Nutritional status in survivors of childhood cancer: Experience from Tata Memorial Hospital, Mumbai.

BACKGROUND: Survivors of childhood cancer are at increased risk for several cardiometabolic complications. Obesity/overweight and metabolic syndrome have been widely reported in Western literature, but data from India are lacking. AIMS: To perform an objective assessment of nutritional status in a cohort of childhood cancer survivors (CCSs) and to find risk factors for extremes in nutritional status. SETTINGS AND DESIGN: The study was a retrospective chart review of CCSs who attended the late effects clinic of a referral pediatric oncology center over the period of 1 year. MATERIALS AND METHODS: An objective assessment of nutritional status was done, and results were analyzed in two groups: Adult survivors (present age >18 years) and child and adolescent survivors (CASs) (<18 years). The data were then analyzed for possible risk factors. RESULTS: Six hundred and forty‑eight survivors were included in the study; of these, 471 were <18 years at follow‑up, and 177 were 18 years or older. The prevalence of obesity, overweight, normal, and undernutrition was 2.6%, 10.8%, 62.7%, and 28.8% (CASs) and 0%, 8.5%, 62.7%, and 28.8% (adult survivors), respectively. Factors predictive of overweight/obesity were an initial diagnosis of acute lymphoblastic leukemia, or brain tumor and follow‑up duration of >20 years or current age >30 years in adult survivors. CONCLUSIONS: The prevalence of obesity/overweight is lower in our cohort when compared to Western literature. It remains to be clarified whether this reflects the underlying undernutrition in our country, or whether our cohort of survivors is indeed distinct from their Western counterparts. Comparison with age/sex‑matched normal controls and baseline parameters would yield more meaningful results.

Comparison of isolates and antibiotic sensitivity pattern in pediatric and adult cancer patients; is it different.

BACKGROUND: Infection is a common cause of mortality and morbidity in cancer patients. Organisms are becoming resistant to antibiotics; age appears to be one of the factors responsible. We analyzed common organisms and their antibiotic sensitivity pattern in the correlation with age. METHODS: This is a single institutional, retrospective analysis of all culture positive adult and pediatric cancer patients from January 2007 to December 2007. For statistical analysis, Chi‑square test for trend was used and P values were obtained. Of 1251 isolates, 262 were from children <12 years of age and 989 were from adolescents and adults (>12 years of age). Gram‑negative organisms were predominant (64.95) while Gram‑positive constituted 35.09% of isolates. RESULTS: The most common source in all age groups was peripheral‑blood, accounting to 47.8% of all samples. The most common organisms in adults were Pseudomonas aeruginosa (15.3%) while in children it was coagulase negative Staphylococcus aureus (19.8%). Antibiotic sensitivity was different in both groups. In pediatric group higher sensitivity was seen for Cefoparazone‑sulbactum, Cefipime, Amikacin, and Tobramycin. No resistance was found for Linezolid. CONCLUSIONS: The isolates in both children and adults were predominantly Gram‑negative though children had proportionately higher Gram‑positive organisms. High‑dose cytarabine use, cotrimoxazole prophylaxis, and frequent use of central lines in children especially in hematological malignancies could explain this observation. Children harbor less antibiotic resistance than adults; Uncontrolled, cumulative exposure to antibiotics in our community with increasing age, age‑related immune factors and variable bacterial flora in different wards might explain the higher antibiotic resistance in adults. Thus age is an important factor to be considered while deciding empirical antibiotic therapy.

Management of febrile neutropenia in malignancy using the MASCC score and other factors: Feasibility and safety in routine clinical practice.

