Vitamin D Deficiency in Pediatric Oncology Patients: A Single-Center Experience in Saudi Arabia.

Background There is a lack of local studies on vitamin D deficiency in children with cancer. This study aims to estimate the prevalence of vitamin D deficiency in the pediatric oncology population at King Abdul-Aziz Medical City (KAMC) in Jeddah, addressing knowledge gaps for improved clinical practice and future research. Methods This retrospective observational study was conducted from 2016 to 2021 at the pediatric oncology clinic in National Guard Hospital, Jeddah. The study focused on children aged 14 or younger at cancer diagnosis, data encompassed patient demographics, cancer details, and treatment information, including serum measurements of vitamin D (25(OH)D, calcium, phosphate, alkaline phosphatase). Vitamin D levels were categorized as deficient (<25 ng/ml), insufficient (25-49 ng/ml), sufficient (≥50- 125 ng/ml), or hypervitaminosis (>125 ng/ml), based on our center reference range and the validation of the assay. Results In this retrospective study of 155 pediatric oncology patients, the majority aged 0 to 10 years (78%), findings reveal a male preponderance (54.2%) and a more prevalent in patients with hematological malignancies (85%). Chemotherapy was administered to 98%, with 7% underwent radiotherapy, and 89% received steroids. Analysis of serum 25-OH vitamin D levels indicated an overall deficiency and insufficiency at diagnosis (63%) and post-therapy (43%). Age and gender had a significant influence on vitamin D levels at diagnosis, with older children and females exhibiting lower concentrations. However, these differences diminished by the end of therapy. Notably, hematological malignancy patients often presented insufficient vitamin D levels, while solid tumor patients frequently had sufficient levels. Clinical outcomes showed a high survival rate (90.7%), limited bone density assessments (18.1%), and a 14.2% prevalence of hypervitaminosis. Conclusion In summary, our study reveals that over two-thirds of pediatric oncology patients experience vitamin D deficiency and insufficiency at the time of diagnosis, particularly notable in females and older children. Notably, those with solid tumors exhibit higher baseline 25-OH vitamin D concentrations compared to counterparts with hematological malignancies. The findings underscore the importance of educating both patients and caregivers on supplementation and sun exposure to mitigate the prevalence of deficient and insufficient vitamin D levels in pediatric oncology cases.

The Characteristics and Follow-Up of SARS-CoV-2 Infection in Pediatric Oncology Patients.

Introduction Clinical data about the first and second most prominent waves of SARS-CoV-2 among pediatric cancer patients were inconsistent. This study aims to retrospectively report the clinical characteristics and outcomes of SARS-CoV-2 infection in pediatric oncology patients. Methods This is an observational, retrospective study conducted in a tertiary care oncology center from March 2020 to May 2022. We reviewed the prevalence, severity of symptoms, and duration of positivity in relation to blood count laboratory data and mortality with a follow-up of 30 days post-infection for SARS-CoV-2. Results A total of 396 PCR tests were performed on 342 pediatric cancer patients. The overall rate of SARS-CoV-2 positivity was 43.1% (2.7% in the first wave and 95.4% in the second wave). Among 342 screened pediatric cancer patients, 72 patients had confirmed SARS-CoV-2 positivity in 92 different episodes. Nearly 59% had a mild or moderate infection, with fever and cough as the predominant presentations. The mean duration of positivity was 18.4±7.76 days. Comparing the laboratory values before and after acquiring the COVID-19 infection, only monocytes, hemoglobin, hematocrit, and platelets were statistically significantly affected, with P-values of 0.002, 0.03, 0.02, and 0.01, respectively. More than 18% of patients had grade 3 to 4 neutropenia (absolute neutrophil count=0.39±0.35) before COVID-19 infection and remained neutropenic throughout the disease, regardless of symptom severity. The mean recovery time was 13.67±8 days, which resulted in a delay in cancer treatment delivery of up to four weeks in 42.2% of patients. Conclusion Our data demonstrated that pediatric cancer patients with SARS-CoV-2 infection have a mild to moderate course of COVID-19 disease, with the majority being symptomatic, yet a great portion of our study population experienced treatment interruptions reaching up to four weeks caused by COVID-19.

