title: High-dose therapy with autologous bone marrow support as consolidation of remission in follicular lymphoma: long-term clinical and molecular follow-up.
abstract: OBJECTIVE
  To evaluate the long-term results of high-dose therapy (HDT) in follicular lymphoma, with specific emphasis on the prognostic significance of polymerase chain reaction (PCR)-detectable Bcl-2/IgH rearrangements.
  
  
  METHODS
  Between June 1985 and October 1995, 99 patients with follicular lymphoma received HDT as consolidation of second or subsequent remission. Bone marrow was treated in vitro with anti-B-cell antibodies and complement.
  
  
  RESULTS
  Sixty-five patients remained alive, 49 treatment-failure free, with a median follow-up of 5.5 years (range, 1.5 to 12.5 years). Four "early" and 10 "late" deaths occurred from treatment-related causes; seven of the latter were due to secondary myelodysplasia (s-MDS) or secondary acute myeloblastic leukemia. Overall, 12 (12%) of the 99 patients developed s-MDS or acute myeloblastic leukemia. Kaplan-Meier estimates of freedom from recurrence (FFR) and survival rates at 5 years were 63% (95% confidence interval [CI], 52% to 72%) and 69% (95% CI, 58% to 78%), respectively. For all 99 patients, in multivariate analysis, absence of the Bcl-2/IgH rearrangement at the time of diagnosis (hazards ratio [HR], 0.39; P =.04) and three or fewer treatment episodes before HDT (HR, 0.03; P =.001) were significant prognostic factors for improved survival. For patients bearing Bcl-2/IgH rearrangements, in univariate and multivariate analyses, absence of a PCR-detectable Bcl-2/IgH rearrangement during follow-up was associated with a significantly lower risk of recurrence (adjusted HR, 0.13; P <.001) and death (HR, 0.25; P =.02), whereas the PCR status of the reinfused bone marrow did not correlate with outcome.
  
  
  CONCLUSIONS
  Prolonged FFR can be achieved in patients with follicular lymphoma after HDT, but as yet there is no survival advantage compared with conventional treatment. These results confirm that elimination of cells bearing the Bcl-2/IgH rearrangement is highly desirable and should be attempted. The incidence of s-MDS is of increasing concern in this setting.
authors.affiliation: Imperial Cancer Research Fund Medical Oncology Unit, Department of Medical Oncology, and Departments of Histopathology and Hematology, St Bartholomew's Hospital, London, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Apostolidis
authors.forename: R K
authors.initials: RK
authors.lastname: Gupta
authors.forename: D
authors.initials: D
authors.lastname: Grenzelias
authors.forename: P W
authors.initials: PW
authors.lastname: Johnson
authors.forename: V I
authors.initials: VI
authors.lastname: Pappa
authors.forename: K E
authors.initials: KE
authors.lastname: Summers
authors.forename: A
authors.initials: A
authors.lastname: Salam
authors.forename: K
authors.initials: K
authors.lastname: Adams
authors.forename: A J
authors.initials: AJ
authors.lastname: Norton
authors.forename: J A
authors.initials: JA
authors.lastname: Amess
authors.forename: J
authors.initials: J
authors.lastname: Matthews
authors.forename: M
authors.initials: M
authors.lastname: Bradburn
authors.forename: T A
authors.initials: TA
authors.lastname: Lister
authors.forename: A Z
authors.initials: AZ
authors.lastname: Rohatiner
mesh_terms: D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D019254:Genes, bcl-2; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy / Q000628:therapy*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012074:Remission Induction; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
chemical_list: D000964:Antimetabolites, Antineoplastic; D007143:Immunoglobulin Heavy Chains; D003520:Cyclophosphamide