An algorithm for utilizing peripheral blood CD34 count as a predictor of the need for plerixafor in autologous stem cell mobilization--cost-effectiveness analysis.

Certain patients who receive granulocyte colony-stimulating factor (GCSF) for autologous hematopoietic stem cell (AHSC) collection fail to mobilize well enough to proceed with transplant. When plerixafor is used with GCSF, the likelihood of achieving the CD34⁺ stem cell target in fewer collections is higher; plerixafor use in all patients is unlikely to be cost-effective. This study retrospectively evaluated the effectiveness of utilizing a peripheral blood CD34⁺ stem cell count (PBCD34) ≤8/µL on day 4 of GCSF-based AHSC mobilization as a threshold for plerixafor administration, and compared the efficacy of collection and cost analysis using historical controls. All patients in the study cohort reached their CD34⁺ targets in ≤3 collections. Significantly more patients who received plerixafor + GCSF versus GCSF alone reached their CD34⁺ target in one collection (P = 0.045); however, there were no significant differences in the number of collections or in cumulative product yields. The historical cohort had 10.3% mobilization failures; the number of collections per patient needed to reach the target was significantly higher in the historical cohort versus study cohort (P = 0.001) as was the number of patients requiring more than one collection to reach their target (P = 0.023). However, the average cost per patient was also significantly higher in the study cohort (P = 0.025). Further refinement of the algorithm may reduce the difference in cost between the two mobilization strategies.

Outcome of allogeneic stem cell transplantation in myelodysplastic syndrome patients: prognostic implication of monosomal karyotype.

OBJECTIVE: Monosomal karyotype (MK) is defined as the presence of two or more autosomal monosomies or a single monosomy associated with a structural abnormality. It was first described as a high-risk cytogenetic abnormality for acute myeloid leukemia and more recently in myelodysplastic syndromes (MDS). However, allotransplant outcome in MDS with MK has not been described. PATIENTS AND METHODS: We retrospectively reviewed data of 79 patients with MDS who underwent allotransplant at the University of Iowa from 1990 to 2009. We recorded patients' cytogenetic data, clinical characteristics and evaluated outcome following allogeneic stem cell transplant stratified by cytogenetic classification. RESULTS: Of 79 patients, 37 (47%) had unfavorable karyotypes (23 complex karyotype, 25 abnormal chromosome 7). Twenty-four patients (30%) had MK. Twenty-four patients (30%) relapsed and 59 (74.7%) died during study period. Patients with MK had higher 2-yr relapse incidence (RI) (51% vs. 29%; P = 0.01), lower 2-yr event-free survival (EFS) (8% vs. 40%; P = 0.02), and lower 2-yr overall survival (OS)(6% vs. 41%; P = 0.02) than patients without MK. We further analyzed the effect of MK in each unfavorable karyotype composite. Although the outcome was not statistically different, unfavorable karyotypes with patients with MK showed a trend toward higher 2-yr RI [hazard ratio (HR), 1.7; P = 0.34], lower 2-yr EFS (HR, 1.5; P = 0.29), and lower 2-yr OS (HR, 1.5; P = 0.28) compared to unfavorable karyotypes without MK. CONCLUSION: Cytogenetic abnormalities remain an important prognostic factor for allotransplant outcome of MDS. Our results suggested poor allotransplant outcomes with high RI and low OS in MDS with MK.

Risk factors for delirium in patients undergoing hematopoietic stem cell transplantation.

