Sidharth Totadri

The deferiprone and deferasirox combination is efficacious in iron overloaded patients with β-thalassemia major: A prospective, single center, open-label study

The high cost, coupled with the need for continuous infusion, renders Desferrioxamine (DFO), a non‐feasible option for iron‐chelation in a large majority of patients with β‐thalassemia major in developing countries. Monotherapy with deferiprone (DFP) or deferasirox (DFX) may not always attain optimal control, particularly in heavily iron‐loaded patients. Combination of DFP and DFX is a potential alternative.

The 5-Year EFS of Multisystem LCH With Risk-Organ Involvement Is Suboptimal: A Single-center Experience From India.

The study describes an 8-year experience of a single center in managing patients with langerhans cell histiocytosis on the basis of the langerhans cell histiocytosis-III platform. A retrospective case-file review of children diagnosed during 2006 to 2013 was performed. Group 1 (multisystem with risk-organ involvement) patients received an initial treatment of 6 to 12 weeks, followed by continuation treatment to complete 12 months. Drugs included vinblastine, prednisolone, and 6-mercaptopurine. Group 2 (multisystem without risk-organ involvement) patients received a similar treatment, except for 6-mercaptopurine. Group 3 (single-system/multifocal bone disease) patients were treated for a duration of 6 months. Forty-nine patients were treated: 24 (49%), 14 (28.6%), and 11 (22.4%) in groups 1, 2, and 3, respectively. The mean age at diagnosis was 31.6±28.4 months (range, 4 to 120 mo). Five patients abandoned treatment. There were 7 deaths, all in group 1. All patients who died had either a partial response or progressive disease after induction (P=0.000). Among patients with liver involvement, those with sclerosing cholangitis had a greater mortality (P=0.007). A relapse was observed in 12 (24.5%) patients. The frequency of relapse was not different in the 3 groups (P=0.833). The 5-year event-free survival in groups 1, 2, and 3 was 29.3±10%, 58.9±14.6%, and 69.3±15%, respectively (P=0.019). The 5-year overall survival was 100% in groups 2/3 and 68.9±9.8% in group 1 (P=0.011).

Common Hematological Disorders in Children

It is common for primary care physicians to be faced with children with hematological disorders in everyday practice. The article seeks to provide realistic information for the first-contact physician in handling common hematological diseases in children. Practical step-wise approach to understanding and investigating anemia and bleeding disorders is illustrated. Requirement of iron in normal children and management of iron deficiency anemia (IDA) and thalassemia is explained. The gold standard for IDA continues to be ferrous sulphate which has good bioavailability and is inexpensive. There is emerging concept of delayed clamping of umbilical cord at birth, particularly in regions with widespread IDA, to augment iron stores in infancy. Typical case scenarios of children with immune thrombocytopenia (ITP) and hemophilia are provided to facilitate the understanding of management in day to day practice. The vital role of the medical practitioner in shared care of patients with acute lymphoblastic leukemia and febrile neutropenia is emphasized. A risk based treatment algorithm for febrile neutropenia is provided.

Do traumatic lumbar punctures lead to greater relapses in acute lymphoblastic leukemia? Experience at a university hospital in India

OBJECTIVE The aim of the study was to evaluate the impact of traumatic lumbar puncture (TLP) at diagnosis of relapse in childhood acute lymphoblastic leukemia (ALL). Risk factors associated with TLP were assessed. MATERIALS AND METHODS A retrospective analysis was performed from the records of children with ALL who were treated from January 2010 to December 2012. RESULTS A total of 311 patients with median age of 5 years (range: 1-13) were treated for ALL. The cerebrospinal fluid analysis obtained from first LP revealed 275: Central nervous system 1 (CNS 1) (no blasts); 8: CNS 3 (blasts positive); and 28: TLP. Twenty-eight (9%) patients relapsed. Twelve (3.9%) had a CNS relapse. A TLP at diagnosis was not associated with an increased risk of systemic or CNS relapse (P = 0.298, 0.295). Three years event-free survival of patients with TLP and without atraumatic LP (ATLP) at diagnosis was 56 ± 5.2% and 51.8 ± 12.4%, (P = 0.520). Three years overall survival with TLP and ATLP was 73.3 ± 3.5% and 70.4 ± 12.5%, respectively, (P = 0.963). Median platelet count in patients with TLP was significantly lower than those without TLP (10,000/μL and 28,000/μL, P < 0.001). A receiver operating characteristic curve was constructed for predicting the risk of TLP based on platelet count. Area under the curve was 0.74 ± 0.05 (95% confidence interval 0.64-0.84). Platelet count < 23.5 × 109/L at the time of LP had 75% sensitivity and 64.4% specificity in predicting a TLP. CONCLUSIONS Low platelet counts are significantly associated with risk of TLP. Traumatic LP at diagnosis was not associated with an increased risk of relapse.

