How should childhood acute lymphoblastic leukemia relapses in low-income and middle-income countries be managed: The AHOPCA-ALL study group experience.

BACKGROUND: Children with relapsed acute lymphoblastic leukemia (ALL) in low-income and middle-income countries rarely survive. The Pediatric Hematology-Oncology Association of Central America (AHOPCA) developed the AHOPCA-ALL REC 2014 protocol to improve outcomes in resource-constrained settings without access to stem cell transplantation. METHODS: The AHOPCA-ALL REC 2014 protocol was based on a modified frontline induction phase 1A, a consolidation therapy with six modified R-blocks derived from the ALL-Berlin-Frankfurt-Munster REZ 2002 protocol and intermittent maintenance therapy. Children with B-lineage ALL were eligible after a late medullary relapse, an early or late combined relapse, or any extramedullary relapses. Those with T-lineage ALL were eligible after early and late extramedullary relapses, as were those with both B-lineage and T-lineage relapses occurring at least 3 months after therapy abandonment. RESULTS: The study population included 190 patients with T-lineage (n = 3) and B-lineage (n = 187) ALL. Of those with B-lineage ALL, 25 patients had a very early extramedullary relapse, 40 had an early relapse (32 extramedullary and 8 combined), and 125 had a late relapse (34 extramedullary, 19 combined, and 72 medullary). The main cause of treatment failure was second relapse (52.1%). The 3-year event-free survival rate (± standard error) was 25.9% ± 3.5%, and the 3-year overall survival rate was 36.7% ± 3.8%. The 3-year event-free survival rate was 47.2% ± 4.7% for late relapses. The most frequently reported toxicity was grade 3 or 4 infection. Mortality during treatment occurred in 17 patients (8.9%), in most cases because of infectious complications. CONCLUSIONS: Selected children with relapsed ALL in Central America can be cured with second-line regimens even without access to consolidation with stem cell transplantation. Children in low-income and middle-income countries who have lower risk relapses of ALL should be treated with curative intent.

Rhabdomyosarcoma in low- and middle-income countries: A report from the Asociacion de Hemato-oncología Pediatrica de Centro América (AHOPCA).

This report describes the results of an observational study dedicated to rhabdomyosarcoma developed by the Asociación de Hemato-oncología Pediatrica de Centro América (AHOPCA) between 2001 and 2018. Overall, 337 previously untreated patients < 18 years old were included in the analysis; 58% had unresected disease, and 19% were metastatic at diagnosis. With a median follow-up of 6.6 years, five-year event-free and overall survival rates were 30% and 33%, respectively. Local progression/relapse was the main cause of treatment failure.

The treatment of childhood acute lymphoblastic leukemia in Guatemala: Biologic features, treatment hurdles, and results.

BACKGROUND: The National Pediatric Oncology Unit (UNOP) is the only pediatric hemato-oncology center in Guatemala. METHODS: Patients ages 1 to 17 years with acute lymphoblastic leukemia (ALL) were treated according to modified ALL Intercontinental Berlin-Frankfurt-Münster (IC-BFM) 2002 protocol. Risk classification was based on age, white blood cell count, immunophenotype, genetics (when available), and early response to therapy. RESULTS: From July 2007 to June 2014, 787 patients were treated, including 160 who had standard-risk ALL, 450 who had intermediate-risk ALL, and 177 who had high-risk ALL. The induction death rate was 6.6%, and the remission rate was 92.9%. The rates of death and treatment abandonment during first complete remission were 4.8% and 2.5%, respectively. At a median observation time of 3.6 years, and with abandonment considered an event, the 5-year event-free survival and overall survival estimates ( ± standard error) were 56.2% ± 2.1% and 64.1% ± 2.1%, respectively, with a 5-year cumulative incidence of relapse of 28.9% ± 2.0%. Twenty-one of 281 patients (7.5%) investigated were positive for the ets variant 6/runt-related transcription factor 1 (ETV6/RUNX1) fusion. CONCLUSIONS: A well organized center in a low-middle-income country can overcome the disadvantages of malnutrition and reduce abandonment. Outcomes remain suboptimal because of late diagnosis, early death, and a high relapse rate, which may have a partly genetic basis. Earlier diagnosis, better management of complications, and better knowledge of ALL will improve outcomes. Cancer 2017;123:436-448. © 2016 American Cancer Society.

