Contributions
Abstract: PB1653
Type: Publication Only
Background
Hepatitis C virus (HCV) infection causing Macrophage Activation Syndrome (MAS) in pediatric population has never been reported previously.
Aims
To describe a case of MAS associated with HCV infection in a pediatric patient.
Methods
We describe a case of MAS associated with HCV infection in a girl with acute lymphoblastic leukemia (ALL) which underwent hematopoietic stem cell transplantation (HSCT) and attained viral suppression with ledipasvir/sofosbuvir.
Results
A 13-year-old Ukranian girl with pro-B cell ALL t(4;11)(q21-q23), and HCV-genotype 1 infection (HCV-RNA 629.500 IU/mL) received chemotherapy according to the AIEOP ALL 2000 protocol and a myeloablative allogeneic HSCT from MUD; the engraftment was at day +19 after HSCT (neutrophils 580/µL). At day +22 the patient presented epigastric pain, icteric skin, fever (39°C), vomiting and diarrhea. Blood exams showed progressive cytopenia (WBC 670/µL, N 120/µL, Hb 9.0 g/dL, PLT 22.000/µL), hypofibrinogenemia (fibrinogen 100 mg/dL), ALT 283U/L, AST 323U/L, hyperbilirubinemia (total bilirubin 11.0 mg/dL, direct bilirubin 10.4 mg/dL), hypertrigliceridemia (tryglicerides 460mg/dL), hyperferritinemia (ferritin 67.769 ng/mL). Blood culture was negative; CMV, EBV Adenovirus-PCR were negative; serology for hepatitis A and HBV-DNA were negative but HCV-RNA was >100.000.000 IU/mL. Clinical examination and abdominal ultrasound revealed hepatosplenomegaly and BOM showed CR for ALL but increased histiocytes and macrophages with hemophagocytosis; no signs of GvHD. MAS secondary to HCV infection was suspected and treatment with high-dose corticosteroids, cyclosporine-A and ledipasvir/sofosbuvir was initiated. At day +38 after HSCT fever disappeared, laboratory exams improved and quantitative PCR for HCV-RNA decreased (19.114.275 IU/mL); after 4 weeks of antiviral treatment HCV-RNA was negative. At day +82 the patient presented fever (39.1°C), headache, left facial droop, right convergent strabismus, aphasia, disequilibrium, gait unsteadiness, absence of deep tendon reflexes, clumsiness of both hands and drowsiness. Brain-MRI showed multiple supra and infratentorial areas of mass-like appearance with central necrosis surrounded by a hyperintense ring; a broad laboratory workup confirmed cerebral reactivation of MAS. Thus, the dose of intravenous corticosteroids was increased and intravenous mannitol was administered to reduce intracranial pressure; phenobarbital and carbamazepine were initiated. The antiviral therapy with ledipasvir/sofosbuvir was discontinued at day +200 (for a total of 6 months). At follow-up, ten months after HSCT the girl developed chronic kidney failure. Twelve months after HSCT the patient is alert, fully oriented, with fluent speech and normal language; she has a permanent left facial droop, a diffuse left lower extremity weakness, reduced deep tendon reflexes and steppage gait on her left. Brain-MRI shows neither new lesions nor an enlargement of the previously described areas; the last quantitative PCR for HCV-RNA is negative and BOM aspirate shows CR for ALL and MAS with full donor chimerism.
Conclusion
In our case MAS was probably triggered by HCV and the early treatment with ledipasvir/sofosbuvir revealed to be highly effective for HCV infection and well tolerated by the patient; despite viral clearance, HLH persisted over time with permanent neurologic impairment and chronic kidney failure.
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, Hematopoietic cell transplantation, Hepatitis C virus, Macrophage
Abstract: PB1653
Type: Publication Only
Background
Hepatitis C virus (HCV) infection causing Macrophage Activation Syndrome (MAS) in pediatric population has never been reported previously.
Aims
To describe a case of MAS associated with HCV infection in a pediatric patient.
Methods
We describe a case of MAS associated with HCV infection in a girl with acute lymphoblastic leukemia (ALL) which underwent hematopoietic stem cell transplantation (HSCT) and attained viral suppression with ledipasvir/sofosbuvir.
Results
A 13-year-old Ukranian girl with pro-B cell ALL t(4;11)(q21-q23), and HCV-genotype 1 infection (HCV-RNA 629.500 IU/mL) received chemotherapy according to the AIEOP ALL 2000 protocol and a myeloablative allogeneic HSCT from MUD; the engraftment was at day +19 after HSCT (neutrophils 580/µL). At day +22 the patient presented epigastric pain, icteric skin, fever (39°C), vomiting and diarrhea. Blood exams showed progressive cytopenia (WBC 670/µL, N 120/µL, Hb 9.0 g/dL, PLT 22.000/µL), hypofibrinogenemia (fibrinogen 100 mg/dL), ALT 283U/L, AST 323U/L, hyperbilirubinemia (total bilirubin 11.0 mg/dL, direct bilirubin 10.4 mg/dL), hypertrigliceridemia (tryglicerides 460mg/dL), hyperferritinemia (ferritin 67.769 ng/mL). Blood culture was negative; CMV, EBV Adenovirus-PCR were negative; serology for hepatitis A and HBV-DNA were negative but HCV-RNA was >100.000.000 IU/mL. Clinical examination and abdominal ultrasound revealed hepatosplenomegaly and BOM showed CR for ALL but increased histiocytes and macrophages with hemophagocytosis; no signs of GvHD. MAS secondary to HCV infection was suspected and treatment with high-dose corticosteroids, cyclosporine-A and ledipasvir/sofosbuvir was initiated. At day +38 after HSCT fever disappeared, laboratory exams improved and quantitative PCR for HCV-RNA decreased (19.114.275 IU/mL); after 4 weeks of antiviral treatment HCV-RNA was negative. At day +82 the patient presented fever (39.1°C), headache, left facial droop, right convergent strabismus, aphasia, disequilibrium, gait unsteadiness, absence of deep tendon reflexes, clumsiness of both hands and drowsiness. Brain-MRI showed multiple supra and infratentorial areas of mass-like appearance with central necrosis surrounded by a hyperintense ring; a broad laboratory workup confirmed cerebral reactivation of MAS. Thus, the dose of intravenous corticosteroids was increased and intravenous mannitol was administered to reduce intracranial pressure; phenobarbital and carbamazepine were initiated. The antiviral therapy with ledipasvir/sofosbuvir was discontinued at day +200 (for a total of 6 months). At follow-up, ten months after HSCT the girl developed chronic kidney failure. Twelve months after HSCT the patient is alert, fully oriented, with fluent speech and normal language; she has a permanent left facial droop, a diffuse left lower extremity weakness, reduced deep tendon reflexes and steppage gait on her left. Brain-MRI shows neither new lesions nor an enlargement of the previously described areas; the last quantitative PCR for HCV-RNA is negative and BOM aspirate shows CR for ALL and MAS with full donor chimerism.
Conclusion
In our case MAS was probably triggered by HCV and the early treatment with ledipasvir/sofosbuvir revealed to be highly effective for HCV infection and well tolerated by the patient; despite viral clearance, HLH persisted over time with permanent neurologic impairment and chronic kidney failure.
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, Hematopoietic cell transplantation, Hepatitis C virus, Macrophage