TY  - CHAP
M1  - Book, Section
TI  - Chronic Myelogenous Leukemia and Related Disorders
A1  - Liesveld, Jane L.
A1  - Lichtman, Marshall A.
A2  - Kaushansky, Kenneth
A2  - Lichtman, Marshall A.
A2  - Prchal, Josef T.
A2  - Levi, Marcel M.
A2  - Press, Oliver W.
A2  - Burns, Linda J.
A2  - Caligiuri, Michael
PY  - 2015
T2  - Williams Hematology, 9e
AB  - SUMMARYThe  chronic  myelogenous  leukemias  (CMLs)  include  BCR  rearrangement-positive  CML,  chronic  myelomonocytic  leukemia,  juvenile  myelomonocytic  leukemia,  chronic  neutrophilic  leukemia,  chronic  eosinophilic  leukemia,  and  chronic  basophilic  leukemia.  The  term  chronic,  in  contrast  to  acute,  once  had  prognostic  implications.  However,  although  the  terms  remain  useful  for  nosology,  they  no  longer  reflect  an  invariable  difference  in  prognosis.  For  example,  acute  myelogenous  leukemia  in  children  and  young  adults  has  higher  remission  and  cure  rates  than  juvenile  or  chronic  myelomonocytic  leukemia  in  children  or  adults,  respectively.  BCR  rearrangement-positive  CML  presents  with  anemia,  exaggerated  granulocytosis,  a  large  proportion  of  myelocytes  and  mature  neutrophils,  absolute  basophilia,  normal  or  elevated  platelet  counts,  and,  frequently,  splenomegaly.  The  marrow  is  intensely  hypercellular,  and  marrow  cells  contain  the  Philadelphia  (Ph)  chromosome  in  approximately  90  percent  of  cases  by  cytogenetic  analysis.  A  rearrangement  of  the  BCR  gene  on  chromosome  22  is  present  by  molecular  diagnostic  analysis  in  approximately  96  percent  of  cases  that  have  a  classic  morphologic  appearance.  The  BCR-rearranged  form  of  the  disease  usually  responds  to  a  tyrosine  kinase  inhibitor,  and  median  survival  has  been  extended  significantly.  Allogeneic  hematopoietic  stem  cell  transplantation  can  cure  the  disease,  especially  if  the  transplantation  is  applied  early  in  the  chronic  phase,  although  this  approach  is  now  uncommon  as  a  result  of  the  effect  of  tyrosine  kinase  inhibitor  therapy.  The  effect  of  stem  cell  transplantation  is  related  in  part  to  a  robust  graft-versus-leukemia  effect,  engendered  by  donor  T  lymphocytes.  The  natural  history  of  the  chronic  phase  is  to  evolve  into  an  accelerated  phase  that  often  terminates  in  acute  leukemia  (blast  crisis),  but  the  frequency  of  this  progression  has  been  markedly  decreased  by  the  advent  of  tyrosine  kinase  inhibitors.  Blast  crisis  results  in  a  myelogenous  leukemic  phenotype  in  75  percent  of  cases  and  a  lymphoblastic  leukemic  phenotype  in  approximately  25  percent  of  cases.  Ph  chromosome–positive  acute  myeloblastic  leukemia  (AML)  may  appear  de  novo  in  approximately  1  percent  of  cases  of  AML,  and  Ph  chromosome–positive  acute  lymphocytic  leukemia  (ALL)  may  occur  de  novo  in  approximately  20  percent  of  cases  of  adult  ALL  and  approximately  5  percent  of  childhood  ALL  cases.  In  Ph  chromosome–positive  ALL,  the  translocation  between  chromosomes  9  and  22  results  in  the  fusion  gene  encoding  a  mutant  tyrosine  kinase  oncoprotein  that  may  be  identical  in  size  to  that  in  classic  CML  (210  kDa)  in  approximately  one-third  of  cases.  A  smaller  mutant  tyrosine  kinase  (190  kDa)  is  encoded  in  approximately  two-thirds  of  cases.  In  children,  the  cells  in  approximately  90  percent  of  cases  contain  a  190-kDa  mutant  tyrosine  kinase.  These  acute  leukemias  may  reflect  (1)  the  presentation  of  CML  in  acute  blastic  transformation  without  a  preceding  chronic  phase  or  (2)  de  novo  cases  resulting  from  a  BCR-ABL1  mutation  occurring  in  a  different  early  hematopoietic  cell  from  the  event  in  CML  or  with  as  yet  unidentified  modifying  gene  alterations.  Chronic  myelomonocytic  leukemia  has  variable  presenting  features.  Anemia  may  be  accompanied  by  mildly  or  moderately  elevated  leukocyte  counts;  an  elevated  total  monocyte  count;  a  low,  normal,  or  elevated  platelet  count;  and  sometimes  splenomegaly.  Although  cytogenetic  abnormalities  may  be  present,  there  is  no  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/18
UR  - accessmedicine.mhmedical.com/content.aspx?aid=1133151949
ER  -