Trust in information sources during the COVID-19 pandemic and its association with vaccine trust among a sample of Hispanic adults.

BACKGROUND: Public response to the COVID-19 pandemic has underscored the importance of trust, particularly among minority populations. Several factors might affect vaccine safety trust, including source trustworthiness. Using data from the Puerto Rico Community Engagement Alliance, we assessed the association between trust in information sources and the COVID-19 vaccine in a sample of Hispanic adults. METHODS: A cross-sectional survey-based study was conducted from November 2021 to March 2022. Participants were telephone-interviewed to assess sociodemographic, clinical, and COVID-19-related variables. Vaccine trust was assessed by how confident respondents were regarding COVID-19 vaccine safety. Trust in COVID-19 information sources was assessed by asking respondents how much they trusted selected sources of information to provide accurate information about COVID-19, including the US and Puerto Rico governments, Centers for Disease Control and Prevention (CDC), health care professionals, and traditional media (television/radio/newspaper/internet). Logistic regression models estimated the odds ratio (OR, 95% CI) of COVID-19 vaccine trust based on trust in information sources. RESULTS: A total of 200 adults aged ≥21 years completed the telephone interview. While most of the study sample (97.5%) had been inoculated with at least one dose of the COVID-19 vaccine, 86% trusted in the COVID-19 vaccine's safety. After adjusting for age and sex, participants who attested greater trust in their healthcare professionals (OR=1.99, 95% CI=0.71, 5.62), the US government (OR=2.44, 95% CI=0.69, 8.68), and the CDC (OR=8.18, 95% CI=2.97, 22.57) reported increased vaccine trust as compared to those not having great confidence in these entities. CONCLUSION: These findings support that trust in information provided by the CDC is positively associated with COVID-19 vaccine trust. Acknowledging predictors of trust regarding COVID-19 vaccination could help address factors that affect vaccine confidence. In turn, it strengthens COVID-19 prevention efforts, benefiting common welfare, reducing health disparities, and aiding underserved populations.

Reduced-intensity therapy for pediatric lymphoblastic leukemia: impact of residual disease early in remission induction.

Legacy data show that ∼40% of children with acute lymphoblastic leukemia (ALL) were cured with limited antimetabolite-based chemotherapy regimens. However, identifying patients with very-low-risk (VLR) ALL remains imprecise. Patients selected based on a combination of presenting features and a minimal residual disease (MRD) level <0.01% on day 19 of induction therapy had excellent outcomes with low-intensity treatment. We investigated the impact of MRD levels between 0.001% and <0.01% early in remission induction on the outcome of VLR ALL treated with a low-intensity regimen. Between October of 2011 and September of 2015, 200 consecutive patients with B-precursor ALL with favorable clinicopathologic features and MRD levels <0.01%, as assessed by flow cytometry in the bone marrow on day 19 and at the end of induction therapy, received reduced-intensity therapy. The 5-year event-free survival was 89.5% (± 2.2% standard error [SE]), and the overall survival was 95.5% (± 1.5% SE). The 5-year cumulative incidence of relapse (CIR) was 7% (95% confidence interval, 4-11%). MRD levels were between 0.001% and <0.01% on day 19 in 29 patients. These patients had a 5-year CIR that was significantly higher than that of patients with undetectable residual leukemia (17.2% ± 7.2% vs 5.3% ± 1.7%, respectively; P = .02). Our study shows that children with VLR ALL can be treated successfully with decreased-intensity therapy, and it suggests that the classification criteria for VLR can be further refined by using a more sensitive MRD assay.

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.

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.

Treatment Interruptions and Mortality Among Puerto Rican Women With Gynecologic Cancers in Puerto Rico After Hurricanes Irma and María: A Retrospective Cohort Study.

