Prognostic implications of the IDH1 synonymous SNP rs11554137 in pediatric and adult AML: a report from the Children's Oncology Group and SWOG.

IDH1 SNP rs11554137 was recently reported in association with poor prognosis in normal karyotype adult acute myeloid leukemia (AML). We aimed to determine the prevalence, clinical associations, and prognostic significance of SNP rs11554137 in unselected pediatric and adult AML patients. Diagnostic marrow specimens from 527 AML patients treated on the pediatric trial Children's Oncology Group-AAML03P1 (N = 253) or adult SWOG trials (N = 274) were analyzed for the presence of the SNP. SNP rs11554137 was present in 11% of all patients. SNP status had no prognostic impact on survival in pediatric patients. In adult AML, overall survival for SNP-positive patients was 10% versus 18% for SNP-negative patients (P = .44). Among the 142 adults who achieved complete remission, 5-year relapse-free survival was significantly worse for SNP-positive patients (0% vs 25%, P = .0014). However, among adults with normal cytogenetics, FLT3/ITD was present in 90% of SNP-positive patients versus 59% of SNP-negative patients (P = .0053). In multivariate analysis, adjusting for the effects of age, cytogenetics, and FLT3/ITD, the independent prognostic effect of SNP positivity was not statistically significant (hazard ratio = 1.72, P = .18). The clinical profile of SNP-positive patients suggests that SNP rs11554137 may have biologic effects that bear further investigation. The clinical trials in this study are registered at http://www.clinicaltrials.gov as #NCT000707174 and #NCT00899171.

AAML03P1, a pilot study of the safety of gemtuzumab ozogamicin in combination with chemotherapy for newly diagnosed childhood acute myeloid leukemia: a report from the Children's Oncology Group.

BACKGROUND: The development of antigen-targeted therapies may provide additional options to improve outcomes in children with acute myeloid leukemia (AML). The Children's Oncology Group AAML03P1 trial sought to determine the safety of adding 2 doses of gemtuzumab ozogamicin, a humanized anti-CD33 antibody-targeted agent, to intensive chemotherapy during remission induction and postremission intensification for children with de novo AML. METHODS: AAML03P1 enrolled 350 children with previously untreated AML. Patients with a matched family donor received 3 courses of chemotherapy followed by hematopoietic stem cell transplantation; those without a matched family donor received 5 courses of chemotherapy. Gemtuzumab ozogamicin 3 mg/m(2)/dose was administered on Day 6 of Course 1 and Day 7 of Course 4. RESULTS: Toxicities observed in all courses of therapy were typical of AML chemotherapy regimens, with infection being most common. Patients achieved a complete remission rate of 83% after 1 course and 87% after 2 courses. The mortality rate was 1.5% after the first gemtuzumab ozogamicin-containing induction course and 2.6% after 2 induction courses. The 3-year event-free survival and overall survival rates were 53 ± 6% and 66 ± 5%, respectively. CONCLUSIONS: This trial determined that it is safe and feasible to include gemtuzumab ozogamicin in combination with intensive chemotherapy. The survival rates compare favorably with the recently published results of clinical trials worldwide.

Phase II study of 2-chlorodeoxyadenosine plus idarubicin for children with acute myeloid leukaemia in first relapse: a paediatric oncology group study.

Relapse remains the leading cause of death in patients with acute myeloid leukaemia (AML). Relatively few new chemotherapy agents have been proven to be effective in this population. We report on a Phase 2 clinical trial using the novel combination of 2-chlorodeoxyadenosine (2-CDA) (8 mg/m² per d x 5 d) plus idarubicin (Ida) (10 mg/m² per d x 3 d). The study involved 109 paediatric patients with AML at first relapse, of whom 104 were available for analysis. The overall response rate was 51% (complete response [CR] + partial response) with a CR rate of 46%. 2-year event-free survival (EFS) and overall survival (OS) were 20% and 26%. The only significant variable in determining response, EFS and OS was duration of initial remission, with patients who had an initial remission >1 year having much worse outcomes overall (response rate 74% vs. 25%, EFS 8% vs. 37% and OS of 16% vs. 39%, P < 0.01 for all). There was an acceptable toxicity profile with one neurological event and no cardiac events observed. The most common grade 3-4 toxicities observed were neutropenia (59%) and thrombocytopenia (68%). This study demonstrated that the novel combination of 2-CDA/Ida was effective and should be considered for incorporation in front line therapy for children with AML.