Renal outcomes in pediatric patients with sickle cell disease: a single center experience in Saudi Arabia.

Background: Sickle cell nephropathy (SCN) is a significant complication of sickle cell disease (SCD) with an asymptomatic onset in childhood and potential progression to chronic kidney disease (CKD). The clinical findings of SCN include hyposthenuria, hematuria, proteinuria, hyperfiltration, and CKD. Data on renal manifestation among patients with SCD in Saudi Arabia is lacking. Therefore, this study aimed to evaluate renal outcomes in patients with SCD who visited a hematology clinic at the National Guard Hospital, Jeddah. Methods: We conducted a retrospective chart review of renal complications in patients with SCD who are within 0-14 years of age and on regular follow-ups at the pediatric hematology clinic in King Abdulaziz Medical City-Jeddah, Saudi Arabia. Results: Among the 140 patients with SCD, 99 met the inclusion criteria. The median age at diagnosis was 18 (1-108) months. Two SCD phenotypes were observed, with 82 (83%) patients having sickle cell anemia (HbSS) and 17 (17%) having HbS/B+ thalassemia. Of the total patients, 92 (93%) were administered hydroxyurea (HU), with a median starting age of 48 (9-168) months. The most common renal complication observed during routine urinalysis was hematuria (38%), followed by proteinuria (11%). After stratifying the sample into four age groups (0-3 years old, 4-7 years old, 8-11 years old, and 12-14 years old), the mean glomerular filtration rate (GFR) values were 96.16, 101.36, 112.69, and 120.11 ml/min/1.73 m2 respectively. Renal imaging revealed abnormal findings in 27 (29%) patients. The most common abnormality observed on US was increased echogenicity (43%). Conclusion: SCN is a significant complication of SCD. In this study, we assessed the renal outcomes in pediatric patients with SCD. After analyzing the clinical findings of SCN, we concluded that the presence of renal complications in pediatric patients presented a progressive pattern.

Outcomes of blinatumomab based therapy in children with relapsed, persistent, or refractory acute lymphoblastic leukemia: a multicenter study focusing on predictors of response and post-treatment immunoglobulin production.

The management of Refractory/Relapsed B-cell Acute Lymphoblastic Leukemia (R/R ALL) remains challenging. Incorporating blinatumomab in R/R ALL treatment has shown encouraging results. We describe the outcome and predictors of response in children receiving blinatumomab as a bridge to definitive therapy. Immunoglobulin (Ig) G and viral serology before and after therapy were evaluated. Thirty-three patients that failed standard first-line treatments due to relapsed ALL (n = 22), persistent minimal residual disease (MRD) (n = 8), or refractory disease (n = 3) received blinatumomab. Grade 2 toxicity occurred in 27.2% of patients. MRD remission (<0.01%) was achieved in 72.7% of patients. Pre-blinatumomab absolute lymphocyte count (ALC) and MRD/ALC ratio significantly associated with MRD-response. Patients with t(1;19) translocation had lower response rate, compared to all other cytogenetic categories (p = 0.013). One-year event-free survival (EFS) and overall survival (OS) were 69.2% and 79.7%, respectively. Analysis of OS and EFS showed pre-blinatumomab MRD level, ALC, MRD/ALC ratio, t(1;19), and post-blinatumomab MRD remission associated with survival. Following blinatumomab, 83% (15/18) of tested patients had low IgG levels. IgG seronegative status was observed in 83% (12/15) for varicella zoster, 35% (6/17) for herpes zoster, 18% (3/17) for cytomegalovirus, and 26% (5/17) for Epstein Barr virus. Blinatumomab produced encouraging results in children with R/R ALL and low disease burden bridging to definitive therapy. Incorporating baseline genetics and biomarkers may help identify subgroups likely to be responsive/resistant to therapy. Viral serological testing pre- and post-blinatumomab is recommended to optimize supportive and preemptive therapy.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2022.2049936 .

