Childhood T-lineage Acute Lymphoblastic Leukemia: Management and Outcome at a Tertiary Care Center in North India.

Objective: To assess the clinical features, prognostic factors and outcome of childhood T-ALL in comparison with B-lineage ALL, treated with a uniform treatment regimen (MCP 841). Setting: Pediatric oncology division of a tertiary care institution in Northern India. Design: Retrospective analysis of clinical data and survival outcome. Participants: 60 children with T-ALL and 139 with Blineage ALL, and less than 15 years of age treated over 15 years. Results: T-ALL was observed in 30%. High risk features at presentation (age 10 years, WBC >50,000/mm3, mediastinal mass, and CNS leukemia) were significantly more frequent in T-ALL as compared to B-lineage ALL (P=0.049, P<0.001, P<0.001 and P=0.02, respectively). Fifty five of 60 T-ALL patients (91.7%) achieved complete remission after induction therapy. There were 3 induction and 10 remission deaths while 11 (18.3%) relapsed. The overall survival and event-free survival of T-lineage ALL (61.5±7.6 and 49.9±7.4, respectively) were similar to that of B-lineage patients (68.7±4.7 and 47.1±5.1, respectively). National Cancer Institute risk groups emerged as significant prognostic factor for event free survival only in B-lineage patients. Conclusions: Even though high risk features were significantly more frequent in T-ALL, survival outcome was similar to that of B-lineage patients. None of the routinely described prognostic parameters significantly impacted survival.

Overt testicular disease at diagnosis in childhood acute lymphoblastic leukemia: Prognostic significance and role of testicular irradiation.

Objective. To analyze the prognostic impact of overt testicular disease (OTD) at diagnosis and role of testicular irradiation in the same. Methods. Data of 579 boys treated at our center over 16 years was reviewed. Results. Fourteen (2.4%) males had OTD. 10 (71.4%) of these had high-risk disease. Patients with OTD, had a significantly higher incidence of mediastinal-adenopathy (p=0.001), hyperleucocytosis (p=0.004) and CNS disease at presentation (p<0.0001) compared to patients in continuous complete remission (CCR). 4 of the 11 patients with OTD, who opted for therapy, had relapse; 2 are in CCR. Although, survival in patients with OTD was inferior (p=0.183) compared to patients without OTD, it was not an independent prognostic factor (p=0.47). In the entire study cohort, symptom-diagnosis interval (p=0.006), white cell (p=0.001) and platelet count (p=0.001) at presentation were significantly associated with survival (Cox multivariate regression analysis). Conclusions. OTD was not an independent prognostic factor, despite association with high-risk features. Survival outcome was inferior. The observations indicate the need of revaluation of the present protocol with incorporation of intermediate dose and subsequently high-dose methotrexate (after assessment for toxicity and tolerance), risk-stratified therapy and plausibly omission of testicular irradiation.

Testicular relapse in childhood acute lymphoblastic leukemia: The challenges and lessons.

Background : Relapse of disease is documented in 15-20% of children with acute lymphoblastic leukemia (ALL). Although testicular relapse is rare with modern risk-adapted treatment protocols, earlier, the testes were a frequently encountered site of relapse and were designated as "drug sanctuaries". Purpose : This descriptive study was designed to assess the pattern of testicular relapse and to identify high-risk factors. Materials and Methods : Data obtained from case records of 407 boys with ALL were analyzed. Fine needle aspiration cytology was carried out in children presenting with painless enlargement of testi(e)s. Bone marrow aspiration and cerebrospinal fluid examination were performed concomitantly to confirm or exclude disease at these sites. Results : Testicular relapse was documented in 30 boys. It was isolated in 17 patients and associated with bone marrow and/or central nervous system relapse in 13. At relapse, nine boys were over the age of 10 years. The majority were very early and early relapsers. Hyperleucocytosis was documented in five of 30 and seven of 137 relapsers and nonrelapsers, respectively (P = 0.04). Twelve of the 30 boys with testicular relapse were treated with testicular irradiation, reinduction and maintenance therapy. The estimated median overall survival was 33 months. Conclusion : Testicular relapse, which depends on the therapy administered, may manifest several months/years after completion of treatment. The high incidence of testicular relapse in our series implicates the need of revaluation of our protocol and incorporation of high/intermediate dose methotrexate therapy upfront.