Prevalence and prognostic significance of KIT mutations in pediatric patients with core binding factor AML enrolled on serial pediatric cooperative trials for de novo AML.

KIT receptor tyrosine kinase mutations are implicated as a prognostic factor in adults with core binding factor (CBF) acute myeloid leukemia (AML). However, their prevalence and prognostic significance in pediatric CBF AML is not well established. We performed KIT mutational analysis (exon 8 and exon 17) on diagnostic specimens from 203 pediatric patients with CBF AML enrolled on 4 pediatric AML protocols. KIT mutations were detected in 38 (19%) of 203 (95% CI, 14%-25%) patient samples of which 20 (52.5%) of 38 (95% CI, 36%-69%) involved exon 8, 17 (45%) of 38 (95% CI, 29%-62%) involved exon 17, and 1 (2.5%; 95% CI, 0%-14%) involved both locations. Patients with KIT mutations had a 5-year event-free survival of 55% (+/- 17%) compared with 59% (+/- 9%) for patients with wild-type KIT (P = .86). Rates of complete remission, overall survival, disease-free survival, or relapse were not significantly different for patients with or without KIT mutations. Location of the KIT mutation and analysis by cytogenetic subtype [t(8;21) vs inv(16)] also lacked prognostic significance. Our study shows that KIT mutations lack prognostic significance in a large series of pediatric patients with CBF AML. This finding, which differs from adult series and a previously published pediatric study, may reflect variations in therapeutic approaches and/or biologic heterogeneity within CBF AML. Two of 4 studies included in this analysis are registered at http://clinicaltrials.gov as NCT00002798 (CCG-2961) and NCT00070174 (COG AAML03P1).

Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group.

CEBPA mutations have been associated with improved outcome in adult acute myeloid leukemia (AML). We evaluated the prevalence and prognostic significance of CEBPA mutations in 847 children with AML treated on 3 consecutive pediatric trials. Two types of CEBPA mutations-N-terminal truncating mutations and in-frame bZip-domain mutations-were detected in 38 (4.5%) of 847 patients tested; 31 (82%) of 38 patients with mutations harbored both mutation types. Mutation status was correlated with laboratory and clinical characteristics and clinical outcome. CEBPA mutations were significantly more common in older patients, patients with FAB M1 or M2, and patients with normal karyotype. Mutations did not occur in patients with either favorable or unfavorable cytogenetics. Actuarial event-free survival at 5 years was 70% versus 38% (P = .015) with a cumulative incidence of relapse from complete remission of 13% versus 44% (P = .007) for those with and without CEBPA mutations. The presence of CEBPA mutations was an independent prognostic factor for improved outcome (HR = 0.24, P = .047). As CEBPA mutations are associated with lower relapse rate and improved survival, CEBPA mutation analysis needs to be incorporated into initial screening for risk identification and therapy allocation at diagnosis.

Parents as Teachers: Teaching Pediatrics Residents the Art of Engaging in Difficult Conversations.