Metastatic 4S neuroblastoma with excellent outcome in Saudi cancer center.

OBJECTIVES: To retrospectively review a small series of infant neuroblastoma (NBL) in a single Saudi medical institution over 10 years, including their presentation, management, and outcomes. METHODS: Fifty-three subjects aged 0 to 14 years with previously untreated NBL who were diagnosed and treated at Princess Nora Oncology Center, King Abdulaziz Medical City (KAMC), Jeddah, Saudi Arabia, between 2010 and 2019. Six infants (11.3%) had stage 4S characteristics. RESULTS: The median age at diagnosis was 3 months (range 52 days - 4 months). Biopsies confirmed that the adrenal gland was the primary tumor site for 3 patients, while the other 2 had retroperitoneal sites. Four patients had favorable histology, and one had unfavorable histology. All patients had liver metastasis, and no bone marrow or skin metastasis was recorded. All patients received chemotherapy except one, and all survived with no disease progression at a median follow up to 5 years. CONCLUSION: Our data confirm that NBL-4S is a curable cancer, especially with early recognition and intervention. Chemotherapy is the first-line treatment for symptomatic patients. Unless the condition is life threatening, radiotherapy is not indicated. Surgical resection may be indicated in younger infants with localized tumors and favorable biology, but otherwise, it is not usually indicated for residual cases.

A clinical approach to non-neutropenic fever in children with cancer.

BACKGROUND: There are a limited number of studies that address non-neutropenic fever episodes in children with cancer, and no standard approach exists. METHOD: We opt to retrospectively analyze the efficacy of the current clinical approach for management of non-neutropenic fever episodes and the associated risk factors among children with cancer at the Princess Noorah Oncology Center from May 2016 through December 2017. RESULTS: A total of 480 non-neutropenic fever episodes were identified in 131 children, of which 62 episodes were triaged as high-risk non-neutropenic fever and 418 as low-risk non-neutropenic fever. Of those 480 non-neutropenic fever, 361 episodes (75.2%) were associated with the presence of central venous catheters. The overall failure rate of ceftriaxone mono-therapy was observed in 75.6% (11.7% in high-risk non-neutropenic fever with a mean C-reactive protein level of 21.1 (±23.2) mmol/L and 63.9% in low-risk non-neutropenic fever with a mean C-reactive protein level of 17.6 (±53.9) mmol/L). The overall bacteremia rate was 14.4%. The type of organisms isolated was mainly high-risk organisms in 59 non-neutropenic fever episodes (85.5%), OR 1.78 (95% CI: 0.45-7.04) p = 0.41. Of note, all bacteremia were associated with the presence of central venous catheter (100%). Of all the examined risk factors of outpatient treatment failure in low-risk non-neutropenic fever, only prolonged fever of more than three days were significantly associated with bacteremia OR 8.107 [95% CI: 1.744-37.691], p = 0.008. Noteworthy is that almost 43% of non-neutropenic fever episodes were associated with respiratory symptoms. This study provides a baseline for future prospective research assessing the pattern of non-neutropenic fever by focusing on associated risk factors.

Intrathecal dose intensification by CNS status at diagnosis in the treatment of children with acute lymphoblastic leukemia.

