Cord Blood Banking for Potential Future Transplantation.

This policy statement is intended to provide information to guide pediatricians, obstetricians, and other medical specialists and health care providers in responding to parents' questions about cord blood donation and banking as well as the types (public versus private) and quality of cord blood banks. Cord blood is an excellent source of stem cells for hematopoietic stem cell transplantation in children with some fatal diseases. Cord blood transplantation offers another method of definitive therapy for infants, children, and adults with certain hematologic malignancies, hemoglobinopathies, severe forms of T-lymphocyte and other immunodeficiencies, and metabolic diseases. The development of universal screening for severe immunodeficiency assay in a growing number of states is likely to increase the number of cord blood transplants. Both public and private cord blood banks worldwide hold hundreds of thousands of cord blood units designated for the treatment of fatal or debilitating illnesses. The procurement, characterization, and cryopreservation of cord blood is free for families who choose public banking. However, the family cost for private banking is significant and not covered by insurance, and the unit may never be used. Quality-assessment reviews by several national and international accrediting bodies show private cord blood banks to be underused for treatment, less regulated for quality control, and more expensive for the family than public cord blood banks. There is an unquestionable need to study the use of cord blood banking to make new and important alternative means of reconstituting the hematopoietic blood system in patients with malignancies and blood disorders and possibly regenerating tissue systems in the future. Recommendations regarding appropriate ethical and operational standards (including informed consent policies, financial disclosures, and conflict-of-interest policies) are provided for physicians, institutions, and organizations that operate or have a relationship with cord blood banking programs. The information on all aspects of cord blood banking gathered in this policy statement will facilitate parental choice for public or private cord blood banking.

A Clinical and Economic Comparison of Rasburicase and Allopurinol in the Treatment of Patients With Clinical or Laboratory Tumor Lysis Syndrome.

BACKGROUND: The aim of the study was to compare reductions in uric acid (UA), length of stay (LOS), and hospitalization costs in patients with tumor lysis syndrome (TLS) treated with rasburicase or allopurinol. PATIENTS AND METHODS: This retrospective study of administrative data included hospitalized pediatric and adult patients who had clinical or laboratory TLS and received rasburicase or allopurinol. Each rasburicase-treated patient was propensity score-matched with 4 allopurinol-treated patients. Mean changes in UA within ≤ 2 days of treatment initiation were determined. Economic outcomes included mean number of days in the intensive care unit (ICU), total LOS, costs/hospitalization, and costs/percentage change in UA. RESULTS: Twenty-six rasburicase-treated patients were matched with 104 allopurinol-treated patients. Reduction in plasma UA was 5.3 mg/dL greater for patients treated with rasburicase than for patients treated with allopurinol (P < .0001). Length of ICU stay was 2.5 days less for patients treated with rasburicase than for patients treated with allopurinol (P < .0001), and total LOS was 5 days less for patients treated with rasburicase than for patients treated with allopurinol (P = .02). Total costs per patient were $20,038 lower for patients treated with rasburicase than for patients treated with allopurinol (P < .02). Cost per percentage UA reduction was also lower for patients treated with rasburicase versus patients treated with allopurinol ($3899 vs. $16,894; P < .001). CONCLUSION: In this analysis of TLS patients who received care in real-world settings, rasburicase versus allopurinol was significantly more effective in treating hyperuricemia and was associated with significantly shorter ICU and overall hospital stays and lower total inpatient costs.

Health-related quality of life (HRQoL): the impact of medical and demographic variables upon pediatric recipients of hematopoietic stem cell transplantation.

BACKGROUND: The trajectory of Heath-Related Quality of Life (HRQoL) in pediatric recipients who have undergone hematopoietic stem cell transplantation (HSCT), as well as the demographic and medical factors that predict HRQoL, has lagged behind the adult research. METHODS: A prospective longitudinal study of HRQoL in pediatric HSCT recipients was conducted with 95 patients at the Columbia University Medical Center between 2002 and 2009. Both children and parents completed the PedsQL 4.0 prior to HSCT and at days 100, 180, and 365-post-HSCT. RESULTS: The majority of patients and their parents reported linear improvements in HRQoL in the first year post-transplant; however, a portion of patients were in the at-risk group at each time point. Latent growth modeling was utilized to examine demographic and medical factors that predicted initial HRQoL and its trajectory. Older age at transplant significant predicted lowered HRQoL at baseline for self- and parent-report. Female gender significantly impacted lowered self-reported physical HRQoL over time. Ethnicity was a significant predictor of HRQoL at baseline and over time for self- and parent-report, with African-American children reporting the highest HRQoL; whereas, the worst decline in psychosocial HRQoL was often reported by parents and children of Asian descent. CONCLUSION: This research identifies the significant impact of ethnicity upon HRQoL following pediatric HSCT. It is likely that an individual's pre-morbid experiences and expectations, particularly with regard to culture, behaviors, and values, influence the parent and child's perceptions and expectations of the HSCT process.

