Association between Neonatal Abstinence Syndrome and Congenital Anomalies in the United States.

OBJECTIVE: Studies exploring the relationship between neonatal abstinence syndrome (NAS) and congenital anomalies (CA) in the United States are limited given the small sample size or data prior to the opioid epidemic. We aimed to determine if there is an association between NAS and CA in a nationally representative cohort of newborn hospitalization in the United States. STUDY DESIGN: This was a cross-sectional analysis of NAS-related hospitalizations within the 2016 Kids Inpatient Database. International Classification of Diseases (ICD-10-CM) diagnostic codes were used to identify NAS hospitalizations and those with and without CA. The primary outcome was the odds of CAs in NAS hospitalizations. Multivariate survey logistic regression was used to analyze the relationship between NAS and CA. RESULTS: Among 3.7 million newborn hospitalizations, 25,394 had NAS (6.7 per 1,000). The prevalence of any CA was higher in those with NAS when compared with non-NAS hospitalizations (10.3 vs. 4.9%; odds ratio = 2.27; 95% confidence interval [CI]: 2.13-2.43). Adjusted analysis showed similar results (adjusted odds ratio: = 1.83, CI: 1.71-1.95). NAS hospitalizations with CA had a higher mortality rate (0.6 vs 0.04%, p < 0.0001) and higher resource use. CONCLUSION: This nationwide study shows that NAS may be associated with increased odds of CAs, suggesting that NAS may be a risk factor for increased morbidity in the newborn period. KEY POINTS: · 1 in 10 newborns with NAS had at least one congenital anomaly.. · NAS hospitalization with congenital anomalies had higher resource use and mortality.. · Pediatricians caring for newborns with NAS should have a high index of suspicion for birth defects..

Temporal Trends of Pediatric Hospitalizations with Acute Disseminated Encephalomyelitis in the United States: An Analysis from 2006 to 2014 using National Inpatient Sample.

OBJECTIVE: To determine the temporal trends in the epidemiology of acute disseminated encephalomyelitis (ADEM) and hospitalization outcomes in the US from 2006 through 2014. STUDY DESIGN: Pediatric (≤18 years of age) hospitalizations with ADEM discharge diagnosis were identified from the National (Nationwide) Inpatient Sample (NIS) for years 2006 through 2014. Trends in the incidence of ADEM with respect to age, sex, race, and region were examined. Outcomes of ADEM in terms of mortality, length of stay (LOS), cost of hospitalization, and seasonal variation were analyzed. NIS includes sampling weight. These weights were used to generate national estimates. P value of < .05 was considered significant. RESULTS: Overall incidence of ADEM associated pediatric hospitalizations from 2006 through 2014 was 0.5 per 100 000 population. Between 2006 through 2008 and 2012 through 2014, the incidence of ADEM increased from 0.4 to 0.6 per 100 000 (P-trend <.001). Black and Hispanic children had a significantly increased incidence of ADEM during the study period (0.2-0.5 per 100 000 population). There was no sex preponderance and 67% of ADEM hospitalizations were in patients <9 years old. From 2006 through 2008 to 2012 through 2014 (1.1%-1.5%; P-trend 0.07) and median LOS (4.8-5.5 days; Ptrend = .3) remained stable. However, median inflation adjusted cost increased from $11 594 in 2006 through 2008 to $16 193 in 2012 through 2014 (Ptrend = .002). CONCLUSION: In this large nationwide cohort of ADEM hospitalizations, the incidence of ADEM increased during the study period. Mortality and LOS have remained stable over time, but inflation adjusted cost of hospitalizations increased.

National Trends in Hospitalization for Fever and Neutropenia in Children with Cancer, 2007-2014.

