In the temporal organization of episodic memory, the hippocampus supports the experience of elapsed time.

Space and time are both essential features of episodic memory, for which the hippocampus is critical (Howard & Eichenbaum, 2015). Spatial tasks have been used effectively to study the behavioral relevance of place cells. However, the behavioral paradigms utilized for the study of time cells have not used time duration as a variable that animals need to be aware of to solve the task. Therefore, the behavioral relevance of this cell firing is unclear. In order to directly study the role of the hippocampus in processing elapsed time, we created a novel time duration discrimination task. Rats learned to make a decision to turn left or right depending on the preceding tone duration (10 s, left turn; 20 s, right turn). Once the rats reached criterion performance of 90% correct on two out of three consecutive days, they received either an excitotoxic hippocampal lesion or a sham-lesion surgery. After recovery, rats were tested to determine hippocampal involvement in discriminating time duration. Rats with hippocampal lesions performed at chance level on their first testing day postlesion, and they were impaired relative to the sham-lesioned rats. Although the hippocampal-lesioned rats began discriminating at above chance level, their performance never returned to criterion even with 50 days of postoperative testing. Furthermore, while sham rats showed no difference in the number of errors they made on 10- versus 20-s delay trials, hippocampal lesion rats similarly improved their performance under the 10-s delay condition, but not under the 20-s delay condition. Results indicate that hippocampal lesions resulted in a selective impairment in discriminating elapsed time only during the longer delay trials. The implications of these results are discussed in relation to the limits of working-memory capacity and to the role of sustained hippocampal time cell activity in memory performance depending on the perceived relevance of the delay period.

Differential effects of an electronic symptom monitoring intervention based on the age of patients with advanced cancer.

BACKGROUND: Symptom monitoring interventions enhance patient outcomes, including quality of life (QoL), health care utilization, and survival, but it remains unclear whether older and younger patients with cancer derive similar benefits. We explored whether age moderates the improved outcomes seen with an outpatient electronic symptom monitoring intervention. PATIENTS AND METHODS: We carried out a secondary analysis of data from a randomized trial of 766 patients receiving chemotherapy for metastatic solid tumors. Patients received an electronic symptom monitoring intervention integrated with oncology care or usual oncology care alone. The intervention consisted of patients reporting their symptoms, which were provided to their physicians at clinic visits, and nurses receiving alerts for severe/worsening symptoms. We used regression models to determine whether age (older or younger than 70 years) moderated the effects of the intervention on QoL (EuroQol EQ-5D), emergency room (ER) visits, hospitalizations, and survival outcomes. RESULTS: Enrollment rates for younger (589/777 = 75.8%) and older (177/230 = 77.0%) patients did not differ. Older patients (median age = 75 years, range 70-91 years) were more likely to have an education level of high school or less (26.6% versus 20.9%, P = 0.029) and to be computer inexperienced (50.3% versus 23.4%, P < 0.001) compared with younger patients (median age = 58 years, range 26-69 years). Younger patients receiving the symptom monitoring intervention experienced lower risk of ER visits [hazard ratio (HR) = 0.74, P = 0.011] and improved survival (HR = 0.76, P = 0.011) compared with younger patients receiving usual care. However, older patients did not experience significantly lower risk of ER visits (HR = 0.90, P = 0.613) or improved survival (HR = 1.06, P = 0.753) with the intervention. We found no moderation effects based on age for QoL and risk of hospitalizations. CONCLUSIONS: Among patients with advanced cancer, age moderated the effects of an electronic symptom monitoring intervention on the risk of ER visits and survival, but not QoL. Symptom monitoring interventions may need to be tailored to the unique needs of older adults with cancer.

Pilot randomized trial of an electronic symptom monitoring intervention for hospitalized patients with cancer.

