Ponni Sivaprakasam - Academia.edu (original) (raw)

Papers by Ponni Sivaprakasam

Bone Reports, 2021

Autosomal recessive osteopetrosis (ARO) is rare, involving increased bone density due to defectiv... more Autosomal recessive osteopetrosis (ARO) is rare, involving increased bone density due to defective osteoclast differentiation or function, with several genetic subtypes. Case This child with compound heterozygous novel loss-of-function TNFRSF11A pathogenic variants causing osteoclast-poor ARO underwent haematopoietic stem cell transplantation (HSCT) aged 3.1 years and experienced episodic severe hypercalcaemia over 2.5 years. She initially presented aged 8 months with craniosynostosis and visual impairment and underwent surgery; no increased bone density evident on skull imaging nor variants in genes associated with craniosynostosis identified. She was subsequently referred for investigation of poor linear growth and low alkaline phosphatase. Clinical abnormalities included asymmetric pectus carinatum, thickened anterior tibia and wrists, and markedly delayed dentition. Skeletal survey revealed generalised osteosclerosis with undertubulation. Management She received haploidentical H...

Background: The incidence of brain tumours in India equate to half of those in the developed worl... more Background: The incidence of brain tumours in India equate to half of those in the developed world. Delayed diagnosis is associated with a higher risk of life-threatening neurological complications at presentation and poor cognitive outcomes amongst survivors. Early detection and treatment is crucial for improving outcomes. Aims: The aim of this study was to analyse baseline diagnostic intervals for paediatric brain tumours in Tamil Nadu. Methods: Data for this retrospective study was collected via questionnaire across 8 different hospitals in Tamil Nadu. It consisted of 14 questions where doctors were asked to record data items including the date of symptom onset, first presentation to healthcare and date of diagnosis. Results: 114 children were diagnosed with a brain tumour between January 2018-October 2020. The average diagnostic interval was 9.3 weeks (median 3.5 weeks), and the average patient interval is 6.1 weeks (median 0.6 weeks.). Low-grade tumours had the longest median total diagnostic interval of 6.6 weeks. The median total diagnostic interval was significantly higher in villages (7.9 weeks), as compared to patients located in District (4.8 weeks) and cities (2.3 weeks). Conclusion: Overall, the diagnostic interval for paediatric brain tumours were comparable to data in the UK. Moreover, all patients received an MRI within a day, indicating excellent infrastructure.. However, many low-grade and optic pathway tumours were unaccounted for. Tamil Nadu has one of the best healthcare systems in India and extending this methodology to areas with poorer healthcare provisions, is required to get representative national data.

Blood, 2010

4223 Background: Pediatric infective endocarditis (IE) continues to be a condition associated wit... more 4223 Background: Pediatric infective endocarditis (IE) continues to be a condition associated with high morbidity and mortality. Contributing factors for IE-related morbidity include thromboembolic complications (TEC) (cerebrovascular events (CVE): acute ischemic stroke (AIS); non-CVEs: arterial/venous TEC outside of the central nervous system). Conversely, reported mortality risk factors include age, gender, vegetation size, and TEC. Objectives: To describe the experience of a single center tertiary pediatric hospital including patients diagnosed and treated with IE over the last three decades. Methods: A retrospective chart review of pediatric patients with definite IE by the Dukes Criteria admitted to the Hospital for Sick Children between January 1978 and January 2008 was conducted. Data distribution was divided into periods I (PI) (1978-1989), PII (1990-1999), and PIII (2000-2008). Thrombotic events were included only if radiologically proven, concomitantly and/or after IE conf...

British Journal of Haematology, 2019

If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.

Biology of Blood and Marrow Transplantation, 2018

Adenovirus (AdV) is an increasingly recognized threat to recipients of allogeneic hematopoietic s... more Adenovirus (AdV) is an increasingly recognized threat to recipients of allogeneic hematopoietic stem cell transplantation (allo-HCT), particularly when infection is prolonged and unresolved. AdVance is the first multinational, multicenter study to evaluate the incidence of AdV infection in both pediatric and adult allo-HCT recipients across European transplantation centers. Medical records for patients undergoing first allo-HCT between January 2013 and September 2015 at 50 participating centers were reviewed. The cumulative incidence of AdV infection (in any sample using any assay) during the 6 months after allo-HCT was 32% (95% confidence interval [CI], 30.9% to 33.4%) among pediatric allo-HCT recipients (n = 1736) and 6% (95% CI, 4.7% to 6.4%) among adult allo-HCT recipients (n = 2540). The incidence of AdV viremia 1000 copies/mL (a common threshold for initiation of preemptive treatment) was 14% (95% CI, 13.0% to 14.8%) in pediatric recipients and 1.5% (95% CI, 1.1% to 2.0%) in adult recipients. Baseline risk factors for developing AdV viremia 1000 copies/mL included younger age, use of T cell depletion, and donor type other than matched related. Baseline demographic factors were broadly comparable across patients of all ages and identified by multivariate analyses. Notably, the incidence of AdV infection decreased stepwise with increasing age; younger adults (age 18 to 34 years) had a similar incidence as older pediatric patients (<18 years). This study provides a contemporary multicenter understanding of the incidence and risk factors for AdV infection following allo-HCT. Our findings may help optimize infection screening and intervention criteria, particularly for younger at-risk adults.