OBJECTIVE: To assess the trends of inpatient resource use and mortality in pediatric hospitalizations for fever with neutropenia in the US from 2007 to 2014. STUDY DESIGN: Using National (Nationwide) Inpatient Sample (NIS) and International Classification of Diseases, Ninth Revision, Clinical Modification codes, we studied pediatric cancer hospitalizations with fever with neutropenia between 2007 and 2014. Using appropriate weights for each NIS discharge, we created national estimates of median cost, length of stay, and in-hospital mortality rates. RESULTS: Between 2007 and 2014, there were 104 315 hospitalizations for pediatric fever with neutropenia. The number of weighted fever with neutropenia hospitalizations increased from 12.9 (2007) to 18.1 (2014) per 100 000 US population. A significant increase in fever with neutropenia hospitalizations trend was seen in the 5- to 14-year age group, male sex, all races, and in Midwest and Western US hospital regions. Overall mortality rate remained low at 0.75%, and the 15- to 19-year age group was at significantly greater risk of mortality (OR 2.23, 95% CI 1.36-3.68, P = .002). Sepsis, pneumonia, meningitis, and mycosis were the comorbidities with greater risk of mortality during fever with neutropenia hospitalizations. Median length of stay (2007: 4 days, 2014: 5 days, P < .001) and cost of hospitalization (2007: $8771, 2014: $11 202, P < .001) also significantly increased during the study period. CONCLUSIONS: Our study provides information regarding inpatient use associated with fever with neutropenia in pediatric hospitalizations. Continued research is needed to develop standardized risk stratification and cost-effective treatment strategies for fever with neutropenia hospitalizations considering increasing costs reported in our study. Future studies also are needed to address the greater observed mortality in adolescents with cancer.

Temporal trends of splenectomy in pediatric hospitalizations with immune thrombocytopenia.

BACKGROUND: Splenectomy is considered an effective treatment for immune thrombocytopenia (ITP) with 70-80% response rate. However, its current use is limited in children with ITP. It is unclear if the rates of splenectomy have changed over time. Using a large nationally representative database, we aimed to study the trends of splenectomy in pediatric hospitalizations with ITP, and the factors associated with splenectomy during these encounters. METHODS: Using National (Nationwide) Inpatient Sample (NIS), and international classification of diseases (9th revision), clinical modification (ICD-9-CM) codes, we studied pediatric ITP hospitalizations with occurrence of total splenectomy between 2005 and 2014. RESULTS: Out of 37,844 weighted ITP hospitalizations from 2005 to 2014; total splenectomy was performed in 954 encounters. Splenectomy rate declined over time (3.4% [2005-2006] to 1.6% [2013-2014], P < 0.001) with the younger age (≤5 years) having the most notable decline (0.91% [2005-2006] to 0.14% [2013-2014], P < 0.001). Splenectomy had higher odds of being performed electively than non-electively (odds ratio [OR]: 19.34, 95% confidence interval [CI]: 12.06-31.02, P < 0.001). Encounters with intracranial bleed were associated with the occurrence of splenectomy (OR: 17.87, 95% CI: 5.07-62.97, P < 0.001). Intracranial bleed (P < 0.001), gastrointestinal bleed (P < 0.01), sepsis (P < 0.001), and thrombosis (P < 0.001) were associated with longer length of stay and higher cost of hospitalization. CONCLUSIONS: Overall, splenectomy rates consistently declined over time. Intracranial hemorrhage during hospitalizations with ITP was associated with occurrence of splenectomy. Future studies should continue to reevaluate the rates of splenectomy in pediatric ITP in the presence of various second-line pharmacologic agents.

Effectiveness of Three Prognostic Scoring Systems in Predicting the Response and Outcome in Pediatric Chronic Myeloid Leukemia Chronic Phase on Frontline Imatinib.