Minimal disease assessment in the treatment of children and adolescents with intermediate-risk (Stage III/IV) B-cell non-Hodgkin lymphoma: a children's oncology group report.

Children/adolescents with mature B-cell non-Hodgkin lymphoma (B-NHL) have an excellent prognosis but relapses still occur. While chromosomal aberrations and/or clonal immunoglobulin (Ig) gene rearrangements may indicate risk of failure, a more universal approach was developed to detect minimal disease (MD). Children/adolescents with intermediate-risk B-NHL were treated with French-British-American/Lymphome Malins de Burkitt 96 (FAB/LMB96) B4 modified chemotherapy and rituximab. Specimens from diagnosis, end of induction (EOI), and end of therapy (EOT) were assayed for MD. Initial specimens were screened for IGHV family usage with primer pools followed by individual primers to identify MD. Thirty-two diagnostic/staging specimens screened positive with primer pools and unique IGHV family primers were identified. Two patients relapsed; first relapse (4 months from diagnosis) was MD-positive at EOI, the second (36 months from diagnosis) was MD-positive at EOT. At EOI, recurrent rates were similar between the MRD-positive and MRD-negative patients (P = 0·40). At EOT, only 13/32 patients had MRD data available with one relapse in the MRD-positive group and no recurrences in the MRD-negative group (P = 0·077). The study demonstrated molecular-disseminated disease in which IgIGHV primer pools could be used to assess MD. This feasibility study supports future investigations to assess the validity and significance of MD screening in a larger cohort of patients with intermediate-risk mature B-NHL.

Rasburicase: future directions in tumor lysis management.

Acute tumor lysis syndrome (TLS) is an oncologic emergency resulting in several metabolic derangements. Hyperuricemia and its associated complications are the most frequent manifestations of TLS. Crucial to the management is the prompt initiation of a hypouricemic agent such as rasburicase. An established dose of 0.2 mg/kg of rasburicase is effective at decreasing uric acid levels significantly in 4 h of administration and to undetectable levels in 48 h of initiation. The mean uric acid AUC is significantly lower for patients treated with rasburicase when compared to those receiving allopurinol. Rasburicase has demonstrated excellent tolerability and is potentially cost-effective in patients at high risk for TLS. Rasburicase is a safe and effective hypouricemic agent for both adults and children at high risk for TLS and for this reason should be considered the uricolytic agent of choice in these patients.

Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review.

PURPOSE: Tumor lysis syndrome (TLS) has recently been subclassified into either laboratory TLS or clinical TLS, and a grading system has been established. Standardized guidelines, however, are needed to aid in the stratification of patients according to risk and to establish prophylaxis and treatment recommendations for patients at risk or with established TLS. METHODS: A panel of experts in pediatric and adult hematologic malignancies and TLS was assembled to develop recommendations and guidelines for TLS based on clinical evidence and standards of care. A review of relevant literature was also used. RESULTS: New guidelines are presented regarding the prevention and management of patients at risk of developing TLS. The best management of TLS is prevention. Prevention strategies include hydration and prophylactic rasburicase in high-risk patients, hydration plus allopurinol or rasburicase for intermediate-risk patients, and close monitoring for low-risk patients. Primary management of established TLS involves similar recommendations, with the addition of aggressive hydration and diuresis, plus allopurinol or rasburicase for hyperuricemia. Alkalinization is not recommended. Although guidelines for rasburicase use in adults are provided, this agent is currently only approved for use in pediatric patients in the United States. CONCLUSION: The potential severity of complications resulting from TLS requires measures for prevention in high-risk patients and prompts treatment in the event that symptoms arise. Recognition of risk factors, monitoring of at-risk patients, and appropriate interventions are the key to preventing or managing TLS. These guidelines should assist in the prevention of TLS and improve the management of patients with established TLS.

A comparison of inpatient length of stay and costs among patients with hematologic malignancies (excluding hodgkin disease) associated with and without acute renal failure.