OBJECTIVE: Cancer patients are among the most vulnerable populations during and after a disaster. We evaluated the impact of treatment interruption on the survival of women with gynecologic cancer in Puerto Rico following Hurricanes Irma and María. METHODS: A retrospective cohort study among a clinic-based sample of women with gynecological cancer diagnosed between January 2016 and September 2017 (n = 112) was done. Women were followed from their diagnosis until December 2019, to assess vital status. Kaplan-Meier survival curves and Cox proportional hazards models were performed. RESULTS: Mean age was 56 (± 12.3) years; corpus uteri (58.9%) was the most common gynecologic cancer. Predominant treatments were surgery (91.1%) and chemotherapy (44.6%). Overall, 75.9% were receiving treatment before the hurricanes, 16.1% experienced treatment interruptions, and 8.9% died during the follow-up period. Factors associated with treatment interruption in bivariate analysis included younger age (≤55 years), having regional/distant disease, and receiving > 1 cancer treatment (P < 0.05). Crude analysis revealed an increased risk of death among women with treatment interruption (HR: 3.88, 95% CI: 1.09-13.77), persisting after adjusting for age and cancer stage (HR: 2.49, 95% CI: 0.69-9.01). CONCLUSIONS: Findings underscore the detrimental impact of treatment interruption on cancer survival in the aftermath of hurricanes, emphasizing the need for emergency response plans for this vulnerable population.

The Puerto Rico community engagement alliance (PR-CEAL) against COVID-19 disparities: outreach and research engagement efforts in disproportionately affected communities.

In September 2020, the National Institutes of Health acted in response to the COVID-19 pandemic, recognizing the critical need to combat misinformation, particularly in communities disproportionately affected by the crisis. The Community Engagement Alliance (CEAL) emerged as an initiative dedicated to fostering reliable, science-based information, diversity, and inclusion; aiming to implement effective strategies to mitigate the spread of COVID-19 nationwide. One of the teams participating in this initiative is Puerto Rico-CEAL (PR-CEAL). Our whose goal was to raise awareness about the coronavirus disease and advance research, mainly focusing on vulnerable and underserved populations. This concept paper seeks to outline PR-CEAL's infrastructure during its initial two cycles, providing insights into the research and community engagement activities designed to enhance prevention, counter misinformation, and foster awareness and uptake of COVID-19 vaccines. Ultimately, our objective is to reflect on the strengths and challenges encountered thus far as we endeavor to sustain this robust infrastructure, addressing ongoing public health issues with a forward-looking approach.

Haploidentical stem cell transplantation for children with high-risk leukemia.

BACKGROUND: The Chilean population is ethnically diverse, and more than 50% of children referred for hematopoietic stem cell transplantation (HSCT) lack a suitable donor. PROCEDURE: To expand the donor pool, we assessed the feasibility, tolerance, and efficacy of using a haploidentical (HI) donor and a reduced-intensity conditioning regimen for high-risk pediatric leukemia. This study was facilitated by technology transfer from St. Jude Children's Research Hospital over the 2 preceding years. RESULTS: Between March 2006 and April 2009, 10 patients (median age, 9.8 years) received T cell-depleted grafts at Calvo Mackenna Hospital in Santiago. Median cell doses were CD34+: 7.45 × 10(6)/kg (range, 4.00-20.20 × 10(6)/kg); CD3+: 0.88 × 10(5)/kg (0.11-1.35 × 10(5)/kg); and CD56+: 71.30 × 10(6)/kg (31.50-131.80 × 10(6)/kg). Nine patients experienced complete engraftment; six of the nine remain alive and clinically well 13-50 months post-HSCT. Three patients died after bone marrow relapse, while only one died of transplant-related causes. Virus reactivation was the main post-transplant complication: 5/10 had positive CMV PCR but none had CMV disease. One patient developed acute GvHD > grade II and only one had chronic GvHD. CONCLUSIONS: HI-HSCT is feasible in our setting, offers a rational treatment option, and expands the donor pool significantly for children with high-risk leukemia in a developing country. This information is especially relevant to other ethnically diverse populations that are poorly represented in international donor registries.

Transfer of complex frontline anticancer therapy to a developing country: the St. Jude osteosarcoma experience in Chile.