INTRODUCTION: The Sokal and Hasford (Euro) scores were developed in the chemotherapy and interferon eras and are widely used as prognostic indicators in patients with chronic myeloid leukemia (CML). Recently, European Treatment and Outcome Study (EUTOS) scoring system was introduced. Data on risk stratification in pediatric CML population was lacking due to its rarity (<3%). OBJECTIVE: To study the effectiveness in predicting the response and outcome with three prognostic scores in pediatric CML-chronic phase patients on front line Imatinib. Materials and Methods: We retrospectively analyzed the hospital records of newly diagnosed CML CP patients (aged ≤18 years) from 2006 to 2010 for their risk score, cytogenetic response at 18 months and event free survival (EFS) at the end of 4 years. Events include loss of hematological response, loss of cytological response, progression to accelerated/blast phase (AP/BC). All received free Imatinib under Gleevac international patient assistance program. RESULTS: Data of 106 children was analyzed with median age of 13.5 (ranged 5-18 years) and male preponderance (M:F = 1.14:1). The distribution of children was 63%, 32% and 5% in Sokal low, intermediate and high risk respectively, 50%, 43% and 5% in Hasford/Euro low, intermediate and high risk respectively, 71% and 29% in EUTOS low and high risk respectively. The overall cumulative complete hematological response at the end of 3 month was 94%, and complete cytogenetic response at 12 months was 75%. The CCyR at 18 month was seen in 90%,74% and 83% among Sokal low, intermediate and high risk groups respectively, 83%, 86% and 83% among Hasford/Euro low, intermediate and high risk groups respectively, 84% and 86% EUTOS low and high risk groups respectively. The EFS at the end of 48 months was seen in 87%,79% and 83% among Sokal low, intermediate and high risk groups respectively, 83%, 86% and 83% among Hasford/Euro low, intermediate and high risk groups respectively, 86% and 80% EUTOS low and high risk groups respectively. CONCLUSION: None of the scoring systems predicted the response and outcome effectively in children with CML CP on front line Imatinib.

Renal Lymphoma: Primary or First Manifestation of Aggressive Pediatric B-cell Lymphoma.

Renal lymphoma is an uncommon renal tumor in children. Unlike renal lymphomas presenting as bilateral disease and renal failure, we report a boy who presented with unilateral renal involvement. After initial nephrectomy, he achieved remission with multiagent chemotherapy but relapsed systemically within 3 months. He was initiated on salvage chemotherapy with autologous bone marrow transplant. Even though the initial manifestation was localized lymphoma eventually, it turned out to be a systemic disease. He succumbed to disease at 14 months from diagnosis.

Impact of treatment protocol on outcome of localized Ewing's sarcoma.

BACKGROUND: The outcome of localized Ewing's sarcoma has improved with multi-disciplinary approach. Survivals of Ewing's sarcoma from the Asian countries differed between centers. METHODS: We retrospectively analyzed the records of newly diagnosed localized Ewing's sarcoma patients from 2002 to 2012. The patients were analyzed in three groups; Group 1(2002-2004) who received non-ifosfomide based regimens, Group 2(2005-2008) who received VDC/IE for 12 cycles, and Group 3(2009-2012), who received VDC/IE for 17 cycles. The groups were compared for their baseline characteristics, treatment protocol and outcome. RESULTS: Seventy three patients were included in the study. The median age of presentation was 15 years, with slight male predominance. Axial primary was seen in 62%. The median RFS of the three groups was 26.4, 31.4 and 36.8 months respectively (P = 0.0018). The median OS was 27.9, 35 and 43 months respectively (P = 0.0007). At a median follow-up of 35 months, the 3 year RFS and OS for the three treatment groups were 17%, 31%, 60% and 35%, 45% and 70% respectively. Larger tumor size, axial primary, high LDH were associated with poorer survival. Radiotherapy was associated with inferior local control and survival. CONCLUSIONS: We found that the survival of our ESFT patients improved over time with intensified multiagent chemotherapy and with lesser time to local therapy. But the results were still inferior to those reported in literature. We had majority of patients presenting in axial site and radiotherapy as the predominant mode of local control. The outcome may further improve with surgery as local control procedure.

Trends in management of acute lymphoblastic leukemia: Influence of insurance based healthcare and treatment compliance on the outcome of adolescents and adults with acute lymphoblastic leukemia.

AIM: In this study, we attempted to analyze the impact of insurance based health care system and treatment compliance on the outcome of adolescent and adults with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Patients who underwent treatment for ALL during the period 2003-2011 were enrolled into this retrospective study. Patients on supportive or palliative care only and patients with age <10 years were excluded. The hospital records and tumor registry records were studied. Patients were stratified into two groups, Group A (prior to the introduction of state health insurance [SHI], 2003-2007) and Group B (after the introduction of SHI, 2008-2011). Overall survival (OS) was calculated using Kaplan-Meier method. RESULTS: A total of 420 patients with suspected or confirmed ALL visited our center during the study period and 179 patients (87 in Group A and 92 in Group B) were considered for inclusion. The median age in years (range) was 18 (10-57) and 18 (10-58) respectively in Groups A and B with males more than females. Median OS (95% CI) was 9 (6.7-11.2) and 12 (7.3-16.7) months in the Groups A and B respectively (P = 0.265). Poor treatment compliance in both groups was high (36% in Group A and 41% in Group B, [P = 0.107]) with lower default rates in Group B (P = 0.019). Patients with good compliance in the total study population and the individual study groups had significantly better OS. CONCLUSIONS: Insurance based health care has improved outcomes in the present study but not compliance to treatment. Significantly better OS was observed in patients with good compliance.