Bone marrow transplantation, Jan 15, 2018

Paediatric therapy-related acute myeloid leukaemia (t-AML) is rare and the outcome is poor. While... more Paediatric therapy-related acute myeloid leukaemia (t-AML) is rare and the outcome is poor. While allogeneic haematopoietic stem cell transplantation (HSCT) is generally the accepted modality of treatment, data regarding salvage chemotherapy, remission induction, conditioning regimens, transplant-related mortality and outcome is scarce. Between 2000 and2016, 36 children with t-AML were treated in seven UK paediatric HSCT centres. The most common salvage protocol for remission induction was FLAG with or without idarubicin and 28 patients were in complete morphological remission prior to BMT. Only 12 patients survived (33%). Transplant-related mortality (TRM) was the leading cause of death.

Pediatric Rheumatology, 2008

Journal of Pediatric Hematology/Oncology, 2011

Despite high survival rates, many survivors of hepatoblastoma develop late effects including otot... more Despite high survival rates, many survivors of hepatoblastoma develop late effects including ototoxicity and cardiomyopathy. With the goal of minimizing long-term toxicities, our institution treated hepatoblastoma with continuous infusion of doxorubicin and cisplatinum (PLADO), rather than short infusion or bolus dosing as used in other treatment protocols. This retrospective cohort study includes consecutive patients diagnosed between 1985 and 2007. Patients were scheduled for treatment with 6 cycles of continuous infusion of PLADO with resection after the third or fourth cycle. Audiograms and echocardiograms were obtained at baseline, after every 2 chemotherapy cycles and yearly after the completion of therapy. Fifty-five patients were treated (34 localized; 21 metastatic). Fifty-one patients received at least 1 cycle of PLADO. Median follow-up was 7.0 years (range, 0.11 to 17.8 y). Event-free and overall survival for these 51 patients were 72.2% (standard error 6.3%) and 75.6% (standard error 6.2%) respectively. Of the 38 survivors treated with cisplatin who had an audiogram during follow-up, 4 (11%) demonstrated severe (Brock grade 3/4) and 13 (34%) mild (Brock grade 1/2) hearing loss. At a median of 10.0 years (range, 5.0 to 13.0 y) after therapy, 2 of 41 (5%) patients who were still alive had evidence of cardiac dysfunction. Overall, continuous infusion of PLADO therapy resulted in survival rates consistent with those observed in intergroup studies, but rates of chronic cardiac and ototoxicity did not differ sufficiently from those observed after shorter infusion of PLADO therapy to warrant the use of continuous infusions.

