Reduced-dose intensity therapy for pediatric lymphoblastic leukemia: long-term results of the Recife RELLA05 pilot study.

Treatment-related mortality is common among children with acute lymphoblastic leukemia (ALL) treated in poor-resource settings. We applied a simplified flow cytometric assay to identify patients with precursor B-cell ALL (B-ALL) at very low risk (VLR) of relapse and treated them with a reduced-intensity treatment plan (RELLA05). VLR criteria include favorable presenting features (age ≥ 1 and < 10 years), white blood cell count of <50 ×109/L, lack of extramedullary leukemia, and minimal residual disease level of <0.01% on remission induction day 19. Except for 2 doses of daunorubicin, treatment of patients with VLR B-ALL consisted of a combination of agents with relatively low myelotoxicity profiles, including corticosteroids, vincristine, L-asparaginase, methotrexate, and 6-mercaptopurine. Cyclophosphamide, systemic cytarabine, and central nervous system radiotherapy were not used. Of 454 patients with ALL treated at the Instituto de Medicina Integral Professor Fernando Figueira in Recife, Brazil, between December 2005 and June 2015, 101 were classified as having VLR B-ALL. There were no cases of death resulting from toxicity or treatment abandonment during remission induction. At a median follow-up of 6.6 years, there were 8 major adverse events: 6 relapses, 1 treatment-related death (from septicemia) during remission, and 1 secondary myeloid leukemia. The estimated 5-year event-free and overall survival rates were 92.0% ± 3.9% and 96.0% ± 2.8%, respectively. The 5-year cumulative risk of relapse was 4.24% ± 2.0%. The treatment was well tolerated. Episodes of neutropenia were of short duration. Patients with B-ALL selected by a combination of presenting features and degree of early response can be successfully treated with a mildly myelosuppressive chemotherapy regimen.

Excess Weight among Survivors of Acute Lymphoblastic Leukemia Survivors Treated at a Center in Northeast Brazil.

Therapeutic advances in the treatment of acute lymphoblastic leukemia (ALL) have increased the number of survivors but have promoted the development of long-term side effects, the best documented of which is obesity. The present retrospective case series analyzed data collected at diagnosis, end of treatment, and last follow-up visit of 210 ALL survivors treated between August 2005 and October 2014. Clinical and anthropometric data were collected from medical records. The nutritional diagnosis was based on z-scores of height-for-age (H/AZ) and body mass index-for-age (BMI/AZ) for males and females provided by the World Health Organization. H/AZ decreased and BMI/AZ increased between baseline and end of treatment, followed by H/AZ catch-up at follow-up. The prevalence of excess weight on the three occasions was 24.3%, 38.3, and 43.3%, respectively. Baseline excess weight (adjusted OR: 12.2; 95% CI: 5.5-27.0) and the ALL risk group (adjusted OR: 2.89; 95% CI: 1.1-7.6) were independently associated with excess weight at the end of treatment, whereas baseline excess weight (adjusted OR: 8.50; 95% CI: 3.93-18.40) and linear growth (adjusted OR: 2.02; 95% CI: 1.05-3.88) were independently associated with excess weight at follow-up. The frequency of excess weight had increased significantly by the end of treatment and persisted at follow-up. Baseline excess weight was the main factor associated with excess weight at the end of treatment and follow-up.

MicroRNA expression profiles discriminate childhood T- from B-acute lymphoblastic leukemia.

MicroRNAs (miRNAs) play a critical role on biological and cellular processes; the search for functional markers may be of importance for differential diagnosis, prognosis, and development of new therapeutic regimens. In this context, we evaluated the bone marrow miRNA profile of Brazilian children exhibiting T- or B-cell acute lymphoblastic leukemia (T-ALL or B-ALL), using massive parallel sequencing, using the HiSeq 2500 platform (Illumina). The differential expression analysis was conducted considering a leave-one-out approach and FDR ≤ 0.05. Machine learning algorithms were applied to search for the disease subset biomarkers. Target prediction, functional enrichment, and classification of biological categories were also performed. Sixteen miRNAs were differentially expressed between T- and B-ALL, of which 10 (miR-708-5p, miR-497-5p, miR-151a-5p, miR-151b, miR-371b-5p, miR-455-5p, miR-195-5p, miR-1266-5p, miR-574-5p, and miR-425-5p) were downregulated and six (miR-450b-5p, miR-450a-5p, miR-542-5p, miR-424-5p, miR-629-5p, and miR-29c-5p) were upregulated in childhood T-ALL. These miRNAs may be used for distinguishing childhood lymphoblastic leukemia subtypes, since it provided the clear separation of patients in these two distinct groups. Six relevant biological pathways were identified according to their role in leukemia, namely, viral carcinogenesis, cell cycle, and B-cell receptor signaling pathways for induced miRNAs and TGF-beta signaling, apoptosis, and NF-kappa B signaling for the repressed miRNAs, of which several miRNA gene targets participate in cell differentiation and hematopoiesis processes. Machine learning analysis pointed out miR-29c-5p expression as the best discriminator between childhood T- and B-ALL, which is involved in calcium signaling, critical for B-cell lymphocyte fate. Further studies are needed to assure the role of the 16 miRNAs and miR-29c-5p on acute lymphoblastic leukemia subtypes and on disease prognosis.

