Multiple drugs

Multiple drugs Reactions 1680, p245 - 2 Dec 2017 Various toxicities: case report A 26-year-old man developed cerebral post-transplant lymphoproliferative disorder (PTLD), reactivation of cytomegalovirus (CMV), Pneumocystis jirovecii pneumonia, sustained leucopenia, sepsis and E.coli and CMV pneumonia [not all outcomes stated] during treatment with dexamethasone, methotrexate, methylprednisolone, mycophenolate sodium [mycofenolate sodium] and rituximab [not all dosages and routes stated]. The man was admitted with a new-onset of headache and blurred vision. He had a history of end-stage kidney disease since 1989 and had undergone a kidney transplant in 1997. On admission, he was on mycophenolate sodium 720mg twice a day and methylprednisolone 4mg once a day. He also had a history of pre-existing renal impairment. A brain CT and MRI scans demonstrated several contrast enhancing intracerebral lesions with perifocal oedema. Treatment with methylprednisolone was discontinued and dexamethasone was started to reduce perifocal oedma. A diagnosis of cerebral PTLD (diffuse large B-cell lymphoma positive for Ebstein-Barr virus) was made histologically. He was started on an initial chemotherapy regimen: five cycles of high dose cytarabin and IV rituximab 375 mg/qm. A repeat MRI showed complete remission of PTLD. However, the impairment of the transplant function exacerbated. In August-September 2013, CMV reactivated and he developed P. jirovecii pneumonia. He was started on antiviral and antibiotic therapy. The chemotherapy was switched to only rituximab 500 mg/qm. The dose of mycophenolate sodium was reduced to 360mg twice a day because of persistent leucopenia and infections. In December 2013, he experienced generalised seizure. A repeat cerebral MRI revealed recurrence of PTLD. The man was started on a high-dose IV methotrexate 4 g/m , folinic acid [leucovorin] and IV rituximab 500 mg/m along with strenuous hydration. The baseline kidney function remained reduced without any sign of acute kidney injury, therefore a high dose methotrexate therapy was continued under supportive high-flux haemodialysis. Heparin [unfractionated heparin] was administered during dialysis sessions. The dialysis procedure was started, 24 hours after the methotrexate administration until the methotrexate serum level was undetectable. However, ten days after the methotrexate use, a lowest level of leucocytes 1.11 /nL was th noted. On the 13 day of chemotherapy administration, he developed severe CMV and E.coli pneumonia, sepsis and acute kidney transplant failure. He was transferred to the ICU and was on invasive ventilation. The sepsis was managed by terminating treatment with mycophenolate sodium, and initiating antiviral and antibiotic therapy. In January 2014, a follow-up MRI scan displayed only small regredience of PTLD. He received radiotherapy but no relevant response was achieved. Author comment: "PTLD are lymphoid and/or plasmatic proliferations, which develop under the condition of continuous immunosuppression". "Substantial additional risk factors such as post-transplant immunosuppressive therapy, impaired kidney function, and rituximab could also have contributed to the development of the infection." "[S]ustained elevated plasma [methotrexate] concentrations, which in turn may lead to increased hematological toxicity." Reshetnik A, et al. High-flux hemodialysis after administering high-dose methotrexate in a patient with posttransplant lymphoproliferative disease and impaired renal function. Clinical Case Reports 3: 932-936, No. 11, Nov 2015. Available from: URL: http://doi.org/10.1002/ccr3.302 - Germany 803284605 0114-9954/17/1680-0001/$14.95 Adis © 2017 Springer International Publishing AG. All rights reserved Reactions 2 Dec 2017 No. 1680 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Reactions Weekly Springer Journals

Multiple drugs

Reactions Weekly , Volume 1680 (1) – Dec 2, 2017
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Publisher
Springer International Publishing
Copyright
Copyright © 2017 by Springer International Publishing AG, part of Springer Nature
Subject
Medicine & Public Health; Drug Safety and Pharmacovigilance; Pharmacology/Toxicology
ISSN
0114-9954
eISSN
1179-2051
D.O.I.
10.1007/s40278-017-39176-2
Publisher site
See Article on Publisher Site

