Acute promyelocytic leukemia (APL) is a rare form of acute myelogenous leukemia (AML). Survival r... more 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. 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. The median age was 10.4 years with a male:female ratio of 1.9. WBC was 10 × 109/l or greater in 57% and CNS involvement was confirmed in 13%. OS, EFS, and CIR were 74 ± 12%, 55 ± 19%, and, 36 ± 17% 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. 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.
Geographic variation and ethnicity have been implicated to influence the outcome of pediatric acu... more 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.
Background: Sickle cell disease (SCD) is associated with many clinical complications, with vaso-o... more Background: Sickle cell disease (SCD) is associated with many clinical complications, with vaso-occlusive crises (VOCs) being a hallmark of the disease. SCD-related complications are largely driven by vaso-occlusion and hemolytic anemia, and can lead to end-organ damage and early death. Analyses of SWAY, a cross-sectional survey, highlighted a substantial global impact of SCD on patients' quality of life (QoL) (James et al. ASH 2019; Osunkwo et al. ASH 2019). However, understanding how the burden of disease differs for pts of different ages could help improve management of SCD over a pt's lifespan. Aim: To assess, using data from SWAY, whether symptoms (excluding VOCs, as previously analyzed by Osunkwo et al. EHA 2020), treatment goals and the perceived impact of SCD were different for pts of different ages. Methods: Between April and October 2019, 2145 SCD pts aged ≥6 years participated in SWAY. The survey was completed by proxy (parent/caregiver/guardian) for pts aged 6-11 years and could be optionally self-completed by pts aged ≥12 years. Opinions were captured using a 1-7 Likert scale for some questions (5-7 indicated high satisfaction/impact/agreement). SWAY was not designed to assess treatment outcomes; all analyses are descriptive. Age groups were not matched and pts were not followed over time. Results: To understand how the most dominant symptoms of SCD differ for pts of different ages, the top 5 most commonly reported symptoms, stratified by age, were analyzed (Figure 1). Fatigue and bone aches were consistently reported, and the proportion of pts reporting them trended towards increasing with age. Furthermore, when asked which symptoms they most wanted to be resolved, fatigue was ranked in the top 3 by 40.7% of pts. Anxiety was a dominant symptom for pts aged 19-25, 36-45 and 46-50 years, whereas low mood was a dominant symptom for pts aged 19-50 and ≥60 years. Poor appetite was a dominant symptom for pts aged 6-16 years. Breathing issues were a dominant symptom for pts aged 6-18, 46-50 and ≥60 years, whereas vision issues were a dominant symptom for pts aged 51-59 years only. Insomnia was dominant for pts aged 46-50. The treatment goals that pts ranked as the most important were similar across age groups. Pts consistently included improving QoL, preventing worsening of SCD, reducing the number of VOCs and improving overall symptoms in their top 3, although the proportions of pts reporting these varied across age groups (Figure 2). Unsurprisingly, 23.0% of pts aged 12-16 years ranked increasing the ability to attend school in their top 3 goals. For pts aged 46-50 and 51-59 years, 27.5% and 20.7%, respectively, ranked reducing fatigue in their top 3 treatment goals. The highest proportions of pts reporting a high impact of SCD on their emotional wellbeing were aged 46-50 years (74.5%) and ≥60 years (73.9%), compared with 59.6% of all pts. Similarly, the highest proportions of pts reporting a high impact of SCD on daily activities were aged 46-50 years (51.0%) and ≥60 years (60.9%), compared with 38.1% of all pts. Limitations: These findings are based on pt and proxy reports, with potential parental bias being introduced for pediatric patients. There were variations in sample sizes, which was most noticeable for patients aged ≥46 years. Discussion: Fatigue and bone aches were consistently reported as dominant symptoms for all ages. Other dominant symptoms that were not consistent across age groups were anxiety, low mood, poor appetite, breathing issues and vision issues. In addition to the 36-45 years and 46-50 years groups, anxiety was a dominant symptom for pts aged 19-25 years. Along with other changes that could occur at this age, a recent transition from pediatric to adult care may contribute to anxiety being a dominant symptom; however, any direct relationship between anxiety and transitioning between care systems requires further investigation. The consistent reporting of low mood among adults, but not pediatrics, may reflect the increasing burden of disease that occurs with age. This is supported by higher proportions of pts aged ≥46 years versus <45 years reporting a high impact on emotional wellbeing and daily life. Improving QoL was consistently ranked the most important treatment goal for pts. This emphasizes, from the pt's perspective, the need for further improvements in the management of SCD. Disclosures Colombatti: Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Addmedica: Membership on an entity's Board of Directors or advisory committees. James:Sickle Cell Society: Current Employment; Novartis: Honoraria. Andemariam:Hemanext: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or…