Cytokines and soluble HLA-G levels in bone marrow stroma and their association with the survival rate of patients exhibiting childhood T-cell acute lymphoblastic leukemia.

Leukemic cells can induce defective expression of soluble factors and change marrow cytokine profile, leading to aberrant cell signaling, cell fixation and cell proliferation in bone marrow. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disorder which accounts for 15% of pediatric ALL. To evaluate the contribution of immunological factors on T-ALL survival, we measured Th1, Th2, Th17 cytokines and soluble HLA-G (sHLA-G) levels in bone marrow from 32 Brazilian children at diagnosis (D0), after induction (D19) and after consolidation (D49) of the chemotherapy phase. Data were analyzed using non-parametric tests, and survival rates were evaluated by Kaplan-Meier method (log-rank test). TNF, IL-10 and IL-6 levels were increased at diagnosis compared to D19 and D49. IL-10 levels<4.57pg/mL at diagnosis were associated with increased survival rate, in presence of positive correlation between IL-2 and IL-17 levels. Increased survival rate was also associated with IFN-γ levels<1.17pg/mL at D49, with a positive correlation observed between IL-4 and IL-2 as well IL-4 and IL-17 levels. In contrast, worse survival rate was associated with IL-2, IL-4 and IL-10 levels imbalance. In addition, increased sHLA-G levels at diagnosis were associated with increased leukocyte count, a well-known factor for poor prognosis. In conclusion, cytokines and sHLA-G play an essential role in marrow T-ALL microenvironment during chemotherapy, especially the immunosuppressive cytokine IL-10 which can be used as biomarker of disease outcome, being also a potential target for novel T-ALL treatments.

A framework to develop adapted treatment regimens to manage pediatric cancer in low- and middle-income countries: The Pediatric Oncology in Developing Countries (PODC) Committee of the International Pediatric Oncology Society (SIOP).

Many children with cancer in low- and middle-income countries are treated in hospitals lacking key infrastructure, including diagnostic capabilities, imaging modalities, treatment components, supportive care, and personnel. Childhood cancer treatment regimens adapted to local conditions provide an opportunity to cure as many children as possible with the available resources, while working to improve services and supportive care. This paper from the Adapted Treatment Regimens Working Group of the Pediatric Oncology in Developing Countries committee of the International Society of Pediatric Oncology outlines the design, development, implementation, and evaluation of adapted regimens and specifies levels of services needed to deliver them.

The Impact of Prospective Telemedicine Implementation in the Management of Childhood Acute Lymphoblastic Leukemia in Recife, Brazil.

BACKGROUND: A gap in childhood cancer outcomes remains between developed and developing countries. Persistence of this gap may be caused by financial, social, or educational disparities. Twinning and distance learning initiatives may improve such disparities. Integrating telemedicine into pediatric oncology twinning programs enhances education and facilitates patient-centered capacity building. MATERIALS AND METHODS: We performed an analysis of Web-based meetings held from August 2005 through July 2009 between the International Outreach Program at St. Jude Children's Research Hospital and the Instituto Materno Infantil de Pernambuco (IMIP) in Recife, Brazil. We determined the effect of these online conferences on the development and implementation of an innovative protocol for children with acute lymphoblastic leukemia (ALL) at IMIP. RESULTS: Meetings occurred in 45 months of the 48-month study period with an average of two meetings per month. A total of 163 new patients were discussed during the study period; we retrieved documentation of patient-related discussions for 147 of them, constituting 286 discussions. On average, each patient was discussed 1.9 times (range, 1-15 discussions/patient). Compared with that of the era predating the online meetings (1993-2005), overall mortality, early death, and relapse of patients with ALL decreased after the telemedicine program was instituted at IMIP. DISCUSSION: Personal dedication and institutional support are essential for successful telemedicine initiatives. Documentation and archival of meetings are important for accurately measuring outcomes and developing methods for improved care. CONCLUSIONS: Integration of telemedicine into twinning programs facilitates communication about interventions, leading to improved outcomes of pediatric patients with cancer.

