Wasil Jastaniah

Improved outcome in pediatric AML due to augmented supportive care

We conducted a retrospective review of patients treated following the MRC acute myeloid leukemia (AML) 10 protocol to determine if supportive care measures sequentially introduced by our institution led to a significant improvement in treatment‐related mortality (TRM) in newly diagnosed pediatric patients with AML. Patients were partitioned based on supportive care measures into era1, from 1996 to 2002 (nu2009=u200920), and era2, from 2003 to 2011 (nu2009=u200940). The introduced supportive care measures reduced the TRM from 23.4% in era1 to 2.5% in era2 (Pu2009=u20090.034). The results demonstrate that supportive care is a significant factor in determining the outcome of childhood AML. Pediatr Blood Cancer 2012; 59: 919–921.

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

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.

Clinical characteristics and outcome of childhood de novo acute myeloid leukemia in Saudi Arabia: A multicenter SAPHOS leukemia group study.

Geographic variation and ethnicity have been implicated to influence the outcome of pediatric acute myeloid leukemia (AML). Furthermore, survival outcomes from developing countries are reported to be inferior to developed nations. We hypothesized that risk- and response-based outcome in high-income resource-rich developing countries would be comparable to developed nations as access to care and supportive measures would be similar. A total of 193 children diagnosed with de novo AML between January 2005 and December 2012 were identified, of those 175 were evaluable for outcome. Patients were stratified into low-risk (LR), intermediate-risk (IR), or high-risk (HR) groups. The complete remission (CR), early death, and induction failure rates were: 85.7%, 2.3%, and 12%; respectively. The 5-year cumulative incidences of relapse (CIR) and non-relapse mortality (NRM) were 43.1% and 9.8% respectively; overall survival (OS) was 58.8±4% and event-free survival (EFS) 40.9±4.1%. The 5-year OS for LR, IR, and HR groups were 72.0±6.9%, 59.8±6.2%, and 45.1±7.4%; respectively (p=0.003); and EFS 50.5±8.0%, 46.3±6.4%, and 23.3±6.4%; respectively (p=0.001). This study demonstrated comparable outcomes to those reported from developed countries. This suggests that utilization of risk- and response-based protocols in developing countries can overcome ethnic and geographic variation, if access to care and supportive measures were similar.

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 Fishers 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 (89.0u2009±u20092.9 vs. 96.0%u2009±u20090.9%); event-free survival of (82.3u2009±u20093.5 vs. 88.7%u2009±u20091.4%); and relapse rate of (15.8 vs. 9.3% (Pu2009=u20090.034)) 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.

Clinical characteristics and outcome of childhood acute promyelocitic leukemia (APL) in Saudi Arabia: a multicenter SAPHOS leukemia group study

ABSTRACT Background: Acute promyelocytic leukemia (APL) is a rare form of acute myelogenous leukemia (AML). Survival rates exceed 80% in developed countries. Successful treatments rely on all-trans retinoic acid with anthracycline-based chemotherapy. Availability of modern care and public knowledge play important roles in pediatric APL survival. Method: A cytogenetic diagnosis of APL was confirmed in 30 (14.5%) out of 207 children consecutively diagnosed with de novo AML between January 2005 and December 2012 at nine cancer care centers in Saudi Arabia. Patients were treated based on the standard protocol used by the center following the PETHEMA or the C9710 treatment protocols. We modeled 5-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) vs. treatment and potential covariates of age at diagnosis, involvement of central nervous system (CNS), and white blood cell (WBC) levels. Results: The median age was 10.4 years with a male:female ratio of 1.9. WBC was 10u2009×u2009109/l or greater in 57% and CNS involvement was confirmed in 13%. OS, EFS, and CIR were 74u2009±u200912%, 55u2009±u200919%, and, 36u2009±u200917% respectively. No significant difference was found by treatment protocol. WBC levels were significantly prognostic for all negative events, but treatment with C9710 significantly ameliorated negative WBC effects. Overall outcomes were comparable to those reported in developed countries. Conclusions: Access to modern care is likely to be a critical factor in successful and comparable outcomes of childhood APL across the globe. In the present study, utilizing a cytarabine-containing protocol improved outcome of high-risk pediatric patients with APL.