BACKGROUND: Hospitalized patients with cancer experience a high symptom burden, which is associated with poor health outcomes and increased health care utilization. However, studies investigating symptom monitoring interventions in this population are lacking. We conducted a pilot randomized trial to assess the feasibility and preliminary efficacy of a symptom monitoring intervention to improve symptom management in hospitalized patients with advanced cancer. PATIENTS AND METHODS: We randomly assigned patients with advanced cancer who were admitted to the inpatient oncology service to a symptom monitoring intervention or usual care. Patients in both arms self-reported their symptoms daily (Edmonton Symptom Assessment System and Patient Health Questionnaire-4). Patients assigned to the intervention had their symptom reports presented graphically with alerts for moderate/severe symptoms during daily team rounds. The primary end point of the study was feasibility. We defined the intervention as feasible if >75% of participants hospitalized >2 days completed >2 symptom reports. We observed daily rounds to determine whether clinicians discussed and developed a plan to address patients' symptoms. We used regression models to assess intervention effects on patients' symptoms throughout their hospitalization, readmission risk, and hospital length of stay (LOS). RESULTS: Among 150 enrolled patients (81.1% enrollment), 94.2% completed >2 symptom reports. Clinicians discussed 60.4% of the symptom reports and developed a plan to address the symptoms highlighted by the symptom reports 20.8% of the time. Compared with usual care, intervention patients had a greater proportion of days with lower psychological distress (B = 0.12, P = 0.008), but no significant difference in the proportion of days with improved Edmonton Symptom Assessment System-physical symptoms (B = 0.07, P = 0.138). Intervention patients had lower readmission risk (hazard ratio = 0.68, P = 0.224), although this difference was not significant. We found no significant intervention effects on hospital LOS (B = 0.16, P = 0.862). CONCLUSIONS: This symptom monitoring intervention is feasible and demonstrates encouraging preliminary efficacy for improving patients' symptoms and readmission risk.ClinicalTrials.gov identifier NCT02891993.

Factors associated with depression and anxiety symptoms in family caregivers of patients with incurable cancer.

BACKGROUND: Family caregivers (FCs) are critically important for patients with cancer, yet they may experience psychological distress related to caregiving demands. We sought to describe rates of depression and anxiety in FCs of patients with incurable cancer and identify factors associated with these symptoms to determine those at greatest risk for psychological distress. PATIENTS AND METHODS: We performed a cross-sectional analysis of baseline data from a randomized trial of early palliative care. We assessed depression and anxiety using the Hospital Anxiety and Depression Scale in patients within 8 weeks of diagnosis of incurable lung or gastrointestinal cancer and their FCs. We also assessed patients' quality of life (Functional Assessment of Cancer Therapy-General), coping strategies (Brief COPE), and their report of the primary goal of their cancer treatment. We used linear regression with purposeful selection of covariates to identify factors associated with FC depression and anxiety symptoms. RESULTS: We enrolled 78.6% (n = 275) of potentially eligible FCs. The majority were female (69.1%) and married to the patient (66.2%). While the proportion of FCs and patients reporting depression did not differ (16.4% versus 21.5%, P = 0.13), FCs were more likely to report anxiety compared with patients (42.2% versus 28.4%, P < 0.001). Patients' use of acceptance coping was associated with lower FC depression (B = -0.42, P < 0.001), while emotional support coping was associated with higher FC depression (B = 0.69, P = 0.001) and lower FC anxiety (B = -0.70, P < 0.001). Patient report that their primary goal of their treatment was to 'cure my cancer' was associated with higher FC depression (B = 0.72, P = 0.03). CONCLUSIONS: Patients with incurable cancer and their FCs report high levels of depression and anxiety symptoms. We demonstrated that patients' coping strategies and prognostic understanding were associated with FC depression and anxiety symptoms, underscoring the importance of targeting these risk factors when seeking to address the psychological distress experienced by FCs.

Industry-relevant magnetron sputtering and cathodic arc ultra-high vacuum deposition system for in situ x-ray diffraction studies of thin film growth using high energy synchrotron radiation.