Clinicopathological features and outcomes in advanced nonsmall cell lung cancer with tailored therapy.

CONTEXT: Lung cancer is an important cause of cancer-related deaths worldwide. There is an increasing incidence of lung cancer in never smokers and a shift of histology from squamous cell to adenocarcinoma globally in the recent past. Data on treatment outcomes with newer platinum doublets is scant from India. AIMS: To study the clinicopathological features, response rates (RRs), progression-free survival (PFS), overall survival (OS), and the 1, 2, and 3 years survival, in patients with advanced nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: Data of all patients who received chemotherapy for Stage IIIB and IV NSCLC between January 2010 and June 2014 were retrospectively analyzed. STATISTICAL ANALYSIS USED: Univariate analysis for OS was done by plotting Kaplan-Meier curves and the log-rank test was used to calculate P values. Logistic regression analysis for OS was carried out using MedCalc statistical software. RESULTS: A total of 353 patients received chemotherapy. Of these, 256 were evaluable for outcome parameters. The median age at presentation was 58 years with a male:female ratio of 2.53:1. The smoker:nonsmoker ratio was 1:1. Adenocarcinomatous histology was the most common both in smokers and nonsmokers reported in 70.8% patients. Epidermal growth factor receptor (EGFR) mutation and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase translocation were seen in 35% and 3% of patients, respectively. The RR, median PFS, OS, 1, 2, and 3 years survival were 80%, 8 months, 12.1 months, 51.5%, 12.7%, and 4.2%, respectively. There was no significant survival difference among the treatment regimen used but the response to I line chemotherapy impacted survival. Female gender, performance status, and nonsquamous histology were significant predictors of OS (P = 0.0443, P = 0.0003, P = 0.048, respectively). CONCLUSIONS: There was an increase in the incidence of nonsmokers. Adenocarcinoma was the most common histology in both smokers and nonsmokers. Treatment outcomes in advanced lung cancer were better compared to the past with the advent of newer platinum doublets and EGFR tyrosine kinase inhibitors. The response to first-line chemotherapy significantly impacts outcomes in advanced NSCLC.

Managing metastatic renal cell carcinoma-challenges, pitfalls, and outcomes in the real world.

INTRODUCTION: Renal cell carcinoma (RCC) is the most common cancer of the kidney accounting for 85% of renal tumors. Metastatic RCC (mRCC) had a poor prognosis and with the introduction of tyrosine-kinase inhibitors, such as sunitinib, pazopanib the outcomes improved. There is only one study reported from India on the use of sunitinib in mRCC. We present our analysis of mRCC and use of sunitinib at our institute over 5 years. MATERIALS AND METHODS: All patients with mRCC receiving sunitinib were analyzed with respect to patient characteristics, response, toxicity, and outcomes. RESULTS: A total of 108 patients were seen during the study period. The male to female ratio was 9.8:1. The median age of patients at presentation was 58 years (range: 15-80 years). Of the 108 patients, 68.51% had metastatic disease at initial presentation. The most common sites of metastases were lung followed by bone. Of the 97 patients eligible for sunitinib, only 76 received at least one cycle of sunitinib, out of which only 48 received further cycles (range: 2-36). The median progression-free survival (PFS) and overall survival (OS) in our patients were 10.2 and 28.2 months, respectively. The most common adverse effect noticed in our population was mucositis followed by hand-foot syndrome. CONCLUSION: Sunitinib is an option for the treatment of mRCC and shows a good PFS in Indian patients. Median OS and PFS in this study are similar to other reported studies despite the presence of poor risk factors in the patient population. The pitfall in this study is significant attrition due to poor compliance to treatment and follow-up, which is a major factor in the clinic thereby compromising outcomes.

