Impact of Malnutrition on Treatment Outcome of Paediatric Acute Myeloid Leukemia.

OBJECTIVE: To analyse the distribution of malnutrition in paediatric acute myeloid leukaemia (AML) and its effect on treatment outcome and survival in Pakistani children. STUDY DESIGN: Descriptive, analytical study. PLACE AND DURATION OF STUDY: Department of Paediatric Oncology, Combined Military Hospital (CMH), Rawalpindi, Pakistan from January 2012 to January 2019. METHODOLOGY: Data of all newly registered cases of paediatric AML was analysed to see the association of nutritional status according to Z-score classification and treatment outcome. The outcome was divided into disease-free and overall survival. RESULTS: A total of 206 cases, including 130 (63.1%) boys and 76 (36.9%) girls were evaluated. The mean age at diagnosis was 5.96 ± 3.58 years. Pallor was the most common clinical feature in 172 (83.5%) followed by fever in 158 (76.7%) cases. AML M-2 was the most frequent French-American-British (FAB) subtype in 94 (45.6%) cases. Majority of the patients (n = 128, 62.1%) were well nourished; and 46 (22.3%) and 32 (15.5%) were moderately and severely malnourished, respectively. Disease-free survival (DFS) was 43.0%, 32.6% and 21.9% in well nourished, moderately malnourished and severely malnourished patients, respectively (p=0.022). Overall survival (OS) was 43.8%, 39.1% and 21.9% in well nourished, moderately malnourished and severely malnourished patients, respectively (p=0.012). CONCLUSION: Malnutrition adversely affects the treatment outcome in paediatric AML. It is significantly associated with increased treatment-related mortality, mainly due to infection and decreased disease-free and overall survival. Key Words: Paediatric acute myeloid leukaemia, Mortality, Nutritional status, Weight-for-age, Z score, Pakistan.

Prognostic Factors in Childhood Acute Myeloid Leukemia; Experience from A Developing Country.

BACKGROUND: In the developed world, 5-years survival of childhood acute myeloid leukaemia (AML) has improved to 70%. However, the survival rates in the developing world are below 40%. The main contributing factors to these reduced survival rates are a late presentation, malnutrition and high treatment-related mortality. AIM: To document the factors affecting treatment outcome of childhood AML at a tertiary care facility of Pakistan. METHODS AND RESULTS: All newly registered cases of AML under 18 years of age from January 1, 2012 onwards who completed their treatment before November 30, 2019 were included. Data of 219 cases of AML containing 140 (63.9%) males and 79 (36.1%) females was analyzed. The mean age was 6.30 ± 3.66 years. Pallor was the commonest presenting features in 180 (82.2%) and M2 was the commonest French American-British (FAB) subtype in 103 (47.0%) cases. In univariate analysis, high white blood cells (WBC) count at presentation (P = .006), poor nutritional status (P = .005), unfavourable cytogenetics (P = .019), certain types of FAB AML subtype (P = .005), and use of etoposide in induction chemotherapy (P = .042) significantly adversely affected overall survival (OS). Neutropenic sepsis and bleeding were the major causes of treatment-related mortality. Response to induction chemotherapy was the most significant prognostic factor in the multivariate analysis (P = <.001). After a median follow-up of 40.96 ± 26.23 months, 5-year OS and DFS of the cohort were 40.6% and 38.3% respectively. CONCLUSIONS: In this largest cohort of childhood AML from Pakistan, high WBC count at presentation, malnutrition, unfavourable cytogenetics and use of etoposide during induction chemotherapy were associated with decreased OS and DFS rates. Response to the induction chemotherapy was the most significant prognostic factor.

Cytogenetic Abnormalities and Their Impact on Treatment Outcome in Paediatric Acute Myeloid Leukaemia in Pakistan.

OBJECTIVE: To determine the impact of cytogenetic abnormalities on the treatment outcome of paediatric acute myeloid leukaemia (AML) at a tertiary care facility of Pakistan. STUDY DESIGN: Retrospective Observational study. PLACE AND DURATION OF STUDY: Paediatric Oncology Ward, Combined Military Hospital, Rawalpindi, from January 2012 to September 2019. METHODOLOGY: All registered cases of AML under 18 years of age, admitted to paediatric oncology ward in Combined Military Hospital, Rawalpindi, who had completed their treatment before 30th September 2019 were included. Their demographic and clinical data including WBC counts, immunophenotyping, cytogenetic abnormalities and impact of cytogenetics on disease outcome was assessed. Data was analysed for descriptive statistics and association of proportions. RESULTS: Data of 138 cases of de novo AML including 90 (65.2%) males and 48 (34.8%) females were analysed. The mean age was 6.37 ±3.51 years. Initial WBC of more than 50x109/L was seen in 43 (31.2%) patients. The most common FAB subtype was M-2 in 74 (53.6%), followed by M-4 in 20 (14.5%) cases. The majority of cases 81 (58.7%) had normal cytogenetics followed by 42 (30.4%) favourable and 15 (10.8%) unfavourable abnormalities. Five-year overall survival was 82.4%, 56.5% and 55.6% for favourable, intermediate and unfavourable risk cytogenetics, respectively (p=0.039). Disease-free survival was 82.4%, 51.6% and 44.4% for favourable, intermediate and unfavourable risk cytogenetics (p=0.008). CONCLUSIONS: Identification of cytogenetic aberrations at diagnosis will help in risk stratification and predicting prognosis in AML. This will further assist in improving treatment strategies for different cytogenetic risk groups. Key Words: Paediatric acute myeloid leukaemia, Cytogenetics, Treatment outcome.