Lumbar punctures in thrombocytopenic children with cancer.

INTRODUCTION: Lumbar punctures (LP) in patients presenting thrombocytopenia are linked to the possibility of bleeding and spinal hematomas. The minimum platelet count required for the safe performance of spinal procedures is still under discussion. Children with some oncology diseases require routinely lumbar punctures; such patients often present thrombocytopenia, making this group an ideal population to study the association between lumbar puncture in thrombocytopenic patients and complications. OBJECTIVES: To determine the platelet count of oncology children undergone lumbar punctures and the occurrence of spinal hematomas. METHOD: Observational longitudinal study. It included a retrospective analysis of electronic medical records of oncology patients submitted to LP for intrathecal chemotherapy between January 2004 and October 2011, carried out at the 'Instituto de Medicina Integral Prof. Fernando Figueira (IMIP)', Recife, Brazil. RESULTS: We evaluated 9088 lumbar punctures performed in 440 patients. The platelet count distribution before lumbar punctures was as follows: 25 punctures had zero to 10,000 platelets per mm(3), 67 punctures had between 10,000 and 20,000 platelets per mm(3), 88 had between 20,000 and 30,000 platelets per mm(3), 92 punctures had between 30,000 and 40,000 platelets per mm(3), 107 punctures had between 40,000 and 50,000 platelets per mm(3), and 729 punctures had between 50,000 and 100,000 platelets per mm(3). In this series, the incidence of bloody tap was 16.9% (1112 lumbar punctures of 6552 had more than ten erythrocytes). No complications were observed. CONCLUSIONS: Even in thrombocytopenic patient, an epidural hematoma would be a relatively rare complication following lumbar puncture. Despite the large number of punctures performed on patients with platelet counts below 100,000 mm(-3) (n = 1108), further studies are necessary in order to determine a lower safe platelet count threshold for the performance of lumbar punctures in healthy patients undergoing neuraxial anesthesia.

Targeted genomic sequencing of pediatric Burkitt lymphoma identifies recurrent alterations in antiapoptotic and chromatin-remodeling genes.

To ascertain the genetic basis of pediatric Burkitt lymphoma (pBL), we performed clinical-grade next-generation sequencing of 182 cancer-related genes on 29 formalin-fixed, paraffin embedded primary pBL samples. Ninety percent of cases had at least one mutation or genetic alteration, most commonly involving MYC and TP53. EBV(-) cases were more likely than EBV(+) cases to have multiple mutations (P < .0001). Alterations in tumor-related genes not previously described in BL were identified. Truncating mutations in ARID1A, a member of the SWI/SNF nucleosome remodeling complex, were seen in 17% of cases. MCL1 pathway alterations were found in 22% of cases and confirmed in an expanded panel. Other clinically relevant genomic alterations were found in 20% of cases. Our data suggest the roles of MCL1 and ARID1A in BL pathogenesis and demonstrate that comprehensive genomic profiling may identify additional treatment options in refractory disease.

Improving the histopathologic diagnosis of pediatric malignancies in a low-resource setting by combining focused training and telepathology strategies.

BACKGROUND: Accurate diagnosis is critical for optimal management of pediatric cancer. Pathologists with experience in pediatric oncology are in short supply in the developing world. Telepathology is increasingly used for consultations but its overall contribution to diagnostic accuracy is unknown. PROCEDURE: We developed a strategy to provide a focused training in pediatric cancer and telepathology support to pathologists in the developing world. After the training period, we compared trainee's diagnoses with those of an experienced pathologist. We next compared the effectiveness of static versus dynamic telepathology review in 127 cases. Results were compared by Fisher's exact test. RESULTS: The diagnoses of the trainee and the expert pathologist differed in only 6.5% of cases (95% CI, 1.2-20.0%). The overall concordance between the telepathology and original diagnoses was 90.6% (115/127; 95% CI, 84.1-94.6%). CONCLUSIONS: Brief, focused training in pediatric cancer histopathology can improve diagnostic accuracy. Dynamic and static telepathology analyses are equally effective for diagnostic review.