Abstract: Standardizing Body Surface Area (BSA) determination is essential for avoiding variation... more Abstract: Standardizing Body Surface Area (BSA) determination is essential for avoiding variation in chemotherapy dosage calculations. In this study we compared variation in BSA calculation using weight and height by the Mosteller formula with weight alone using recently adapted table at the Princess Norah Oncology Center (PNOC). Methods: Cross-sectional study of pediatric oncology patients presenting to the pediatric oncology clinic at PNOC over a week period of time. Results: One hundred consecutive pediatric oncology patients presented to the clinic. The mean BSA calculated by the Mosteller formula was 0.83m2 (Standard Deviation = 0.24) and the mean BSA determined by the table (based on weight alone) was 0.82m2 (Standard Deviation = 0.25). The mean variation in dosing between the two methods was 1.64% (Standard Deviation = 3.4). Only 13 out of 100 patients (13%) had equal dosing using both methods and 21 out of 100 patients (21%) had dosing variation greater than 5%. When comparing both methods, using paired t-test, the difference was statistically significant (t(99) = 3.99 and P < 0.001). Conclusion: Significant differences in BSA-based chemotherapy dosing exist in our center. The Mosteller method should remain the standard until prospective studies are performed to determine the significance of this dosing variability on toxicity and survival outcome.
Complex regional pain syndrome, characterized by pain, autonomic dysfunction, and decreased range... more Complex regional pain syndrome, characterized by pain, autonomic dysfunction, and decreased range of motion, developed after hepatitis B vaccination in four grade-6 children since the introduction of the vaccination program in British Columbia in 1992. The reaction may result from injection trauma or may be secondary to a vaccine constituent.
The prevalence of obstructive sleep apnea syndrome (OSAS) is elevated in some high-risk populatio... more The prevalence of obstructive sleep apnea syndrome (OSAS) is elevated in some high-risk populations. Children with sickle cell disease (SCD) are known to have many comorbidities, including OSAS. The objectives of this study were to assess the prevalence of and risk factors for OSAS among children with SCD in two major tertiary health care facilities in Jeddah, Saudi Arabia. This multicenter cross-sectional study took place in two major tertiary health care facilities—King Abdulaziz University Hospital and King Khalid National Guard Hospital, Jeddah, Saudi Arabia. Children with SCD who were admitted between January 2010 and December 2017 were enrolled. The Pediatric Sleep Questionnaire (PSQ) was used to screen for OSAS. Data were collected from 150 children with SCD aged between 2 and 18 years. Eighty-five percent of the children had sickle cell anemia (SCA) with HbSS, and the rest had sickle beta-thalassemia (HbS/ß-thalassemia). Based on the PSQ, 33 of the 150 (22%) children had OSAS (score ≥ 7). The average score on the PSQ was 3.8/22 (± 3.8). A history of adenotonsillar hypertrophy was found to be a significant risk factor in bivariate and multivariate analyses [aOR 5.5; 95% CI 1.84–16.35 ( P < 0.001)]. The odds of having OSAS were ninefold higher in children who had periodic limb movements than in those who did not after adjustment [95% CI 1.75–48.03 ( P < 0.001)]. OSAS is a highly prevalent disease among children with SCD. Many factors were associated with OSAS in the bivariate analysis, including nationality, education level, a history of adenotonsillar hypertrophy, and a history of periodic limb movements.
Journal of Pediatric Hematology Oncology, Mar 1, 2012
An 8-year-old, human immune virus-negative boy received full human leukocyte antigen-matched rela... more An 8-year-old, human immune virus-negative boy received full human leukocyte antigen-matched related allogenic hematopoietic stem cell transplantation (HSCT) for relapsed acute myeloid leukemia. While on cyclosporine A and prednisolone therapy for graft versus host disease, he developed extensive gingival, cutaneous, and respiratory tract human herpes virus-8-associated Kaposi sarcoma (KS). Withdrawal of cyclosporine, tapering of prednisolone, recovery of lymphocyte count, and local supportive measures resulted in resolution of his gingival and respiratory tract lesions. To our knowledge this is the first case of gingival and extensive respiratory tract KS to be reported in a child post HSCT.