Itopride and pantoprazole outcomes in diabetic gastroparesis trial (IPOD trial).

The most common cause of gastroparesis is diabetes mellitus. The present study was carried out to asses the combination of itopride and pantoprazole in the treatment of diabetic gastroparesis. The study was an open label, multicentre, conducted in 743 patients with diabetic gastroparesis for a period of 3 weeks. The efficacy parameters included nausea, vomiting, early satiety, bloating, postprandial fullness, epigastric pain and regurgitation. The patients were evaluated based on the frequency and severity of symptoms and compared with the baseline scores. There were significant improvement in severity as well as the frequency of all the symptom parameters of the disease (p<0.001). The physicians' evaluation to the therapy was rated either excellent or good.

In vitro study to compare sensitivity of amoxicillin+clavulanic acid and cefpodoxime+clavulanic acid among beta-lactamase positive clinical isolates of gram-positive and gram-negative pathogens.

The present study was carried out to compare the in vitro sensitivity of cefpodoxime + clavulanic acid and amoxicillin + clavulanic acid against 55 Gram-positive and 123 Gram-negative beta-lactamase positive clinical isolates. Micro-organisms isolated from different clinical specimens were tested for beta-lactamase/ESBL by using nitrocefin disc test and for metallo beta-lactamase by using double disc synergy test. A total of 299 (93 Gram-positive and 206 Gram-negative) clinical isolates were tested for beta-lactamase. Among 93 Gram-positive clinical isolates 25 (78.12%) out of 32 coagulase positive S. aureus, 23 (60.52%) out of 38 coagulase negative S aureus, 7 (63.63%) out of 11 enterococci and 0 (0%) out of 12 Strept pneumoniae were positive for beta-lactamase /ESBL. Notably Strept pneumoniae was found to be beta-lactamase/ESBL negative. Among 206 Gram-negative clinical isolates, 25 (69.44%) out of 36 acinetobacter spp, 20 (41.66%) out of 48 Branhamella catarrhalis, 24 (64.86%) out of 37 E. coli, 7 (46.66%) out of 15 H influenzae and 22 (62.85%) out of 35 proteus were positive for beta-lactamase/ ESBL/metallo beta-lactamase. Positive strains were tested for comparative sensitivity to amoxicillin+ clavulanic acid and cefpodoxime+clavulanic acid by Kirby Bauer disc diffusion method. As regards comparative sensitivity among beta-lactamase/ESBL positive Gram-positive strains, 84% and 92% strains of coagulase positive S aureus, 65.21% and 86.95% strains of coagulase negative S. aureus, 83.33% and 100% strains of Strept pneumoniae and 71.42% and 100% strains of enterococci were found sensitive to amoxicillin +clavulanic acid and cefpodoxime + clavulanic acid respectively. Sensitivity to amoxicillin+ clavulanic acid and cefpodoxime +clavulanic acid among beta lactamase/ESBL positive Gram-negative strains of acinetobacter spp, Branhamella catarrhalis, E. coli, H. influenzae and proteus spp were found to be 20% and 28%, 100% and 100%, 50% and 75%, 71.42% and 100%, 50% and 68.18% respectively. This study demonstrated that cefpodoxime +clavulanic acid combination has more potent in vitro activity in comparison to amoxicillin+ clavulanic acid combination against beta-lactamase producing strains of Gram-positive and Gram-negative bacteria. Given this broad spectrum of activity, cefpodoxime+clavulanic acid appears well suited for use in the treatment of a variety of healthcare-associated infections.

