Susan K. Parsons

Factor Structure of the Brief Symptom Inventory--18 in Adult Survivors of Childhood Cancer: Results from the Childhood Cancer Survivor Study.

The factor structure of the Brief Symptom Inventory--18 (BSI-18; L. R. Derogatis, 2000) was investigated in a sample of adult survivors of childhood cancer enrolled in the Childhood Cancer Survivor Study (CCSS; N = 8,945). An exploratory factor analysis with a randomly chosen subsample supported a 3-factor structure closely corresponding to the 3 BSI-18 subscales: Depression, Anxiety, and Somatization. Confirmatory factor analysis with structural equation modeling validated this 3-dimensional structure in a separate subsample, though an alternative 4-factor model also fit the data. Analysis of the 3-factor model showed consistent fit in male and female participants. Compared with available community-based norms, survivors reported fewer symptoms of psychological distress. Together, results support the hypothesized 3-dimensional structure of the BSI-18 and indicate the measure may be useful in assessing psychological distress in this growing population of cancer survivors.

Significant Improvement in Survival After Allogeneic Hematopoietic Cell Transplantation During a Period of Significantly Increased Use, Older Recipient Age, and Use of Unrelated Donors

PURPOSE Over the past four decades, allogeneic hematopoietic cell transplantation (alloHCT) has evolved as a curative modality for patients with hematologic diseases. This study describes changes in use, technique, and survival in a population-based cohort. PATIENTS AND METHODS The study included 38,060 patients with hematologic malignancies or disorders who underwent first alloHCT in a US or Canadian center from 1994 to 2005 and were reported to the Center for International Blood and Marrow Transplant Research. RESULTS AlloHCT as treatment for acute lymphoblastic (ALL) and myeloid leukemias (AML), myelodysplastic syndrome (MDS), and Hodgkin and non-Hodgkin lymphomas increased by 45%, from 2,520 to 3,668 patients annually. From 1994 to 2005, use of both peripheral (7% to 63%) [corrected] and cord blood increased (2% to 10%), whereas use of marrow decreased (90% to 27%). Despite a median age increase from 33 to 40 years and 165% [corrected] increase in unrelated donors for alloHCT, overall survival (OS) at day 100 significantly improved for patients with AML in first complete remission after myeloablative sibling alloHCT (85% to 94%; P < .001) and unrelated alloHCT (63% to 86%; P < .001); 1-year OS improved among those undergoing unrelated alloHCT (48% to 63%; P = .003) but not among those undergoing sibling alloHCT. Similar results were seen for ALL and MDS. Day-100 OS after cord blood alloHCT improved significantly from 60% to 78% (P < .001) for AML, ALL, MDS, and chronic myeloid leukemia. Use of reduced-intensity regimens increased, yielding OS rates similar to those of myeloablative regimens. CONCLUSION Survival for those undergoing alloHCT has significantly improved over time. However, new approaches are needed to further improve 1-year OS.

Polysaccharide conjugate vaccine responses in bone marrow transplant patients

Bone marrow transplant patients have impaired responses to pure polysaccharide (PS) vaccines and are at an increased risk for disease caused by PS encapsulated pathogens such as Haemophilus influenzae type B (HIB) and Streptococcus pneumoniae. We immunized 35 BMT patients (21 allogeneic and 14 autologous) ages 2-45 years with pure PS pneumococcal (Pnu-imune 23) HIB-conjugate (HibTITER), and tetanus toxoid vaccines. Patients were assigned to receive vaccines at either 12 and 24 months after transplantation or at 24 months only. Only 19% of all enrolled patients developed protective antibody concentrations (> or = 0.300 microgram antibody nitrogen/ml) to the 6 pneumococcal serotypes measured after the 24-month immunization. Poor response to pneumococcal vaccine was not different for the 2 study groups and was similar to previous studies. In contrast, HIB-conjugate vaccine elicited protective concentrations of antibody (> or = 1.0 microgram/ml) in 56% of patients after 1 dose and in 80% after 2 doses. The group that received 2 doses of HIB-conjugate vaccine had a significantly higher geometric mean antibody concentration of 14.5 micrograms/ml as compared with 1.43 micrograms/ml for those receiving only 1 dose (P = 0.012). Responses to tetanus toxoid vaccine were similar to HIB-conjugate vaccine, with a booster response documented after the second dose. In summary, 2 doses of HIB-conjugate vaccine given at 12 and 24 months after transplantation produced protective antibody concentrations in 80% of patients. While the response to pure PS pneumococcal vaccine was poor, the results with HIB-conjugate vaccine suggest that future pneumococcal conjugate vaccines may also benefit BMT patients.

