RT Book, Section
A1 Spinner, Michael A.
A1 Mou, Eric
A1 Advani, Ranjana H.
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 1180447961
T1 Hodgkin Lymphoma
T2 Williams Hematology, 10e
YR 2021
FD 2021
PB McGraw-Hill Education
PP New York, NY
SN 9781260464122
LK hemonc.mhmedical.com/content.aspx?aid=1180447961
RD 2024/04/18
AB SUMMARYHodgkin  lymphoma  is  divided  into  two  distinct  entities  by  the  2016  World  Health  Organization  classification,  classic  Hodgkin  lymphoma  (cHL)  and  nodular  lymphocyte-predominant  Hodgkin  lymphoma  (NLPHL),  constituting  approximately  95%  and  5%  of  cases,  respectively.  Both  cHL  and  NLPHL  are  derived  from  malignant  transformation  of  a  mature  B  cell  at  the  germinal  center  stage  of  differentiation,  but  their  morphologic,  immunophenotypic,  and  clinical  features  are  distinct.  cHL  is  characterized  pathologically  by  multinucleated  Hodgkin  and  Reed-Sternberg  (HRS)  cells  embedded  within  a  mixed  infiltrate  of  inflammatory  cells.  HRS  cells  contain  monoclonal  immunoglobulin  gene  rearrangements  but  have  lost  most  of  the  B-cell–specific  expression  program.  Multiple  signaling  pathways  and  transcription  factors  are  deregulated  in  cHL,  and  genetic  lesions  involving  the  Janus  kinase–signal  transducer  and  activator  of  transcription  and  nuclear  factor-κB  (NF-κB)  pathways  are  commonly  identified.  HRS  cells  harbor  near  universal  genetic  alterations  of  chromosome  9p24.1,  leading  to  overexpression  of  the  programmed  death-1  (PD-1)  ligands,  PD-L1  and  PD-L2,  contributing  to  immune  evasion.  Epstein-Barr  virus  (EBV)  is  an  important  environmental  factor  in  the  pathogenesis  of  cHL  and  also  leads  to  upregulation  of  PD-L1  and  PD-L2  and  activation  of  the  NF-κB  pathway.  cHL  typically  spreads  in  a  predictable,  contiguous  manner  and  is  classified  into  four  stages,  I  to  IV.  cHL  is  treated  with  the  intent  to  cure  the  disease  in  all  stages,  and  the  long-term  survival  rate  exceeds  85%.  Doxorubicin-containing  chemotherapy  plays  a  major  role  in  treatment  of  all  stages  of  the  disease,  and  consolidative  radiotherapy  is  commonly  used  after  an  abbreviated  course  of  chemotherapy  for  early-stage  disease.  Positron  emission  tomography  is  a  valuable  diagnostic  test  for  staging,  response  assessment,  and  modification  of  therapy  based  on  initial  response.  Autologous  stem  cell  transplantation  is  effective  in  patients  with  chemosensitive  relapsed  disease  and  provides  long-term  cures  for  approximately  half  of  such  patients.  Several  novel  biologic  agents  are  now  available  and  highly  active  for  relapsed  or  refractory  cHL,  including  brentuximab  vedotin  (an  anti-CD30  antibody–drug  conjugate)  as  well  as  nivolumab  and  pembrolizumab  (PD-1–blocking  antibodies).  NLPHL  is  characterized  by  malignant  lymphocyte-predominant  (LP)  cells  or  “popcorn  cells”  embedded  within  B-cell  rich  nodules.  In  contrast  to  HRS  cells,  LP  cells  express  typical  B-cell  antigens,  including  CD20,  OCT2,  and  BOB.1,  and  only  rarely  express  CD30,  CD15,  or  EBV.  NLPHL  commonly  presents  with  early-stage  disease  and  peripheral  adenopathy,  and  radiotherapy  is  an  integral  part  of  therapy  for  most  patients.  A  tendency  for  late  relapses  and  the  risk  of  transformation  to  diffuse  large  B-cell  lymphoma  are  characteristic  features  with  important  implications  for  management  and  follow-up.  Concerns  regarding  late  treatment  effects  guide  therapy  and  follow-up  decisions  in  both  cHL  and  NLPHL,  which  disproportionately  affect  adolescents  and  young  adults.  Ongoing  challenges  include  the  maintenance  of  high  cure  rates  with  fewer  short-  and  long-term  complications,  biomarker  identification  of  the  small  refractory  subgroup,  and  integration  of  novel  biologic  therapies  into  frontline  treatment  paradigms.