Carboplatin/thiotepa

Abstract

In a case series, a 5-year-old girl and a 6-month-old boy were described, who developed pulmonary arterial hypertension while receiving carboplatin and thiotepa [routes and dosages not stated].Case 1: The girl, who had a history of prematurity completing 27 weeks gestation presented to hospital and underwent imaging scan, which demonstrated a posterior fossa mass with associated hydrocephalus, and surgical resection was performed immediately. Pathology confirmed medulloblastoma of WHO Grade IV and extensive metastatic disease. She was enrolled in Head Start 4 study and initiated on three induction cycles of vincristine, cisplatin, cyclophosphamide, etoposide and methotrexate. Subsequently, she received three tandem cycles of consolidation chemotherapy of carboplatin and thiotepa followed by autologous haematopoietic stem cell transplant (HSCT). Her pre-induction echocardiography was normal. After 1 month of her third autologous HSCT, she presented to ICU for tachypnoea and oxygen desaturation. Chest CT demonstrated pulmonary artery dilation and multiple patchy ground glass opacities in the lung parenchyma. Echocardiogram showed an estimated systolic pulmonary artery pressure (PAP) measuring three-quarters systemic. N-terminal pro brain natriuretic peptide level (NT-pro BNP) raised at 4454 pg/mL. She was then started on digoxin, furosemide and spironolactone. She could not complete a 6 minute walk test because of limitations in her gait. Polysomnography showed evidences of moderate obstructive sleep apnea. No aspiration was observed in swallow studies and treatment was given for gastroesophageal reflux. Cardiac catheterisation confirmed pulmonary arterial hypertension (PAH) with a mean PAP of 34mm Hg and pulmonary vascular resistance index (PVRi) of 5.4 Wood Units m 2 . Sildenafil was initiated and supplemental oxygen support was given for 10 weeks. Her clinical symptoms improved with continued therapy with normalisation of echocardiogram findings and NT-pro BNP levels within 4 months. Digoxin and diuretics were tapered off. And, sildenafil was discontinued after a year. However, her tumor recurred. After 6 months, she suffered a severe stroke. Unfortunately, she died in hospice care.Case 2: The boy, who presented to the hospital with macrocephaly, vomiting, lethargy and abnormal eye movements underwent brain MRI, which showed a large and heterogeneous right temporal-parietal region mass, and immediate debulking was performed. An atypical teratoid rhabdoid tumor of WHO grade IV was confirmed. He received 3 cycles of induction therapy of vincristine, cisplatin, cyclophosphamide, etoposide and methotrexate. Subsequently, he received consolidation chemotherapy of carboplatin, thiotepa and HSCT. After 2 weeks of the second cycle of consolidation therapy, he developed hypoxia, requiring supplemental oxygen and shifted in the ICU. Echocardiogram demonstrated elevated systolic PAP, mild right ventricular dilation with fair systolic function and a small pericardial effusion. NT-pro BNP was 1396 pg/mL. He then received fur...