Optimum Induction Chemotherapy for Pediatric Acute Myeloid Leukemia: Experience From A Developing Country.

OBJECTIVES: Treatment outcome in children with acute myeloid leukemia (AML) has improved in the developed world but remains poor in developing countries. We assessed the role of etoposide in induction chemotherapy in pediatric AML. METHODS: This analysis retrospectively compared 2 induction chemotherapy regimens consisting of daunorubicin and cytarabine with etoposide (ADE) and without etoposide (AD). All newly diagnosed cases of AML younger than 18 years from January 1, 2012, onwards who completed their treatment before January 31, 2019, were included. Data of 186 cases, including 117 males (62.9%) and 69 females (37.1%), were analyzed. Demographic, initial presentation blood counts, and AML subtypes were almost identical in both groups. RESULTS: Complete remission rates were almost identical for the ADE versus the AD group (78.8% vs 80.0%, p = 0.980). Treatment-related mortality was higher, albeit not significantly, in the ADE (25 of 105; 23.8%) versus the AD (16 of 81; 19.8%) group (p = 0.508). Overall survival was 32 of 105 (30.5%) in the ADE and 43 of 81 (53.1%) in the AD group (p = 0.079), and disease-free survival was 29 of 105 (27.6%) and 39 of 81 (48.1%) in ADE and AD groups (p = 0.056), respectively. CONCLUSIONS: Etoposide in induction treatment of pediatric AML is associated with increased episodes of bacterial and fungal infections and high treatment-related mortality. Moreover, it does not offer any survival benefit. In low- and middle-income countries like Pakistan, it should not be used in the induction treatment protocol.

Predictors of treatment outcome of Wilms Tumour in low-income country; single centre experience from Pakistan.

BACKGROUND: Wilms tumor (WT) represents around 85% of pediatric renal tumors. In high-income countries, 5-years survival of WT is above 90% but survival in developing countries is inferior. OBJECTIVE: To identify the predictors of treatment outcome of WT in a developing country. METHODS: A retrospective study conducted at the pediatric oncology department, Combined Military Hospital Rawalpindi, Pakistan. All newly diagnosed WT cases from 1st January 2012 who completed their treatment before 31st August 2019 were evaluated. Treatment was based on SIOP Wilms Tumour 2001/UK version 5. Patients presenting before nephrectomy received pre-operative chemotherapy. The postoperative chemotherapy regimen was decided according to the stage, risk stratification and metastatic status of the patient. RESULTS: Data of 84 cases, including 40 (47.6%) males and 44 (52.4%) females was analyzed. The mean diagnostic age was 38.87 ± 28.66 months and 68 (81%) cases were less than five years of age. The commonest presenting features were abdominal mass in 75 (89.3%) cases. The right kidney was affected in 43 (51.2%) cases. Stage I disease was documented in 27 (32.1%) cases, stage II in 25 (29.8%), stage III in 13 (15.5%), and stage IV in 17 (20.2%) cases. In univariate analysis, advanced stage (P = < 0.001) and metastatic disease (P=< 0.001) adversely affected the treatment outcome. Multivariate analysis demonstrated that advanced stage WT was associated with the worst outcome (P= < 0.05). Four (4.8%) cases had treatment-related mortality (TRM). With a median follow-up time of 28.26 ± 23.03 months, OS and EFS were 66 (78.6%) and 63 (75.0%) respectively. DISCUSSION: Delayed presentation with advanced-stage metastatic disease is quite common in the developing courtiers and is the major contributor to decreased EFS and OS. In the present study, 20.2% cases had metastatic disease, which is similar to reported from other developing countries. OS decreased from 92.6% in stage I to 47.1% in stage IV disease (P=< 0.001) and EFS decreased from 92.6% in stage I to 43.8% in stage IV disease (P=< 0.001). Very similar results are reported by a regional study [17]. Results in stage I and II disease are comparable to documented in the western world and inferior in advanced-stage disease. The strength of the present study is that multiple factors, affecting the treatment outcome of WT over almost seven years period were evaluated. CONCLUSIONS: Stage of the disease is the most important prognostic factor. Delayed presentation with metastatic disease has a poor outcome.

Mortality in paediatric acute myeloid leukaemia.

OBJECTIVE: To analyse the common causes of death in paediatric acute myeloid leukaemia cases at a tertiary care facility. METHODOLOGY: The retrospective study was conducted at the Paediatric Oncology Department of the Combined Military Hospital, Rawalpindi, Pakistan, and comprised newly-registered cases of acute myeloid leukaemia aged <18 years from January 1, 2012, onwards and who completed their treatment before January 31, 2019. Data was retrieved from medical records and was analysed using SPSS 23. RESULTS: Of the 206 cases, 130(63.1%) were males and 76(36.9%) were females. Overall mean age at diagnosis was 5.96±3.57 years (range: 9 months to 15 years). Of the total, 6(2.9%) patients died before the start of treatment. Of the remaining, 43(21.5%) patients died during 1st induction chemotherapy, and 16(8%) during the post-induction period, with overall treatment-related mortality being 65(31.5%). The main cause of death during the first two weeks of induction was infection, while infection followed by multi-organ failure was the main cause of mortality in the second phase. A total of 130(63%) patients completed the treatment. Overall survival was 81(62.3%) while disease-free survival was 77 (59.2%). CONCLUSIONS: Overall treatment-related mortality rate in paediatric acute myeloid leukaemia cases was found to be high. Pregnancies achieved by IVF/ICSI, being complicated with severe OHSS could be related to gestational hypertension.