BACKGROUND: Physicians often lack the skills and confidence needed to have difficult conversations with patients and their families. Patients and families who have experienced these conversations can provide valuable insight for resident physicians. OBJECTIVE: We developed a communication skills workshop for pediatrics residents using parents and a team of social workers, nurses, chaplains, and physician facilitators in role-playing exercises. METHODS: From 2007 to 2016, half-day "difficult conversation" workshops were held annually for postgraduate year 1 (PGY-1) and PGY-2 residents that included an interprofessional team and parents of children with life-threatening diagnoses. Questionnaires assessed residents' prior training, effectiveness of the sessions, and narrative feedback on the impact of this approach. Parents and team members were surveyed on the effectiveness of the training and the value of parent involvement. RESULTS: Median self-reported confidence levels for incoming PGY-1 residents following the workshop rose from 2 to 4 on a 5-point Likert scale (99% response rate [128 of 129 surveyed], P < .001). The majority of PGY-2 residents (91%, 115 of 126) reported the workshop increased their confidence in engaging in difficult conversations (91% response rate [126 of 139]). Parents and clinical care team members agreed that parents would likely be preferable to standardized actors for these types of role-playing exercises (84% response rate [37 of 44]). CONCLUSIONS: Involving patients' parents and an interprofessional team in role-playing scenarios was a well-received method for teaching residents how to engage in difficult conversations with patients and families, and improved their self-reported confidence when having these conversations.

The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia.

BACKGROUND: Doxorubicin chemotherapy is very effective in children with acute lymphoblastic leukemia (ALL) but also injures myocardial cells. Dexrazoxane, a free-radical scavenger, may protect the heart from doxorubicin-associated damage. METHODS: To determine whether dexrazoxane decreases doxorubicin-associated injury of cardiomyocytes, we randomly assigned 101 children with ALL to receive doxorubicin alone (30 mg per square meter of body-surface area every three weeks for 10 doses) and 105 to receive dexrazoxane (300 mg per square meter) followed immediately by doxorubicin. Serial measurements of serum cardiac troponin T were obtained in 76 of 101 patients in the doxorubicin group and 82 of 105 patients in the group given dexrazoxane and doxorubicin. A total of 2377 serum samples (mean, 15.1 samples per patient) were obtained before, during, and after treatment with doxorubicin. Troponin T levels were evaluated in a blinded fashion to determine whether they were elevated (>0.01 ng per milliliter)--the primary end point--or extremely elevated (>0.025 ng per milliliter). RESULTS: Elevations of troponin T occurred in 35 percent of the patients (55 of 158). Patients treated with doxorubicin alone were more likely than those who received dexrazoxane and doxorubicin to have elevated troponin T levels (50 percent vs. 21 percent, P<0.001) and extremely elevated troponin T levels (32 percent vs. 10 percent, P<0.001). The median follow-up was 2.7 years. The rate of event-free survival at 2.5 years was 83 percent in both groups (P=0.87 by the log-rank test). CONCLUSIONS: Dexrazoxane prevents or reduces cardiac injury, as reflected by elevations in troponin T, that is associated with the use of doxorubicin for childhood ALL without compromising the antileukemic efficacy of doxorubicin. Longer follow-up will be necessary to determine the influence of dexrazoxane on echocardiographic findings at four years and on event-free survival.

Use of [18F]fluorodeoxyglucose positron emission tomography in evaluating locally recurrent and metastatic adrenocortical carcinoma.

CONTEXT: Adrenocortical carcinomas are uncommon, and their evaluation by [(18)F]fluorodeoxyglucose positron emission tomography (FDG PET) has not been well evaluated. OBJECTIVE: The purpose of this study was to examine the potential utility of FDG PET in the detection of recurrent or metastatic adrenocortical carcinoma. DESIGN: In patients with known adrenocortical carcinoma who underwent FDG-PET imaging for suspected recurrence or metastasis, FDG activity was compared with other imaging findings, clinical features, and the presence or absence of disease as confirmed by resection, biopsy, or clinical follow-up. SETTING: The study took place at four tertiary referral centers. PATIENTS OR OTHER PARTICIPANTS: Twelve patients (10 females and two males, 5-71 yr of age) were evaluated. MAIN OUTCOME MEASURES: The main outcome measures were FDG activity, other imaging findings, and clinical features. RESULTS: Abnormal FDG uptake correctly indicated tumor recurrence in 10 patients. One patient with no abnormal FDG activity had a morphological abnormality subsequently proven to be a postoperative scar. Two patients, one with very small pulmonary lesions and one with a hepatic metastasis, had false-negative findings. CONCLUSIONS: Most adrenocortical carcinomas accumulate and retain FDG and thus can be visualized by PET. However, false-negative findings are possible, especially with very small lesions.

