title: Chemoresistance can be overcome with high-dose chemotherapy and autologous stem-cell transplantation for relapsed and refractory Hodgkin lymphoma.
abstract: BACKGROUND
  High-dose therapy and autologous stem-cell transplant (HDT/ASCT) is the preferred treatment of chemosensitive relapsed/refractory Hodgkin lymphoma (HL). The role for HDT/ASCT in chemoresistant HL is less well defined. We evaluated long-term outcomes of relapsed/refractory HL patients whose disease was refractory to secondary chemotherapy preceding HDT/ASCT.
  
  
  METHODS
  All HL patients who underwent HDT/ASCT in British Columbia for primary progression (PP, defined as progression within 3 months of initial therapy completion) or first relapse (REL1) were reviewed. Patients were grouped based on response to secondary chemotherapy as sensitive (S), resistant (R), and untested/unknown (U).
  
  
  RESULTS
  A total of 256 patients underwent HDT/ASCT for PP (35%) or REL1 (65%) between 1985 and 2011. At median follow-up of 11.7 years, 58% were alive without HL, 36% relapsed; 6% died of transplant-related mortality, 3% secondary malignancies, and 3% unrelated causes. For PP/S, PP/R, and PP/U groups, 10-year FFS were 47%, 31%, and 38%; 10-year OS were 52%, 29%, and 37%, respectively. For REL1/S, REL1/R, and REL1/U groups, 10-year FFS were 64%, 51%, and 81%; 10-year OS were 71%, 59%, and 79%, respectively. In multivariate analysis, resistance to secondary chemotherapy predicted for post-transplant mortality in the PP (P = 0.04) but not REL1 (P = 0.16) groups.
  
  
  CONCLUSIONS
  In this large uniformly treated cohort of HL patients with long-term follow-up, chemoresistance preceding HDT/ASCT was identified as a poor prognostic factor; however, this factor can be partially overcome by HDT/ASCT, resulting in cure in 30%-50% of patients. HDT/ASCT should therefore be considered in all transplant eligible patients, regardless of responsiveness to salvage chemotherapy.
authors.affiliation: Leukemia/Bone Marrow Transplant Program of British Columbia and the Division of Hematology, British Columbia Cancer Agency and the University of British Columbia; Center for Lymphoid Cancer Research and the Division of Medical Oncology, British Columbia Cancer Agency and the University of British Columbia, Vancouver, Canada. Electronic address: agerrie@bccancer.bc.ca.
authors.forename: A S
authors.initials: AS
authors.lastname: Gerrie
authors.affiliation: Leukemia/Bone Marrow Transplant Program of British Columbia and the Division of Hematology, British Columbia Cancer Agency and the University of British Columbia.
authors.forename: M M
authors.initials: MM
authors.lastname: Power
authors.affiliation: Leukemia/Bone Marrow Transplant Program of British Columbia and the Division of Hematology, British Columbia Cancer Agency and the University of British Columbia.
authors.forename: J D
authors.initials: JD
authors.lastname: Shepherd
authors.affiliation: Center for Lymphoid Cancer Research and the Division of Medical Oncology, British Columbia Cancer Agency and the University of British Columbia, Vancouver, Canada.
authors.forename: K J
authors.initials: KJ
authors.lastname: Savage
authors.affiliation: Center for Lymphoid Cancer Research and the Division of Medical Oncology, British Columbia Cancer Agency and the University of British Columbia, Vancouver, Canada.
authors.forename: L H
authors.initials: LH
authors.lastname: Sehn
authors.affiliation: Center for Lymphoid Cancer Research and the Division of Medical Oncology, British Columbia Cancer Agency and the University of British Columbia, Vancouver, Canada.
authors.forename: J M
authors.initials: JM
authors.lastname: Connors
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous; D016896:Treatment Outcome
keywords: Hodgkin lymphoma; chemoresistance; refractory; relapsed; stem-cell transplant; therapy