OBJECTIVES: Acute lymphoblastic leukemia (ALL) with CNS2 status predicts inferior outcome and a high rate of CNS relapse, similar to overt CNS leukemia (CNS3). The purpose of this study was to determine if intrathecal (IT) dose intensification during induction would improve outcomes and reduce CNS relapse for CNS2 disease. METHODS: From January 2001 to December 2014, children (1-14 years) with newly diagnosed ALL were treated at the Princess Noorah Oncology Centre (PNOC) following modifications of the Children's Oncology Group (COG) protocols. We intensified IT methotrexate (ITM) during induction for patients with CNS2 disease. Patients were evaluated for overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse (CIR). RESULTS: 449 children with T-cell (14.3%) or B-cell (85.7%) ALL were treated using PNOC-SR or PNOC-HR regimens (Jan 2001- Dec 2007) or CALL08 regimens (Arm A [SR], Arm B [IR], and Arm C [HR]) (Jan 2008 - Dec 2014). The 5-year OS, DFS, and CIR were 87.2 ± 1.6%, 81.7 ± 1.9%, and 13.0 ± 1.7%, respectively. The OS and DFS of patients with CNS2 were significantly superior to that of patients with CNS3 (P = 0.025 and P = 0.019, respectively). Patients with CNS2 had similar OS and DFS to those with CNS1. None of the patients with CNS2 at initial diagnosis experienced CNS relapse. CONCLUSIONS: ITM intensification during induction was associated with elimination of CNS recurrence in patients with CNS2 disease and childhood ALL. Controlled studies are needed to confirm this observation.

FLAG/FLAG-IDA regimen for children with relapsed/refractory acute leukemia in the era of targeted novel therapies.

BACKGROUND: Outcomes of relapsed/refractory childhood acute leukemia remain poor. We analyzed the safety/efficacy of fludarabine, cytarabine, and granulocyte colony stimulating factor, with/without idarubicin (FLAG ± IDA) as salvage therapy compared with recent published results of novel therapies. METHODS: This retrospective study included children aged 1 to 15 years with relapsed/refractory acute leukemia who received FLAG ± IDA salvage therapy from January 2000 to December 2014. Patients with infant leukemia, mixed lineage leukemia, Philadelphia-positive acute leukemia, or secondary leukemia were excluded. RESULT: Fifty patients were identified: 25 with acute lymphoblastic leukemia and 25 with acute myeloid leukemia. The median age at initiation of FLAG ± IDA was seven years. Site of relapse was the bone marrow in 29, isolated central nervous system in 11, and combined in 10 patients. FLAG ± IDA was used after first relapse in 68% and after multiple relapses in 32%. Complete remission was achieved in 34 (68%) patients. No variables predictive of complete remission were identified. Grade 3 or greater toxicity was observed in 96% and 6% died from toxicity. Toxicities included hematologic toxicity (96%), infection (52%), and enterocolitis (28%). Twenty-four of 50 (48%) patients achieved a sustained complete remission and survived to bone marrow transplantation. The five-year overall survival was 23.9% ± 6.9%. Patients achieving second complete remission and patients proceeding to bone marrow transplantation following second complete remission demonstrated significantly improved overall survival (p = 0.001). CONCLUSION: Despite a 68% complete remission rate using FLAG ± IDA, only 48% of patients survived to bone marrow transplantation. The regimen was associated with 96% toxicity and only one in four patients was alive at five years. This underscores the need to find more effective lower toxicity salvage regimens.

Early vs. late MRD response- and risk-based treatment intensification of childhood acute lymphoblastic leukemia: a prospective pilot study from Saudi Arabia.