Identifying prognostic factors that influence outcome of childhood acute myeloid leukemia in first relapse in Saudi Arabia: Results of the multicenter SAPHOS study

Background: The outcome of childhood acute myeloid leukemia (AML) in first relapse (rAML) remains poor. Reported overall survival (OS) rates vary between high‐income developed countries and those with fewer resources. The OS of rAML in high‐income developing countries (HIDCs) has not been reported. Patients and Materials: A multicenter study was performed in an HIDC. The outcome of patients with relapsed non‐M3/non‐Down syndrome AML was evaluated. Three‐year OS was computed using the Kaplan‐Meier method, and predictors of OS were analyzed using a Cox proportional hazards model. Results: A total of 88 patients with non‐M3/non‐Down syndrome AML diagnosed between January 2005 and December 2012 with a first relapse were identified. Their 3‐year OS was 22.6% ± 5.4%. Patients with inv(16) and t(8;21) had an OS of 75.0% ± 21.7% and 36.0% ± 16.1%, respectively. Worse outcomes were associated with “other intermediate” and 11q23 rearrangement AML (OS of 9.4% ± 8.7% and 10.7% ± 9.6%, respectively). Patients experiencing time to relapse (TTR) less than 1 year had shorter OS than those with a longer TTR (14.6% ± 5.4% vs. 41.1% ± 11.5%; P = .006). The outcome of patients after stem cell transplantation (SCT) in second complete remission (CR2) was superior compared with no SCT (50.9% ± 11.2% vs. 7.7% ± 4.6%; P = .001). TTR, risk group, CR2, and SCT in CR2 were the most significant predictors for survival. Conclusions: rAML remains a clinical challenge. Genetic variability in outcomes was observed. A majority of patients with inv(16) were successfully salvaged post‐relapse, whereas patients with 11q23 rearrangement had a poor prognosis. Only one‐third of those with t(8;21) rAML survived. Better access to SCT in HIDCs is needed.

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

BackgroundTreatment 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 methodsThis study retrospectively evaluated 59 children consecutively diagnosed with LGG between January 2001 and June 2016.ResultsMedian age at diagnosis was 6.0xa0years. 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 90.6u2009±u20094.7 and 54.3u2009±u20098.4%, 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 56.3u2009±u200915.6, 53.3u2009±u200914.0, 22.9u2009±u200919.7, 33.3u2009±u200927.2, and 88.9u2009±u200910.5%, respectively (pu2009=u20090.006). 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 87.5u2009±u200911.7% compared to 27.6u2009±u200910.8% for subtotal resection/biopsy and 62.2u2009±u200917.0% for no surgery (pu2009=u20090.013). Adjuvant therapy for residual tumor improved survival with 5-year PFS of 66.7u2009±u200919.2% for chemotherapy and 100% for radiotherapy compared to 12.5u2009±u200911.4% for observation (pu2009=u20090.033).ConclusionsWe 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.

Treatment results in children with myeloid leukemia of Down syndrome in Saudi Arabia: A multicenter SAPHOS leukemia group study

Despite the high incidence of Down syndrome (DS) in Arab countires, the incidence and outcomes of myeloid leukemia of DS (ML-DS) have not been studied. We evaluated 206 pediatric acute myeloid leukemia (AML) patients diagnosed between 2005 and 2012 and identified 31 (15%) ML-DS. The incidence of ML-DS was 48 per 100,000 compared to 0.6 per 100,000 for AML in non-DS children. Thus, patients with DS had 80-fold increased risk of ML-DS compared to AML in non-DS children. The median age at diagnosis was 1.8 years, male/female ratio was 1.2, majority (84%) of patients had FAB-M7 subtype, and the cytogenetic abnormalities were normal karyotype (constitutional trisomy 21) in 48%, additional trisomy in 23%, and other aberrations in 29%. Complete remission, cumulative incidences of relapse (CIR), toxic-death, and 5-year event-free survival (EFS) rates were 96.8%, 19.4%, 13.1%, and 67.7±8.4%; respectively. In the present study, multivariate analysis revealed favorable outcome (5-year EFS 86.7±8.8%) for patients with normal karyotype. The incidence and clinical characteristics of ML-DS in Saudi patients were comparable to other reports. However, there is a need to optimize risk stratification and treatment intensity to reduce CIR and toxic death rates to further improve outcomes of patients with ML-DS.

Demands and challenges for patients with sickle-cell disease requiring hematopoietic stem cell transplantation in Saudi Arabia.

Allogeneic HSCT is the only curative treatment for SCD. In this study, we estimated the number of Saudi patients with SCD who are candidates for HSCT. We used the presence of overt stroke, recurrent ACS, and frequent severe pain crisis as indications for HSCT. We calculated the frequencies of these complications among a Saudi SCD cohort of 376 patients with SCD, 250 from SW and 126 from Eastern (E) provinces. We found that 59 (23.6%) of SW patients were transplant candidates compared to 22 (17.4%) from E province. It is estimated that about 61 000 patients with SCD live in Saudi Arabia. Thus, the projected number of Saudi patients with SCD who are candidates for HSCT is 10 536 patients. Of those, 2148 are children. The burden of SCD on HSCT centers in Saudi Arabia is substantial and is difficult currently to meet the demand. We recommend recruiting/training more transplant physicians and nurses, expand current capacity of centers if feasible, and open new transplant centers to make HSCT a practical therapeutic option for patients with severe SCD in Saudi Arabia.