Mediators and Moderators of Active Music Engagement to Reduce Traumatic Stress Symptoms and Improve Well-being in Parents of Young Children With Cancer.

OBJECTIVE: This trial examined the effects of proximal/distal mediators and moderators of an Active Music Engagement (AME) intervention on young child/parent distress, quality of life, and family function outcomes. METHODS: Child/parent dyads (n = 125) were randomized to AME or Audio-storybooks attention control condition. Each group received 3 sessions with a credentialed music therapist for 3 consecutive days with data collection at baseline, post-intervention (T2), and 30-days later (T3). Potential proximal mediators included within session child and parent engagement. Potential distal mediators included changes in perceived family normalcy, parent self-efficacy, and independent use of play materials. Potential moderators included parent/child distress with prior hospitalizations, parent traumatic stress screener (PCL-6), and child age. Outcomes included child emotional distress and quality of life; parent emotion, traumatic stress symptoms (IES-R), well-being; and family function. Mediation effects were estimated using ANCOVA, with indirect effects estimated using the percentile bootstrap approach. Moderation effects were tested by including appropriate interaction terms in models. RESULTS: No significant mediation effects were observed. Child distress with prior hospitalizations moderated AME effects for IES-R intrusion subscale scores at T2 (P = .01) and avoidance subscale scores at T3 (P = .007). Traumatic stress screener scores (PCL-6) moderated intervention effects for IES-R hyperarousal subscale scores at T2 (P = .01). There were no moderation effects for child age. CONCLUSIONS: AME is a promising intervention for mitigating traumatic stress symptoms and supporting well-being in parents of children with cancer, particularly for parents who screen high for traumatic stress and whose children are more highly distressed with hospitalization.

Randomized Clinical Trial of a Self-care and Communication Intervention for Parents of Adolescent/Young Adults Undergoing High-Risk Cancer Treatment: A Report From the Children's Oncology Group.

BACKGROUND: Parents of adolescents and young adults (AYAs) with cancer offer primary support to their children and often experience their own high levels of distress, affecting parent-AYA communication and quality of life. OBJECTIVE: To reduce parent distress and improve communication during high-risk cancer treatment, we examined efficacy of a self-care and communication intervention for parents and indirect benefit for AYAs receiving a therapeutic music video (TMV) intervention. METHODS: In this study, we conducted a multisite, randomized controlled trial with AYAs and parents enrolled as dyads (n = 110). Parents were randomized to intervention or low-dose control; all AYAs received TMV. Data collection occurred at baseline, 2 weeks post intervention (T2), and 90 days post intervention (T3). RESULTS: There were no significant between-group differences on primary outcomes for parents or AYAs. We did find significant differences favoring the parent intervention group on parenting confidence at T2 and marginally better outcomes for family adaptability/cohesion at T3. Both groups exhibited significant within-group improvement for parent distress (state anxiety, T3; perceived stress, T2 and T3; mood, T3), state anxiety (T2) intervention only, and family strengths control group only. Qualitative data demonstrate the parent intervention raised self-awareness and parent confidence in the short term. CONCLUSION: Parents found their intervention helpful. Absence of significant results may be due to short intervention duration, need for tailored content, underpowered sample, and potential indirect parent benefit from AYA participation in TMV. The parent intervention did not provide an indirect benefit for AYAs. IMPLICATIONS FOR NURSING: Parents identified their own need for communication and support from nurses. Nurses can optimize AYA care by attending to parent needs through supportive listening and encouraging self-care.

Pilot Randomized Trial of Active Music Engagement Intervention Parent Delivery for Young Children With Cancer.

Objectives: To examine the feasibility/acceptability of a parent-delivered Active Music Engagement (AME + P) intervention for young children with cancer and their parents. Secondary aim to explore changes in AME + P child emotional distress (facial affect) and parent emotional distress (mood; traumatic stress symptoms) relative to controls. Methods: A pilot two-group randomized trial was conducted with parents/children (ages 3-8 years) receiving AME + P ( n = 9) or attention control ( n = 7). Feasibility of parent delivery was assessed using a delivery checklist and child engagement; acceptability through parent interviews; preliminary outcomes at baseline, postintervention, 30 days postintervention. Results: Parent delivery was feasible, as they successfully delivered AME activities, but interviews indicated parent delivery was not acceptable to parents. Emotional distress was lower for AME + P children, but parents derived no benefit. Conclusions: Despite child benefit, findings do not support parent delivery of AME + P.

