The treatment of childhood acute lymphoblastic leukemia in Guatemala: Biologic features, treatment hurdles, and results (original) (raw)
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Treatment-related mortality in children with acute lymphoblastic leukemia in Central America
Cancer, 2011
BACKGROUND: The objectives of this study were to describe the incidence, timing, and predictors of treatmentrelated mortality (TRM) among children with acute lymphoblastic leukemia (ALL) in El Salvador, Guatemala, and Honduras. METHODS: Patients aged <20 years who were diagnosed with ALL between January 2000 and March 2008, who received treatment in any of the 3 countries, and who started induction chemotherapy were included in the study. Almost all patients were treated on the El Salvador-Guatemala-Honduras II protocol, which was based on the St. Jude Total XIII and XV protocols. Biologic, socioeconomic, and nutritional variables were examined as predictors of TRM. RESULTS: Of 1670 patients, TRM occurred as a first event in 156 children (9.3%); TRM occurred during remission induction therapy in 92 of 156 children (59%), between remission induction and maintenance therapy in 27 of 156 children (17%), and during maintenance therapy in 37 of 156 children (24%). Although the TRM rate decreased in patients who were diagnosed after July 1, 2004 (11.2% vs 7.9%; P ¼ .02), the rate of induction death did not change (5.2% vs 5.8%; P ¼ .58). Independent predictors of induction death included higher risk ALL (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.03-3.27; P ¼ .04), lower initial platelet counts (OR per 10 Â 10 9 /L, 0.94; 95% CI, 0.89-0.98; P ¼ .005), and longer travel time to the clinic (OR, 1.06 per hour; 95% CI, 1.01-1.14; P ¼ .03). CONCLUSIONS: In Central America, TRM remains an important cause of treatment failure in children with ALL. A large proportion of TRM occurs in maintenance, although this proportion has decreased over time. Supportive care interventions should especially target children who present with low platelet counts. Further study on transfusion ability and the location of induction deaths is required. Cancer 2011;117:4788-95
Pediatric Blood & Cancer, 2013
Background. Five Asociaci on de Hemato-Oncología de Centroamérica (AHOPCA) countries have used an adapted BFM-based protocol for childhood acute lymphoblastic leukemia (ALL). Procedure. In the AHOPCA-ALL 2008 protocol, patients were stratified by age, white blood cell count, immunophenotype, central nervous system involvement, day 8 prednisone response, and morphologic bone marrow response to induction therapy. Patients at Standard Risk (SR) received a three-drug induction regimen, a reinduction phase, and maintenance with protracted intrathecal therapy. Those at Intermediate (IR) and High Risk (HR) received, in addition, daunorubicin during induction therapy, a consolidation phase and two or three reinduction phases respectively. Results. From August 2008 through July 2012, 1,313 patients were enrolled: 353 in SR, 548 in IR, 412 in HR. During induction therapy, 3.0% of patients died, 2.7% abandoned treatment, 1.1% had resistant ALL, and 93.2% achieved morphological complete remission (CR). Deaths and abandonment in first CR occurred in 2.7% and in 7.0% of patients, respectively. The relapse rate at a median observation time of 2.1 years was 15.0%. At 3 years, the eventfree survival (EFS) and overall survival (OS), with abandonment considered as an event, were 59.4% (SE 1.7) and 68.2% (SE 1.6). Three-year EFS was 68.5% (SE 3.0), 62.1% (SE 2.6), and 47.8% (SE 3.2) for SR, IR, and HR groups. Adolescents had a significantly higher relapse rate (P ¼ 0.001). Conclusions. This experience shows that common international studies are feasible in lower-middle income countries. Toxic deaths, abandonment of treatment, and relapses remain major obstacles to the successful treatment. Alternative treatment strategies may be beneficial.
