ABSTRACT
Post-transplant lymphoproliferative disorder (PTLD) in the central nervous system (CNS) is a very rare complication of haematopoietic stem cell transplant (HSCT) and has a dismal prognosis. We report the successful treatment of this disorder with intrathecal rituximab therapy in two children who developed isolated CNS PTLD after HSCT. These children had failed to respond to standard chemotherapy, intravenous rituximab and EBV specific cellular therapy.
Subject(s)
Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antineoplastic Agents/administration & dosage , Central Nervous System Diseases/drug therapy , Epstein-Barr Virus Infections/drug therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Lymphoproliferative Disorders/drug therapy , Virus Activation , Central Nervous System Diseases/etiology , Central Nervous System Diseases/pathology , Child, Preschool , Epstein-Barr Virus Infections/etiology , Humans , Injections, Spinal , Leukemia, B-Cell/drug therapy , Leukemia, B-Cell/etiology , Leukemia, B-Cell/pathology , Lymphohistiocytosis, Hemophagocytic/drug therapy , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphohistiocytosis, Hemophagocytic/pathology , Lymphoproliferative Disorders/etiology , Lymphoproliferative Disorders/pathology , Magnetic Resonance Imaging , Male , RituximabABSTRACT
Niemann-Pick disease type C2 (NPC2) is caused by the inherited deficiency of a lysosomal cholesterol transport protein, NPC2 protein. Many cases of NPC2 present in early infancy with inflammatory lung disease, with subsequent severe neurological disease and death in early childhood. This disease is theoretically correctable by bone marrow transplantation (BMT), as the NPC2 protein is small and soluble and secreted and recaptured by the mannose-6-phosphate pathway. In this report we describe the first successful allogeneic bone marrow transplantation for this condition in a 16-month-old boy homozygous for the NPC2 p.E20X mutation, which has hitherto been reported to cause disease with a severe phenotype. During BMT there was an initial improvement of the established respiratory illness, with the immune suppression associated with transplant conditioning, but there was subsequent marked deterioration at the time of immune reconstitution and donor cell engraftment. This 'graft versus substrate' reaction was managed with intensive immune suppressant therapy, and it gradually resolved as the substrate was cleared by the engrafted donor macrophages. All immune suppression was withdrawn 18 months after transplantation, and his respiratory illness has resolved. He walked independently at 24 months and is continuing to reach development milestones after receiving his transplant. We conclude that the successful treatment of Niemann-Pick C2 therefore seems likely to be associated with a severe post-transplantation 'graft versus substrate' reaction that requires intense immune suppression before eventual resolution.
Subject(s)
Bone Marrow Transplantation/adverse effects , Carrier Proteins/genetics , Glycoproteins/genetics , Graft vs Host Disease/diagnosis , Graft vs Host Disease/immunology , Immunosuppressive Agents/therapeutic use , Macrophages/transplantation , Niemann-Pick Disease, Type C/surgery , Respiratory Tract Infections/immunology , Transplantation Conditioning/methods , Brain/pathology , Child Development , Drug Administration Schedule , Glutamic Acid , Glycoproteins/deficiency , Graft vs Host Disease/drug therapy , Graft vs Host Disease/therapy , Homozygote , Humans , Immune Reconstitution Inflammatory Syndrome/immunology , Immunosuppressive Agents/administration & dosage , Infant , Macrophages/drug effects , Macrophages/immunology , Magnetic Resonance Imaging , Male , Motor Skills , Mutation , Niemann-Pick Disease, Type C/genetics , Phenotype , Pneumonia/immunology , Respiratory Tract Infections/therapy , Severity of Illness Index , Transplantation, Homologous , Treatment Outcome , Vesicular Transport ProteinsABSTRACT
A 9-year-old girl presented with apparent meningococcal septicemia and developed acute renal failure after 48 hours of treatment with antibiotics and analgesics. Early ultrasound scanning demonstrated mild bilateral hydronephrosis and hydroureter. Intravenous urography showed slow contrast uptake with delay nephrogram and no contrast entering the bladder. Repeat ultrasonography revealed bilateral papillary irregularity and echogenic debris in the distal ureters. Bilateral double-J stents were inserted cystoscopically, resulting in prompt polyuria and a return of normal renal function. Although rare, recognition of sloughed papilla in papillary necrosis causing ureteral obstruction can lead to early management with no long-term sequelae.
Subject(s)
Kidney Papillary Necrosis/complications , Kidney Papillary Necrosis/diagnosis , Ureteral Obstruction/etiology , Acute Disease , Acute Kidney Injury/etiology , Child , Cystoscopy , Female , Humans , Hydronephrosis/diagnostic imaging , Hydronephrosis/etiology , Kidney/diagnostic imaging , Kidney Papillary Necrosis/diagnostic imaging , Kidney Papillary Necrosis/etiology , Sepsis/complications , Stents , Ultrasonography , Ureteral Obstruction/therapy , Urinary CatheterizationABSTRACT
The incidence of bladder diverticula is low and identification is usually straightforward with contrast studies. We present a case of a child who had a clearly identified bladder diverticulum as well as a soft-tissue lesion in the posterior wall of the bladder that was suspected to be a rhabdomyosarcoma. Despite ultrasound scanning, micturating cystourethrogram, computed tomography and cystoscopy, open surgery was required to rule out tumour.