A Step Toward High Reliability: Implementation of a Daily Safety Brief in a Children's Hospital.

OBJECTIVES: Health care is a high-risk industry. To improve communication about daily events and begin the journey toward a high reliability organization, the Riley Hospital for Children at Indiana University Health implemented a daily safety brief. METHODS: Various departments in our children's hospital were asked to participate in a daily safety brief, reporting daily events and unexpected outcomes within their scope of responsibility. Participants were surveyed before and after implementation of the safety brief about communication and awareness of events in the hospital. The length of the brief and percentage of departments reporting unexpected outcomes were measured. RESULTS: The analysis of the presurvey and the postsurvey showed a statistically significant improvement in the questions related to the awareness of daily events as well as communication and relationships between departments. The monthly mean length of time for the brief was 15 minutes or less. Unexpected outcomes were reported by 50% of the departments for 8 months. CONCLUSIONS: A daily safety brief can be successfully implemented in a children's hospital. Communication between departments and awareness of daily events were improved. Implementation of a daily safety brief is a step toward becoming a high reliability organization.

Randomized clinical trial of therapeutic music video intervention for resilience outcomes in adolescents/young adults undergoing hematopoietic stem cell transplant: a report from the Children's Oncology Group.

BACKGROUND: To reduce the risk of adjustment problems associated with hematopoietic stem cell transplant (HSCT) for adolescents/young adults (AYAs), we examined efficacy of a therapeutic music video (TMV) intervention delivered during the acute phase of HSCT to: 1) increase protective factors of spiritual perspective, social integration, family environment, courageous coping, and hope-derived meaning; 2) decrease risk factors of illness-related distress and defensive coping; and 3) increase outcomes of self-transcendence and resilience. METHODS: This was a multisite randomized, controlled trial (COG-ANUR0631) conducted at 8 Children's Oncology Group sites involving 113 AYAs aged 11-24 years undergoing myeloablative HSCT. Participants, randomized to the TMV or low-dose control (audiobooks) group, completed 6 sessions over 3 weeks with a board-certified music therapist. Variables were based on Haase's Resilience in Illness Model (RIM). Participants completed measures related to latent variables of illness-related distress, social integration, spiritual perspective, family environment, coping, hope-derived meaning, and resilience at baseline (T1), postintervention (T2), and 100 days posttransplant (T3). RESULTS: At T2, the TMV group reported significantly better courageous coping (Effect Size [ES], 0.505; P = .030). At T3, the TMV group reported significantly better social integration (ES, 0.543; P = .028) and family environment (ES, 0.663; P = .008), as well as moderate nonsignificant effect sizes for spiritual perspective (ES, 0.450; P = .071) and self-transcendence (ES, 0.424; P = .088). CONCLUSIONS: The TMV intervention improves positive health outcomes of courageous coping, social integration, and family environment during a high-risk cancer treatment. We recommend the TMV be examined in a broader population of AYAs with high-risk cancers.

Progression-free survival of two cases of high-risk neuroblastoma with refractory/relapsed disease following surgery alone.

Outcome for the vast majority of high-risk neuroblastoma patients with refractory or relapsed disease is dismal. We report two high-risk patients who remain progression-free for more than 113 and 18 months following the diagnosis of refractory/relapsed disease who were treated with surgery alone. Complete resolution of a refractory thoracic mass and relapsed liver nodules was observed in one patient. The refractory/relapsed disease in the second patient has remained stable. In both cases, the tumor showed histologic evidence of neuroblastoma maturation. These cases demonstrate that refractory/relapsed neuroblastoma is clinically heterogeneous and highlight the need for better biomarkers to optimize patient care.

Oxygenation index predicts mortality in pediatric stem cell transplant recipients requiring mechanical ventilation.

The mortality in the ICU for pediatric HSCT recipients remains high. Early pulmonary complications continue to be an obstacle to the survival. We hypothesize OI is a predictor for mortality in critically ill pediatric HSCT recipients. Retrospective review of pediatric HSCT recipients between 2002 and 2010 who required intensive care during the same hospital admission as their transplant. Twenty-eight patients accounted for 31 ICU admissions. Twenty-six (84%) admissions required mechanical ventilation. Ten (38%) mechanically ventilated admissions were placed on HFOV. Mortality of those mechanically ventilated was 70%. An OI ≥ 20 at any point during ventilation was associated with 94% mortality, while an OI ≥ 25 had 100% mortality. There was a significant association between maximum OI at any point during mechanical ventilation and ICU mortality, with the odds of dying increasing by 13% for each unit increase of max OI (OR = 1.13, 95% CI = 1.01-1.26, p = 0.03). An OI of 20 had a sensitivity of 0.89 and specificity of 0.83 for predicting mortality. OI has a strong association with ICU mortality among pediatric stem cell recipients.