BACKGROUND: A frontline protocol for newly diagnosed osteosarcoma was conducted simultaneously at St. Jude Children's Research Hospital (sponsor) and Calvo Mackenna Hospital (CMH, partner), a public pediatric hospital and national center for the treatment of bone tumors in Santiago, Chile. PROCEDURE: Of 72 eligible patients, 22 (31%) were enrolled and managed in Santiago, without travel to Memphis. Pathology specimens and imaging material were centrally reviewed at St. Jude. Patients received 12 intensive courses of systemic chemotherapy with hematopoietic growth factor support over 35 weeks, and amputation or limb-salvage surgery as indicated for local control. The sponsor assisted the partner site to establish a clinical research infrastructure and obtain hematopoietic growth factor. Communication among medical and nursing teams was maintained throughout the study. Patient-care and protocol issues were discussed frequently between the two centers via scheduled videoconferences and electronic communications. Auditors monitored appropriate study conduct at the international site. RESULTS: No major discrepancies were identified in histologic findings, staging, or imaging studies. Preliminary results demonstrated similar outcome and treatment tolerance; the 2-year event-free survival estimate was 78.5% (95% CI, 51-100%) for patients treated at CMH (median follow-up, 1.6 years) and 74.3% (95% CI, 62-87%) for patients treated at St. Jude (median follow-up, 4 years). Overall per-patient costs were significantly lower in Chile. CONCLUSIONS: Through a twinning mechanism, it is feasible to simultaneously conduct complex front-line osteosarcoma clinical trials at two institutions in countries with different levels of resources.

Extended follow-up of long-term survivors of childhood acute lymphoblastic leukemia.

BACKGROUND: Children who survive acute lymphoblastic leukemia are at risk for leukemia-related or treatment-related complications, which can adversely affect survival and socioeconomic status. We determined the long-term survival and the rates of health insurance coverage, marriage, and employment among patients who had attained at least 10 years of event-free survival. METHODS: A total of 856 eligible patients were treated between 1962 and 1992 in 13 consecutive clinical trials. Survival rates, the cumulative risk of a second neoplasm, and selected indicators of socioeconomic status were analyzed for the entire group and for patients who did or did not receive cranial or craniospinal radiation therapy during initial treatment. RESULTS: Fifty-six patients had major adverse events, including 8 deaths during remission, 4 relapses, and 44 second neoplasms (41 of them radiation-related); most of the second neoplasms were benign or of a low grade of malignant potential. The risk of a second neoplasm was significantly higher in the 597 patients who received radiation therapy (irradiated group) than in the 259 patients who did not receive radiation therapy (nonirradiated group) (P=0.04; estimated cumulative risk [+/-SE] at 20 years, 20.9+/-3.9 percent vs. 0.95+/-0.9 percent). The death rate for the irradiated group slightly exceeded the expected rate in the general U.S. population (standardized mortality ratio, 1.90; 95 percent confidence interval, 1.12 to 3.00), whereas that for the nonirradiated group did not differ from the population norm (standardized mortality ratio, 1.75; 95 percent confidence interval, 0.34 to 5.00). The rates of health insurance coverage, marriage, and employment in the nonirradiated group were similar to the age- and sex-adjusted national averages. Despite having health insurance rates similar to those in the general population, men and women in the irradiated group had higher-than-average unemployment rates (15.1 percent vs. 5.4 percent and 35.4 percent vs. 5.2 percent, respectively), and women in the irradiated group were less likely to be married (35.2 percent vs. 48.8 percent). CONCLUSIONS: Children with acute lymphoblastic leukemia who did not receive radiation therapy and who have attained 10 or more years of event-free survival can expect a normal long-term survival. Irradiation is associated with the development of second neoplasms, a slight excess in mortality, and an increased unemployment rate.

Cumulative incidence of secondary neoplasms as a first event after childhood acute lymphoblastic leukemia.

CONTEXT: Little is known about the incidence of secondary neoplasms after 15 to 20 years in children and adolescents who were treated for acute lymphoblastic leukemia. OBJECTIVES: To investigate the cumulative incidence of secondary neoplasms in pediatric patients treated for acute lymphoblastic leukemia over 30 years and to characterize late-occurring tumors. DESIGN, SETTING, AND PATIENTS: Retrospective study of 2169 patients with acute lymphoblastic leukemia treated between 1962 and 1998 at St Jude Children's Research Hospital, Memphis, Tenn, who achieved complete remission and had a median follow-up time of 18.7 years (range, 2.4-41.3 years). MAIN OUTCOME MEASURES: Cumulative incidences of secondary neoplasms in first remission and standard incidence ratios of observed rates compared with rates of cancer development in the general US population. RESULTS: Secondary neoplasms developed as the first event in 123 patients and comprised 46 myeloid malignancies, 3 lymphomas, 14 basal cell carcinomas, 16 other carcinomas, 6 sarcomas, 16 meningiomas, and 22 other brain tumors. The cumulative incidence of secondary neoplasm was 4.17% (SE, 0.46%) at 15 years and increased substantially after 20 years, reaching 10.85% (SE, 1.27%) at 30 years. When meningiomas and basal cell carcinomas were excluded, the overall cumulative incidence was 3.99% (SE, 0.44%) at 15 years and 6.27% (SE, 0.83%) at 30 years, representing a 13.5-fold increase in overall risk compared with the general population. The cumulative incidence of each tumor type at 30 years was 2.19% (SE, 0.32%) for myeloid malignancy, 0.17% (SE, 0.10%) for lymphoma, 3.00% (SE, 0.59%) for brain tumor, 4.91% (SE, 1.04%) for carcinoma, and 0.57% (SE, 0.37%) for sarcoma. CONCLUSIONS: The cumulative incidence of secondary neoplasms increases steadily over 30 years after treatment of acute lymphoblastic leukemia. Although the majority of the late-occurring secondary neoplasms are low-grade tumors, the increase in incidence of more aggressive malignant neoplasms is significantly higher than expected in the general population. These results suggest that lifelong follow-up of acute lymphoblastic leukemia survivors is needed to ascertain the full impact of treatment and other leukemia-related factors on secondary neoplasm development.