Invasive bacterial infections in a pediatric oncology unit in a tertiary care center

BACKGROUND Multidrug resistant (MDR) pathogens are becoming a major problem worldwide, more so in the immunocompromised hosts resulting in the urgent need of antibiotic stewardship. PURPOSE To analyze the organisms isolated and the drug resistance pattern in a pediatric oncology unit. RESULTS Data pertaining to infections with 128 positive cultures in patients with febrile neutropenia over a period of 1-year are presented. The unit antibiotic policy is decided depending on the sensitivity of the prevailing common organisms. We isolated Gram-negative organisms in 56% cases. Escherichia coli and Klebseilla were the most frequent lactose fermenting Gram-negative Bacilli and Pseudomonas and Acinetobacter the nonfermenting Gram-negative Bacilli. Only 20-30% of the Gram-negative organisms cultured were sensitive to a 3rd/4th generation cephalosporin. The combination of a beta-lactam/inhibitor covered 2/3rd of Gram-negative organisms. About 80% of the organisms were sensitive to carbapenems. There was no colistin resistance. About 44% of our cultures grew a Gram-positive bacterial organism and included coagulase negative Staphylococcus. We had an incidence of methicillin resistant Staphylococcus aureus to be 30%. About 30% of the enterococci isolated in our unit were vancomycin-resistant enterococci. About 23% of patients with a positive bacterial culture died. CONCLUSIONS Infections in pediatric cancer patients account for about 15-20% of the deaths in developing countries as these patients are at a high risk for developing MDR infections. Resistance rates among Gram-positive and Gram-negative organisms have increased worldwide. Every unit needs a rational antibiotic policy. Antibiotic de-escalation and judicious decrease in the duration of antibiotics needs to be practiced.

Can Radiotherapy Be Omitted in Children With Hodgkin Lymphoma Who Achieve Metabolic Remission on Interim Positron Emission Tomography? Experience of a Tertiary Care Cancer Referral Center

Purpose Treating pediatric Hodgkin lymphoma (HL) involves a delicate balance between cure and reducing late toxicity. Fluorodeoxyglucose positron emission tomography (PET) combined with computed tomography (CT) identifies patients with early response to chemotherapy, for whom radiotherapy may be avoided. The role of PET-CT in upfront risk stratification and response–adapted treatment is evaluated in this study. Methods Patients with HL, who were younger than 18 years, were included. PET-CT was performed at baseline and after two cycles of chemotherapy. Patients were stratified into three risk groups: group 1 (stage I or II with no unfavorable features); group 2 (stage I or II with bulky disease/B symptoms); and group 3 (stage III/IV). A doxorubicin, bleomycin, vinblastine, dacarbazine–based regimen was used in early disease. A cyclophosphamide, vincristine, prednisolone, procarbazine, doxorubicin, bleomycin, vinblastine–based regimen was used in advanced disease. Results Forty-nine patients were included. Fifteen (31%), seven (14%), and 27 (55%) patients were included in groups 1, 2, and 3, respectively. Among 36 patients who underwent staging by PET-CT at diagnosis, seven (19%) patients were upstaged and one (3%) patient was downstaged by PET compared with CT. On the basis of negative interim PET responses, 39 (80%) patients were treated without radiotherapy. The 3-year event-free survival for the entire cohort was 91% (± 5.2%) and overall survival was 100%. Conclusion PET-CT is an excellent stand-alone staging modality in HL. The omission of radiotherapy can be considered in patients who achieve metabolic remission on interim PET.

Hepatic and Cardiac Iron-load in Children on Long-term Chelation with Deferiprone for Thalassemia Major

ObjectiveTo evaluate the efficacy of prolonged deferiprone monotherapy in patients with β-thalassemia major.MethodsThis cross-sectional study included 40 patients (age range 9 to 38 years) with thalassemia major receiving deferiprone for ≥5 years. Serum ferritin, and myocardial iron concentration (MIC) and liver iron concentration (LIC) assessed by T2*MRI were recorded.ResultsThe patients were receiving deferiprone for a mean (SD) duration of 12.1 (4.7) years. The median (IQR) dose of deferiprone was 85 (74.3, 95) mg/kg/day. The MIC was normal or had a mild, moderate or severe elevation in 29 (72.5%), 3 (7.5%), 3 (7.5%), and 5 (12.5%) patients. The LIC was normal or had a mild, moderate or severe elevation in 2 (5%), 4 (10%), 11 (27.5%) and 23 (57.5%) patients.ConclusionsThe majority of patients receiving deferiprone had a moderate/severe hepatic but normal cardiac iron load. Prolonged deferiprone monotherapy was suboptimal for hepatic iron load in the majority.