Lung function before and after pediatric allogeneic hematopoietic stem cell transplantation: a predictive role for DLCOa/VA.

BACKGROUND: Pre-allogeneic hematopoietic stem cell transplantation (aHSCT) and post-aHSCT lung function of 41 eligible patients at Riley Hospital for Children were assessed to identify risk factors for post-aHSCT morbidity and mortality. OBSERVATIONS: One year post-aHSCT pulmonary function tests were significantly lower compared with baseline. These findings recovered at 2 years post-aHSCT. Refractory disease before aHSCT correlated with lower pulmonary function tests after aHSCT. Graft-versus-host disease was significantly associated with higher post-aHSCT residual volume. Importantly, low pre-aHSCT carbon monoxide diffusing capacity adjusted for hemoglobin and alveolar volume was predictive of death. CONCLUSIONS: Among survivors, lung function improves over time after pediatric aHSCT. Measurement of carbon monoxide diffusing capacity adjusted for hemoglobin and alveolar volume before pediatric aHSCT should be further investigated as a predictor of pulmonary dysfunction and mortality.

Pulmonary, gonadal, and central nervous system status after bone marrow transplantation for sickle cell disease.

We conducted a prospective, multicenter investigation of human-leukocyte antigen (HLA) identical sibling bone marrow transplantation (BMT) in children with severe sickle cell disease (SCD) between 1991 and 2000. To determine if children were protected from complications of SCD after successful BMT, we extended our initial study of BMT for SCD to conduct assessments of the central nervous system (CNS) and of pulmonary function 2 or more years after transplantation. In addition, the impact on gonadal function was studied. After BMT, patients with stroke who had stable engraftment of donor cells experienced no subsequent stroke events after BMT, and brain magnetic resonance imaging (MRI) exams demonstrated stable or improved appearance. However, 2 patients with graft rejection had a second stroke after BMT. After transplantation, most patients also had unchanged or improved pulmonary function. Among the 11 patients who had restrictive lung changes at baseline, 5 were improved and 6 had persistent restrictive disease after BMT. Of the 2 patients who had obstructive changes at baseline, 1 improved and 1 had worsened obstructive disease after BMT. There was, however, significant gonadal toxicity after BMT, particularly among female recipients. In summary, individuals who had stable donor engraftment did not experience sickle-related complications after BMT, and were protected from progressive CNS and pulmonary disease.

Impact of conditioning regimen in allogeneic hematopoetic stem cell transplantation for children with acute myelogenous leukemia beyond first complete remission: a pediatric blood and marrow transplant consortium (PBMTC) study.

Total body irradiation (TBI)-based conditioning regimens for pediatric patients with acute myelogenous leukemia (AML) beyond first complete remission (CR1) are controversial. Because the long-term morbidity of busulfan (Bu)-based regimens appears to be lower, determining efficacy is critical. We retrospectively evaluated 151 pediatric patients with AML beyond CR1, comparing outcomes in 90 patients who received a TBI-based conditioning regimen and 61 patients who received a Bu-based conditioning regimen. There were no differences between the 2 groups with respect to age, sex, duration of CR1, time from most recent remission to transplantation, or donor source. The probability of relapse at 2 years also did not differ between the 2 groups (26% and 27%, respectively; P=.93). No significant difference in event-free survival (EFS) (P=.29) or overall survival (OS) (P=.11) was noted between the 2 groups. These findings were supported by a multivariate analysis in which TBI was not associated with improved EFS (hazard ratio [HR]=1.17; 95% confidence interval [CI]=0.66-2.10; P=.58) or OS (HR=1.42; 95% CI=0.76-2.64; P=.27). Shorter CR1 and receiving an HLA-mismatched transplant adversely affected EFS and OS in this cohort. Our study provides no evidence of an advantage to using TBI in children with AML beyond CR1. A prospective, randomized study is needed to confirm these results.

Unrelated cord blood transplantation for severe congenital neutropenia: report of two cases with very different transplant courses.