VAMP and low-dose, involved-field radiation for children and adolescents with favorable, early-stage Hodgkin's disease: results of a prospective clinical trial.

PURPOSE: To evaluate outcome and assess toxicity of children and adolescents with early-stage, favorable Hodgkin's disease treated with vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and low-dose, involved-field radiation. PATIENTS AND METHODS: One hundred ten patients with clinical stages I and II, favorable (nonbulky) Hodgkin's disease were treated with four cycles of VAMP chemotherapy and 15 Gy involved-field radiation for those who achieved a complete response, or 25.5 Gy for those who achieved a partial response to two cycles of VAMP. RESULTS: With a median follow-up of 5.6 years (range, 1.1 to 10.4 years), the 5-year survival and event-free survival were 99% (lower confidence limit [CL], 97.4%) and 93% (lower CL, 88.6%), respectively. Factors associated with event-free survival of 100% were complete response to two cycles of VAMP and histology other than nodular sclerosing Hodgkin's disease (NSHD). No serious early or late toxicity has been observed. Patients presenting with clinical stages I and IIA, nonbulky disease involving fewer than three nodal sites have a projected survival and event-free survival of 100% and 97% (lower CL, 93%), respectively, at 5 years. CONCLUSION: Risk-adapted, combined-modality therapy using only four cycles of VAMP chemotherapy with 15 to 25.5 Gy of involved-field radiation for patients with early-stage/favorable Hodgkin's disease is highly effective and without demonstrable late effects. These results indicate that pediatric patients with stages I and II favorable Hodgkin's disease can be cured with limited therapy that does not include an alkylating agent, bleomycin, etoposide, or high-dose, extended-field radiation therapy.

Risk-adapted, combined-modality therapy with VAMP/COP and response-based, involved-field radiation for unfavorable pediatric Hodgkin's disease.

PURPOSE: To evaluate the efficacy of vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and cyclophosphamide, vincristine, and procarbazine (COP) chemotherapy and response-based, involved-field radiation, a combined-modality regimen that limits doses of alkylating agents, anthracyclines, and radiation, in children with advanced and unfavorable Hodgkin's disease. PATIENTS AND METHODS: From 1993 to 2000, 159 children and adolescents with unfavorable Hodgkin's disease received three alternating cycles (total of six cycles) of VAMP/COP chemotherapy followed by response-based, involved-field radiation therapy: 15 Gy was administered to patients achieving a complete response, and 25.5 Gy was administered to those achieving a partial response after the first two cycles of chemotherapy and to all sites of bulky lymphadenopathy. Unfavorable disease was defined as clinical stage I and II with bulky peripheral nodal disease greater than 6 cm, initial bulky mediastinal mass 33% or more of the intrathoracic diameter, and/or "B" symptoms and all stage III and IV. RESULTS: Study enrollment was closed after an interim analysis estimated a 5-year event-free survival (EFS) rate below a predefined level. Disease presentation was localized (stage I/II) in 77 patients (48.4%) and advanced (stage III/IV) in 82 patients (51.6%). At a median follow-up of 5.8 years (range, 1.3 to 10.0 years), 38 patients had events, including relapse/progression (n = 35), second malignancy (n = 2), and accidental death (n = 1); nine relapses (25.7%) occurred greater than 4 years from diagnosis. Five-year survival and EFS estimates are 92.7% +/- 2.5% and 75.6% +/- 4.1%, respectively. CONCLUSION: Risk-adapted combined-modality therapy with VAMP/COP and response-based, involved-field radiation therapy results in an unsatisfactory outcome for pediatric patients with unfavorable presentations of Hodgkin's disease.