We present an industry-relevant, large-scale, ultra-high vacuum (UHV) magnetron sputtering and cathodic arc deposition system purposefully designed for time-resolved in situ thin film deposition/annealing studies using high-energy (>50 keV), high photon flux (>10(12) ph/s) synchrotron radiation. The high photon flux, combined with a fast-acquisition-time (<1 s) two-dimensional (2D) detector, permits time-resolved in situ structural analysis of thin film formation processes. The high-energy synchrotron-radiation based x-rays result in small scattering angles (<11°), allowing large areas of reciprocal space to be imaged with a 2D detector. The system has been designed for use on the 1-tonne, ultra-high load, high-resolution hexapod at the P07 High Energy Materials Science beamline at PETRA III at the Deutsches Elektronen-Synchrotron in Hamburg, Germany. The deposition system includes standard features of a typical UHV deposition system plus a range of special features suited for synchrotron radiation studies and industry-relevant processes. We openly encourage the materials research community to contact us for collaborative opportunities using this unique and versatile scientific instrument.

Prognostic understanding, quality of life and mood in patients undergoing hematopoietic stem cell transplantation.

Little is known about how patients undergoing hematopoietic stem cell transplantation (HCT) and their family caregivers (FC) perceive their prognosis. We examined prognostic understanding in patients undergoing HCT and their FC and its relationship with quality of life (QOL) and mood. We conducted a longitudinal study of patients (and FC) hospitalized for HCT. We used a questionnaire to measure participants' prognostic understanding and asked the oncologists to estimate patients' prognosis prior to HCT. We assessed QOL and mood weekly and evaluated the relationship between prognostic understanding, and QOL and mood using multivariable linear mixed models. We enrolled 90 patients undergoing (autologous (n=30), myeloablative (n=30) or reduced intensity allogeneic (n=30)) HCT. About 88.9% of patients and 87.1% of FC reported it is 'extremely' or 'very' important to know about prognosis. However, 77.6% of patients and 71.7% of FC reported a discordance and more optimistic prognostic perception compared to the oncologist (P<0.0001). Patients with a concordant prognostic understanding with their oncologists reported worse QOL (ß=-9.4, P=0.01) and greater depression at baseline (ß=1.7, P=0.02) and over time ((ß=1.2, P<0.0001). Therefore, Interventions are needed to improve prognostic understanding, while providing patients with adequate psychological support.

Six-month freedom from treatment failure is an important end point for acute GVHD clinical trials.

We studied the American Society for Blood and Marrow Transplantation (ASBMT) 6-month (m) freedom from treatment failure (FFTF) as a predictor of survival for patients with acute GVHD (aGVHD) requiring treatment. Adult patients undergoing allogeneic hematopoietic cell transplant (HCT) from February 2007 to March 2009 who were enrolled in a prospective biomarker clinical trial and developed aGVHD requiring systemic corticosteroids by day +100 were included (N=44). Six-month FFTF was defined as per the ASBMT guidelines (absence of death, malignancy relapse/progression or systemic immunosuppression change within 6 months of starting steroids and before chronic GVHD development). aGVHD was treated with systemic corticosteroids in 44 patients. Day 28 response after steroid initiation (complete response+very good partial response+partial response) occurred in 38 (87%) patients, but only 28 (64%) HCT recipients met the 6-m FFTF end point. Day 28 response predicted 6-m FFTF. Achieving 6-m FFTF was associated with improved 2-year (y) OS (81% vs 48%; P=0.03) and decreased 2-y non-relapse mortality (8% vs 49%; P=0.01). In multivariate analysis, 6-m FFTF continued to predict improved OS (hazard ratio, 0.27; P=0.03). The 6-m FFTF end point measures fixed outcomes, predicts long-term therapeutic success and could be less prone to measurement error than aGVHD clinical response at day 28.

Ph+ ALL patients in first complete remission have similar survival after reduced intensity and myeloablative allogeneic transplantation: impact of tyrosine kinase inhibitor and minimal residual disease.