Delayed diagnosis of leukemia and association with morbid-mortality in children in Pernambuco, Brazil.

The objectives of this study were to describe the interval between symptom onset and diagnosis of acute leukemia, to assess risk factors for delayed diagnosis, and its effect on early morbid-mortality and event-free survival (EFS). Records of children aged 1 month to 18 years diagnosed with acute leukemia were reviewed for clinical, demographic, and health care provider factors, and for time to diagnosis. Of 288 patients diagnosed, 55% had a delay in diagnosis. The median time to diagnosis was 31 days. There were significant associations between the diagnostic delay and the distance from the tertiary care hospital (P=0.04), initial consultation in an outpatient clinic (P=0.04), presenting symptoms of bone/joint pain (P=0.04), family with more than 3 children (P=0.02), birth order of third or greater (P=0.009), paternal age <30 years (P=0.03), and paternal education <8 years (P=0.008). There was no association between delayed diagnosis and early morbid-mortality or EFS at 5 years. Initial consultation in an outpatient setting, presenting symptoms of bone/joint pain, and birth order of third or greater remained statistically significant in multivariate analyses, but the delay did not have an impact on early morbid-mortality or EFS. Education of primary care providers in atypical presentations of acute leukemia may decrease the diagnostic delay.

Intellectual impairment after treatment for medulloblastoma and astrocytoma in childhood: the Brazilian experience.

BACKGROUND: This study investigated the impact of posterior fossa tumors and their respective treatments, and the impact of clinical and sociodemographic variables, on the intelligence quotient (IQ) of Brazilian children. METHODS: Twenty patients took part in the study, of which 13 were diagnosed with astrocytoma (average age at evaluation 10.2 y) and 7 with medulloblastoma (average age at evaluation 9.2 y). The first subgroup was submitted exclusively to tumor resection surgery and the second subgroup underwent surgery, chemotherapy (Vincristine, Cisplatine, and Carmustine), and radiotherapy (total dose of 54 Gy). The Wechsler Intelligence Scale for Children (WISCIII) was used. RESULTS: The following statistically significant effects were identified: treatment modality on performance intelligence quotient scores (P=0.02) and processing speed index (PSI) (P=0.01); presence of hydrocephalus at diagnosis on verbal intelligence quotient (P=0.04); tumor localization on perceptual organization index (P=0.03); time interval between diagnosis and neuropsychological evaluation on PSI (P=0.05) and freedom from distraction index (P=0.03); and level of parental formal education on full scale IQ (P=0.02). CONCLUSIONS: Exposure to radiotherapy has a significant effect on processing speed and consequently on global intellectual capacity. The impact on intelligence of clinical and sociodemographic variables such as tumor localization, time interval between diagnosis and cognitive evaluation, and parental level of formal education is confirmed in the specific setting of a developing country.

Molecular findings in childhood leukemia in Brazil: high frequency of MLL-ENL Fusion/t(11;19) in infant leukemia.

Translocations involving chromosome 11q23 are frequently found in pediatric leukemia, especially in infants. The mixed lineage leukemia (MLL)-AF4 fusion/t(4;11) is mostly found in acute lymphoblastic leukemia (ALL) and MLL-AF9 fusion/t(9;11) in acute myeloid leukemia (AML). We study 441 consecutive new cases of childhood leukemia diagnosed in Brazil. Chromosomal translocation was determined solely by conventional polymerase chain reaction (PCR) in 72 out of 265 ALL and in 43 out of 103 AML. MLL-AF4 fusion/t(4;11) was detected in 3 out of 265 ALL and MLL-AF9 fusion/t(9;11) in 4 out of 103 of AML. MLL-rearrangements were presented in 7 out of 23 infant leukemia, whose 5 were MLL-ENL fusion/t(11;19). No fusion MLL-AF4 fusion/t(4;11) was found. Other translocation frequencies differed from that reported for an American population suggesting interethnic differences on chromosomal translocations frequencies in acute leukemia.

Evaluation of the Reproducibility of the Dejour Classification for Femoropatellar Instability.