SCN is characterized by neutropenia, life-threatening infections, and progression to myelodysplastic syndrome/acute myelogenous leukemia. The only curative option is SCT, but few reports using UCB as a stem cell source exist. Here, we report two SCN patients transplanted with UCB. Patient 1 was transplanted at seven yr of age due to increasingly large injections of G-CSF (>100 microg/kg/day) and the risk of developing leukemia. He engrafted promptly and is clinically well and immune reconstituted >2 yr post-transplant. Patient 2 underwent UCB SCT at nine months of age for recurrent severe infections, despite high doses of G-CSF. He rejected his first graft, having 100% host cells on day +35, and immediately underwent a second UCB SCT. He engrafted but experienced late graft rejection six months after the second transplant. He received a third UCB SCT following a more immunosuppressive conditioning regimen. His course was complicated by HHV-6 viremia and gut GVHD, but he is now clinically well and has 99% donor engraftment >20 months post-transplant. We conclude that UCB is an acceptable stem cell source for SCN patients, but conditioning must be adequately immunosuppressive to ensure engraftment in patients without prior chemotherapy.

Disseminated toxoplasmosis resulting in graft failure in a cord blood stem cell transplant recipient.

Toxoplasmosis is an infrequent infection with a high mortality rate in hematopoietic stem cell transplant recipients, and is usually caused by reactivation of prior, latent infection upon intensive immunosuppression. We report a case of fatal disseminated toxoplasmosis, diagnosed at autopsy, in a 7-year-old boy who received a cord blood graft for recurrent acute lymphoblastic leukemia. This case represents both the first reported case of toxoplasmosis in an engrafted cord blood recipient, and also of graft failure due to toxoplasmosis. Recommendations for toxoplasmosis diagnosis, treatment, and prophylaxis in stem cell transplant recipients are reviewed.

Incidence, etiology, and risk factors for liver dysfunction in children following hematopoietic stem cell transplantation.

AIMS: To identify risk factors which predispose children to develop liver dysfunction (LD) during the initial 100 days following hematopoietic stem cell transplantation (HSCT). METHODS: Retrospective analysis of all patients (<21 yr) who had undergone HSCT from July 1998 to June 2003. LD was defined by the presence of clinical jaundice and/or elevated alanine aminotransferase (ALT) or gamma-glutamyl transferase (GGT) (1.5 times normal). RESULTS: One hundred and six patients underwent HSCT during the study period. LD was seen in 91 (85.5%) patients and the majority (58.2%) had moderate to severe LD. The primary cause of LD could be ascertained in 2/3 of patients and was multifactorial in the rest. The odds ratio and 95% CI for risk factors associated with LD following HSCT on univariate analysis were as follows: allogeneic source of stem cells 4.2 (1.2-14.2), engraftment >12 days 4.3 (1.3-14.2), total parenteral nutrition >35 days 8.2 (1.1-66.2), pretransplant ALT >40 U/L 7.4 (0.9-58.6), use of cyclosporine and methotrexate 9.5 (1.2-77.9), and use of amphotericin-B 3.1 (0.9-10.6). On multivariate analysis only elevated pre transplantation ALT and delayed engraftment were associated with post-HSCT LD. LD was seen in all 13 patients who died within 100 days following HSCT, and it was felt to be the primary cause of death in six (46%) patients. The factors associated with increased risk of mortality were: allogeneic source of stem cells, delayed engraftment (>18 days), higher mean peak GGT (>250 U/L), and total bilirubin (>6 mg/dL). CONCLUSION: LD was common and severe in the majority of children following HSCT. Risk of LD was higher in children who had elevated pretransplantation ALT or had delayed engraftment. LD contributes significantly to morbidity and mortality following HSCT.

Serial transplantation resulting in tolerance to an unrelated cord blood graft.

Unrelated cord blood (UCB) hematopoietic stem cells were serially transplanted into two human leukocyte antigen (HLA)-identical siblings with T cell, B cell, natural killer cell severe combined immunodeficiency. Brother A received a 4/6-matched, HLA DRbeta1-identical but class I-disparate UCB graft after myeloablative dosages of busulfan, melphalan, and antithymocyte globulin. He experienced complete donor chimerism, severe acute gastrointestinal graft-versus-host disease (GVHD), and limited chronic skin GVHD that resolved with treatment. Two years later, brother B received unfractionated marrow from brother A after reduced-intensity conditioning with cyclophosphamide and antithymocyte globulin. Brother B experienced mixed-donor (i.e. original UCB) chimerism and no histologically documented GVHD. Both brothers are clinically well; brother A is in a fully immunologically reconstituted state. The uneventful course and progressive increase in donor chimerism after the second transplantation indicates that hematopoietic cells derived from the older brother's marrow engrafted without causing GVHD, suggesting that acquired tolerance to disparate unrelated HLA antigens was achieved.