The efficacy of reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) for Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is uncertain. We analyzed 197 adults with Ph+ ALL in first complete remission; 67 patients receiving RIC were matched with 130 receiving myeloablative conditioning (MAC) for age, donor type and HCT year. Over 75% received pre-HCT tyrosine kinase inhibitors (TKIs), mostly imatinib; 39% (RIC) and 49% (MAC) were minimal residual disease (MRD)(neg) pre-HCT. At a median 4.5 years follow-up, 1-year transplant-related mortality (TRM) was lower in RIC (13%) than MAC (36%; P=0.001) while the 3-year relapse rate was 49% in RIC and 28% in MAC (P=0.058). Overall survival (OS) was similar (RIC 39% (95% confidence interval (CI) 27-52) vs 35% (95% CI 27-44); P=0.62). Patients MRD(pos) pre-HCT had higher risk of relapse with RIC vs MAC (hazard ratio (HR) 1.97; P=0.026). However, patients receiving pre-HCT TKI in combination with MRD negativity pre-RIC HCT had superior OS (55%) compared with a similar MRD population after MAC (33%; P=0.0042). In multivariate analysis, RIC lowered TRM (HR 0.6; P=0.057), but absence of pre-HCT TKI (HR 1.88; P=0.018), RIC (HR 1.891; P=0.054) and pre-HCT MRD(pos) (HR 1.6; P=0.070) increased relapse risk. RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRD(neg) status is preferred pre-HCT.

Allo-SCT for high-risk AML-CR1 in the molecular era: impact of FLT3/ITD outweighs the conventional markers.

Seventy-nine patients with AML in CR1 received allo-SCT between May 2006 and May 2011, and the prognostic impact of FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) mutation was evaluated in the context of other clinical prognostic factors. Patients with FLT3/ITD + AML had significantly inferior DFS (2-year DFS: 19% vs 64%, P = 0.0027), increased risk of relapse (1-year: 59% vs 19%, P = 0.01), and a trend towards decreased OS (P = 0.08) compared with patients without FLT3/ITD. Multivariate analysis confirmed FLT3/ITD + independently predicted a shorter DFS (HR, 3.0; 95% CI), 1.4-6.5; P = 0.01) and increased risk of relapse (HR, 4.9; 95% CI, 2.0-12.3, P = 0.01). Time to relapse in patients with FLT3/ITD + was short with 100-day cumulative risk of 45% (95% CI, 33-57). Our data suggest that the poor prognostic implication of FLT3/ITD positivity remains even after early allo-SCT in patients with FLT3/ITD + AML, and patients remain at high risk of early relapse. FLT3/ITD positivity also outweighs other conventional prognostic markers in predicting relapse.

Prevalence and risk factors associated with development of ocular GVHD defined by NIH consensus criteria.

We studied 172 patients for development of ocular graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT) from 2002 to 2009. Ocular GVHD was diagnosed in 60 patients (38%), with 27 (16%) being diagnosed at days 100 and 33 (23%) beyond day 100 for a 2-year cumulative incidence of 35% (95% confidence interval (CI), 28-43). The positive and negative predictive values of a Schirmer I test score (using 5 mm as a cutoff) in predicting ocular GVHD (day 100) were 41 and 82%, respectively. In patients with ocular GVHD beyond day 100, extraocular manifestations of GVHD preceded the development of ocular GVHD in most patients (27 of 33, 81%). Prior acute skin GVHD (odds ratio 2.57, 95% CI 1.17-5.64, P=0.019) and male recipients of female donors (odds ratio 2.57, 95% CI 1.09-6.06, P=0.03) were independent risk factors for ocular GVHD. We recommend comprehensive ocular evaluation rather than a screening Schirmer's test to establish the diagnosis of ocular GVHD. Early diagnosis and preventive strategies in high-risk populations need to be studied in clinical trials to prevent devastating impact on quality of life in patients with prolonged ocular GVHD.

Long-term outcome after autologous or allogeneic stem cell transplantation in patients with recurrent follicular lymphoma.

Thirty-five consecutive patients with follicular lymphoma (FL) receiving SCT at our institution between January 2000 and December 2010 were included in this study. At the time of presentation, 30 (86%) had advanced stage disease and 25 (71%) received three or more chemotherapy regimens prior to transplantation. In all, 12 (34%) patients were in complete response pre-SCT following salvage therapy. At the time of analysis (median follow-up 6 years from diagnosis and 4 years from transplantation), 24 patients were alive with an estimated 5-year OS and PFS of 66.5 and 53%, respectively. OS and PFS in patients receiving auto-SCT (91.7%, 73.3%) were superior compared with patients receiving allo-SCT (53.9%, 43%). Our data support early use of auto-SCT in patients with FL and suggest the need to improve allo-SCT outcome. Integrating novel agents in a combined modality approach may improve long-term outcome in FL.