Invasive Fungal Disease in Children with Acute Leukemia: The Elusive Culprit

Febrile neutropenia is an every day concern in the practice of pediatric oncology [1]. A microbiologically documented infection is evident in approximately 10–20% of episodes and encompasses a diverse range of organisms including bacteria, viruses, and fungi [2]. Patients with acute myeloid leukemia, relapsed or high risk acute lymphoblastic leukemia and recipients of allogeneic hematopoietic stem cell transplant are at an increased risk for invasive infections secondary to opportunistic fungal pathogens [3]. The range of case-fatality figures secondary to invasive fungal disease (IFD) is 20–70%, underscoring the importance of early diagnosis and treatment [3]. In comparison to bacterial infections, which are often promptly demonstrated by the culture of blood or appropriate specimens, establishing fungal etiology represents a diagnostic problem. Therapeutic options are limited and often involve prolonged antifungal therapy that may often be empirical. Parenteral route of administration, adverse effects and last but not least, cost, in resource-constrained settings are treatment-related challenges. This issue of the journal carries a prospective study describing the prevalence and predictors of IFD in children with acute leukemia [4]. The study describes a sizeable cohort of patients with IFD and classifies them according to the conventional definitions proposed by the European Organization for Research and Treatment of Cancer and Mycoses Study Group [5]. Guidelines for febrile neutropenia recommend the initiation of empirical antifungal therapy in a febrile neutropenia episode prolonged beyond 96 h of broad-spectrum antibiotics [6]. Though this enables early initiation of antifungal drugs, it is vital to subsequently establish (or exclude) a fungal etiology to decide the duration and choice of antifungal therapy. Imaging of the lungs by computerized tomography (CT) scan is an essential investigation for revealing a possible fungal etiology, a fact that is reiterated by the study [4]. The most common CT finding in children suspected with IFD is the presence of dense well-circumscribed lung nodules, with or without groundglassing [4]. Lung nodules although characteristic, are not restricted to IFD and can be observed with bacterial and viral infections too [7]. Since a child can experience multiple episodes of febrile neutropenia while receiving cytotoxic therapy, potential radiation exposure from repeated CTscans is undesirable. In this regard, rapid lung magnetic resonance imaging (MRI) offers an attractive alternative [8]. Studies performed on limited numbers of patients have demonstrated a good correlation with CT findings [8, 9]. Optimal MRI imaging of the pediatric lung parenchyma is, however, hindered by intrinsic physical limitations [9]. Advances in technology may simplify protocols for lung imaging by MRI in the future [9]. In a child with a possible IFD, ascertaining the nature of the fungal pathogen is often arduous. Performing invasive procedures such as bronchoalveolar lavage (BAL) or lung biopsy is tricky in cytopenic and unwell patients. There is a lack of data to justify the fear of bleeding following BAL in thrombocytopenic patients. A retrospective study in adults observed a low incidence of bleeding in patients with low platelet counts undergoing bronchoscopy [10]. BAL has been shown to have a similar yield with a lesser incidence of complications when compared to lung biopsy [11]. The study describes performing BAL/biopsy in the methodology. Identification of fungi from these specimens does not feature in the results [4]. Aspergillus has predominantly been isolated from sputum. A productive cough is uncommon in young children and identifying aspergillus from sputum is insufficient for a definitive diagnosis of invasive aspergillosis, limiting the utility of this test [12]. Serum galactomannan, positive in all patients with sputum positivity for Aspergillus in the study is an attractive, readily available investigation [13]. However, recent guidelines discourage its routine use in identifying fungal etiology in children due to a * Deepak Bansal deepakbansaldr@gmail.com

Addressing Psychosocial Support in Children with Cancer in Low- and Middle-Income Countries