BACKGROUND: Refinement of risk-based treatment stratification by minimal residual disease (MRD) at different time points has improved outcomes of childhood acute lymphoblastic leukemia (ALL). In this prospective study we evaluated effects of such stratification, including intensification of therapy based on response assessment at day-15 and MRD at day-29 of induction to test if treatment intensification would improve outcomes. METHODS: 241 patients, 1-14 years old, newly diagnosed with ALL, were recruited and stratified by risk and MRD response into three treatment Arms (A, B, or C). Arm A was modified from COG AALL0331, B from AALL0232, and C from AALL0232 and AALL0434. Assignments were according to NCI risk, phenotype, rapid vs. slow early response (SER), steroid pretreatment, MLL rearrangement (MLLR), CNS3, and testicular involvement. Patients on Arm A had treatment intensified early based on day-15 marrow results or late based on end-of-induction MRD. RESULTS: 5-year OS, EFS, and CIR were 89.5% ± 4.0%, 87.6% ± 4.3%, and 7.1% ± 3.5%. No significant difference was found by B- vs. T cell phenotype. 5-year OS, EFS, and CIR for B-cell ALL were 90.5% ± 2.4%, 88.7% ± 2.6%, and 6.4% ± 2.0%. Outcomes for patients with t(1;19)/TCF3-PBX1 and MLLR were significantly (p ≤ 0.05) worse than for other patients. MRD level at end-of-induction associated with outcomes, but association with a specific MRD value at end-of-induction varied significantly by NCI-risk group. Late treatment intensification based on end-of-induction MRD significantly improved survival outcomes for NCI-SR patients, however, patients with NCI-HR and positive MRD at end-of-induction had significantly inferior outcomes despite intensification. MRD transitions between day-15 and day-29 of induction associated with differences for OS and EFS. CONCLUSIONS: Arm switching to a more intensive protocol had mixed results. Assigning patients by end-of-induction MRD-risk alone did not reflect response kinetics of the different NCI-risk groups. Although late treatment intensification improved outcomes of NCI-SR patients with positive MRD at end-of-induction, further refinement is needed to improve outcomes of NCI-HR with SER. Integration of NCI-risk group with specific MRD value and time point allows more refined treatment stratification.Trial Registration Protocols were approved by King Abdullah International Medical Research Center and Ethics Review Committee RC08053J.

High-dose methotrexate vs. Capizzi methotrexate for the treatment of childhood T-cell acute lymphoblastic leukemia.

Sixty-three children (1-14 years of age) newly diagnosed with T-cell acute lymphoblastic leukemia were treated from January 2001 to December 2014. Patient outcomes were evaluated based on the regimen received; Capizzi methotrexate (C-MTX) vs. high-dose methotrexate (HDMTX). Complete remission (CR) was achieved in 54 of 60 (90.0%) patients and 3 patients died during induction. The 5-year overall survival (OS) and disease-free survival (DFS) were 88.3 ±â€¯6.5% and 85 ±â€¯7.5%, respectively. Post-induction, 35 patients were treated with HDMTX and 25 with C-MTX. There was no difference in OS or DFS for patients treated with HDMTX vs. C-MTX (P > 0.05 for both). Central nervous system involvement (CNS3) was associated with inferior survival outcomes compared to Non-CNS3 patients (OS, CNS3 73.3 ±â€¯9.1% vs.non-CNS3 93.2 ±â€¯2.6%, (P = 0.045) and DFS, CNS3 66.7 ±â€¯10.4% vs. non-CNS3 90.9 ±â€¯3.1% (P = 0.0163)). Delayed radiation in CNS3 was associated with relapse (P = 0.0037) regardless of regimen. Thus optimization of CNS-directed therapy for patients with CNS3 is needed.

Challenges in the management of childhood low-grade glioma in a developing country.