Doxorubicin administration by continuous infusion is not cardioprotective: the Dana-Farber 91-01 Acute Lymphoblastic Leukemia protocol.

PURPOSE: Acute doxorubicin-induced cardiotoxicity can be prevented in adults by continuous infusion of the drug, but mechanisms of cardiotoxicity are different in children. We compared cardiac outcomes in children receiving bolus or continuous infusion of doxorubicin. PATIENTS AND METHODS: In a randomized study, children with high-risk acute lymphoblastic leukemia received doxorubicin 360 mg/m(2) in 30-mg/m(2) doses every 3 weeks either by bolus (within 1 hour, n = 57) or by continuous infusion (over 48 hours, n = 64). Echocardiograms obtained before doxorubicin and at longest follow-up times were centrally remeasured, and z scores of cardiac measurements were calculated based on a healthy population. RESULTS: The groups were similar in age, sex distribution, doxorubicin dose, and duration of follow-up. Before treatment, measures of left ventricular (LV) structure and function did not reveal dilated cardiomyopathy and were not statistically different between bolus and continuous-infusion groups. The follow-up echocardiograms demonstrated no significant difference between the two groups for any cardiac characteristic, but both groups showed significant abnormalities of LV structure and function compared with normal and with baseline. For example, the mean LV fractional shortening fell by approximately two SD in both groups between the two echocardiograms. LV contractility was depressed in both groups (for bolus patients, median z score = -0.70 SD, P =.006; for continuous-infusion patients, median z score = -0.765, P =.005). Dilated cardiomyopathy and inadequate LV hypertrophy were noted in both groups. Clinical cardiac manifestations and event-free survival did not differ. CONCLUSION: Continuous doxorubicin infusion over 48 hours for childhood leukemia did not offer a cardioprotective advantage over bolus infusion. Both regimens were associated with progressive subclinical cardiotoxicity. Other cardioprotective strategies should be explored.

Height and weight in children treated for acute lymphoblastic leukemia: relationship to CNS treatment.

PURPOSE: We evaluated the long-term effects of treatment on height and weight in children with acute lymphoblastic leukemia (ALL) treated with one of the following three different CNS therapies: intrathecal therapy alone, intrathecal therapy with conventional cranial radiation, or intrathecal therapy with twice-daily radiation. PATIENTS AND METHODS: Between 1987 and 1995, 618 children treated on two consecutive Dana-Farber Cancer Institute Consortium protocols for ALL were measured for height and weight at diagnosis, and approximately every 6 months thereafter. Patient height, weight, and body mass index (BMI) were converted to z scores for age and sex using the 2000 Centers for Disease Control and Prevention growth charts for the United States. RESULTS: Children younger than 13 years at diagnosis had a statistically significant decrease in their height z scores and an increase in their BMI z scores, regardless of whether they had received cranial radiation. Young age at diagnosis and increased chemotherapy intensity were major risk factors. Unexpectedly, there was no significant difference in long-term height between children who received radiation and those who did not. CONCLUSION: Final height is compromised in survivors of ALL. The detrimental effects on height occur during therapy without the ability for long-term catch-up growth. Although patients became overweight for height, this seemed to be a result of relative height loss with normal weight gain rather than accelerated weight gain. The type of CNS treatment received did not affect changes in height, weight, or BMI.

Treatment of childhood acute lymphoblastic leukemia: results of Dana-Farber ALL Consortium Protocol 87-01.