Pharmacokinetics and pharmacodynamics of oral etoposide in children with relapsed or refractory acute lymphoblastic leukemia.

PURPOSE: To study the pharmacokinetics and pharmacodynamics of once- versus twice-daily oral etoposide in children with relapsed or refractory acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Fifty-eight patients were randomly assigned to etoposide at 50 mg/m(2)/d with once- versus twice-daily doses for 22 days. On day 8, vincristine, asparaginase, and dexamethasone were started. Etoposide pharmacokinetics and pharmacodynamics were studied for 47, 28, and 26 patients on day 1, 8, and 22, respectively, of remission reinduction therapy. RESULTS: Of 48 patients with pharmacokinetic data, 42 (87.5%) achieved complete remission, three (6.3%) failed to achieve remission, and three (6.3%) died during induction. Median etoposide day 8 area under concentration-time curve (AUC) and cumulative AUC tended to be greater (P =.06 and P =.07, respectively) in patients (n = 23) who achieved complete remission (24 and 522 micro mol/L x h, respectively) than in patients (n = 3) who did not (14 and 303 micro mol/L x h, respectively). Three of eight patients with plasma concentrations exceeding 1.7 micro M (1 micro g/mL) for more than 8 hours daily, compared with one of 20 patients with concentrations exceeding 1.7 micro M for

Antagonism by methotrexate on mercaptopurine disposition in lymphoblasts during up-front treatment of acute lymphoblastic leukemia.

BACKGROUND: Methotrexate is postulated to enhance mercaptopurine activation to thioguanine (INN, tioguanine) nucleotides, but the interaction has never been studied in vivo in cancer cells. METHODS: We investigated the effect of methotrexate on mercaptopurine disposition in plasma and leukemic blasts during up-front treatment of 233 children with newly diagnosed acute lymphoblastic leukemia. Children were randomized to receive intravenous mercaptopurine (1 g/m(2) over a 6-hour period) or to receive methotrexate (low dose, 6 oral doses of 30 mg/m(2), or high dose, 1 g/m(2) intravenously), followed by intravenous mercaptopurine. All combinations have been previously used in frontline trials for acute lymphoblastic leukemia. RESULTS: Compared with mercaptopurine alone, methotrexate resulted in higher plasma mercaptopurine concentrations (30.3 +/- 14.7 micromol/L versus 23.5 +/- 18.0 micromol/L, P <.001) but, conversely, a 13-fold lower thioguanine nucleotide concentration (0.57 +/- 0.66 pmol/5 x 10(6) cells versus 7.4 +/- 15.2 pmol/5 x 10(6) cells, P <.001) in bone marrow leukemic lymphoblasts. Methotrexate was also associated with higher plasma hypoxanthine concentrations compared with those of patients given mercaptopurine alone (8.7 +/- 13.5 micromol/L versus 3.8 +/- 2.5 micromol/L, P =.029). The percentage change in leukocyte counts measured over a 3-day period showed that mercaptopurine alone had little effect (mean decrease, 20% +/- 33%). In contrast, despite causing lower intracellular thiopurine active metabolite concentrations, methotrexate produced a greater decrease in leukocyte counts (mean, 53% +/- 35%) compared with those in patients receiving mercaptopurine alone (P <.0001). CONCLUSION: These pharmacologic findings in the target tissue are consistent with the recently demonstrated lack of clinical benefit of intravenous mercaptopurine in combination with methotrexate. We conclude that, in the setting of newly diagnosed acute lymphoblastic leukemia, methotrexate antagonizes thiopurine metabolite disposition in leukemic blasts after intravenous mercaptopurine.

