RT Book, Section
A1 Byrd, John C.
A1 Kittai, Adam S.
A1 Awan, Farrukh T.
A2 Kaushansky, Kenneth
A2 Prchal, Josef T.
A2 Burns, Linda J.
A2 Lichtman, Marshall A.
A2 Levi, Marcel
A2 Linch, David C.
SR Print(0)
ID 1178750621
T1 Chronic Lymphocytic Leukemia
T2 Williams Hematology, 10e
YR 2021
FD 2021
PB McGraw-Hill Education
PP New York, NY
SN 9781260464122
LK accessmedicine.mhmedical.com/content.aspx?aid=1178750621
RD 2024/04/17
AB SUMMARYChronic  lymphocytic  leukemia  (CLL)  is  a  malignancy  of  small  B  cells  characterized  by  progressive  lymphocytosis,  lymphadenopathy,  splenomegaly,  and  cytopenias.  The  progressive  accumulation  of  leukemic  B  cells  is  a  consequence  of  the  constitutive  B-cell  receptor  activation,  defective  apoptosis,  and  inappropriate  survival  signals  derived  from  the  microenvironment.  The  median  age  of  onset  of  CLL  is  70  years  and  it  is  very  uncommon  in  younger  adults  and  rare  in  children.  It  has  a  relatively  high  coincidence  in  family  members.  The  disease  is  characterized  by  a  monoclonal  B-cell  lymphocytosis,  and  replacement  of  marrow  with  neoplastic  B  lymphocytes,  which  may  result  in  anemia  and  thrombocytopenia,  superficial  and  deep  lymphadenopathy,  and  splenomegaly.  The  monoclonal  B  cells  are  characteristically  positive  for  CD19,  dim  CD20,  and  dim  surface  immunoglobulin,  and  are  negative  for  CD10,  CD79b,  and  FMC7  by  flow  cytometry.  Progressive  disease  results  in  dysregulation  of  the  cellular  and  humoral  components  of  the  effector  immune  system  and  hypogammaglobulinemia  with  a  resultant  increase  in  the  incidence  of  infectious  complications,  which  constitutes  the  leading  cause  of  morbidity  and  mortality  in  this  disease.  Autoimmune  hemolytic  anemia  and  or  autoimmune  thrombocytopenia  occur  in  a  significant  minority  of  patients.  Monoclonal  B-cell  lymphocytosis  is  often  a  precursor  of  CLL.  The  former  is  defined  as  the  presence  of  a  monoclonal  population  of  B  lymphocytes  in  the  blood  at  a  level  less  than  5  ×  109  monoclonal  B  cells/L  and  an  absence  of  other  signs  of  CLL.  Approximately  1%  of  such  individuals  per  year  have  progression  to  CLL.  Significant  therapeutic  advances  for  CLL  have  been  realized,  especially  with  the  development  of  well-tolerated  targeted  small  molecules  directed  at  inhibiting  B-cell  receptor  signaling,  antiapoptotic  networks,  and  microenvironmental  protection.  Although  not  curative,  these  therapies  are  replacing  older  chemotherapy  approaches  in  many  situations,  with  significant  improvements  in  patient  outcomes.  Challenges  for  the  future  of  CLL  management  include  responding  to  development  of  resistance  to  these  agents,  survivorship  issues  that  arise  from  them,  the  propensity  to  Richter  transformation,  a  more  aggressive  B-cell  malignancy,  and  disease-related  immune  suppression  that  contributes  to  morbidity  and  mortality  of  this  disease.