BACKGROUND: The current standards for empirical broad‑spectrum intravenous antibiotic (AB) treatment, combined with hospitalization, are cautious and safe, but lead to over‑treatment of a substantial group of patients. We need to validate parameters to identify these low‑risk febrile‑neutropenia (FN) patients, who could then be safely treated in an outpatient setting with minimal/no AB treatment. MATERIALS AND METHODS: A retrospective analysis for validation of a risk‑assessment model in FN patients was done on a patient population from January 2007 to December 2008. Inclusion criteria were a histological diagnosis of malignancy, FN secondary to chemotherapy, absolute‑neutrophil‑count of ≤500/μl, axillary temperature of ≥38°C, and age ≥14 years. Other clinical and laboratory parameters were explored for risk stratification during the FN episodes. Receiver‑operating characteristic curves were used to find the threshold value, and Chi‑square analysis was done to find the association between the outcome and the parameters. RESULTS: A total of 178 FN episodes were documented; 22 in solid tumors and 156 in hematolymphoid malignancies. Culture positivity was documented in 59 episodes; peripheral blood was the most common source, with Escherichia coli being the most common organism identified. Risk stratification was done using the Multinational Association of Supportive Care in Cancer (MASCC) risk‑index score. The association between the MASCC score and risk stratification could not be established (P = not significant) at a score of ≤21; however, it was found to be significant at a score of ≤18. The total number of complications was 23 (sepsis 22, mortality 23). Other factors found to be significantly associated with a high risk of complications in the univariate analysis were, mucositis (P = 0.03), maximum temperature ≥103°F (P = 0.01), tachycardia (P < 0.001), tachypnea (P = <0.001), age (P = 0.006), high dose of steroid (P < 0.001), total duration of fever (≥2.5 days (for which sensitivity (S) and specificity (Sp) were 87 and 81%, respectively), serum‑creatinine (≥0.45 mg%, S = 100%, Sp = 97%), serum‑bilirubin (≥0.5 mg/dl, S = 100%. Sp = 90%), requirement of second‑line antibiotics (P = 0.02), intensive‑care (P ≤ 0.001), ventilatory support (P < 0.001), and requirement of packed cell (PC) transfusion (P = 0.02). In the multivariate analysis, mucositis (P = 0.02), HD steroid use (P = 0.026), and PC requirement (0.026) were identified as independent variables. CONCLUSIONS: The MASCC risk‑index score was found to be meaningful at a score of ≤18. Other clinical and laboratory parameters were found to have a strong association with risk stratification in cancer patients during FN episodes.

A randomized comparative trial evaluating the safety and efficacy of liposomal amphotericin B (Fungisome TM ) versus conventional amphotericin B in the empirical treatment of febrile neutropenia in India.

Background: In patients with persistent fever and netropenia, amphotericin B is administered empirically for early treatment and prevention of systemic fungal infections. Despite this treatment, there are chances of breakthrough fungal infections and drug is also toxic. Materials and Methods: A multicentric, randomized, controlled clinical trial was conducted to compare liposomal amphotericin B two doses with conventional amphotericin B as empirical antifungal therapy. Results: The average body weight of patients was 26.4±14.8 (n=22), 32.9±19.4 (n=23) and 37.9±20.0 (n=20) kg in 1 mg, 3 mg Fungisome (liposomal amphotericin B) and 1 mg/kg/day conventional amphotericin B group, respectively. The mean age was 16.2±13.4, 16.0±10.9 and 22.7±16.2 yrs in 1 and 3 mg/kg/day Fungisome and 1 mg/kg/day conventional AMP B group, respectively. The average duration of treatment with 1 mg and 3 mg/kg/day Fungisome and 1 mg/kg/day conventional amphotericin B was 17±9.8, 16.2±8.3, and 14.7±10.7 days, respectively. The time to resolve fever was 13.3±10.2, 10.9±7.1, 10.1±6.7 days, and for absolute neutrophil count (ANC) to be above 500 cells per microliter, it took 13.4±9.6, 10.6±7.6 and 7.3±3.4 days, respectively. Liposomal formulations were well-tolerated compared to conventional amphotericin B. Conclusions: This small randomized study showed that the indigenous liposomal formulation Fungisome TM appears to be equally efficacious and safer than conventional amphotericin B. Also, the lower dose Fungisome (1 mg/kg/day) appears to be equally efficacious and was well-tolerated as compared to higher dose Fungisome (3 mg/kg/day). Treatment cost would be a major factor for limiting use of higher dose of Fungisome.

