RT Book, Section
A1 Kiel, Patrick J.
A1 Grove, Meagan
A2 DiPiro, Joseph T.
A2 Yee, Gary C.
A2 Posey, L. Michael
A2 Haines, Stuart T.
A2 Nolin, Thomas D.
A2 Ellingrod, Vicki
SR Print(0)
ID 1182476157
T1 Chronic Leukemias
T2 Pharmacotherapy: A Pathophysiologic Approach, 11e
YR 2020
FD 2020
PB McGraw-Hill Education
PP New York, NY
SN 9781260116816
LK accesspharmacy.mhmedical.com/content.aspx?aid=1182476157
RD 2024/04/23
AB KEY  CONCEPTS  Chronic  myeloid  leukemia  (CML)  is  defined  by  the  presence  of  the  Philadelphia  chromosome  (Ph),  a  translocation  between  chromosomes  9  and  22.  The  resulting  abnormal  fusion  protein,  p210  BCR-ABL,  phosphorylates  tyrosine  kinase  residues  and  is  constitutively  active,  resulting  in  uncontrolled  hematopoietic  cell  proliferation.  Without  treatment,  the  disease  course  of  CML  is  characterized  by  a  progressive  increase  in  white  blood  cells  over  a  period  of  years  that  ultimately  transforms  into  acute  leukemia.  The  commercially  available  tyrosine  kinase  inhibitors,  imatinib,  dasatinib,  nilotinib,  bosutinib,  and  ponatinib  have  demonstrated  efficacy  in  the  treatment  of  newly  diagnosed  CML  patients  and  in  patients  with  either  accelerated  phase  or  blast  crisis.  CML  monitoring  requires  the  assessment  of  milestones  throughout  the  therapy  such  as  hematologic,  cytogenetic,  and  molecular  responses,  the  ideal  of  which  is  a  molecular  response.  Allogeneic  hematopoietic  stem  cell  transplant  (HSCT)  is  the  only  known  curative  treatment  option  for  CML  and  is  reserved  for  patients  with  a  suitable  donor  and  progression  after  treatment  with  tyrosine  kinase-based  therapy.  The  management  of  chronic  lymphocytic  leukemia  (CLL)  is  highly  individualized  and  includes  observation  in  patients  with  early-stage  disease  and  treatment  with  targeted  therapy,  chemotherapy,  biologic  therapy,  or  both  in  patients  with  more  advanced  disease.  Alemtuzumab,  ofatumumab,  obinutuzumab,  and  rituximab  are  monoclonal  antibodies  that  are  indicated  for  the  treatment  of  CLL.  Regimens  such  as  fludarabine,  cyclophosphamide,  and  rituximab  are  considered  as  first-line  therapy  for  patients  with  CLL  who  are  younger  or  have  more  aggressive  disease.  Novel  agents  such  as  ibrutinib,  idelalisib,  duvelisib,  venetoclax,  and  acalabrutinib  provide  an  orally  administered  option  for  the  treatment  of  CLL.  Ibrutinib  is  approved  for  treatment  of  previously  untreated  patients  and  for  patients  with  relapsed  disease  who  have  received  at  least  one  prior  therapy.  Oral  agents  such  as  venetoclax  and  idelalisib  in  combination  with  monoclonal  antibodies  are  now  first-line  treatment  options  in  patients  with  comorbidities.