Acute promyelocytic leukemia (APL) is a rare form of acute myelogenous leukemia (AML). Survival r... more 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. 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. The median age was 10.4 years with a male:female ratio of 1.9. WBC was 10 × 109/l or greater in 57% and CNS involvement was confirmed in 13%. OS, EFS, and CIR were 74 ± 12%, 55 ± 19%, and, 36 ± 17% 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. 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.
Geographic variation and ethnicity have been implicated to influence the outcome of pediatric acu... more 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.
Background: Sickle cell disease (SCD) is associated with many clinical complications, with vaso-o... more Background: Sickle cell disease (SCD) is associated with many clinical complications, with vaso-occlusive crises (VOCs) being a hallmark of the disease. SCD-related complications are largely driven by vaso-occlusion and hemolytic anemia, and can lead to end-organ damage and early death. Analyses of SWAY, a cross-sectional survey, highlighted a substantial global impact of SCD on patients&amp;#39; quality of life (QoL) (James et al. ASH 2019; Osunkwo et al. ASH 2019). However, understanding how the burden of disease differs for pts of different ages could help improve management of SCD over a pt&amp;#39;s lifespan. Aim: To assess, using data from SWAY, whether symptoms (excluding VOCs, as previously analyzed by Osunkwo et al. EHA 2020), treatment goals and the perceived impact of SCD were different for pts of different ages. Methods: Between April and October 2019, 2145 SCD pts aged ≥6 years participated in SWAY. The survey was completed by proxy (parent/caregiver/guardian) for pts aged 6-11 years and could be optionally self-completed by pts aged ≥12 years. Opinions were captured using a 1-7 Likert scale for some questions (5-7 indicated high satisfaction/impact/agreement). SWAY was not designed to assess treatment outcomes; all analyses are descriptive. Age groups were not matched and pts were not followed over time. Results: To understand how the most dominant symptoms of SCD differ for pts of different ages, the top 5 most commonly reported symptoms, stratified by age, were analyzed (Figure 1). Fatigue and bone aches were consistently reported, and the proportion of pts reporting them trended towards increasing with age. Furthermore, when asked which symptoms they most wanted to be resolved, fatigue was ranked in the top 3 by 40.7% of pts. Anxiety was a dominant symptom for pts aged 19-25, 36-45 and 46-50 years, whereas low mood was a dominant symptom for pts aged 19-50 and ≥60 years. Poor appetite was a dominant symptom for pts aged 6-16 years. Breathing issues were a dominant symptom for pts aged 6-18, 46-50 and ≥60 years, whereas vision issues were a dominant symptom for pts aged 51-59 years only. Insomnia was dominant for pts aged 46-50. The treatment goals that pts ranked as the most important were similar across age groups. Pts consistently included improving QoL, preventing worsening of SCD, reducing the number of VOCs and improving overall symptoms in their top 3, although the proportions of pts reporting these varied across age groups (Figure 2). Unsurprisingly, 23.0% of pts aged 12-16 years ranked increasing the ability to attend school in their top 3 goals. For pts aged 46-50 and 51-59 years, 27.5% and 20.7%, respectively, ranked reducing fatigue in their top 3 treatment goals. The highest proportions of pts reporting a high impact of SCD on their emotional wellbeing were aged 46-50 years (74.5%) and ≥60 years (73.9%), compared with 59.6% of all pts. Similarly, the highest proportions of pts reporting a high impact of SCD on daily activities were aged 46-50 years (51.0%) and ≥60 years (60.9%), compared with 38.1% of all pts. Limitations: These findings are based on pt and proxy reports, with potential parental bias being introduced for pediatric patients. There were variations in sample sizes, which was most noticeable for patients aged ≥46 years. Discussion: Fatigue and bone aches were consistently reported as dominant symptoms for all ages. Other dominant symptoms that were not consistent across age groups were anxiety, low mood, poor appetite, breathing issues and vision issues. In addition to the 36-45 years and 46-50 years groups, anxiety was a dominant symptom for pts aged 19-25 years. Along with other changes that could occur at this age, a recent transition from pediatric to adult care may contribute to anxiety being a dominant symptom; however, any direct relationship between anxiety and transitioning between care systems requires further investigation. The consistent reporting of low mood among adults, but not pediatrics, may reflect the increasing burden of disease that occurs with age. This is supported by higher proportions of pts aged ≥46 years versus &amp;amp;lt;45 years reporting a high impact on emotional wellbeing and daily life. Improving QoL was consistently ranked the most important treatment goal for pts. This emphasizes, from the pt&amp;#39;s perspective, the need for further improvements in the management of SCD. Disclosures Colombatti: Global Blood Therapeutics: Membership on an entity&amp;#39;s Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity&amp;#39;s Board of Directors or advisory committees; Addmedica: Membership on an entity&amp;#39;s Board of Directors or advisory committees. James:Sickle Cell Society: Current Employment; Novartis: Honoraria. Andemariam:Hemanext: Membership on an entity&amp;#39;s Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity&amp;#39;s Board of Directors or…
