 4 mg/L and 23 episodes with a daptomycin MIC of 2 mg/L. Patients in the higher daptomycin MIC group were more likely to be male, to be stem cell transplant recipients, and to have received high-dose daptomycin treatment (>6 mg/kg). In unadjusted analyses, microbiological failure in the daptomycin MICs 3 to 4 mg/L versus 2 mg/L groups (odds ratio = 1.79, 95% CI, 0.52–6.11; P = 0.35), the median duration of bacteremia (4 days in daptomycin MICs 3–4 mg/L vs 3 days in daptomycin MIC 2 mg/L; P = 0.18) and all-cause 30-day mortality (21% in daptomycin MICs 3–4 mg/L vs 35% in daptomycin MIC 2 mg/L group; P = 0.49) were not different. In adjusted analyses, the association between higher Pitt bacteremia scores and all-cause 30-day mortality was statistically significant (P = 0.0006), whereas the association between daptomycin MICs of 3 to 4 mg/L and all-cause 30-day mortality approached statistical significance (P = 0.06). Duration of bacteremia and microbiological failure rates did not differ by daptomycin MICs in VRE BSI episodes in our patients, composed of adult stem cell transplant recipients and patients with hematologic malignancies. There was a nonsignificant trend in multivariable analysis suggesting that all-cause 30-day mortality was lower in patients whose VRE bloodstream isolates were with daptomycin MICs of 3 to 4 mg/L.

In patients who had undergone stem-cell transplantation, lenalidomide maintenance therapy improved progression-free and overall survival, though at the expense of some increased hematologic toxicity and second malignant tumors. A goal of therapy for multiple myeloma, to induce complete remission and prolong survival, is usually accomplished with combination therapy. 1 , 2 Autologous hematopoietic stem-cell transplantation is often used after induction chemotherapy to improve the response or to consolidate complete remission. 1 , 2 However, since most patients with multiple myeloma have disease recurrence or progression after transplantation, maintenance therapies have been used to prolong complete remission and prevent relapse or progressive disease. Low-dose melphalan, interferon alfa, and glucocorticoids have been used for maintenance after primary therapy, but their long-term use is limited by toxicity and modest efficacy. 3 – 6 Five studies involving patients who . . .

This randomized study showed that including autologous transplantation as part of primary treatment improved progression-free survival but not overall survival among high-intermediate-risk and high-risk patients with aggressive lymphoma. Autologous stem-cell transplantation has long been known to improve both progression-free survival and overall survival among patients with diffuse, aggressive non-Hodgkin's lymphoma in second remission. 1 When it became possible to identify patients at diagnosis who have less than a 50% chance of sustained remission, as defined by the International Prognostic Index 2 (IPI) (see Table S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org), trials of up-front transplantation in this group were conducted. In the first trial, LNH-87, patients received full-course induction chemotherapy, regardless of their IPI risk category; those with a complete response were randomly . . .

The preferred post-remission therapy for older patients with acute myeloid leukemia (AML) in first complete remission (CR1) remains uncertain. In this retrospective, multicenter study, we compared the outcomes for older AML patients (age 60–77 years) receiving allogeneic hematopoietic cell transplantation (alloHCT) ( n  = 431) with those treated on prospective National Clinical Trials Network induction and nontransplantation chemotherapy (CT) consolidation trials ( n  = 211). AlloHCT patients were younger (median age: 64.2 versus 67.9 years, p  < 0.001), but more frequently had high-risk AML (high WBC, secondary AML, and unfavorable cytogenetics). Overall survival (OS) was worse in alloHCT during the first 9 months after CR1 (HR = 1.52, p  = 0.02), but was significantly better thereafter (HR = 0.53, p  < 0.0001) relative to CT. Treatment-related mortality (TRM) following HCT was worse in the first 9 months (HR = 2.8, 95% CI: 1.5–5.2, p  = 0.0009), while post-HCT relapse was significantly less frequent beyond 9 months (HR = 0.42, 95% CI: 0.29–0.61, p  < 0.0001). Despite higher early TRM, alloHCT recipients had superior long-term OS [29% (24–34%) versus CT 13.8% (9–21%) at 5 years]. Although this is a retrospective analysis with potential biases, it indicates that alloHCT led to heightened early risks from TRM, yet reduced relapse and superior long-term survival relative to CT in older AML patients in CR1.

PurposeCognitive impairment is common and consequential in patients with cancer who undergo allogeneic hematopoietic stem cell transplantation (HSCT). However, there is no standard of care for evaluating cognition in patients prior to or after receiving HSCT, and it is not known which patients are at highest risk for cognitive impairment. The objectives of this study were to describe cognitive function in patients prior to allogeneic HSCT and identify demographic, disease-related, and psychosocial factors associated with cognitive function.MethodsPrior to HSCT, participants completed the Montreal Cognitive Assessment (MoCA). We assessed bivariable associations between continuous MoCA scores and demographic, disease-related, and psychosocial variables using linear regression. Variables significant at the p < 0.2 level were adjusted for age, sex, and years of education in multiple linear regression analyses.ResultsOver 50% of participants demonstrated evidence of cognitive impairment (MoCA < 26) prior to transplantation. When adjusted for demographic variables, two characteristics were significantly associated with worse cognitive function: the hematopoietic cell transplantation-comorbidity index score (p = 0.01) and history of alcohol or substance abuse (p = 0.02). Pre-HSCT cancer and cancer treatment–specific variables were not associated with cognitive function.ConclusionCognitive impairment is common in patients scheduled to receive HSCT. Pre-transplantation evaluation of medical comorbidities and history of substance abuse may be important in identifying patients at risk for cognitive impairment. Further research characterizing the trajectory and impact of cognitive impairment on patient symptom burden and function may help improve outcomes.

Summary Purpose Amplification or over-expression of the mitotic Aurora A kinase (AAK) has been reported in several heme-lymphatic malignancies. MLN8237 (alisertib) is a novel inhibitor of AAK that is being developed for the treatment of advanced malignancies. The objectives of this phase I study were to establish the safety, tolerability, and pharmacokinetic profiles of escalating doses of MLN8237 in patients with relapsed or refractory heme-lymphatic malignancies. Methods Sequential cohorts of patients received MLN8237 orally as either a powder-in-capsule (PIC) or enteric-coated tablet (ECT) formulation. Patients received MLN8237 PIC 25–90 mg for 14 or 21 consecutive days plus 14 or 7 days’ rest, respectively, or MLN8237 ECT, at a starting dose of 40 mg/day once-daily (QD) for 14 days plus 14 days’ rest, all in 28-day cycles. Subsequent cohorts received MLN8237 ECT 30–50 mg twice-daily (BID) for 7 days plus 14 days’ rest in 21-day cycles. Results Fifty-eight patients were enrolled (PIC n  = 28, ECT n  = 30). The most frequent grade ≥3 drug-related toxicities were neutropenia (45 %), thrombocytopenia (28 %), anemia (19 %), and leukopenia (19 %). The maximum tolerated dose on the ECT 7-day schedule was 50 mg BID. The terminal half-life of MLN8237 was approximately 19 h. Six (13 %) patients achieved partial responses and 13 (28 %) stable disease. Conclusion The recommended phase II dose of MLN8237 ECT is 50 mg BID for 7 days in 21-day cycles, which is currently being evaluated as a single agent in phase II/III trials in patients with peripheral T-cell lymphoma.