Objective To evaluate the classification proposed by David Dejour to describe trochlear dysplasia of the knee through inter- and intraobserver reproducibility measurements. Methods Ten patients with trochlear dysplasia were studied. Three physicians, members of the Sociedade Brasileira de Cirurgia do Joelho (Brazilian Society of Knee Surgery), were invited to evaluate the images. Intra- and interobserver analyses were performed at one-week intervals. Reproducibility was evaluated in four scenarios: using only radiography; using radiography and tomography; using radiography and consulting the classification; and using radiography and tomography, consulting the classification. Results The intraobserver evaluation presented discordant results. In the interobserver analysis, the degree of agreement was low for the analyses that used only radiography and excellent for those in which both radiography and tomography were used. Conclusion The Dejour classification presented a low intra- and interobserver reproducibility when only the profile radiography was used. It was demonstrated that the use of the radiography alone for classification may generate lack of uniformity even among experienced observers. However, when radiography and tomography were combined, reproducibility improved.

Evidence of anomalous switching of the in-plane magnetic easy axis with temperature in Fe3O4 film on SrTiO3:Nb by v-MOKE and ferromagnetic resonance.

The evolution of the magnetic anisotropy directions has been studied in a magnetite (Fe3O4) thin film grown by infrared pulsed-laser deposition on SrTiO3(100):Nb substrate. The magnetic easy axes at room temperature are found along the in-plane 〈100〉 film directions, which means a rotation of the easy axis by 45° with respect to the directions typically reported for bulk magnetite and films grown on single-crystal substrates. Moreover, when undergoing the Verwey transition temperature, TV, the easy axis orientation evolves to the 〈110〉 film directions. This anomalous behavior has been demonstrated by measuring first the angular dependence of coercivity and remanence well above and below TV by high-resolution vectorial magneto-optical Kerr effect (v-MOKE). Ferromagnetic resonance (FMR) measurements have additionally proven a well-defined fourfold magnetic anisotropy induced during growth with confirmed easy axis directions along 〈100〉 for T > TV and 〈110〉 for T < TV. These results provide a clear proof of the possibility of tuning magnetic anisotropy in Fe3O4 thin films by proper control on the growth parameters and substrate choice.

Implementation of a simplified flow cytometric assays for minimal residual disease monitoring in childhood acute lymphoblastic leukemia.

BACKGROUND: Monitoring minimal residual disease (MRD) in B-lineage acute lymphoblastic leukemia (ALL) to assess treatment response is crucial for risk assignment. Flow cytometry can be used to monitor MRD in ALL but the implementation of this approach requires extensive expertise. If resources are limited, the costs of full flow cytometric MRD testing might be prohibitive. OBJECTIVE: We evaluated the applicability of a previously reported simplified MRD assay, designed to distinguish leukemic from normal lymphoblastic during remission induction therapy. METHODS: Fifty-nine samples from children with ALL, enrolled in the RE-LLA study at a pediatric oncology center in Recife (Brazil), were evaluated for MRD on day 19 and on day 26 of remission induction therapy. We compared results obtained by a trainee in Recife and an expert. RESULTS: The method was implemented successfully and the concordance between results obtained by the trainee and the expert was practically absolute at the end of the study. CONCLUSIONS: It is possible to implement reliable measurements of MRD during remission induction therapy in childhood ALL despite limited resources. The simplicity of the MRD method used in this study does not require extensive prior training in leukemia immunophenotyping. © 2016 International Clinical Cytometry Society.

Non-Hodgkin's lymphoma in childhood: clinical and epidemiological characteristics and survival analysis at a single center in Northeast Brazil.

OBJECTIVE: To describe the clinical and demographic characteristics of non-Hodgkin's lymphoma patients diagnosed at the Pediatric Oncology Unit at the Instituto Materno-Infantil Professor Fernando Figueira (IMIP) over a 9-year period, and also to describe their survival rates and possible associations between the survival rates and the clinical and demographic characteristics analyzed in the study. METHODS: This was a cross-sectional study. Data were collected by a retrospective review of the charts of all 110 patients admitted to our unit during the period of May 1994 through May 2003. Probability of survival was calculated in accordance with the techniques of Kaplan-Meier, using log rank to evaluate differences between the groups. RESULTS: The average age was 6.1 years. The male/female ratio was 2.4:1. The most frequent histological subtype was Burkitt's lymphoma. The majority of patients had been diagnosed with advanced disease (stage III or IV of Murphy's Classification) and was from rural areas. Family income per capita was lower than 1/2 minimum wage in 36.4% of cases; maternal illiteracy was observed in 12.7% of cases. The 5-year overall survival and disease-free survival rates were 70+/-4% and 68.4+/-4%, respectively. None of the clinical-demographic characteristics had a significant association with the probability of survival (p > 0.05). CONCLUSION: Children admitted to the IMIP seemed to be affected by non-Hodgkin lymphoma at a younger age, with a higher incidence of Burkitt's lymphoma and with survival rates similar to those described in the literature of developed countries. No clinical demographic characteristics had a statistically significant association with prognosis

Global Pediatric Oncology: Lessons From Partnerships Between High-Income Countries and Low- to Mid-Income Countries.