Efficacy and safety of oxum in treatment of the venous ulcer.

The present study was carried out to find out the efficacy and safety of oxum in the treatment of venous ulcers. The oxum (superoxidised water) is a pH neutral, non-irritating, aqueous solution that possesses a good antiseptic, antimicrobial activity and wound healing properties. The study was conducted in 30 patients of venous ulcers with a culture examination positive for pathogenic microbial flora. All patients received a gauze dressing impregnated with oxum followed by compression bandage for 28 days. The primary endpoint was the calculation of ulcer size using ulcer tracing. Assessment of periwound oedema, periwound erythema, wound fibrin and wound granulations were considered as secondary endpoints. There was a singificant reduction in ulcer size starting from day 7 of the treatment. Significant improvements in secondary endpoints were observed. This study has demonstrated that oxum improved the clinical status, reduced the signs of inflammation in venous ulcers in addition to its well confirmed anti-infective properties.

Distal arthrogryposis syndrome.

A 5-month-old male infant presented with weak cry, decreased body movements, tightness of whole body since birth, and one episode of generalized seizure on day 4 of life. He was born at term by elective caesarian section performed for breech presentation. The child had failure to thrive, contractures at elbow and knee joints, hypertonia, microcephaly, small mouth, retrognathia, and camptodactyly. There was global developmental delay. Abdominal examination revealed umbilical and bilateral inguinal hernia. Visual evoked response and brainstem evoked response audiometry were abnormal. Nerve conduction velocity was normal. Magnetic resonance imaging of brain revealed paucity of white matter in bilateral cerebral hemispheres with cerebellar and brain stem atrophy. The differential diagnoses considered in the index patient were distal arthrogryposis (DA) syndrome, cerebroculofacioskeletal syndrome, and Pena Shokier syndrome. The index patient most likely represents a variant of DA: Sheldon Hall syndrome.

Effects of antacid therapy in asymptomatic patients with presence of amoeba in stool report.

Amoebic infection caused by the protozoan parasite Entamoeba histolytica is a prevalent infection in the developing countries. Milder form of this infection is associated with loose stool, flatulence and borborygmi, may or may not be associated with pain in abdomen and treated symptomatically by some physicians by antacid. To find out the effects of antacid (sorbacid) therapy in patients with amoeba in stools by examining the changes in the stool report, a study was conducted among 25 patients enrolled in the study with complaints of "gas" in the abdomen with stool reports positive for amoeba. Antacid (sorbacid) in a dose of one teaspoonful (5 ml) was given three times a day for 3 days and stool examination was repeated. The report showed a significant reduction in the amoeba and mucus in stool (p<0.05) and a trend towards reduction in the presence of occult blood. Other parameters in stool reports did not change. Moreover, all the patients gave the history of passing formed stools and no complaints of "gas" in abdomen thus providing the symptomatic benefit. Antacids may have some beneficial effects in amoebiasis. More studies are required to confirm the above finding and to find out the place of antacid as an adjuvant therapy along with the standard anti-amoebic drugs.

Chloramphenicol: screening and review to evaluate its potential beneficial effects in leukaemia.

Chloramphenicol is an antimicrobial agent having a very broad-spectrum of activity including Gram-positive bacteria, Gram-negative bacteria and anaerobes. However the use of chloramphenicol has reduced over a period of time due to the adverse effects of causing bone marrow depression or in some cases severe aplastic anaemia. As the effects are seen on the bone marrow cell, it was intended to find out if these adverse effects could be used for the benefits in leukaemia patients, using in-vitro study on leukaemic cell lines. The study showed inhibition of growth of the leukaemia cells by chloramphenicol which was comparable to or better than daunorubicin in some cell lines. The article also discusses the other adverse effect profile of chloramphenicol compared with anticancer drugs and its potential benefit in leukaemia and in neutropenic fever.