BACKGROUND: Treatment modality impacts outcome of childhood low-grade glioma (LGG). Optimizing management in developing countries can be challenging. This study evaluates the clinical characteristics, treatment, and factors influencing outcome of childhood LGG in Saudi Arabia. PATIENTS AND METHODS: This study retrospectively evaluated 59 children consecutively diagnosed with LGG between January 2001 and June 2016. RESULTS: Median age at diagnosis was 6.0 years. Pilocytic astrocytoma represented 64.9% of cases. The anatomic site was cerebellar in 23.7%, cerebral in 18.6%, hypothalamic-optic pathway in 33.9%, and midline in 23.7%. The 5-year overall survival (OS) and progression-free survival (PFS) were 90.6 ± 4.7 and 54.3 ± 8.4%, respectively. Initial treatment was observation in 28.8%, surgery alone in 35.6%, chemotherapy in 13.6%, radiotherapy in 5.1%, and combined in 16.9% of cases. The corresponding 5-year PFS was 56.3 ± 15.6, 53.3 ± 14.0, 22.9 ± 19.7, 33.3 ± 27.2, and 88.9 ± 10.5%, respectively (p = 0.006). Among the 61% who had surgical intervention (either alone or in combination with other therapies), 22% achieved complete resection with 5-year radiation/progression-free survival (RPFS) of 87.5 ± 11.7% compared to 27.6 ± 10.8% for subtotal resection/biopsy and 62.2 ± 17.0% for no surgery (p = 0.013). Adjuvant therapy for residual tumor improved survival with 5-year PFS of 66.7 ± 19.2% for chemotherapy and 100% for radiotherapy compared to 12.5 ± 11.4% for observation (p = 0.033). CONCLUSIONS: We identified variability in the outcomes of LGG. Fewer surgeries with lower rates of total resection were noted, compared to reports from international cooperative groups. The extent of resection was predictive of RPFS. Adjuvant therapy improved the outcome of patients with residual disease, resulting in PFS rates comparable to international data.

The prognostic significance of hypertension at diagnosis in children with wilms tumor.

OBJECTIVES: To determine the prognostic effect of hypertension at diagnosis on outcomes of children with Wilms tumor (WT).   Methods: A single center retrospective analysis was conducted on 85 consecutive children with WT diagnosed between January 2000 and August 2013. Patients were classified as hypertensive or normotensive at diagnosis. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Cox regression was used to determine the predictive significance of hypertension and other clinical factors.  Results: Seventy-one patients had complete data. Of this, 25 (35.2%) were hypertensive and 46 (64.8%) normotensive with corresponding remission rates of 56.0% versus 82.6%, p=0.032; and death as first event of 7% versus 0%, p=0.004. The 5-year OS in the hypertensive versus normotensive patients were (67.1±10.3% versus 89.6±4.9%, p=0.009) and the corresponding 5-year PFS were (53.4±10.4% versus 79.1±6.2%, p=0.007). With univariate analysis, hypertension and local stage were predictors of OS (p=0.012 and p=0.029) and PFS (p=0.030 and p=0.008). In the multivariate analysis, hypertension, local stage, and histopathology were identified as independent prognostic factors of OS (p=0.004, p=0.034, and p=0.038); and hypertension  and local stage as prognostic for PFS (p=0.010 and p=0.012).  Conclusion: Hypertension at diagnosis is a prognostic predictor of poor outcome in WT and may signify tumor resistance.

Comparison of clinical trial versus non-clinical trial treatment outcomes of childhood acute lymphoblastic leukemia using comparable regimens.

OBJECTIVES: Treatment regimens tested in major clinical trials, conducted by cooperative groups, are often adapted as standard of care by cancer centers with the hope to replicate the treatment outcomes reported in these landmark studies. It is therefore postulated that applying clinical trial regimens in a non-clinical trial setting yield similar outcomes. The aim of the present study was to explore this hypothesis in the context of childhood acute lymphoblastic leukemia (ALL) in our institution. METHODS: We retrospectively evaluated 224 consecutive pediatric ALL cases treated between January 2001 and December 2007. Standard-risk (SR) patients were treated on CCG-1991 (regimen OD) while high-risk (HR) patients were treated on CCG-1961 (regimen D). Results were compared with those of the equivalent regimen in the original clinical trials. Statistical analysis was carried using chi-square or Fisher's exact test, Kaplan-Meier and log-rank tests. RESULTS: Comparison of treatment outcomes revealed that SR patients had inferior 5-year overall survival (OS) of (89.0 ± 2.9 vs. 96.0% ± 0.9%); event-free survival of (82.3 ± 3.5 vs. 88.7% ± 1.4%); and relapse rate of (15.8 vs. 9.3% (P = 0.034)) compared to patients treated in the clinical trial. However, no statistically significant difference in treatment outcomes was observed between HR patients. CONCLUSIONS: Despite using comparable regimens, suboptimal outcomes were noted in SR patients implying that similar treatments do not necessarily yield similar outcomes. This underscores the need to evaluate outcomes of adapted regimens to identify areas that need further improvement in centers not enrolling patients on prospective collaborative clinical trials.