Partnerships between medical institutions in high-income countries (HICs) and low- to mid-income countries (LMICs) have succeeded in initiating and expanding pediatric cancer control efforts. The long-term goal is consistently a sustainable national pediatric cancer program. Here, we review the elements required for successful implementation, development, and long-term sustainability of pediatric cancer programs in LMICs that first arise as partnerships with institutions in HICs. Although plans must be adapted to each country's resources, certain components are unfailingly necessary. First, an essential step is provision of treatment regardless of ability to pay. Second, financial support for program development and long-term sustainability must be sought from sources both international and local, public and private. A local leader, typically a well-trained pediatric oncologist who devotes full-time effort to the project, should direct medical care and collaborate with hospital, governmental, and community leadership and international agencies. Third, nurses must be trained in pediatric cancer care and allowed to practice this specialty full-time. It is also essential to develop a grassroots organization, such as a foundation, dedicated solely to pediatric oncology. Its members must be trained and educated to provide pediatric cancer advocacy, fundraising, and (in concert with government) program sustainability. Finally, a project mentor in the HIC is crucial and should explore the possibility of collaborative research in the LMIC, which may offer significant opportunities. Relationships between the partnership's leaders and influential individuals in the community, hospital, grassroots foundation, and government will lay the foundation for productive collaboration and a sustainable pediatric oncology program.

Establishment of a pediatric oncology program and outcomes of childhood acute lymphoblastic leukemia in a resource-poor area.

CONTEXT: The cure rate for childhood acute lymphoblastic leukemia (ALL) differs markedly between developed and developing countries. OBJECTIVE: To assess the effect of a multidisciplinary team approach and protocol-based therapy on the event-free survival of children with ALL in an area with limited resources. DESIGN, POPULATION, AND SETTING: A retrospective cohort study at a pediatric hospital in the resource-poor city of Recife, Brazil. We reviewed medical records of the outcomes of 375 children with ALL diagnosed between 1980 and 2002. Eighty-three children were diagnosed in the early period (1980-1989), in the absence of a dedicated pediatric oncology unit, protocol-based therapy, specially trained nurses, 24-hour on-site physician coverage, and ready access to intensive care. Seventy-eight children were treated (all according to protocol) during the middle period (July 1994 to March 1997). During the recent period (April 1997 to December 2002), 214 children were treated with protocol in a dedicated pediatric oncology unit staffed 24 hours by pediatric oncologists and oncology nurses. Improvements were implemented gradually during the middle period and were completed during the recent period. MAIN OUTCOME MEASURE: Event-free survival was estimated by the Kaplan-Meier method. Events included death from toxicity, disease progression or relapse, and abandonment of treatment. RESULTS: The 5-year event-free survival improved steadily: 32% (95% CI, 21%-43%) in the early period, 47% (95% CI, 36%-58%) in the middle period, and 63% (95% CI, 55%-71%) in the recent period. The probability of cause-specific treatment failure in the early, middle, and late periods, respectively, within 1 year of diagnosis was 14% vs 3.8% vs 3.3% for relapse; 6.0% vs 12% vs 9.8% for death from infection; 2.4% vs 13% vs 4.2% for death from noninfectious toxicity; and 16% vs 1.3% vs 0.5% for abandonment of therapy. CONCLUSION: Treatment of childhood ALL in a dedicated pediatric oncology unit using a comprehensive multidisciplinary team approach, protocol-based therapy, and local support and funding is associated with improved outcomes in a resource-poor area.

Guidelines for the recurrence of pediatric cancer.

OBJECTIVES: To provide practice guidelines to assist patients and parents in coping with a return of disease. DATA SOURCES: Delphi studies, review, and research articles. CONCLUSIONS: When a child's cancer recurs, the patient and parents are at risk of physical and psychologic difficulties. Guidelines to assist patients and parents to cope have shown positive response. IMPLICATIONS FOR NURSING PRACTICE: Practice guidelines to assist patients and parents cope with a return of cancer can help health care professionals develop interventions for particular families.