BACKGROUND: Using data from the Healthcare Cost and Utilization Project 2004 Nationwide Inpatient Sample, we estimated inpatient resource utilization among patients with hematologic malignancies, with and without concomitant acute renal failure. PATIENTS AND METHODS: We analyzed patients with hematologic malignancies (excluding Hodgkin disease), acute renal failure, and renal dialysis. Subgroup analyses were performed on specific types of hematologic malignancies, with and without acute renal failure and with and without renal dialysis. RESULTS: Among those with hematologic malignancies, acute renal failure, with and without concomitant renal dialysis, increases inpatient length of stay and costs. Mean length of stay and costs for all patients with acute renal failure and renal dialysis (n = 5148), acute renal failure without renal dialysis (n = 27,654), and no acute renal failure or renal dialysis (n = 350,601) were 17.6, 12.2, and 7.4 days, and $44,619, $25,638, and $13,947, respectively. CONCLUSION: Treatment of hematologic malignancies and concomitant acute renal failure and renal dialysis places an economic burden on the health care system. Reducing the incidence of acute renal failure and concomitant renal dialysis with supportive care in patients with hematologic malignancies can reduce inpatient resource use.

Rasburicase: a new approach for preventing and/or treating tumor lysis syndrome.

Tumor lysis syndrome (TLS) is an oncologic emergency requiring prompt attention to the management of potentially life-threatening metabolic derangements. Hyperuricaemia is one of the prominent features of TLS which, if not adequately prevented or treated, may lead to renal failure, requiring dialysis. Conventional management of hyperuricaemia involved the use of aggressive hydration, urinary alkalinization and allopurinol. Despite these measures, as many as 14.1% of high-risk patients may still develop renal failure. With the advent of newer agents such as rasburicase, the paradigm of TLS management has shifted towards risk stratification and the use of rasburicase in conjunction with hydration in patients at high risk for TLS. The advantage of rasburicase over allopurinol is its rapid onset of action, lack of need for urine alkalinization, which may worsen hyperphosphataemia and a satisfactory safety profile. Overall, rasburicase offers a safe and more effective alternative to allopurinol in patients at highest risk for TLS. Some of the unanswered questions requiring further investigation with regard to rasburicase use include the optimal number of doses needed, optimal dose based on uric acid levels and tumor burden, dosing in obese patients and maximum dose.

A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome.

Bone marrow transplantation (BMT) can cure myelodysplastic syndrome (MDS), although transplantation carries significant risks of morbidity and mortality. Because the optimal timing of HLA-matched BMT for MDS is unknown, we constructed a Markov model to examine 3 transplantation strategies for newly diagnosed MDS: transplantation at diagnosis, transplantation at leukemic progression, and transplantation at an interval from diagnosis but prior to leukemic progression. Analyses using individual patient risk-assessment data from transplantation and nontransplantation registries were performed for all 4 International Prognostic Scoring System (IPSS) risk groups with adjustments for quality of life (QoL). For low and intermediate-1 IPSS groups, delayed transplantation maximized overall survival. Transplantation prior to leukemic transformation was associated with a greater number of life years than transplantation at the time of leukemic progression. In a cohort of patients under the age of 40 years, an even more marked survival advantage for delayed transplantation was noted. For intermediate-2 and high IPSS groups, transplantation at diagnosis maximized overall survival. No changes in the optimal transplantation strategies were noted when QoL adjustments were incorporated. For low- and intermediate-1-risk MDS, delayed BMT is associated with maximal life expectancy, whereas immediate transplantation for intermediate-2- and high-risk disease is associated with maximal life expectancy.

Assessment of minimal residual disease in childhood non-hodgkin lymphoma by polymerase chain reaction using patient-specific primers.

A feasibility study was undertaken to identify patient-specific primers (PSPs) from childhood non-Hodgkin lymphoma (NHL) specimens to detect minimal residual disease (MRD). Eleven tumor specimens were amplified using immunoglobulin heavy chain and T-cell receptor primers to identify PSPs, which were then used to evaluate staging/follow-up specimens. Disease was detected in 19 of 21 staging and 16 of 17 follow-up specimens. Among seven patients in remission by 1 month, PSPs identified MRD in follow-up specimens. This study demonstrated the feasibility of PSPs to identify disease in staging and follow-up specimens, which could be used to develop strategies for MRD analysis in a larger setting.