PURPOSE: To improve efficacy and reduce toxicity of treatment for children with acute lymphoblastic leukemia. PATIENTS AND METHODS: Patients from all risk groups, including infants and those with T-cell disease, were treated between 1987 and 1991. Standard-risk (SR) patients did not receive cranial irradiation, whereas high-risk (HR) and very high-risk (VHR) patients participated in a randomized comparison of 18 Gy of cranial irradiation conventionally fractionated versus two fractions per day (hyperfractionated). RESULTS: At a median follow-up of 9.2 years, the 9-year event-free survival (EFS +/- SE) was 75% +/- 2% for all 369 patients, 77% +/- 4% for the 142 SR patients, and 73% +/- 3% for the 227 HR/VHR patients (P =.37 comparing SR and HR/VHR). The CNS, with or without concomitant bone marrow involvement, was the first site of relapse in 19 (13%) of the 142 SR patients: 16 (20%) of 79 SR boys and three (5%) of 63 SR girls. This high incidence of relapses necessitated a recall of SR boys for additional therapy. CNS relapse occurred in only two (1%) of 227 HR and VHR patients. There were no outcome differences found among randomized treatment groups. Nine-year overall survival was 84% +/- 2% for the entire population, 93% +/- 2% for SR children, and 79% +/- 3% for HR and VHR children (P <.01 comparing SR and HR/VHR). CONCLUSION: A high overall survival outcome was obtained for SR patients despite the high risk of CNS relapse for SR boys, which was presumed to be associated with eliminating cranial radiation without intensifying systemic or intrathecal chemotherapy. For HR/VHR patients, inability to salvage after relapse (nearly all of which were in the bone marrow) remains a significant clinical problem.

Adenocarcinoma of the cervix metastatic from a colon primary and diagnosed from a routine pap smear in a 17-year-old woman: a case report.

BACKGROUND: Carcinoma metastatic to the uterine cervix is very rare. The most frequent nongenital primary sites are the stomach and colon. CASE: A 17-year-old woman presented to the office for an annual gynecologic examination. The Pap smear and cervical biopsy of a 1.5-cm lesion were positive for adenocarcinoma. Subsequent surgery revealed a sigmoid tumor with extensive abdominal and pelvic carcinomatosis. Following 2 cycles of ineffective chemotherapy, the patient died 4 months after her initial visit to the gynecologist. CONCLUSION: To our knowledge, this was the youngest patient in the literature with colon cancer metastatic to the cervix. This case focuses attention on the diagnostic challenge posed by an incidental finding of a cervical adenocarcinoma in the presence of an asymptomatic primary tumor.

Caring for the child with cancer at the close of life: "there are people who make it, and I'm hoping I'm one of them".

Approximately 25% of children with cancer die of their disease. Early in the course of a patient's illness, it is often impossible to determine whether the disease will be cured with cancer-directed treatment. When potentially curative therapy is no longer an option, the patient, family, and oncology team face enormous medical, psychological, and spiritual challenges. Optimal palliative care requires willingness on the part of the physician and caregiver team to engage the patient and family in discussions of their hopes and fears and to provide solace and support for emotional and physical pain. Using the comments of a child in the terminal phase of acute leukemia, his mother, and his physician, we describe opportunities and important lessons often revealed only when families and their caregivers face the end of a child's life. A broad-minded assessment of the patient's and family's physical, emotional, and spiritual needs and clarification of realistic goals and hopes not only improves the clinical care that the patient receives but also contributes to the sense of satisfaction and meaning that the physician can gain from the experience of caring for children at the end of life.

High expression of the very late antigen-4 integrin independently predicts reduced risk of relapse and improved outcome in pediatric acute myeloid leukemia: a report from the children's oncology group.