Journal of Pediatric Hematology/Oncology, 2012

To the Editor: A 16-year-old girl (30 kg) was diagnosed with intermediate-risk acute myeloid leuk... more To the Editor: A 16-year-old girl (30 kg) was diagnosed with intermediate-risk acute myeloid leukemia and induced with daunorubicin 60mg/m for 3 days and cytarabine 100mg/m for 7 days. On day 8, she developed febrile neutropenia, with sinusitis and persistent cough. Computerized tomography revealed nodular infiltrates in lungs with perilesional haloes and mucosal thickening of the maxillary sinuses with mass in the nasal cavity. A histologic examination of the nasal mass showed filamentous fungi suggesting invasive aspergillosis. She had earlier been started on empiric antibiotics (imipenem+cilastatin and vancomycin) and amphotericin B deoxycholate (1mg/ kg/d). The culture of the fungal specimen revealed Aspergillus flavus resistant to amphotericin B, intermediate to itraconazole, and highly sensitive to voriconazole. She was started on oral voriconazole (300mg bd on day 1 followed by 200mg bd). She showed improvement in respiratory function and reduction in facial edema within 48 hours. There was no hepatic or renal dysfunction before or after starting voriconazole, and she tolerated the drug well except for transient visual hallucinations. Twelve days after starting voriconazle, she developed severe epigastric pain unresponsive to pantoprazole. Serum amylase was elevated (234 IU/mL) and computerized tomography showed pancreatitis. The neutrophils had recovered and the infection was resolving. Azole-associated pancreatitis was considered and voriconazole was stopped. The pancreatitis was managed conservatively and the patient improved. Amylase normalized within 12 days. She was in remission, and considering proven aspergillosis, there was a need for continued antifungals during consolidation using high-dose cytarabine. As the isolate was resistant to amphotericin B and caspofungin was unaffordable, voriconazole was reintroduced at 100mg bd as prophylaxis. She tolerated it well and had an uneventful course. On the day 15 of the second high-dose cytarabine course, she developed epigastric pain and vomiting. Serum amylase was elevated (637U/mL). Medication review showed that the patient was wrongly taking a dose of 200mg bd of voriconazole in the 1 week before the episode. Voriconazole was stopped and she improved with conservative management. The third course of cytarabine was uneventfully delivered without antifungal prophylaxis. Eight months after completion of therapy, she remains in remission and has had no recurrence of abdominal problems. Pancreatitis has been reported as a complication of azole use.1,2 Although other drugs including cytarabine have been implicated in the causation of pancreatitis,3 the temporal relationships noted above and the nonoccurrence of the event when cytarabine was used without azoles in the third cycle strongly point toward voriconazole as the culprit in our patient. Passier et al2 described 4 patients with itraconazole-induced pancreatitis and 42 other cases have been mentioned. The mechanism of azole-induced pancreatitis is not clear and may be idiosyncratic considering the poor predictability and low incidence. The drug literature of voriconazole mentions pancreatitis as a side effect in pediatric patients, but there are no reports in the English literature.4 Although it may be idiosyncratic, the occurrence in pediatric patients may suggest dose dependence. In our patient, pancreatitis occurred only when a higher dose of the drug was used (7mg/kg/dose) and not otherwise. We can only conjecture on the ways to avoid this side effect. Meticulous attention to doses in pediatric patients and drug level monitoring whenever such facilities are available maybe of help.5,6 Intravenous administration of voriconazole may be less toxic to the gastrointestinal tract.7 Pancreatitis is a serious toxicity of voriconazole in pediatric patients and must be kept in mind as the use of this drug is expanding.

Indian Journal of Medical and Paediatric Oncology, 2011

Peripheral T-cell lymphoma (PTCL) represents approximately 12% of lymphoid neoplasms. They are ev... more Peripheral T-cell lymphoma (PTCL) represents approximately 12% of lymphoid neoplasms. They are even rarer in children and represent only 1% of Non-Hodgkin′s lymphoma in this age group. We report a case of PTCL in a 1-year-old female child for its rarity.

Blood, 2017

Key Points Brincidofovir has superior antiadenoviral activity and safety profile compared with ci... more Key Points Brincidofovir has superior antiadenoviral activity and safety profile compared with cidofovir. Brincidofovir is highly efficacious in controlling adenoviremia during the lymphopenic phase of HCT.

Journal of Pediatric Hematology Oncology, 2007

Adenovirus is a common cause of morbidity and mortality after hemopoietic stem cell transplantati... more Adenovirus is a common cause of morbidity and mortality after hemopoietic stem cell transplantation in children. Recently the incidence, risk factors, and outcome of such infections have been better defined using improved virologic detection methods, in particular polymerase chain reaction. We have introduced intensive virologic surveillance for adenovirus in our institution including at least weekly polymerase chain reaction testing of blood and stool samples. We report on 71 prospectively monitored transplants, including 40 from unrelated donors. In total, there were 8 cases of invasive adenovirus infection, 3 of whom died. Mortality was less than in previous studies as cases were managed with antiviral chemotherapy and reduction of immune suppression. In fatal cases, there was concurrent difficult graft versus host disease making withdrawal of immune suppression therapy impossible. We describe 2 cases of graft failure in association with adenovirus viremia and its treatment that were successfully managed with further donor cell infusion.

Pediatric Blood & Cancer, 2009

We present a case of a healthy 7-year-old female with an incidental finding of a growing splenic ... more We present a case of a healthy 7-year-old female with an incidental finding of a growing splenic lesion, diagnosed as a splenic hamartoma after splenectomy. This case highlights the diagnostic challenge of splenic lesions and that the role of positron emission tomography/computerized tomography (PET/CT) in defining splenic lesions in the pediatric population remains to be defined. Pediatr Blood Cancer 2009;53:114–116. © 2009 Wiley-Liss, Inc.