The effect of age on the bacteria isolated and the antibiotic-sensitivity pattern in infections among cancer patients.

Background: Patients with cancer are predisposed to infections. Antimicrobial patterns and antibiotic sensitivity change with increasing age, making choice of empirical therapy more complicated. Materials and Methods: This single-center study aims to try and assess the influence of age on microbiology and antibiotic sensitivity of organisms causing infection in patients with malignant disease. Results : The five most common bacterial pathogens isolated were Pseudomonas sp (245, 26.2%) > Enterocococcus sp (109, 11.66%) > Staphylococcus aureus (107, 11.44%) > Escherichia coli (106, 11.34%) > Klebsiella sp (99, 10.59%). There was no significant change in the distribution of Gram-positive and Gram-negative bacteria with age. However, there was an increase in the occurrence of the Enterobacteriacea group and a decrease in infections caused by nonlactose fermenters with increasing age. The ESBL production increased from 10.52% (12-19 years) to 24.88% (>50 years) as did oxacillin resistance (from 14.3% to 28.1%) among S. aureus isolates. The activity of most antimicrobial agents decreased with increasing age. The decreasing trend of activity was statistically significant for meropenam (73.3-41.2%) against Pseudomonas sp. and for the activity of the aminoglycosides for Acinetobacter sp (61.1-17.4% for amikacin). Conclusions : This suggests that empirical antibiotic therapy needs to be changed on the basis of the age of the patient. It also appears that combination therapy is essential for the empirical treatment of infections in elderly patients with cancer.

Blood stream infections in cancer patients: A single center experience of isolates and sensitivity pattern.

Background : Up to 10% of patients who develop a nosocomial blood stream infection (BSI) in the hospital have an underlying malignancy. The treatment of infections in patients with malignancy often relies on the use of established guidelines along with the consideration of the local microbiology and antibiotic sensitivity patterns of possible etiologic agents. AIMS: This study attempts to identify the likely etiologic agents and the antibiotic sensitivity profile of BSIs in cancer patients. Settings and Design: This was a retrospective study. Methods and Material: The study was conducted at a tertiary care center for cancer patients, in which samples representing blood stream infections sent from the Medical Oncology services of the hospital during the year of 2007 were analysed. The microbiological profile and antibiotic sensitivity pattern of these isolates was studied. Results: There were 484 isolates that represented BSIs. The most common bacterial isolates from patients with cancer were Pseudomonas spp. (30.37%), Staphylococcus aureus (12.6%) and Acinetobacter spp. (11.57%). Meropenem was the most effective antibiotic with 71.2% sensitivity to the bacterial isolates it was tested against. Oxacillin resistance was seen in 18% of S. aureus isolates. Conclusion: Gram-negative bacteria were more common as etiologic agents of BSIs in cancer patients. The poor activity of the primary empirical agents for infections in cancer namely ceftazidime and piperacillin-tazobactam is alarming.Strict regulation of vancomycin use should be considered in areas where there is a low prevalence of methicillin-resistant S. aureus (MRSA).

Comparison of in vitro activities of ceftazidime, piperacillin-tazobactam, and cefoperazone-sulbactam, and the implication on empirical therapy in patients with cancer.

Background: Infection is a common cause of morbidity and mortality in cancer patients. In most of these cases empirical treatment is provided because the focus of infection is not identified. Empiric antibiotics provided to these patients are based on isolates, sensitivity, and on guidelines. Here we have compared three antibiotics recommended as empirical treatment by the Infectious Disease Society of America (IDSA). Aims: To compare the three antibiotic sensitivities for gram negative isolates at our institute. Objective: To choose the optimal antibiotic as the empirical treatment for cancer patients developing infections. Materials and Methods: We collected the data on isolates and antibiotic sensitivity patterns of isolates for ceftazidime, piperacillin + tazobactum, and cefoperazone from the medical oncology department. We subsequently compared the sensitivity of these three antibiotics. Statistical Methods: The isolates were mapped using the WHONET 5.4 software. The analysis was conducted using SPSS 15.0 for Windows. McNemar Chi-square test was used to compare the sensitivity percentages between any two antibiotics. The agreement between the antibiotic and the gold standard was calculated using the Kappa statistic. Two tailed p values were reported. Results: The results showed that there was a difference among sensitivities for these antibiotics. It appears that the sensitivity of ceftazidime was inferior to the two other antibiotics. Also cefoperazone has better sensitivity as compared to piperacillin + tazobactum. Conclusion: In spite of these three antibiotics being recommended by IDSA our data suggest that it should not be followed blindly and local sensitivity data is important for formulating institutional guidelines for using antibiotics.