Serology in autoimmune pancreatitis.

Autoimmune pancreatitis (AIP) is the pancreatic manifestation of a systemic immune-driven, inflammatory process that can involve organs such as the bile duct, salivary glands and lymph nodes, in addition to the pancreas. Many of the presenting signs and symptoms of AIP, including painless jaundice, weight loss and mild epigastric pain, are characteristic of pancreatic adenocarcinoma; thus, obtaining an accurate diagnosis to avoid unnecessary surgery is imperative. AIP responds very well to steroid treatment, although it may recur in up to 20% to 40% of cases. The diagnostic criteria for AIP are histological, radiographic, clinical and laboratory-based in nature. Although no international consensus on diagnostic criteria has yet been made, some of the diagnostic features of AIP include elevated gamma globulin, immunoglobulin, and, in particular, immunoglobulin G4 fraction (IgG4). The search for a distinct serological marker of AIP has included antibodies to a wide range of antigenic stimuli. To date, there have been studies of AIP and antibodies to lactoferrin, carbonic anhydrase isoforms II and IV, pancreatic secretory trypsin inhibitor (PSTI or SPINK) as well as to less sensitive or specific markers of autoimmunity, such as antinuclear antibody and rheumatoid factor. Although there are some preliminary strengths of association with PSTI antibodies, none of these biomarkers appears to be sensitive or specific enough to serve as distinctive evidence of AIP. At the current time, elevations of IgG4 to greater than 280 mg/dL remain the most reliable and reproducible indicator that a patient has AIP.

ATP sensitivity of preBötzinger complex neurones in neonatal rat in vitro: mechanism underlying a P2 receptor-mediated increase in inspiratory frequency.

P2 receptor (R) signalling plays an important role in the central ventilatory response to hypoxia. The frequency increase that results from activation of P2Y(1)Rs in the preBötzinger complex (preBötC; putative site of inspiratory rhythm generation) may contribute, but neither the cellular nor ionic mechanism(s) underlying these effects are known. We applied whole-cell recording to rhythmically-active medullary slices from neonatal rat to define, in preBötC neurones, the candidate cellular and ionic mechanisms through which ATP influences rhythm, and tested the hypothesis that putative rhythmogenic preBötC neurones are uniquely sensitive to ATP. ATP (1 mm) evoked inward currents in all non-respiratory neurones and the majority of respiratory neurons, which included inspiratory, expiratory and putative rhythmogenic inspiratory neurones identified by sensitivity to substance P (1 microM) and DAMGO (50 microM) or by voltage-dependent pacemaker-like activity. ATP current densities were similar in all classes of preBötC respiratory neurone. Reversal potentials and input resistance changes for ATP currents in respiratory neurones suggested they resulted from either inhibition of a K(+) channel or activation of a mixed cationic conductance. The P2YR agonist 2MeSADP (1 mm) evoked only the latter type of current in inspiratory and pacemaker-like neurones. In summary, putative rhythmogenic preBötC neurones were sensitive to ATP. However, this sensitivity was not unique; ATP evoked similar currents in all types of preBötC respiratory neurone. The P2Y(1)R-mediated frequency increase is therefore more likely to reflect activation of a mixed cationic conductance in multiple types of preBötC neurone than excitation of one, highly sensitive group.

Pegfilgrastim after high-dose chemotherapy and autologous peripheral blood stem cell transplant: phase II study.