PURPOSE: To evaluate the prognostic significance of the integrin cell adhesion molecule very late antigen-4 (VLA-4) in acute myeloid leukemia (AML). PATIENTS AND METHODS: We prospectively quantified VLA-4 expression in 216 patients enrolled onto COG-AAML03P1 by flow cytometry and correlated expression levels with disease characteristics and clinical outcome. RESULTS: VLA-4 mean fluorescence intensity (MFI) varied 35-fold (range, 30 to 1,110; median, 219.5). High VLA-4 expression (> median MFI), compared with low expression, was associated with younger age (7.1 v 12.1 years, respectively; P < .001), lower FLT3 internal tandem duplication prevalence (4% v 21%, respectively; P < .001), and higher likelihood of extramedullary disease (16% v 5%, respectively; P = .013). In low- and high-expression groups, rates of remission (89% v 80%, respectively; P = .137) and minimal residual disease (29% v 25%, respectively; P = .700) were similar. Patients with low VLA-4 expression, compared with high expression, had a higher relapse rate (RR; 44% +/- 10% v 24% +/- 9%, respectively; P = .011) and lower disease-free survival (DFS; 48% +/- 11% v 67% +/- 10%, respectively; P = .023) after 3 years. Multivariate analyses showed that low VLA-4 expression was an independent adverse prognostic factor for DFS (hazard ratio [HR] = 1.98; P = .038) and RR (HR = 2.77; P = .009). Subgroup analyses indicated that the prognostic role of VLA-4 expression was most prominent in patients with standard-risk AML, in whom low VLA-4 expression was associated with inferior DFS (34% +/- 16% v 69% +/- 14% for high expression; P = .011) and higher RR (61% +/- 16% v 26% +/- 14% for high expression; P = .009). A similar trend was seen in low-risk but not high-risk patients. CONCLUSION: High VLA-4 expression is associated with better clinical outcome in pediatric AML and is an independent predictor of relapse that may refine our abilities to stratify patients without identifiable cytogenetic or molecular risk factors.

Availability and use of palliative care and end-of-life services for pediatric oncology patients.

PURPOSE: Palliative care prevents or relieves the symptoms caused by life-threatening medical conditions. Previous surveys have shown both underuse and lack of availability of these services for children with cancer throughout North America. We sought to investigate the current practices and resources surrounding palliative and end-of-life care among participating institutions of the Children's Oncology Group (COG). METHODS: A survey regarding practices and resources was developed by the COG palliative care subcommittee and was sent to all 232 institutions to complete for the calendar year 2005. RESULTS: The survey was completed by 81% of the institutions. Per institution, there were a mean of 64.6 newly diagnosed patients and 17.7 patients experiencing relapse. A palliative care team was available in 58% of institutions, a pain service in 90%, a hospice in 60%, a psychosocial support team in 80%, and a bereavement program in 59%. Complementary and alternative medicine was available in 39% of institutions and in 95% of the COG institution's community. Most services, even when available, were not well used by patients. CONCLUSION: Despite the well-established benefit of pediatric palliative care, it is only offered in 58% of COG institutions caring for children with cancer. In an era where the benefit of palliative care has been clearly established, this number should approach 100%. Efforts should be directed toward understanding barriers to provision of such services, so that they are available and well used at all childhood cancer centers.

Safety and efficacy of gemtuzumab ozogamicin in combination with chemotherapy for pediatric acute myeloid leukemia: a report from the Children's Oncology Group.

PURPOSE: While gemtuzumab ozogamicin (GTMZ) is commonly used in the treatment of acute myeloid leukemia (AML) in combination with standard chemotherapy agents, the pediatric maximum-tolerated dose (MTD) of GMTZ in combination with chemotherapy has not been determined. PATIENTS AND METHODS: The Children's Oncology Group AAML00P2 trial sought to define the MTD of GMTZ in combination with cytarabine and mitoxantrone and cytarabine and l-asparaginase chemotherapy regimens. RESULTS: The MTD for GMTZ in combination with cytarabine and mitoxantrone was 3 mg/m(2) while the MTD in combination with cytarabine and l-asparaginase was 2 mg/m(2). Toxicities observed in both treatment regimens were typical of those seen in the relapsed AML setting and consisted primarily of infectious complications. The overall remission response rate (mean +/- SE) was 45% +/- 15% and the 1 year event-free survival and overall survival estimates were 38% +/- 14% and 53% +/- 15%, respectively. CONCLUSION: This trial determined the pediatric MTD for GMTZ with two commonly used AML chemotherapy combinations. Based on these results, an ongoing phase III trial conducted within the Children's Oncology Group is evaluating the effect of GMTZ when added to standard AML therapy.