Scintigraphic response by 123I-metaiodobenzylguanidine scan correlates with event-free survival in high-risk neuroblastoma.

PURPOSE: To investigate whether response to induction therapy, evaluated by metaiodobenzylguanadine (MIBG) and bone scintigraphy, correlates with event-free survival (EFS) in children with high-risk neuroblastoma (NB). PATIENTS AND METHODS: Twenty-nine high-risk NB patients were treated prospectively with an intensive induction regimen and consolidated with three cycles of high-dose therapy with peripheral blood stem-cell rescue. The scintigraphic response was evaluated by MIBG and bone scans using a semi-quantitative scoring system. The prognostic significance of the imaging scores at diagnosis and following induction therapy was evaluated. RESULTS: A trend associating worse 4-year EFS rates for patients with versus without osteomedullary uptake on MIBG scintigraphs at diagnosis was seen (35% +/- 11% v 80% +/- 18%, respectively; P =.13). Similarly, patients with positive bone scans at diagnosis had worse EFS than those with negative scans, although the difference did not receive statistical significance (34% +/- 10% v 83% +/- 15%, respectively; P =.06). However, significantly worse EFS was observed in patients with a postinduction MIBG score of >/= 3 compared to those with scores of less than 3 (0% v 58% +/- 11%; P =.002). There was no correlation between bone scan scores and outcome following induction therapy. CONCLUSION: MIBG scores >/= 3 following induction therapy identifies a subset of NB patients who are likely to relapse following three cycles of high-dose therapy with peripheral blood stem-cell rescue, local radiotherapy, and 13-cis-retinoic acid. Alternative therapeutic strategies should be considered for patients with a poor response to induction therapy.

Treatment of relapsed Wilms' tumor with high-dose therapy and autologous hematopoietic stem-cell rescue: the experience at Children's Memorial Hospital.

PURPOSE: To investigate whether high-dose therapy with hematopoietic stem-cell rescue (HSCR) will improve survival for patients with relapsed Wilms' tumor. PATIENTS AND METHODS: Thirteen children with relapsed Wilms' tumor were treated with one or two cycles of high-dose chemotherapy (HDT) followed by autologous HSCR. Twelve of 13 patients received reinduction chemotherapy before HDT and HSCR. The median age at diagnosis was 4.8 years, and the median time to relapse was 12 months. The histology was favorable in 12 of 13 patients. The ablative regimens included: (1) thiotepa (TT)/cyclophosphamide (CTX)/carboplatin (CP; n = 2); (2) TT/CTX (n = 5); (3) TT/etoposide (ETP; n = 1); and (4) CP/ETP/CTX (n = 1). Four patients received two cycles of HDT and HSCR. Cycle 1 consisted of CP/ETP/CTX, and melphalan/CTX were used in cycle 2. RESULTS: Seven of 13 patients are alive without evidence of disease, with a median follow-up of 30 months. The 4-year estimated event-free survival (EFS) rate is 60% (95% CI, 0.40 to 6.88), and the overall survival (OS) at 4 years is 73% (95% CI, 0.40 to 6.86). There was no transplant-related mortality. All patients engrafted to an absolute neutrophil count 500/microL at a median of 13 days (range, 8 to 62 days) and had an unsustained platelet count > 20.0 micro at a median of 16 days (range, 10 to 202 days). CONCLUSION: Our results suggest that HDT with HSCR is an effective treatment for patients with Wilms' tumor who experience relapse.

Related umbilical cord blood transplantation in patients with thalassemia and sickle cell disease.