Pegfilgrastim is equivalent to daily filgrastim after standard dose chemotherapy in decreasing the duration of neutropenia. Daily filgrastim started within 1-4 days after autologous stem cell transplant (ASCT) leads to significant decrease in time to neutrophil engraftment. We undertook a study of pegfilgrastim after high-dose chemotherapy (HDC) and ASCT. In all, 38 patients with multiple myeloma or lymphoma, eligible to undergo HDC and ASCT, were enrolled. Patients received a single dose of 6 mg pegfilgrastim subcutaneously 24 h after ASCT. There were no adverse events secondary to pegfilgrastim. All patients engrafted neutrophils and platelets with a median of 10 and 18 days, respectively. The incidence of febrile neutropenia was 49% (18/37). Neutrophil engraftment results were compared to a historical cohort of patients who received no growth factors or prophylactic filgrastim after ASCT. Time to neutrophil engraftment using pegfilgrastim was comparable to daily filgrastim and was shorter than in a historical group receiving no filgrastim (10 vs 13.7 days, P<0.001). Pegfilgrastim given as a single fixed dose of 6 mg appears to be safe after HDC and ASCT. It accelerates neutrophil engraftment comparable to daily filgrastim after ASCT. Pegfilgrastim may be convenient to use in outpatient transplant units.

T cell and NK cell lymphoproliferative disorders.

This review covers the diagnosis and management of natural killer and peripheral T-cell lymphomas (PTCL). Problems with PTCL include their rarity, representing usually 10-15% of non-Hodgkin's lymphomas in the Western Hemisphere, morphologic heterogeneity, and lack of immunophenotypic markers for clonality. Additionally, their clinical behavior is variable and may not correlate with morphology. Dr. Kinney gives a general overview of the diagnosis of PTCL and NK cell neoplasms. Emphasis will be placed on extranodal T cell and natural killer (NK) cell lymphomas such as hepatosplenic lymphoma, subcutaneous panniculitis-like lymphoma and nasal/nasal type T/NK-cell lymphoma. The use of ALK gene regulation in the classification of anaplastic large cell lymphoma is also reviewed. Dr. Loughran describes current understanding of the pathogenesis of large granular lymphocyte (LGL) leukemia. The discussion focuses on LGL leukemia as an instructive model of dysregulated apoptosis causing both malignant and autoimmune disease. Current management options and mechanisms of therapeutic response are also described. Dr. Greer addresses whether PTCL should be treated differently from the more common diffuse large B cell lymphomas. He discusses the therapeutic options for anaplastic large cell lymphoma (ALCL), from a conservative approach for primary cutaneous ALCL to combination chemotherapy for the highly chemosensitive ALCL expressing anaplastic lymphoma kinase. He reviews therapy options for the extranodal subtypes of PTCL by drawing from series in adults, pediatrics, dermatology, and the Far East.

Age and cytogenetics as predictors of event free survival in patients with acute non-lymphocytic leukemia receiving high dose cytosine arabinoside and daunorubicin as consolidation chemotherapy.

Between 1991 and 1999, 67 patients with acute non-lymphocytic leukemia (ANLL) in complete remission received high dose cytarabine (HiDAC) 3 gm/m2 q12h x 12 doses followed by daunorubicin 45 mg/m2/day x 3 days as consolidation therapy. Five year actuarial event free survival (EFS) was 34% +/- 6%. Age was significantly associated with EFS. EFS was 60% +/- 15% in patients age 20 to 29, 48% +/- 16% in patients age 30 to 39, 23% +/- 10% in patients age 40 to 49, 31% +/- 11% in patients age 50 to 59, and 0% in patients age > or = 60. Contrary to other reports which have used different HiDAC regimens, we found no relationship between cytogenetics and EFS. Cytogenetics were defined as favorable risk: t(8;21), inv (16), and del (16); neutral risk: normal or t(15;17); and unfavorable risk: any abnormality not included in favorable risk or neutral risk. EFS was 29% +/- 17% in patients with favorable cytogenetics, 37% +/- 14% in patients with neutral cytogenetics, and 31% +/- 12% in patients with unfavorable cytogenetics. These differences were not statistically significant. Because of the successful use of allogeneic transplantation at relapse in patients with matched related donors, five year actuarial survival (S) in this series was 40% +/- 6%. Five year actuarial survival was 57% +/- 9% for patients age < or = 44 and 25% +/- 8% for patients age > or = 45. This difference is statistically significant, p < .025. Clinicians should be cautious about making clinical decisions regarding consolidation therapy of ANLL on the basis of the presence or absence of cytogenetic abnormalities as the importance of cytogenetics may depend on the specific therapy which is employed.