Prevalence and outcome of epidermal growth factor receptor mutations in non-squamous non-small cell lung cancer patients.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation analysis has become an important part of the initial workup of non-squamous non-small cell lung cancer (NS-NSCLC) patients as it is now recognized both as a prognostic and predictive marker to therapy with EGFR tyrosine kinase inhibitors (TKI). AIM: In this retrospective study conducted at a University hospital, we evaluated the prevalence of EGFR mutations in patients with NS-NSCLC, clinico-pathological correlation and outcome to treatment with EGFR TKIs. MATERIALS AND METHODS: Case records of 147 patients of NS-NSCLC in whom EGFR mutation status was tested were screened. EGFR mutation analysis was done using DNA sequencing by real time polymerase chain reaction method from tissue and cell blocks prepared from core biopsy, fine needle aspiration cytology and pleural fluid specimens. RESULTS: EGFR mutations were seen in 30.6% of the 111 evaluable specimens, with a significantly higher rate in females (44% vs 19.6% P = 0.0072) as compared to men and non-smokers (41% vs 12% P = 0.0013) as against smokers. Most common mutations were observed in exons 19 (71%) and 21 (25%). The estimated median progression free survival for patients with and without mutations when treated with upfront TKIs was 12 months and 3 months respectively and the estimated median overall survival for patients with and without mutations was 20 and 9 months respectively. CONCLUSION: This study from India, further establishes the importance of upfront EGFR mutation testing in all NS-NSCLC patients, not only to prognosticate, but also to identify that subset of patients who could benefit from EGFR TKI therapy, early in the course of their disease.

Clinical profile and outcome of adult Hodgkin lymphoma: Experience from a tertiary care institution.

UNLABELLED: Treatment and outcome of Hodgkin lymphoma (HL) are the true success story of modern medicine. The data from the developing countries on long-term outcome of patients with HL is sparse. AIMS: Primary objective is to assess the progression-free survival (PFS). Secondary objective are overall survival (OS) and toxicities. SETTINGS AND DESIGN: This is a retrospective analysis from the case records from a single institution. MATERIALS AND METHODS: Institutional Ethical Committee approval was obtained. Between January 1991 and December 2010, 301 patients (age ≥18 years) underwent treatment at our institution. STATISTICAL ANALYSIS: Kaplan-Meyer curves were used to calculate the PFS and OS. RESULTS: The median age at presentation was 36 years, range from 19 to 75 years. The male to female ratio was 2.9:1. Seventy-five percent of patients had B symptoms. Majority presented in advanced stage (Stage III and IV) disease (64.7%). Mixed cellularity (74.4%) was the most common histology, followed by nodular sclerosis (13.9%). The most common chemotherapy regimen used was ABVD (61%). CONCLUSIONS: Median follow-up of the cohort was 18.5 months (range 2-225). PFS and OS rate at 5 years is 66.3% and 79.7% respectively.

Thiopurine methyltransferase polymorphisms in children with acute lymphoblastic leukemia.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. 6-mercaptopurine (6-MP) and methotrexate are backbone drugs for maintenance phase of treatment. Purine Analogs 6-MP/6-thioguanine/azathiopurine are metabolized to its inactive form by the enzyme thiopurine methyltransferase (TPMT). Ninety percent of the population harbor wild type on both alleles (TPMT wild/wild), 10% are heterozygous, that is, one allele is mutant (TPMT wild/mutant) and 0.3% are homozygous, that is, both allele are mutant (TPMT mutant/mutant). In heterozygous and homozygous variant, activity of enzyme is low, leading to a higher incidence of toxicity (myelosuppression). AIM: The primary objective was to access the polymorphism of the enzyme, TPMT, in Children with ALL. Secondary objective was to correlate TPMT genotype with 6-MP toxicities. MATERIALS AND METHODS: Seventy-two children with newly diagnosed ALL during first maintenance phase were serially enrolled after obtaining consent. Five ml of peripheral blood was drawn and DNA extracted. TPMT 2 polymorphisms were performed using Allele specific polymerase chain reaction (PCR) and TPMT 3B and 3C are performed by PCR-restriction fragment length polymorphism. RESULTS: Sixty-nine children of 72 (95.8%) were wild for TPMT polymorphism and 3 (4.2%) were heterozygous for TPMT. Among the heterozygous variant one each (33.3%) were heterozygous for 2A, 3A, 3C. Febrile neutropenia was the most common toxicity in both wild and heterozygous group. CONCLUSION: The frequency of TPMT polymorphisms in children with ALL is 4.2%. Heterozygous variant is this study are one each (33%) of 2A, 3A, 3C.