Impact of Continuous vs Bolus Feeding on Splanchnic Perfusion in Very Low Birth Weight Infants: A Randomized Trial.

OBJECTIVE: To detect changes in splanchnic perfusion and oxygenation induced by 2 different feeding regimens in infants with intrauterine growth restriction (IUGR) and those without IUGR. STUDY DESIGN: This was a randomized trial in 40 very low birth weight infants. When an enteral intake of 100 mL/kg/day was achieved, patients with IUGR and those without IUGR were randomized into 2 groups. Group A (n = 20) received a feed by bolus (in 10 minutes), then, after at least 3 hours, received the same amount of formula by continuous nutrition over 3 hours. Group B (n = 20) received a feed administered continuously over 3 hours, followed by a bolus administration (in 10 minutes) of the same amount of formula after at least 3 hours. On the day of randomization, intestinal and cerebral regional oximetry was measured via near-infrared spectroscopy and Doppler ultrasound (US) of the superior mesenteric artery was performed. Examinations were performed before the feed and at 30 minutes after the feed by bolus and before the feed, at 30 minutes after the start of the feed, and at 30 minutes after the end of the feed for the 3-hour continuous feed. RESULTS: Superior mesenteric artery Doppler US showed significantly higher perfusion values after the bolus feeds than after the continuous feeds. Near-infrared spectroscopy values remained stable before and after feeds. Infants with IUGR and those without IUGR showed the same perfusion and oxygenation patterns. CONCLUSION: According to our Doppler US results, bolus feeding is more effective than continuous feeding in increasing splanchnic perfusion. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01341236.

Asociación de Hemato-Oncología Pediátrica de Centro América (AHOPCA): a model for sustainable development in pediatric oncology.

Bridging the survival gap for children with cancer, between those (the great majority) in low and middle income countries (LMIC) and their economically advantaged counterparts, is a challenge that has been addressed by twinning institutions in high income countries with centers in LMIC. The long-established partnership between a Central American consortium--Asociación de Hemato-Oncología Pediátrica de Centro América (AHOPCA)--and institutions in Europe and North America provides a striking example of such a twinning program. The demonstrable success of this endeavor offers a model for improving the health outcomes of children with cancer worldwide. As this remarkable enterprise celebrates its 15th anniversary, it is appropriate to reflect on its origin, subsequent growth and development, and the lessons it provides for others embarking on or already engaged in similar journeys. Many challenges have been encountered and not all yet overcome. Commitment to the endeavor, collaboration in its achievements and determination to overcome obstacles collectively are the hallmarks that stamp AHOPCA as a particularly successful partnership in advancing pediatric oncology in the developing world.

Childhood acute lymphoblastic leukemia in Nicaragua: long-term results in the context of an international cooperative program.