A mathematical model of in vivo methotrexate accumulation in acute lymphoblastic leukemia.

Methotrexate (MTX) is one of the most widely used drugs for the treatment of childhood acute lymphoblastic leukemia (ALL). Interindividual differences in lymphoblast accumulation of MTX and its active metabolites, methotrexate polyglutamates (MTXPG), may contribute to the effectiveness of treatment among ALL subtypes. To better understand these differences in MTXPG accumulation, we developed a model to characterize the cellular influx and efflux of MTX, formation of MTXPG by the addition of glutamyl residues catalyzed by FPGS (folylpolyglutamate synthetase), and cleavage of glutamyl residues from MTXPG by GGH (gamma-glutamyl hydrolase). The model was fitted to in vivo intracellular MTXPG concentrations measured serially in leukemic blasts from 20 newly diagnosed patients with ALL treated with 24-h intravenous infusions of MTX. The observed median concentrations of total MTXPG at 44 h was higher in B-lineage than in T-cell ALL (1706 vs 518 pmol/10(9) cells, P<0.025), consistent with the higher estimated Vmax for FPGS activity in B-lineage vs T-lineage blasts (414 vs 93 pmol/10(9) cells/h, P<0.008). Simulations based on the model-estimated parameters indicated greater accumulation of MTX, MTXPGs (MTXPG(2-7)) and total MTX (MTXPG(1-7)) with longer MTX infusions and with higher MTX doses, with the highest concentrations in hyperdiploid B-lineage, intermediate in non-hyperdiploid B-lineage, and lowest in T-cell ALL. These differences provide mechanistic and treatment insights for lineage and ploidy differences in MTXPG accumulation in human leukemia cells in vivo.

Results of therapy for acute lymphoblastic leukemia in black and white children.

CONTEXT: Treatment results for acute lymphoblastic leukemia (ALL) clearly have improved over the past decade, but black children have not fared as well as white children in large national trials. OBJECTIVE: To compare the clinical outcomes of therapy for black and white children with ALL treated at a single institution. DESIGN, SETTING, AND PATIENTS: A retrospective analysis of 412 children and adolescents (68 black, 338 white, and 6 other race) with newly diagnosed ALL who were treated consecutively at a pediatric cancer center in Memphis, Tenn. Patients were enrolled from December 1991 to July 1998 in successive Total Therapy studies regardless of race, ethnicity, or ability to pay and received risk-directed therapy according to stringent criteria. INTERVENTIONS: All patients received the same intensive, remission-induction therapy followed by 120 weeks of risk-assigned postremission therapy that included reinduction treatment, pulses of high-dose methotrexate, and early intensification of intrathecal chemotherapy. MAIN OUTCOME MEASURES: Event-free and overall survival rates for black and white children were estimated by the method of Kaplan and Meier and compared with the Mantel-Haenszel test and by Cox proportional hazards regression analysis, adjusting for known prognostic factors. RESULTS: The 68 black children were significantly more likely than the 338 white children to have higher-risk prognostic features, including an initial leukocyte count greater than 100 x 10(3)/ microL, a T-cell immunophenotype, and the t(1;19) chromosomal translocation with E2A-PBX1 fusion, and were less likely to have hyperdiploid blast cells, a favorable prognostic factor in childhood ALL. However, the clinical outcomes for these 2 cohorts were not significantly different: 5-year event-free and overall survival rates were 80.7% (95% confidence interval [CI], 70.3%-91.1%) and 86.2% (95% CI, 77.2%-95.2%) for black children vs 79.4% (95% CI, 74.7%-84.1%) and 85.0% (95% CI, 80.9%-89.1%) for white children. Ten-year results also were comparable, but the CIs were wide because of the small numbers of patients who had been followed up for 10 years or more. The lack of a racial effect on the long-term outcome of therapy was still apparent in a multivariate Cox regression analysis, adjusting for sex, age, presenting leukocyte count, leukemic cell DNA index, immunophenotype, and central nervous system status. CONCLUSION: With equal access to effective antileukemic therapy, black and white children with ALL can expect the same high rate of cure.