Effective management of children with cancer is quantified by statistical figures such as overall and event-free-survival [1]. The numbers reflect the proportions of children that survive, irrespective of the quality of life. The world has witnessed a dramatic increase in survival of children with cancer. The cornerstone of managing children with cancer typically includes ensuring universal access to treatment, achieving cure and minimizing the toxicity of cytotoxic therapy. International groups now recognize psychosocial support as an additional vital component in oncological services, to provide a good quality of life to children and their families [2]. Low-and-middle income countries (LMIC) such as India continue to lag behind the developed world in the survival of children with cancers [3]. Centers offering pediatric oncology services in LMIC need to address obstacles such as socioeconomic and educational disparity, sub-optimal infrastructure, an unfavorable trained health professional to patient ratio and treatment abandonment [3]. Adapted treatment protocols aimed at maximizing cure and minimizing treatment-related morbidity/mortality are prioritized in LMIC [4]. Consequently, non-pharmacological interventions such as psychosocial support tend to take a back-seat. The term Bpalliative care^ is often erroneously interpreted by health professionals as a service limited to patients who have relapsed/refractory cancer. Palliative care represents wholesome management encompassing physical, psychosocial and spiritual aspects intended to improve the quality of life of patients with life-threatening illness and their families [5]. Early integration of palliative care into the management of patients with cancer has led to improvement in outcomes and quality of life in adults, inspiring a similar approach in children [6]. This issue of the journal carries a study that evaluates a psychosocial support program in a tertiary care institute in North India [7]. The authors have aptly referred to patients, caregivers and treatment providers as the ‘comprehensive triad’ who complete the circle of the practice of pediatric oncology. The study offers a refreshing insight into the individual needs and challenges of children with cancer and their families. Focussed group discussions provide time, space and opportunity to discuss concerns and remediation that are often not possible during visits to busy out-patient clinics or physician conducted rounds in the wards. The study offers a snapshot of several issues spanning physical, psychosocial, emotional, behavioral and cognitive domains which are often suppressed and ignored during treatment [7]. Although acknowledging the problems is in itself a significant step, one needs to contemplate solutions to tackle the issues raised. Examples include periodic counseling sessions, play therapy, assistance in arranging financial help and a part-time informal school to continue basic lessons for children who have had to discontinue schooling. Further, dedicated sessions conducted for children is a distinctive aspect of the study. There is often a lack of clarity and consensus on the inclusion of children in decisions related to their management; and the extent of disclosure of information regarding diagnosis and prognosis. The study provides impetus to conduct similar studies evaluating the quality of life and multi-dimensional aspects of the well-being of children and their families during therapy for cancer. A recent review addressed the disparity in psychological intervention studies conducted in India and the developed world and recognized the need for a generic intervention tool adapted to the Indian socio-cultural milieu [8]. Themajority of pediatric oncology units in LMICs lack in supportive care staff. Centers offering pediatric oncology services should endeavor to create vacancies and employ qualified personnels including psychologists, counselors and social workers. Setting apart time for group discussions and counseling is often a challenge for the healthcare providers who have to deal with a large number of patients. Nonetheless, it is crucial to conduct regular group discussions and counseling sessions * Deepak Bansal deepakbansaldr@gmail.com

Pediatric nonblastic non-hodgkin's lymphoma: A perspective from India

Background: There is a paucity of data on pediatric nonblastic non-Hodgkins lymphoma (NHL) from developing countries. We conducted this study to study outcome and identify risk factors that can predict survival in pediatric nonblastic NHL at our center. Methods: Patients <18 years of age who were diagnosed with nonlymphoblastic NHL at our hospital from January 1, 2005, to December 31, 2014, were included. Data were collected retrospectively from case records. Results: One hundred and two patients with median age of 12 years (range: 1–18) were included in the study. There were 69/102 (68%) male and 33/102 (32%) female patients. The most common histological diagnosis was Burkitts lymphoma (BL) in 59/102 (58%) patients followed by anaplastic large cell lymphoma (ALCL) in 28/102 (28%) patients and diffuse large B-cell lymphoma (DLBCL) in 12/102 (12%) patients, T-cell lymphoma in 2/102 patients, and primary mediastinal B-cell lymphoma in 1/102 patients. The LMB-89 protocol was the most common protocol used for treatment in 74/102 (72%) patients. The 2-year event-free survival (EFS) for patients with BL, ALCL, and DLBCL was 72%, 55.8%, and 27.5%, respectively (P = 0.037). On univariate analysis, factors that significantly predicted poor EFS included non-BL histological subtype, poor performance status, malnutrition, use of less intense chemotherapy, and not achieving complete response on interim radiological assessment. Conclusions: Outcomes in nonblastic NHL from our center are worse compared to data from the west. This is because a large proportion of patients present with advanced stage and in moribund condition. Patients with BL have better outcome compared to other subtypes.