BACKGROUND: The aim of this paper is to describe the results of acute lymphoblastic leukemia (ALL) treatment in Nicaragua from 1995 to 2005 in the context of an international cooperation program. PROCEDURES: Patients <18 years with ALL were treated with two consecutive protocols (1995 and 2000). After a steroid prophase, a three-drug induction was administered in protocol 1995, and a four-drug induction, including asparaginase, was administered in protocol 2000. In protocol 2000, a modified BFM phase IB with cyclophosphamide, 6-mercaptopurine and cytosine arabinoside was administered to patients at high risk (HR), who also received IV methotrexate (500 mg/m(2)) in the consolidation phase. Reinduction consisted of dexamethasone, vincristine, doxorubicin, cytosine arabinoside, and 6-thioguanine administered over 7 (protocol 1995) or 4 (protocol 2000) weeks; reinduction was repeated twice for patients at HR. Maintenance consisted of p.o. 6-mercaptopurine and methotrexate, and vincristine and dexamethasone pulses were added in the 2000 study. The total duration of therapy was 24 months. RESULTS: In total, 540 patients were treated. Overall, 7% of patients died during induction, and 9% abandoned treatment. At 5 and 10 years from diagnosis, event-free survival (EFS) rates of 38.1% and 36.6%, respectively, and overall survival rates of 48.0% and 39.6%, respectively, were obtained, considering abandonment as an event. CONCLUSIONS: In our experience, a 10-year EFS of 36.6% was achieved in a country with limited resources. Factors limiting a higher success rate were treatment abandonment and a high relapse rate.

Nutritional status of children during treatment for acute lymphoblastic leukemia in Guatemala.

BACKGROUND: Most children with cancer live in developing countries where the prevalence of malnutrition may reach 50% and influence the course of the disease. This study examined the prevalence and severity of malnutrition at diagnosis, as well as after 3 and 6 months of chemotherapy, in children with acute lymphoblastic leukemia (ALL) in Guatemala. METHODS: Triceps skin fold thickness (TSFT) and mid upper arm circumference (MUAC) provided measures of nutritional status (NS) in three categories: adequately nourished (A): TSFT and MUAC > 10th percentile; severely depleted (SD): TSFT or MUAC < 5th percentile; and moderately depleted (MD): all the remaining patients. RESULTS: Of 331 new patients, 241 had NS assessed at diagnosis. A = 113 (46.9%); MD = 28 (11.6%); SD = 100 (41.5%). At 3 months A = 106 (52.2%); MD = 25 (12.3%); SD = 72 (35.5%). At 6 months A = 146 (76.0%); MD = 12 (6.3%); SD = 34 (17.7%). In multivariate analysis, SD children at 6 months of treatment had a hazard of death that was 2.4-fold the hazard of those A or MD (95% CI: 1.3-4.7) CONCLUSIONS: Malnutrition is prevalent in newly diagnosed children with ALL in Guatemala and severe nutritional depletion is apparently predictive of abandonment of therapy and relapse of disease, but if children survive and improve their NS in the first 6 months after diagnosis, their chances of survival may improve significantly to approximate those in children not presenting with nutritional depletion.

Nutritional status at diagnosis is related to clinical outcomes in children and adolescents with cancer: a perspective from Central America.

BACKGROUND: The prevalence of malnutrition in children may exceed 50% in countries with limited resources. The aims of this study were to assess nutritional status at diagnosis in children and adolescents with cancer, and to correlate it with clinical outcomes in the Spanish speaking countries of Central America that formed the AHOPCA (Asociacion de Hemato-Oncologia Pediatrica de Centro America) consortium. METHODS: Patients aged 1-18 years, diagnosed with cancer between 1st October 2004 and 30th September 2007, were eligible for study. Weight (kg) and height or length (m), mid upper arm circumference--MUAC and triceps skin fold thickness--TSFT were measured and their Z-scores or percentiles were calculated. Three categories of nutritional status were defined according to these parameters. RESULTS: A total of 2954 new patients were enrolled; 1787 had all anthropometric measurements performed and 1513 also had measurements of serum albumin. By arm anthropometry 322/1787 patients (18%) had moderate nutritional depletion and 813/1787 patients (45%) were severely depleted. Adding serum albumin, the proportion classified as severely depleted rose to 59%. Malnourished children more often abandoned therapy and their event free survival was inferior to that of other children. CONCLUSIONS: Arm anthropometry in children with cancer is a sensitive measure of nutritional status. Since malnutrition at diagnosis was related to important clinical outcomes, an opportunity exists to devise simple, cost-effective nutritional interventions in such children that may enhance their prospects for survival.