Journal of Pediatric Hematology/Oncology, 2000
To improve outcome and study biology of childhood acute lymphoblastic leukemia (ALL) in El Salvador. Patients and Methods: Between January 1994 and December 1996, 153 children of El Salvador had newly diagnosed ALL treated in a collaborative program between Hospital Benjamin Bloom and St. Jude Children's Research Hospital (SJCRH). Therapy was based on a modified SJCRH protocol, with uniform remission induction (prednisone, vincristine, Lasparaginase) followed-up by consolidation with teniposide/ cytarabine and/or high-dose methotrexate. Continuation treatment was risk-stratified: 123 patients assigned to the highrisk group received weekly rotational drug pairs, and 16 assigned to the standard-risk group received daily 6-mercaptopurine, weekly methotrexate, and monthly pulses of vincristine plus dexamethasone. High risk was defined as: DNA index <1.16, age 12 months or younger, white blood cell count Ն 50 × 10 9 /L, T-cell immunophenotype, anterior mediastinal mass, central nervous system leukemia at diagnosis, or t(4;11), t(1;19), or t(9;22). Duration of the continuation treatment was 2.5 years in both groups. The median age at diagnosis of all patients was 4.8 (range 1 d-17 yrs), median leukocyte count was 15 (range 1-766) × 10 9 /L, and sex distribution was equal. Results: Immunophenotypes were early -progenitor in 79%, T-cell in 3.9%, and inconclusive in 17% of cases. DNA index was <1.16 in 80.5% and was Ն1.16 in 19.5% of the 123 known cases. For the analyzes, patients who refused therapy (abandoned treatment) were considered to have treatment failure as of their last follow-up dates. Complete remission was achieved in 126 of 151 (82.4%) patients (11 abandoned therapy during induction). The overall 4-year event-free survival (EFS) rate ± 1 standard error was 48 ± 6%. The 4-year EFS rates in patients at high-risk and standard-risk were 46 ± 7% (n ס 121) and 69 ± 15% (n ס 16), respectively (P ס 0.20). When patients who refused further treatment are censored, the corresponding 4-year estimates of EFS are 51 ± 8% and 75 ± 14%, respectively. Conclusions: These results suggest that the biology of childhood ALL in El Salvador appears to be similar to that seen in the United States. Risk-directed chemotherapy can successfully be used in developing countries, but risk factors must be carefully determined and applied.
BioMed Research International, 2015
Our aim in this paper is to describe the results of treatment of acute lymphoblastic leukaemia (ALL) in Mexican children treated from 2006 to 2010 under the protocol from the Dana-Farber Cancer Institute (DFCI) 00-01. The children were younger than 16 years of age and had a diagnosis of ALL de novo. The patients were classified as standard risk if they were 1-9.9 years old and had a leucocyte count <50 × 10 9 /L, precursor B cell immunophenotype, no mediastinal mass, CSF free of blasts, and a good response to prednisone. The rest of the patients were defined as high risk. Of a total of 302 children, 51.7% were at high risk. The global survival rate was 63.9%, and the event-free survival rate was 52.3% after an average follow-up of 3.9 years. The percentages of patients who died were 7% on induction and 14.2% in complete remission; death was associated mainly with infection (21.5%). The relapse rate was 26.2%. The main factor associated with the occurrence of an event was a leucocyte count >100 × 10 9 /L. The poor outcomes were associated with toxic death during induction, complete remission, and relapse. These factors remain the main obstacles to the success of this treatment in our population.
Jornal de pediatria, 2018
Acute lymphoblastic leukemia is the most common childhood cancer, yet surprisingly, very few studies have reported the treatment outcomes and the relapse rate of patients from low/middle-income countries. This study was a 5-year retrospective cohort study. It was conducted at Oncology Center of Mansoura University in Egypt and aimed to estimate the treatment outcomes and the relapse rates of newly diagnosed acute lymphoblastic leukemia in children. Two hundred children suffering from acute lymphoblastic leukemia were studied; forty-six patients (23%) died during induction and most of those deaths were related to infection. Forty-one patients (27%) relapsed out of the 152 patients who achieved complete remission. The most common site of relapse was the bone marrow, followed by the isolated central nervous system, 53.7% and 31.7%, respectively. Seventy-eight percent of relapses occurred very early/early rather than later. The majority of relapse patients' deaths were related to in...
Incidence and predictors of treatment-related mortality in paediatric acute leukaemia in El Salvador
British Journal of Cancer, 2009
Survival rates among children with leukaemia in low-income countries are lower than those in high-income countries. This has been attributed in part to higher treatment-related mortality (TRM). We examined the demographics, treatment, and outcomes of paediatric patients in El Salvador with acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML) to determine the incidence, causes, and risk factors for TRM. Two trained data managers collected data prospectively; no patients were excluded. Biological, socioeconomic and nutritional predictors were examined. A total of 469 patients with ALL and 78 patients with AML were included. The 2-year cumulative incidence of TRM was significantly higher among children with AML (35.4 ± 6.4%) than those with ALL (12.5±1.7%; Po0.0001). However, the proportion of deaths attributable to the toxicity of treatment did not differ significantly between AML (25/47, 53.2%) and ALL (55/107, 51.4%; P ¼ 0.98). Among children with ALL, low monthly income (P ¼ 0.04) and low parental education (P ¼ 0.02) significantly increased the risk of TRM. Among children with AML, biological, socioeconomic, and nutritional variables were not associated with TRM. In this low-income country, toxic death significantly contributes to mortality in both ALL and AML. A better understanding of the effect of socioeconomic status on TRM may suggest specific strategies for patients with ALL.