Activity and toxicity of 2-CDA in Langerhans cell histiocytosis: a single institutional experience.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disorder characterized by clonal proliferation of immature and abnormal bone marrow derived langerhans cells. Treatment is usually multimodal. Potent anti-monocyte as well as immunomodulatory activity of 2-CDA and its proven efficacy in many lymphoproliferative disorders has made 2-CDA a rational choice in treatment of LCH. AIM: To evaluate the efficacy and toxicity profile of 2-CDA in children with relapsed or refractory LCH. SETTING AND DESIGN: This is a pilot study and we present the initial data of the first seven patients treated at our institution. MATERIALS AND METHODS: Seven patients of relapsed and refractory LCH were enrolled from July 2000 to June 2004. The cohort of seven patients included six males and one female with a median age at initiation of cladribine was 2.25 years (range, 1.67 to 7.0 years). Three patients had received one prior chemotherapy regimen while the rest were heavily pretreated. Cladribine was administered over two hours IV daily for five days and repeated every four weeks. RESULTS: After a median of six courses of cladribine (range, 2 to 9), two (33%) patients achieved PR and two (33%) patients have SD on imaging but are clinically better. None experienced grade 3 or 4 hematologic toxicity. At a median follow-up of 19 months (range, 8 to 52 months), five patients remain alive and one patient has died. CONCLUSION: Our study shows that single agent 2-CDA is active and well-tolerated in children with relapsed or refractory LCH.

Primitive neuroectodermal tumor (PNET) as second malignancy after treatment of Hodgkin's disease.

Hodgkin's disease survivors are at an increased risk of developing second malignant neoplasms including secondary bone tumors. Common secondary bone tumors are osteogenic sarcoma and fibrosarcoma. Secondary primitive neuroectodermal tumor is extremely rare in this group. We present below, a rare case of secondary PNET in an 8-year-old child with Hodgkin's disease which developed unusually early outside the radiation portal and discuss potential factors responsible for its causation.

Ewing's sarcoma with cutaneous metastasis--a rare entity: report of three cases.

Ewing's sarcoma (ES) is a small round cell tumor, usually arising from flat bones and diaphyseal region of long bones. It is commonly found in the first two decades of life. It is curable when diagnosed in the localized stage and requires multimodality treatment. ES is a chemosensitive tumor. It metastasizes commonly to lung, pleura and other bones. Less common sites of metastasis are lymph nodes, CNS and liver. Skin metastasis is extremely uncommon. It occurs in up to 9% of all patients with cancer. Growth pattern of cutaneous metastasis is unpredictable and may not reflect that of primary tumor. We hereby report three cases of Ewing's sarcoma that developed skin metastasis.

Childhood cancers: perspectives in India.

The authors have described the different perspectives like epidemiology, biology and outcome, barriers to optimal treatment of childhood cancers in India along with a brief review of literature in the present article.