BACKGROUND: Delirium is common after hematopoietic stem cell transplantation (HSCT) and is associated with increased morbidity and mortality. Early recognition and treatment have been shown to improve long-term outcomes. We sought to investigate the relationship between potential risk factors and the development of delirium following HSCT. METHODS: Fifty-four inpatients admitted for HSCT were assessed prospectively for delirium every 2 to 3 days during their inpatient stay using standardized delirium and neuropsychological measures. Self reports of medical history, medical records, and neurocognitive and psychiatric assessments were used to identify risk factors. Both pre- and post-HSCT risk factors were examined. RESULTS: Delirium incidence was 35% and occurred with highest frequency in the 2 weeks following transplant. The only pre-transplantation risk factor was lower oxygen saturation (P = .003). Post-transplantation risk factors for delirium included higher creatinine (P < .0001), higher blood urea nitrogen levels (P = .005), lower creatinine clearance (P = .0006), lower oxygen saturation (P = .001), lower hemoglobin (P = .04), and lower albumin (P = .03). There was no observed association with level of cognitive performance, transplant type, disease severity, medical comorbidity index, age, or conditioning regimen. CONCLUSIONS: Routine laboratory values can assist in the identification of high-risk patients before delirium onset to improve early detection and treatment of delirium after HSCT.

Proton Magnetic Resonance Spectroscopy in adult cancer patients with delirium.

Delirium is associated with a host of negative outcomes, including increased risk of mortality, longer hospital stay, and poor long-term cognitive function. The pathophysiology of delirium is not well understood. Cancer patients undergoing a bone marrow transplant (BMT) are at high risk for developing delirium and Proton Magnetic Resonance Spectroscopy ((1)H MRS) could lead to better understanding of the delirium process. Fourteen BMT patients and 10 controls completed (1)H MRS, positioned above the corpus callosum, shortly after delirium onset or at study end if no delirium occurred. In the BMT-delirium group, statistically significantly elevated tCho/tCr was found in contrast to the BMT-no delirium group. The BMT-delirium group also showed statistically significantly lesser NAA/tCho compared with both controls and the BMT-no delirium group. Elevated choline and reduced NAA indicate inflammatory processes and white matter damage as well as neuronal metabolic impairment. Further research is needed to separate the choline peaks, as well as more detailed collection of medication regimens to determine whether a higher choline concentration is a function of the delirium process or cancer treatment effects.

Clinical and ultrasonic evaluation of spleen size during peripheral blood progenitor cell mobilization by filgrastim: results of an open-label trial in normal donors.

Rare reports of splenic rupture have been associated with filgrastim treatment during peripheral blood progenitor cell (PBPC) mobilization in allogeneic donors. We performed a prospective study of spleen volume change in 309 normal donors who received filgrastim according to local institutional practices. Splenic assessments consisted of ultrasonography and clinical examination at baseline and on the first day of leukapheresis in 304 donors. Of these, 90 donors were also examined 2 and 4 days after the first leukapheresis and 7 days after the last leukapheresis. Median spleen volume increased 1.47-fold (range: 0.63 to 2.60) on the first leukapheresis day and declined to near pretreatment levels at 7 days after last leukapheresis. Nine percent of donors had > or =2-fold increase in splenic volume. Spleen palpability did not correlate with change in spleen volume. No donors experienced a splenic rupture. There was no correlation between change in spleen volume and filgrastim dosage, number of doses/day, peak absolute neutrophil count (ANC), CD34+ yield, or donor baseline weight. Most donors experienced > or =1 adverse event, with 6 donors reporting serious adverse events. We conclude that the increase in splenic volume during PBPC mobilization in donors was transient, and that filgrastim was well tolerated in this study. This trial was registered at www.ClinicalTrials.gov as NCT00115128.

A fatal case of West Nile virus infection in a bone marrow transplant recipient.

West Nile virus (WNV) can cause severe, potentially fatal neurological illnesses, which include encephalitis, meningitis, Guillain-Barré syndrome, and anterior myelitis. Because of the short viremic phase, WNV infection is most commonly diagnosed by detection of immunoglobulin M antibody to WNV in serum or cerebrospinal fluid (CSF). We describe a patient with T cell lymphoma who had undergone a T cell-depleted bone marrow transplantation and developed fatal WNV infection. The results of serological tests of blood samples and of CSF tests were negative. Diagnosis was made postmortem by a positive result of reverse-transcriptase polymerase chain reaction (ABI 7700; TaqMan) for WNV in stored CSF and serum samples.