Valacyclovir for the prevention of cytomegalovirus infection after allogeneic stem cell transplantation: a single institution retrospective cohort analysis.

A retrospective single center study was performed to evaluate the safety and efficacy of valacyclovir for prevention of cytomegalovirus (CMV) infection (reactivation) after allogeneic stem cell transplantation (SCT). We compared a group of 31 patients at risk for CMV reactivation (donor, recipient or both seropositive for CMV) who received valacyclovir at an oral dose of 1 g three times a day for CMV prophylaxis with a matched cohort of 31 patients who did not receive the drug or any other form of CMV prophylaxis. Valacyclovir was used as primary prophylaxis in 12 patients and as secondary prophylaxis (after a prior CMV reactivation was effectively treated with either ganciclovir or foscarnet and without CMV antigenemia at the start of valacyclovir) in the remaining 19 patients. The two treatment groups were well matched for the donor-recipient CMV serological status and other pre-transplant characteristics. CMV reactivation was detected by blood antigenemia testing using a commercially available immunofluorescence assay for CMV lower matrix protein pp65 in circulating leukocytes. For primary prophylaxis, 3/12 patients who received valacyclovir reactivated CMV compared to 24/31 patients in the control group (P < 0.001). For secondary prophylaxis, 5/19 valacyclovir patients reactivated compared to 16/24 control patients (P < 0.05). Valacyclovir was well tolerated except for infrequent and mild gastrointestinal side-effects. There was no difference in the incidence of CMV disease in the two groups. Prophylaxis with valacyclovir appears to be safe and efficacious in preventing both primary and secondary CMV reactivation in at-risk patients after allogeneic SCT. Larger prospective randomized studies will be required to confirm these observations.

Limited efficacy of intensified preparative regimens and autologous transplantation as salvage therapy in high grade non-Hodgkin's lymphoma.

Between 9/86 and 6/98, 22 patients with relapsed or refractory high grade lymphoma received intensified preparative therapy and underwent autologous transplantation at a single institution. Two intensified preparative regimens were used--cyclophosphamide, etoposide, total body irradiation (CY-VP-TBI) (N=17) and cyclophosphamide, BCNU, etoposide (CBV) (N=5). For all patients undergoing autologous transplantation, 5 year actuarial survival (S) and 5 year event free survival (EFS) were only 18% +/- 8%. Treatment related mortality was 14% overall but only 8% in patients receiving G-CSF or GM-CSF. Survival was significantly inferior to the survival observed in a concurrent series of patients with intermediate grade lymphoma, 34% +/- 6%, p < .05. Using high dose therapy in conjunction with autologous transplantation at the time of relapse may not be as valuable a strategy in high-grade lymphoma as in intermediate grade lymphoma although most studies combine the two disorders. Alternative strategies for the use of transplantation in high grade lymphoma, such as the use of transplantation as consolidation therapy, need to be investigated.

Is total body irradiation a necessary component of preparative therapy for autologous transplantation in non-Hodgkin's lymphoma.

Between September 1986 and June 1998, 157 patients with low grade, intermediate grade, or high grade lymphoma underwent autologous transplantation at a single institution. Two preparative regimens were used: cyclophosphamide, etoposide, total body irradiation (CY-VP-TBI) (N=110) and cyclophosphamide, BCNU, etoposide (CBV) (N=47). The two groups were not significantly different with respect to source of stem cells, gender, stage at presentation, incidence of prior bone marrow involvement, sensitivity to salvage therapy, or histologic grade of lymphoma. The CBV group was significantly older, 49% of patients over age 50, as compared to 26% of patients over age 50 for the CY-VP-TBI group. Response rates and the incidence of fatal toxicity were similar for the two groups. Five year actuarial survival was 31% +/- 9% for CBV and 38% +/- 5% for CY-VP-TBI, p =.85. In a multivariate analysis, in which preparative regimen, age, histologic grade of lymphoma, and sensitivity to salvage therapy were the independent variables, TBI was not significantly associated with survival, and the direction of the trend was for TBI to be less effective than CBV. TBI does not appear to be an essential component of preparative therapy for autologous transplantation in patients with lymphoma.