Allogeneic bone marrow transplantation (BMT) from HLA-identical siblings is an accepted treatment for both thalassemia and sickle cell disease (SCD). However, it is associated with decided risk of both transplant-related mortality (TRM) and chronic graft-versus-host disease (GVHD). We analyzed 44 patients (median age, 5 years; range, 1-20 years) given an allogeneic related cord blood transplant for either thalassemia (n = 33) or SCD (n = 11). Thirty children were given cyclosporin A (CsA) alone as GVHD prophylaxis, 10 received CsA and methotrexate (MTX), and 4 patients received other combinations of immunosuppressive drugs. The median number of nucleated cells infused was 4.0 x 10(7)/kg (range, 1.2-10 x 10(7)/kg). No patient died and 36 of 44 children remain free of disease, with a median follow-up of 24 months (range, 4-76 months). Only one patient with SCD did not have sustained donor engraftment as compared with 7 of the 33 patients with thalassemia. Three of these 8 patients had sustained donor engraftment after BMT from the same donor. Four patients experienced grade 2 acute GVHD; only 2 of the 36 patients at risk developed limited chronic GVHD. The 2-year probability of event-free survival is 79% and 90% for patients with thalassemia and SCD, respectively. Use of MTX for GVHD prophylaxis was associated with a greater risk of treatment failure. Related CBT for hemoglobinopathies offers a good probability of success and is associated with a low risk of GVHD. Optimization of transplantation strategies could further improve these results.

Novel therapeutic approaches in the treatment of children with hepatoblastoma.

Hepatoblastoma is the most common liver tumor diagnosed in children. Children with persistently unresectable disease, metastatic disease at presentation, recurrent disease, or slowly declining alpha-fetoprotein levels are at high risk for recurrence, exhibit an extremely poor prognosis, and are in desperate need of novel therapeutic agents and strategies. Four high-risk patients were treated. One patient with a local recurrence was treated with irinotecan followed by orthotopic liver transplant. Three patients were treated with tandem high-dose chemotherapy (HDT) with autologous stem cell rescue (two with primary metastatic disease and one with recurrent disease). All three of the patients treated with HDT had relapse (two of them subsequently received irinotecan); the remaining patient underwent surgical resection of a solitary recurrent pulmonary metastasis. Irinotecan demonstrated significant antitumor effects in all three treated patients and was well tolerated. None of the three patients treated with HDT remained disease-free, although the patient who underwent surgical resection of a solitary recurrent pulmonary metastasis remains disease-free 6 years from diagnosis. Further exploration of the use of irinotecan is warranted in high-risk patients with hepatoblastoma.

Induction of a transient graft vs. leukemia effect following unrelated cord blood transplantation.

Umbilical cord blood (UCB) has become a frequent source of allogeneic hematopoietic stem cells for transplantation. Of theoretical concern is a potential decrease in the graft vs. leukemia (GvL) effect, given the lesser degree of graft vs. host disease (GvHD) with this donor source. We report a case of recurrent acute non-lymphoblastic leukemia (ANLL) following stem cell transplantation with unrelated mismatched UCB, which responded to the induction of GvHD. The response was documented both morphologically and by evaluation of chimeric engraftment by molecular DNA techniques. In addition, WT-1, a purported marker of minimal residual disease in acute leukemia, correlated with remission status in this patient. In summary, the GvL effect is seen with allogeneic UCB transplantation and has the potential to be induced along with GvHD.

Treatment of high-risk neuroblastoma with triple-tandem high-dose therapy and stem-cell rescue: results of the Chicago Pilot II Study.

PURPOSE: To investigate whether intensive induction therapy followed by triple-tandem cycles of high-dose therapy with peripheral-blood stem-cell rescue and local irradiation will improve event-free survival for patients with high-risk neuroblastoma. PATIENTS AND METHODS: From August 1995 to January 2000, 25 consecutive newly diagnosed high-risk neuroblastoma patients and one child with recurrent MYCN-amplified disease were enrolled onto the Chicago Pilot II Protocol. After induction therapy and surgery, peripheral-blood stem cells were mobilized with three cycles of high-dose cyclophosphamide and granulocyte colony-stimulating factor. Patients then underwent triple-tandem cycles of high-dose therapy with peripheral-blood stem-cell rescue followed by radiation to the primary site. RESULTS: Twenty-two of the 26 patients successfully completed induction therapy and were eligible for the triple-tandem consolidation high-dose therapy. Sufficient numbers of peripheral-blood stem cells were collected in all but one patient. Seventeen patients were able to complete all three cycles of high-dose therapy and peripheral-blood stem-cell rescue, two patients completed two cycles, and three patients completed one cycle. There was one toxic death, and one patient died from complications of treatment for graft failure. With a median follow-up of 38 months, the 3-year event-free survival and survival rates are 57% +/- 11% and 79% +/- 10%, respectively. CONCLUSION: The results of this pilot study demonstrate that it is feasible to intensify consolidation with triple-tandem high-dose chemotherapy and peripheral-blood stem-cell rescue and local irradiation, and suggest that this treatment strategy may lead to improved survival for patients with high-risk neuroblastoma.