The neuropsychological course of acute delirium in adult hematopoietic stem cell transplantation patients.

Although delirium is a common medical comorbidity with altered cognition as its defining feature, few publications have addressed the neuropsychological prodrome, profile, and recovery of patients tested during delirium. We characterize neuropsychological performance in 54 hemapoietic stem cell/bone marrow transplantation (BMT) patients shortly before, during, and after delirium and in BMT patients without delirium and 10 healthy adults. Patients were assessed prospectively before and after transplantation using a brief battery. BMT patients with delirium performed more poorly than comparisons and those without delirium on cross-sectional and trend analyses. Deficits were in expected areas of attention and memory, but also in psychomotor speed and learning. The patients with delirium did not return to normative "average" on any test during observation. Most tests showed a mild decline in the visit before delirium, a sharp decline with delirium onset, and variable performance in the following days. This study adds to the few investigations of neuropsychological performance surrounding delirium and provides targets for monitoring and early detection; Trails A and B, RBANS Coding, and List Recall may be useful for delirium assessment.

18-Fluoro-deoxyglucose positron emission tomography report interpretation as predictor of outcome in diffuse large B-cell lymphoma including analysis of 'indeterminate' reports.

This study evaluates the predictive value of post-therapy 18-fluoro-deoxyglucose positron emission tomography (FDG-PET), including indeterminate studies, following curative-intent therapy in diffuse large B-cell lymphoma (DLBCL). Consecutive patients from September 2002 to December 2005 were prospectively offered enrollment in an observational registry. Available FDG-PET reports after primary therapy were interpreted by hematologist-oncologists as positive, negative, or indeterminate. One hundred twenty-five patients with DLBCL had a median follow-up of 35.2 months. Ninety-three percent were treated with R-CHOP-like therapy. Twenty percent of PET reports were judged indeterminate. Event-free survival (EFS) at 3 years for the negative and indeterminate groups was 85% and 71%, respectively (p = 0.28 by log-rank). Overall survival (OS) at 3 years for negative, indeterminate, and positive groups was 89%, 88%, and 48%. Combining the pre-therapy International Prognostic Index (IPI) with the post-therapy FDG-PET result added to the predictive value of the study for patients. Three-year EFS for patients with low or low-intermediate IPI risk and an indeterminate FDG-PET report was 93%, while for those with high or high-intermediate pre-therapy IPI the 3-year EFS was 45% (p < 0.02). Interpreting FDG-PET reports following curative-intent chemotherapy in patients is informative but imprecise, and incorporation of pre-therapy prognosis can improve predictive utility.

Neuropsychological and psychiatric functioning pre- and posthematopoietic stem cell transplantation in adult cancer patients: a preliminary study.

The current study characterizes cognitive and psychiatric status in hematopoietic stem cell transplantation (HSCT) patients shortly before and after transplant. Thirty adult patients were assessed prospectively 1-2 weeks before transplantation and 100 days posttransplantation on neuropsychological and psychiatric measures. Before transplant, participants showed mild impairments on several neuropsychological measures, with the poorest performances occurring on learning and attention. Psychiatric functioning was significantly elevated compared with normative data. Significant improvements, however, were observed on neuropsychological measures by 100 days after transplant. Depression and anxiety scores also improved. Candidates for HSCT experienced mild diffuse cognitive dysfunction and psychiatric morbidity before the procedure, but these symptoms significantly improved by 3 months following their transplant in this small sample. Education about these possible pretransplant sequelae and the potential for rebound may be helpful to patients and families as they prepare for this treatment and the recovery period.

Incidence of delirium and associated mortality in hematopoietic stem cell transplantation patients.