Response to imatinib mesylate in childhood chronic myeloid leukemia in chronic phase.

INTRODUCTION: Childhood chronic myeloid leukemia (CML) accounts for less than 3% of all childhood leukemias, hence, data on imatinib (IM) in adult CML patients has been largely extrapolated to children. We have analyzed our data to add to the existing literature. AIMS: Primary objective is to assess the progression-free survival (PFS). Secondary objective are cytogenetic response, overall survival (OS), and toxicities. SETTINGS AND DESIGN: This is a retrospective analysis from the case records from a single institution. MATERIALS AND METHODS: Institutional ethics committee approval was obtained. All the children diagnosed CML in chronic phase (CML-CP) aged less than 18 years registered between 2000 and 2009 were enrolled. All the patients were started on IM at 260 mg/m(2). STATISTICAL ANALYSIS: Kaplan-Meier curves were used to calculate the PFS and OS. RESULTS: There were 64 children with median age of 13 years (range, 1-18) with male predominance (male:female (M: F) - 1.85:1). Sixty-one patients (95.4%) achieved complete hematological response (CHR) at median of 8 weeks. Thirty-seven (57.8%) patients had evaluation of cytogenetic response and were subjects for outcome analysis. The median time to best cytogenetic response evaluation was 13 months (range, 4-52). Twenty-nine patients (78.3%) achieved complete cytogenetic response (CCyR). At a median follow-up of 36 months (range 5-75), 21 (56.8%) remained progression free and 35 (94.5%) are alive. Adverse events were tolerable. CONCLUSIONS: PFS at a median follow-up of 36 months is 56.8% and OS 94.5%.

Incidence of Bcr-Abl kinase domain mutations in imatinib refractory chronic myeloid leukemia patients from South India.

Mutations in the Bcr-Abl kinase domain (KD) are a major cause for acquired resistance to imatinib (IM) treatment and have been associated with progression and poor prognosis in chronic myeloid leukemia patients. The present study includes 63 patients resistant to standard imatinib dose of 400 mg according to ELN guidelines. Direct sequencing method is used for mutational analysis. The present study revealed 15 exonic mutations in 46.03 % of patients; among them, seven cases (24.13 %) had multiple mutations. Mutations were found to be higher in sokal high- (45.0 %) and intermediate- (68.42 %) compared to low-risk (29.16 %) group. Mutations were observed in 38.09 % of patients with EUTOS (European Treatment and Outcome Study) high risk and in 50.0 % with low risk. The frequency of mutations was 50.0 % in advanced phase, 47.36 % in late chronic-phase, and 43.33 % in chronic-phase patients. 42.10 % of patients with primary resistance and 52.0 % with secondary resistance had mutations. P-loop and T315I mutations were associated with poor survival in advanced phase patients (85.71 %) (P = 0.03). No significant variation was observed with Bcr-Abl transcript levels between the patients with the presence or absence of mutations (P = 0.73). Bcr-Abl levels were found to be significantly elevated in P-loop and T315I mutation carriers (P = 0.001) and also in T315I mutation-positive patients (P = 0.01). P-loop mutations and T315I are frequent in advanced phases and strongly associated with poor prognosis and survival. Hence, the identification of mutations in IM-resistant CML patients will help in treatment optimization with 2nd- or 3rd-generation tyrosine kinase inhibitors (TKIs).

Early molecular response in chronic myeloid leukemia patients predicts future response status.