Recovery after stem-cell transplantation for hematologic diseases

PURPOSE Although the number of autologous and allogeneic stem-cell transplantations (SCT) is increasing, relatively little information about recovery after transplantation is available. Quantitative information appropriate for patient counseling is difficult to discern from the literature. We sought to suggest reasonable expectations for recovery and symptoms after SCT for hematologic malignancies and other disorders using the following measures: (1) objective measures of health status, such as frequency of clinic visits, need for rehospitalization, medication usage, work status, and overall and event-free survival; (2) qualitative assessment of quality of life, such as returning to a normal life, resumption of normal activities, satisfaction with appearance, and whether recovery has occurred; and (3) quantification of specific bothersome symptoms. PATIENTS AND METHODS Autologous and allogeneic SCT recipients at a tertiary-care transplant center participated in the prospective, longitudinal questionnaire study. RESULTS Three hundred twenty patients were studied. Questionnaire response rates at 6, 12, and 24 months range from 85% to 88% among survivors. Although autologous patients had better event-free and overall survival, fewer symptoms, and more complete recovery at 6 months, these advantages had largely equalized by 12 months. Specific bothersome symptoms were reported by less than 24% of patients after transplantation, except for fatigue and financial and sexual difficulties, which were more prevalent. CONCLUSION These findings may help counsel patients considering transplantation and educate them about reasonable expectations for recovery. Overall, the low level of bothersome symptoms and continued recovery through the first year after transplantation are encouraging.

Improved survival for patients with acute myelogenous leukemia.

PURPOSE Despite improvement in chemotherapy and supportive care over the past two decades, overall survival for patients with acute myelogenous leukemia (AML) remains poor; only 25% to 30% of individuals with this disorder will be cured. In 1987, we initiated a prospective multiinstitution study designed to improve long-term survival in adults with AML. METHODS We modified the usual 7-day treatment scheme of daunorubicin and cytarabine with high-dose cytarabine (HiDAC) on days 8 through 10 (3 + 7 + 3). Allogeneic or autologous bone marrow transplantation (BMT) was offered to all patients who entered complete remission (CR) to decrease the rate of leukemic relapse. Data were analyzed by intention to treat. RESULTS CRs were achieved in 84 of 94 patients (89%; 95% confidence interval [CI], 83 to 95). Because of the high remission rate, factors previously thought to predict outcome, such as cytogenetics, WBC count, French-American-British (FAB) classification, sex, and age, were not useful prognostic variables. The overall survival rate for the entire cohort of patients from data of diagnosis is 55% at 5 years. Sixty percent of all patients who achieved a CR underwent marrow grafting. There was no significant difference in event-free survival (EFS) at 5 years comparing patients assigned to receive allogeneic BMT with patients assigned to receive autologous BMT (56% v 45%, P = .54). CONCLUSION The long-term disease-free survival observed in this study is excellent compared with historical data. This improvement in survival is probably due to the high rate of remission induction, as well as to the effective nature of the consolidation therapy.

Current practice patterns in the treatment of perforated appendicitis in children

BACKGROUND The treatment of perforated appendicitis in children often involves a combination of surgical and medical therapy. The aim of this study was to document the degree of consensus in the current management of perforated appendicitis in children. STUDY DESIGN A survey was sent to all practicing pediatric surgeons in North America in April 2000 who were members of the American Pediatric Surgical Association for 1999-2000. Survey questions pertained to preoperative, perioperative, and postoperative practice patterns, particularly those issues related to use of antibiotic therapy. RESULTS Among eligible surgeons, 80.2% completed the survey. Although more than 80% of respondents practiced in an academic setting, only 17% of surgeons used a formal clinical practice guideline to direct care. Responses varied substantially in the duration of postoperative antibiotic therapy, the use of intravenous or oral agents or both, and the duration of hospitalization. A considerable number of patients are receiving a portion of their intravenous antibiotic therapy as outpatients. CONCLUSIONS There is little apparent consensus in the many aspects of perioperative and postoperative care of perforated appendicitis in children across North America. Only a fraction of surgeons currently uses a formal clinical practice guideline for treatment of perforated appendicitis, although increased pressures to develop more cost-effective therapeutic strategies can encourage development of additional guidelines. Definitive evidence to inform development of such guidelines and enhance consensus is lacking. Further studies are needed across institutions to better inform clinical decisions in light of a changing practice environment and treatment alternatives.

Evaluation of risk prediction criteria for episodes of febrile neutropenia in children with cancer.

Purpose To evaluate the feasibility of risk stratification of children with cancer and febrile neutropenia using a simple set of criteria from data available to the clinician at the time of the patients presentation. Patients and Methods This study is a retrospective cohort study of all children with cancer admitted to a single institution with fever and neutropenia (defined as an absolute neutrophil count <500 cells/mm 3 ) in a 1-year period. Patients were defined a priori as low risk if they were outpatients at the time of presentation with febrile neutropenia, had an anticipated duration of neutropenia less than 7 days, and had no significant comorbidity. All others were considered high risk. Data was analyzed by first admission for each patient and secondarily for all admissions for febrile neutropenia. Results There were 188 admissions in 104 patients for febrile neutropenia during the study period. Of these 47% were high risk and 53% were low risk. The duration of fever was not significantly different in the two groups. However, the duration of neutropenia and the length of hospital stay were significantly longer in the high-risk group. The frequency of bacteremia, other documented infection, and serious medical complications was significantly different in the two groups. Overall, the rate of any adverse event was 4% in the low-risk group versus 41% in the high-risk group. Conclusions Simple criteria available to the clinician at the time of evaluation of the child with cancer who has fever and neutropenia allow the selection of a population at low risk for bacteremia or serious medical complication. A prospective study is planned using these risk criteria, evaluating outpatient oral antibiotic therapy in low-risk children with cancer.