Improving treatment of children with acute lymphoblastic leukemia in developing countries through technology sharing, collaboration and partnerships.

Cure rates for pediatric acute lymphoblastic leukemia differ markedly in higher- and lower-income countries due to disparate hospital infrastructure and resources. Where means are limited, treatment-related mortality is higher and compliance may be suboptimal. Upfront risk assignment is aimed at individualizing therapy according to presenting features in order to avoid over- or under-treatment. However, the necessary technical resources and expertise are not always readily available. The authors provide suggestions for management of childhood acute lymphoblastic leukemia in developing nations. To improve patient care locally, the authors recommend that communication technology be used to sustain partnerships between sponsoring and partner pediatric oncology programs. The aims of these collaborations should be to prioritize resources, identify existing problems and reduce treatment intensity and hence treatment-related morbidity and mortality in patients at lower risk of relapse.

The Latin American Center for Pediatric Oncology Nursing Education: development, implementation, and accomplishments.

BACKGROUND: Pediatric oncology nurses in low- and middle-income countries have limited access to specialized education and clinical training. This is a major impediment for treating children with cancer and contributes to the disparity in survival rates between high- and low-income countries. The International Outreach Nursing Program at St Jude Children's Research Hospital established full-time nurse educator positions at partner sites throughout Latin America. Experienced nurses were hired as educators; however, they had no formal pediatric oncology education, limited teaching experience, and no mentors as this was a new nursing role in low- and middle-income countries. OBJECTIVE: Our objective was to create a regional education center to prepare nurse educators to succeed in this pioneering role. INTERVENTIONS: The Latin American Center for Pediatric Oncology Nursing Education was created at Calvo Mackenna Hospital in Santiago, Chile, to provide education, resources, and support to educators. Education resources, including a comprehensive orientation program and courses in chemotherapy and central venous line care, were developed. A 4-week on-site comprehensive educator course and an organized support system were implemented. RESULTS: Education, resources, and support have been provided to 13 nurse educators representing 7 Latin American countries. The educators have provided pediatric oncology education to more than 1000 nurses. CONCLUSIONS: The center promotes excellence in pediatric oncology nursing by preparing and supporting educators, who in turn educate the entire nursing staff at partner sites. IMPLICATIONS FOR PRACTICE: Nurse educators equipped with knowledge and skills can improve the quality of care and ultimately survival of patients throughout Latin America.

Phase II study of topotecan in combination with dexamethasone, asparaginase, and vincristine in pediatric patients with acute lymphoblastic leukemia in first relapse.

BACKGROUND: The authors evaluated the response rate, toxicity, and pharmacokinetics of topotecan given before standard induction therapy for childhood acute lymphoblastic leukemia (ALL) in first relapse. METHODS: Patients received topotecan (2.4 mg/m(2) daily as a 30-minute infusion) for 5 days before induction therapy with dexamethasone, vincristine, and asparaginase (native or pegylated Escherichia coli). The pharmacokinetics of topotecan were measured with the first dose of treatment in 23 patients. RESULTS: Twenty-eight of 31 patients with circulating blast cells were evaluable for response to topotecan. Twenty-five patients (89.3%) had a response (>25% decrease in circulating blast cells). The leukocyte count (P = .0001) and blast cell count (P = .0009) declined significantly during topotecan therapy. The median (range) topotecan lactone area under the concentration-time curve after the first dose was 85.4 L/hour/m(2) (range, 38.7-229.3 L/hour/m(2)). At the end of induction, 23 patients (74.2%) had a complete response, 1 patient (3.2%) had a partial response, 5 patients (16.1%) had no response, and 2 patients had died of infection. Six of the 17 patients who were studied for minimal residual disease (MRD) achieved MRD-negative status at the end of induction. The main toxicities were hematologic, gastrointestinal, and hepatic. The estimated 5-year survival rate, event-free survival rate, and cumulative incidence of second relapse were 24.1% +/- 7.9%, 18.2% +/- 7.4%, and 22.8% +/- 8.7%, respectively, in the 29 patients who had a hematologic first relapse. CONCLUSIONS: A regimen comprising single-agent topotecan given with a standard 3-drug combination was effective in inducing remission in pediatric patients with relapsed ALL and was tolerated well.