TY - JOUR
T1 - Resistant or refractory cytomegalovirus infections after hematopoietic cell transplantation
T2 - Diagnosis and management
AU - Khawaja, Fareed
AU - Batista, Marjorie V.
AU - El Haddad, Lynn
AU - Chemaly, Roy F.
N1 - Publisher Copyright:
© 2019 Lippincott Williams and Wilkins. All rights reserved.
PY - 2019
Y1 - 2019
N2 - Purpose of review Refractory or resistant cytomegalovirus (CMV) infections are challenging complications after hematopoietic cell transplantation (HCT). Most refractory or resistant CMV infections are associated with poor outcomes and increased mortality. Prompt recognition of resistant or refractory CMV infections, understanding the resistance pathways, and the treatment options in HCT recipients are imperative. Recent findings New definitions for refractory and resistant CMV infections in HCT recipients have been introduced for future clinical trials. Interestingly, refractory CMV infections are more commonly encountered in HCT recipients when compared with resistant CMV infections. CMV terminase complex mutations in UL56, UL89, and UL51 could be associated with letermovir resistance; specific mutations in UL56 are the most commonly encountered in clinical practice. Finally, brincidofovir, maribavir, letermovir, and CMV-specific cytotoxic T-cell therapy expanded our treatment options for refractory or resistant CMV infections. Summary Many advances have been made to optimize future clinical trials for management of refractory or resistant CMV infections, and to better understand new resistance mechanisms to novel drugs. New drugs or strategies with limited toxicities are needed to improve outcomes of difficult to treat CMV infections in HCT recipients.
AB - Purpose of review Refractory or resistant cytomegalovirus (CMV) infections are challenging complications after hematopoietic cell transplantation (HCT). Most refractory or resistant CMV infections are associated with poor outcomes and increased mortality. Prompt recognition of resistant or refractory CMV infections, understanding the resistance pathways, and the treatment options in HCT recipients are imperative. Recent findings New definitions for refractory and resistant CMV infections in HCT recipients have been introduced for future clinical trials. Interestingly, refractory CMV infections are more commonly encountered in HCT recipients when compared with resistant CMV infections. CMV terminase complex mutations in UL56, UL89, and UL51 could be associated with letermovir resistance; specific mutations in UL56 are the most commonly encountered in clinical practice. Finally, brincidofovir, maribavir, letermovir, and CMV-specific cytotoxic T-cell therapy expanded our treatment options for refractory or resistant CMV infections. Summary Many advances have been made to optimize future clinical trials for management of refractory or resistant CMV infections, and to better understand new resistance mechanisms to novel drugs. New drugs or strategies with limited toxicities are needed to improve outcomes of difficult to treat CMV infections in HCT recipients.
KW - cytomegalovirus
KW - letermovir
KW - refractory
KW - resistance
KW - stem cell transplant
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U2 - 10.1097/QCO.0000000000000607
DO - 10.1097/QCO.0000000000000607
M3 - Review article
C2 - 31567572
AN - SCOPUS:85072639841
SN - 0951-7375
JO - Current opinion in infectious diseases
JF - Current opinion in infectious diseases
ER -