Severe ototoxicity following carboplatin-containing conditioning regimen for autologous marrow transplantation for neuroblastoma

Children with neuroblastoma receiving high-dose carboplatin as part of their conditioning regimen for autologous marrow transplantation have a high incidence of speech frequency hearing loss. We evaluated hearing loss in 11 children with advanced stage neuroblastoma who underwent autologous marrow transplantation, following a conditioning regimen containing high-dose carboplatin (2 g/m2, total dose). Audiometric evaluations were obtained at diagnosis, prior to and following transplant. Exposure to other known ototoxins also was assessed. All patients sustained worsening of hearing following high-dose carboplatin. Nine of the 11 children (82%) had evidence of speech frequency hearing loss post transplant for which hearing aids were recommended (grades 3–4). Three of the nine children had speech frequency loss prior to transplant which progressed following transplant. The entire group was heavily pre-treated with platinum-containing chemotherapy pre-BMT and had extensive exposure to other ototoxins, including aminoglycoside antibiotics, diuretics, and noise exposure – all of which could have exacerbated the effects of carboplatin. High-dose carboplatin is ototoxic, particularly in patients who have been primed with previous platinum therapy or other ototoxic agents. We conclude that further efforts are needed to monitor and minimize this complication. In cases where hearing loss is inevitable due to cumulative ototoxic exposures, families need to be adequately prepared for the tradeoffs of potentially curable therapy.

Role of Cytotoxic Therapy with Hematopoietic Stem Cell Transplantation in the Treatment of Pediatric Acute Lymphoblastic Leukemia: Update of the 2005 Evidence-Based Review

Clinical research published since the first evidence-based review on the role of hematopoietic stem cell transplantation (SCT) in the treatment of pediatric acute lymphoblastic leukemia (ALL) is presented and critically evaluated in this update. Treatment recommendations are provided by an expert panel. Allogeneic SCT is recommended for children who: are in second complete remission (CR2) after experiencing an early marrow relapse for precursor-B ALL; experienced primary induction failure, but subsequently achieved a CR1; have T-lineage ALL in CR2; or have ALL in third or greater remission. Although the 2005 pediatric ALL evidence-based review (EBR) recommended allogeneic SCT for children with Philadelphia chromosome positive (Ph+) ALL in CR1, preliminary tyrosine kinase inhibitor (TKI) data demonstrate that early outcomes are comparable for allogeneic SCT and chemotherapy + imatinib. Based on the evidence, autologous SCT is not recommended for ALL in CR1. Allogeneic SCT is not recommended for: T-lineage ALL in CR1; mixed-lineage leukemia (MLL)+ ALL when it is the sole adverse risk factor; isolated central nervous system (CNS) relapse in precursor-B ALL. Based on expert opinion, allogeneic SCT may be considered for hypodiploid ALL and persistent minimal residual disease [corrected] (MRD) positivity in ALL in CR1 or greater, although these are areas that need further study. Treatment recommendations pertaining to various transplantation techniques are also provided, as are areas of needed future research.

Prevalence of hematopoietic cell transplant survivors in the United States

Advances in hematopoietic cell transplantation (HCT) have led to an increasing number of transplant survivors. To adequately support their healthcare needs, there is a need to know the prevalence of HCT survivors. We used data on 170,628 recipients of autologous and allogeneic HCT reported to the Center for International Blood and Marrow Transplant Research from 1968 to 2009 to estimate the current and future number of HCT survivors in the United States. Stacked cohort simulation models were used to estimate the number of HCT survivors in the United States in 2009 and to make projections for HCT survivors by the year 2030. There were 108,900 (range, 100,500 to 115,200) HCT survivors in the United States in 2009. This included 67,000 autologous HCT and 41,900 allogeneic HCT survivors. The number of HCT survivors is estimated to increase by 2.5 times by the year 2020 (242,000 survivors) and 5 times by the year 2030 (502,000 survivors). By 2030, the age at transplant will be < 18 years for 14% of all survivors (n = 64,000), 18 to 59 years for 61% survivors (n = 276,000), and 60 years and older for 25% of survivors (n = 113,000). In coming decades, a large number of individuals will be HCT survivors. Transplant center providers, hematologists, oncologists, primary care physicians, and other specialty providers will need to be familiar with the unique and complex health issues faced by this population.