Abstract

Reactions 1680, p245 - 2 Dec 2017 Various toxicities: case report A 26-year-old man developed cerebral post-transplant lymphoproliferative disorder (PTLD), reactivation of cytomegalovirus (CMV), Pneumocystis jirovecii pneumonia, sustained leucopenia, sepsis and E.coli and CMV pneumonia [not all outcomes stated] during treatment with dexamethasone, methotrexate, methylprednisolone, mycophenolate sodium [mycofenolate sodium] and rituximab [not all dosages and routes stated]. The man was admitted with a new-onset of headache and blurred vision. He had a history of end-stage kidney disease since 1989 and had undergone a kidney transplant in 1997. On admission, he was on mycophenolate sodium 720mg twice a day and methylprednisolone 4mg once a day. He also had a history of pre-existing renal impairment. A brain CT and MRI scans demonstrated several contrast enhancing intracerebral lesions with perifocal oedema. Treatment with methylprednisolone was discontinued and dexamethasone was started to reduce perifocal oedma. A diagnosis of cerebral PTLD (diffuse large B-cell lymphoma positive for Ebstein-Barr virus) was made histologically. He was started on an initial chemotherapy regimen: five cycles of high dose cytarabin and IV rituximab 375 mg/qm. A repeat MRI showed complete remission of PTLD. However, the impairment of the transplant function exacerbated. In August-September 2013, CMV reactivated and he developed P. jirovecii pneumonia. He was started on antiviral and antibiotic therapy. The chemotherapy was switched to only rituximab 500 mg/qm. The dose of mycophenolate sodium was reduced to 360mg twice a day because of persistent leucopenia and infections. In December 2013, he experienced generalised seizure. A repeat cerebral MRI revealed recurrence of PTLD. The man was started on a high-dose IV methotrexate 4 g/m , folinic acid [leucovorin] and IV rituximab 500 mg/m along with strenuous hydration. The baseline kidney function remained reduced without any sign of acute kidney injury, therefore a high dose methotrexate therapy was continued under supportive high-flux haemodialysis. Heparin [unfractionated heparin] was administered during dialysis sessions. The dialysis procedure was started, 24 hours after the methotrexate administration until the methotrexate serum level was undetectable. However, ten days after the methotrexate use, a lowest level of leucocytes 1.11 /nL was th noted. On the 13 day of chemotherapy administration, he developed severe CMV and E.coli pneumonia, sepsis and acute kidney transplant failure. He was transferred to the ICU and was on invasive ventilation. The sepsis was managed by terminating treatment with mycophenolate sodium, and initiating antiviral and antibiotic therapy. In January 2014, a follow-up MRI scan displayed only small regredience of PTLD. He received radiotherapy but no relevant response was achieved. Author comment: "PTLD are lymphoid and/or plasmatic proliferations, which develop under the condition of continuous immunosuppression". "Substantial additional risk factors such as post-transplant immunosuppressive therapy, impaired kidney function, and rituximab could also have contributed to the development of the infection." "[S]ustained elevated plasma [methotrexate] concentrations, which in turn may lead to increased hematological toxicity." Reshetnik A, et al. High-flux hemodialysis after administering high-dose methotrexate in a patient with posttransplant lymphoproliferative disease and impaired renal function. Clinical Case Reports 3: 932-936, No. 11, Nov 2015. Available from: URL: http://doi.org/10.1002/ccr3.302 - Germany 803284605 0114-9954/17/1680-0001/$14.95 Adis © 2017 Springer International Publishing AG. All rights reserved Reactions 2 Dec 2017 No. 1680

Journal

Reactions WeeklySpringer Journals

Published: Dec 2, 2017

References

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