Does the early intensification of intrathecal therapy improve outcomes in pediatric acute lymphoblastic leukemia patients with CNS2/TLP+ status at diagnosis?

OBJECTIVES: We aimed to determine whether the addition of two extra intrathecal methotrexate (ITM) doses during induction in acute lymphoblastic leukemia (ALL) patients eliminate the prognostic significance of CNS2/TLP+ status. METHODS: We retrospectively analyzed 224 patients according to the central nervous system (CNS) involvement at diagnosis: CNS1, CNS2, or CNS3. Patients with CNS2/TLP+ received two additional ITM doses during induction. Patients were treated according to the Children's Cancer Group (CCG)-1991/1961 protocols between January 2001 and December 2007. RESULTS: The 5-year relapse-free survival (RFS) rates for the ALL patients in the CNS1, CNS2, and CNS3 groups were 80.4 ± 3.0, 100, and 73.5 ± 11.3%, respectively; a non-significant difference was observed between the groups (P = 0.063). However, the patients with CNS2 had significantly better survival compared with the CNS3 patients (P = 0.03). The 5-year cumulative incidence of relapse (CIR) rates for the three groups were 17 (95% confidence interval (CI): 11.9-22.9), 0, and 18.8% (95% CI: 4.3-41.1), respectively; (P = 0.214) and those of isolated or combined CNS relapse were 9.6 (95% CI: 5.8-14.5), 0 and 6.3% (95% CI: 0.3-25.8), respectively (P = 0.424). CONCLUSIONS: This study shows that the intensification of ITM therapy during induction improves outcomes in patients with CNS2/TLP+ status and eliminates its prognostic significance. This suggests that early intensification using CNS-directed therapy is beneficial in controlling minimal CNS disease.

Identifying causes of variability in outcomes in children with acute lymphoblastic leukemia treated in a resource-rich developing country.

BACKGROUND: The outcome of children with acute lymphoblastic leukemia (ALL) in developing countries is less favorable than in developed countries, primarily due to resource constraints. However, it is unknown whether the therapeutic results differ. Thus, we hypothesized that outcomes in resource-rich developing countries would be similar to those in industrialized regions. PROCEDURE: We performed a retrospective analysis of 224 consecutive children with ALL, who were treated according to the Children's Cancer Group (CCG) protocols between January 2001 and December 2007. High-risk (HR) and standard-risk (SR) patients were treated with modified CCG-1961 and CCG-1991 protocols, respectively. Modifications included substitution of dexamethasone for prednisone in HR patients and addition of two intrathecal methotrexate treatments for CNS2 patients during induction. All patients received double delayed intensification with two interim maintenance phases. RESULTS: Five-year overall survival (OS), event-free survival (EFS) and disease-free survival (DFS) were 84.7 ± 2.4%, 77.0 ± 2.9%, and 81.4 ± 2.7%, respectively. Remission was achieved in 98.1% of the patients. Induction failure and relapse rates were 1.9% and 15.1%, respectively. Death as the first event occurred in 6.4% of cases, of which 2.7% and 3.7% involved deaths in induction and remission, respectively. Interestingly, a significant reduction in induction deaths was observed over time. CONCLUSIONS: Despite the encouraging results observed in the present study, our patients displayed significantly lower survival outcomes compared to subjects treated in major clinical trials conducted by leading leukemia cooperative groups. Furthermore, this work underscores the need for targeted interventions to reduce death as the first event in developing regions.