Desmoplastic small round cell tumor: extra abdominal and abdominal presentations and the results of treatment.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare malignant neoplasm of adolescent males. Current multimodality treatment prolongs life and rarely achieves cure. AIM: To review the presenting features, histopathology and outcome of 18 patients with DSRCT treated at a single institution. SETTING AND DESIGN: This is a retrospective observational study of patients with DSRCT who presented at the Tata Memorial Hospital between January 1994 to January 2005. MATERIALS AND METHODS: Eighteen patients of DSRCT seen during this period were evaluated for their clinical presentation, response to chemotherapy and other multimodality treatment and overall survival. The cohort of 18 patients included 11 males (61%) and 7 females (39%) with a mean age of 16 years (Range 1(1/2)--30 years). Majority (83%) presented with abdomino-pelvic disease. The others, involving chest wall and extremities. There were 6 patients (33%) with metastatic disease at presentation. RESULTS: The treatment primarily included a multimodality approach using a combination of multiagent chemotherapy with adjuvant surgery and radiotherapy as applicable. A response rate of 39% (CR-1, PR-6), with chemotherapy was observed. The overall response rate after multimodality treatment was 39% (CR-5, PR-2). The overall survival was poor except in patients who had complete excision of the tumor. Conclusion:0 Abdomino-pelvic site was the commonest presentation, the disease can occur at other non-serosal surfaces also. Despite aggressive treatment the outcome was poor. However, complete surgical excision seems to provide a better survival.

Yolk sac tumor of vagina.

Yolk sac tumors are common in children. By virtue of being chemosensitive, they are amenable to cure by chemotherapy alone and radical surgery is often not required. Yolk sac tumors occurring in the vagina are rare and thus may not be recognized early or may be inadvertently subjected to radical surgery. The authors report a case that presented to them after radical surgery with elevated Alpha-fetoprotein level is reported. The management of this case and review of the relevant literature are discussed here.

Childhood cancer survivors--living beyond cure.

Advances in diagnosis and treatment along with improved supportive care have contributed to the current survival rates for pediatric malignancies. Recent concept of a truly "cured child" in pediatric oncology envisages not only a biological cure of the disease but a child on par with peers in growth and development physically and in achievements and aspirations, both mentally and emotionally. Because of the young age of these survivors and their potential for longevity, the delayed consequences of therapy may have a serious impact on their lives and family at large than do the acute complications of the cytotoxic therapies that they had experienced. Though figures from India are not available, it has been estimated that, in USA, the prevalence of childhood cancer survivors is expected to increase from 1 in 900 persons among young adults to 1:250 persons by 2010. Although this constitutes a remarkable medical achievement, the late morbidity in this growing survivor population has become an area for concern. It is estimated that 50% of the survivors are likely to develop disabilities that alter the quality of life.

Low incidence of CNS relapse with cranial radiotherapy and intrathecal methotrexate in acute lymphoblastic leukemia.

OBJECTIVES: To assess the incidence of isolated central nervous system (CNS) relapses in patients of acute lymphoblastic leukemia (ALL) treated with a protocol containing cranial irradiation and intrathecal methotrexate as CNS directed therapy. DESIGN: Prospective non randomized study. SETTING: Department of Medical Oncology, Tata Memorial Hospital. SUBJECTS: 623 children of ALL on MCP 841. METHODS: CNS relapse was diagnosed, if upon examination of the CSF, more than 50 cells/microliter were observed, or a count of 5 cells which were unequivocally lymphoblasts. RESULTS: The incidence of isolated CNS relapse was 1.75% with the use of this treatment. Age, sex, white blood cell count, platelet count, lactic dehydrogenase and immunophenotyping were not significantly related to isolated CNS relapse. CONCLUSION: A low incidence of isolated CNS relapse demonstrates the adequacy of the presymptomatic CNS therapy.

Evaluating efficiency of bone marrow harvest and its manipulation--role of CD 34 positivity.

We evaluated harvested marrow cells for total nucleated cells (27.49 x 10(9)), absolute 'lymphocyte' count (6.29 x 10(9)) and CD 34 positive cells (3.57 x 10(9)). The same parameters were studied after in vitro manipulation to remove RBCs and plasma. Reinfused WBCs contained 12.87 x 10(9) nucleated cells, 4.25 x 10(9) absolute 'lymphocyutes' and 3.34 x 10(9) CD 34 positive cells. The corresponding figures for loss during in vitro manipulation (tubing, RBCs and plasma) are 14.62 (53.18%), 2.04 (32.43%) and 0.23 x 10(9) (6.44%) cells respectively. Therefore CD 34 positivity may be a better indicator of total yield, loss during manipulation and reinfusion of hemopoietic progenitor cells in bone marrow transplantation.