Abstract: Standardizing Body Surface Area (BSA) determination is essential for avoiding variation... more Abstract: Standardizing Body Surface Area (BSA) determination is essential for avoiding variation in chemotherapy dosage calculations. In this study we compared variation in BSA calculation using weight and height by the Mosteller formula with weight alone using recently adapted table at the Princess Norah Oncology Center (PNOC). Methods: Cross-sectional study of pediatric oncology patients presenting to the pediatric oncology clinic at PNOC over a week period of time. Results: One hundred consecutive pediatric oncology patients presented to the clinic. The mean BSA calculated by the Mosteller formula was 0.83m2 (Standard Deviation = 0.24) and the mean BSA determined by the table (based on weight alone) was 0.82m2 (Standard Deviation = 0.25). The mean variation in dosing between the two methods was 1.64% (Standard Deviation = 3.4). Only 13 out of 100 patients (13%) had equal dosing using both methods and 21 out of 100 patients (21%) had dosing variation greater than 5%. When comparing both methods, using paired t-test, the difference was statistically significant (t(99) = 3.99 and P &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Conclusion: Significant differences in BSA-based chemotherapy dosing exist in our center. The Mosteller method should remain the standard until prospective studies are performed to determine the significance of this dosing variability on toxicity and survival outcome.
Complex regional pain syndrome, characterized by pain, autonomic dysfunction, and decreased range... more Complex regional pain syndrome, characterized by pain, autonomic dysfunction, and decreased range of motion, developed after hepatitis B vaccination in four grade-6 children since the introduction of the vaccination program in British Columbia in 1992. The reaction may result from injection trauma or may be secondary to a vaccine constituent.
The prevalence of obstructive sleep apnea syndrome (OSAS) is elevated in some high-risk populatio... more The prevalence of obstructive sleep apnea syndrome (OSAS) is elevated in some high-risk populations. Children with sickle cell disease (SCD) are known to have many comorbidities, including OSAS. The objectives of this study were to assess the prevalence of and risk factors for OSAS among children with SCD in two major tertiary health care facilities in Jeddah, Saudi Arabia. This multicenter cross-sectional study took place in two major tertiary health care facilities—King Abdulaziz University Hospital and King Khalid National Guard Hospital, Jeddah, Saudi Arabia. Children with SCD who were admitted between January 2010 and December 2017 were enrolled. The Pediatric Sleep Questionnaire (PSQ) was used to screen for OSAS. Data were collected from 150 children with SCD aged between 2 and 18 years. Eighty-five percent of the children had sickle cell anemia (SCA) with HbSS, and the rest had sickle beta-thalassemia (HbS/ß-thalassemia). Based on the PSQ, 33 of the 150 (22%) children had OSAS (score ≥ 7). The average score on the PSQ was 3.8/22 (± 3.8). A history of adenotonsillar hypertrophy was found to be a significant risk factor in bivariate and multivariate analyses [aOR 5.5; 95% CI 1.84–16.35 ( P < 0.001)]. The odds of having OSAS were ninefold higher in children who had periodic limb movements than in those who did not after adjustment [95% CI 1.75–48.03 ( P < 0.001)]. OSAS is a highly prevalent disease among children with SCD. Many factors were associated with OSAS in the bivariate analysis, including nationality, education level, a history of adenotonsillar hypertrophy, and a history of periodic limb movements.
Journal of Pediatric Hematology Oncology, Mar 1, 2012
An 8-year-old, human immune virus-negative boy received full human leukocyte antigen-matched rela... more An 8-year-old, human immune virus-negative boy received full human leukocyte antigen-matched related allogenic hematopoietic stem cell transplantation (HSCT) for relapsed acute myeloid leukemia. While on cyclosporine A and prednisolone therapy for graft versus host disease, he developed extensive gingival, cutaneous, and respiratory tract human herpes virus-8-associated Kaposi sarcoma (KS). Withdrawal of cyclosporine, tapering of prednisolone, recovery of lymphocyte count, and local supportive measures resulted in resolution of his gingival and respiratory tract lesions. To our knowledge this is the first case of gingival and extensive respiratory tract KS to be reported in a child post HSCT.
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