Delirium has been associated with a high risk of mortality in medical patients. Despite the high incidence of delirium in patients who undergo hemapoietic stem cell transplantation (HSCT), delirium as a risk factor for death has not been examined in this population. Thirty adult patients undergoing HSCT who were admitted to the University of Iowa Blood and Marrow Transplantation Program inpatient unit were assessed prospectively from 1 to 2 weeks before transplantation, throughout their inpatient stay, and at 100 days after transplantation. The Delirium Rating Scale and Memorial Delirium Assessment Scale were used twice weekly during the inpatient period to assess delirium severity and occurence. Patients' self-reports of medical history, computerized medical records, and neuropsychological and psychiatric assessments were used to identify pretransplantation risk factors. The incidence of delirium (Delirium Rating Scale score >12 or Memorial Delirium Assessment Scale score >or=8) was 43% and occurred with highest frequency in the first 2 weeks after transplantion. The presence of delirium at any point during hospitalization after transplantation and transplant type (allogeneic) were highly predictive of mortality (p < .0005; odds ratios, 14.0 and 14.4). In conclusion, this study highlights the importance of monitoring for delirium during the acute recovery period after transplantation and suggests that early or even prophylactic treatment for delirium should be studied. Studies to determine the factors that connect delerium soon after transplantation to mortality are highly warranted.

The effect of unrelated donor marrow transplantation on health-related quality of life: a report of the unrelated donor marrow transplantation trial (T-cell depletion trial).

The primary objective of this study was to compare health-related quality of life (HRQL) in adult patients undergoing either ex vivo T cell-depleted bone marrow transplantation or conventional marrow transplantation. Data on patients' HRQL were gathered as part of a multicenter randomized trial comparing the effect of ex vivo T-cell depletion versus methotrexate and cyclosporine immunosuppression on disease-free survival. HRQL assessments were conducted at baseline, day +100, 6 months, 1 year, and 3 years. There were no treatment arm differences 1 year after transplantation on the Functional Assessment of Cancer Therapy, Bone Marrow Transplantation, the Medical Outcomes Study Short-Form 36, and the Centers for Epidemiological Studies of Depression. The lack of treatment differences was robust across types of data analyses that took baseline functioning into account and that recognized the sensitivity of outcome measures to assumptions concerning missing data. The trajectory of recovery revealed an initial decrease in function and then a recovery to pretreatment levels that were similar for both treatment arms. Furthermore, the patients in both treatment groups returned to a functional level that approximated general US population norms. Even though the incidence of acute graft-versus-host disease was slightly higher in the conventional treatment arm, T-cell depletion did not differentially affect HRQL at 1 year after transplantation.

Influence of T-cell depletion on chronic graft-versus-host disease: results of a multicenter randomized trial in unrelated marrow donor transplantation.

Donor-derived T cells have been proposed to play a role in pathogenesis of chronic graft-versus-host disease (cGVHD). The impact of ex vivo T-cell depletion (TCD) on cGVHD was analyzed in a randomized multicenter trial involving unrelated donor marrow transplants. A total of 404 patients diagnosed with hematologic malignancies received a total body irradiation-based myeloablative conditioning regimen. GVHD prophylaxis included TCD plus cyclosporine (CSA) or unmodified grafts with CSA plus methotrexate (M/C). Median recipient age was 31.2 years (range, 0.5-55.6 years); median follow-up time since randomization was 4.2 years. The mean number of T cells infused was 1 log lower on the TCD arm. The incidence of cGVHD at 2 years was similar between the TCD and M/C arms, 29% versus 34% (P = .27), respectively. Survival at 3 years from diagnosis of cGVHD was also similar, (TCD 51% versus M/C 58%; P = .29). The proportion of patients with cGVHD who discontinued immunosuppression at 5 years was not different (TCD 72% versus M/C 63%; P = .27), and incidence of serious infections and leukemia relapse were similar on both treatment arms. In spite of a significant reduction of acute GVHD, TCD did not reduce the incidence of cGVHD or improve survival in patients who developed cGVHD.