Imatinib is the frontline therapy for chronic myeloid leukemia (CML) management. Most of the CML patients achieve major responses, but a proportion (nearly 25-35%) of them develop drug resistance. Molecular monitoring using quantitative real-time PCR at regular intervals according to European LeukemiaNet (ELN) helps in the assessment of long-term outcomes in imatinib-treated CML patients. Eighty-four CML patient samples (42 at diagnosis and 42 at 3-month intervals from the same patients) were analyzed for Bcr-Abl transcript levels. Quantification results revealed that the patients with <10% Bcr-Abl levels at 3 months had higher rates of complete cytogenetic response (CCyR) and optimal responses compared to patients with >10% Bcr-Abl levels (P < 0.0001). Patients with >10% Bcr-Abl levels were found to have 25.0% of suboptimal response and 3.57% of failure to imatinib at standard dose. Hence, the present study confirms that early molecular monitoring at 3 months after imatinib initiation helps in predicting the concurrent cytogenetic response and treatment optimization in CML patients.

Nutritional assessment of children with hematological malignancies and their subsequent tolerance to chemotherapy.

BACKGROUND: Our research goals were to assess the prevalence of malnutrition in children with cancer, observe malnutrition's effect on tolerance to chemotherapy, and establish malnutrition at onset as one of the prognostic factors in children with hematological malignancies. METHODS: This prospective study examined children ages 1-15 years with a confirmed diagnosis of acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma. Each child was subjected to a detailed history, anthropometric examination, and laboratory investigations. Based on the anthropometric measurements that used weight-for-age Z scores, we divided the children into 4 groups: group 1, without malnutrition; group 2, mild malnutrition; group 3, moderate malnutrition; and group 4, severe malnutrition. We analyzed data for each group regarding the behavior of blood indices, the quantum of hematological support, bone marrow remission status on day 28, adherence to protocol schedules, and complications in the first 4 months of intensive chemotherapy. RESULTS: Of the 34 patients in the study (mean age, 7.1 years; male:female ratio, 1.6:1), 79% had deficient calorie intake and 74% had deficient protein intake. Packed cell requirements and complications were significantly higher in malnourished children, whereas the requirement for platelet transfusions was statistically insignificant. Also, 50%, 40%, 38%, and 44% of children in groups 1, 2, 3, and 4, respectively, completed chemotherapy within the specified time period. At the end of the induction phase, 92%, 60%, 87%, and 77% of the patients in groups 1, 2, 3, and 4, respectively, achieved bone marrow remission. No deaths occurred in group 1; 1 death each occurred in groups 3 and 4, and 2 in group 2. When these deaths were extrapolated to the weight/height ratio (acute malnutrition), we found that all occurred in children with malnutrition, a statistically significant result. CONCLUSIONS: Malnutrition is widely prevalent in children with ALL in India and has a significant bearing on the occurrence of life-threatening complications and short-term outcomes in these children. Malnutrition is also a significant factor influencing treatment planning and therapeutic decisions.

Genetic variants of thiopurine and folate metabolic pathways determine 6-MP-mediated hematological toxicity in childhood ALL.

AIM: The rationale of this study was to explore the contribution of genetic variants of the folate pathway to toxicity of 6-mercaptopurine (6-MP)-mediated hematological toxicity in children with acute lymphoblastic leukemia (ALL) and to explore the interaction of these variants with TPMT and ITPA haplotypes using multifactor dimensionality reduction analysis. MATERIALS & METHODS: Children with ALL (n = 96) were screened for GCPII C1561T, RFC1 G80A, cSHMT C1420T, TYMS 5´-UTR 2R3R, TYMS 3´-UTR ins6/del6, MTHFR C677T, MTR A2756G polymorphisms using PCR-RFLP and PCR-amplified fragment length polymorphism techniques. RESULTS: GCPII C1561T showed independent association with toxicity. The following synergetic interactions appeared to increase the toxicity of 6-mercaptopurine: TPMT*12 × RFC1 G80A; TPMT CTTAT haplotype × RFC1 G80A; TPMT CTTAT haplotype × RFC1 G80A × TYMS 2R3R. The genetic variants of thiopurine and folate pathway cumulatively appeared to increase the predictability of toxicity (r(2) = 0.41) in a multiple linear regression model. For the observed toxicity grades of 1, 2, 3 and 4, the respective predicted toxicity grades were 1.65 ± 0.29, 1.68 ± 0.24, 2.56 ± 0.58 and 2.99 ± 1.03, p(trend) < 0.0001. CONCLUSION: Gene-gene interaction between thiopurine and folate pathways inflate the 6-MP-mediated toxicity in Indian children with ALL illustrating the importance of ethnicity in the toxicity of 6-MP.