title: Sequential high-dose therapy with peripheral-blood progenitor-cell support in low-grade non-Hodgkin's lymphoma.
abstract: OBJECTIVE
  To evaluate the feasibility of a sequential high-dose therapy with peripheral-blood progenitor-cell (PBPC) support in patients with follicular lymphoma.
  
  
  METHODS
  Since July 1991, we have included 30 patients (17 men and 13 women) with a median age of 41 years (range, 26 to 55) in the study. At the time of study entry, 17 patients were in first and six in second or higher remission. Another six patients had relapse of disease and one had tumor progression. PBPC were collected during filgrastim-supported leukocyte recovery following high-dose cytarabine (ara-C)/mitoxantrone (HAM).
  
  
  RESULTS
  A median of two leukaphereses (range, one to seven) resulted in a median of 5.7 x 10(6) CD34+ cells/kg (range, 2.9 to 23.7 x 10(6). A distinct population of B-lymphoid progenitors (CD34+/CD19+) was not detectable in the autografts, and the content of CD19+ B cells was remarkably low, comprising a median of 0.07% of the mononuclear cells. Using the polymerase chain reaction (PCR) assay for the major breakpoint regions (MBR) of the bcl-2/immunoglobulin H (IgH) translocation, 22 patients had autografts positive for the t(14;18) translocation, whereas seven patients had PCR-negative transplants. The autograft of one patient could not be assessed. Following myeloablative therapy, hematologic recovery was rapid without cytokine support. The median times to reach a platelet count > or = 20 x 10(9)/L and neutrophil count > or = 0.5 x 10(9)/L were 11 and 13 days, respectively. Nonhematologic toxicity was moderate. Twenty-nine patients were alive in remission after a median follow-up duration of 6 months (range, 1 to 18). Of 22 patients autografted with t(14;18)-positive harvests, 11 had PCR-detectable cells in bone marrow and/or peripheral blood as long as 16 months posttransplantation. In contrast, six patients became PCR-negative between 3 and 16 months after reinfusion. Follow-up examinations with PCR data for the remaining five patients are not yet available.
  
  
  CONCLUSIONS
  Conversion to PCR negativity in patients autografted with PCR-positive harvests suggests that the myeloablative regimen is effective and that any reinfused t(14;18)-positive cells may not be sustained. Because conventional chemotherapy provides no cure, we believe that high-dose therapy including total-body irradiation (TBI) should be explored in these particularly radiosensitive lymphomas.
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Haas
authors.forename: M
authors.initials: M
authors.lastname: Moos
authors.forename: A
authors.initials: A
authors.lastname: Karcher
authors.forename: R
authors.initials: R
authors.lastname: Möhle
authors.forename: B
authors.initials: B
authors.lastname: Witt
authors.forename: H
authors.initials: H
authors.lastname: Goldschmidt
authors.forename: S
authors.initials: S
authors.lastname: Frühauf
authors.forename: M
authors.initials: M
authors.lastname: Flentje
authors.forename: M
authors.initials: M
authors.lastname: Wannenmacher
authors.forename: W
authors.initials: W
authors.lastname: Hunstein
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001483:Base Sequence; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D000069585:Filgrastim; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016179:Granulocyte Colony-Stimulating Factor; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D008969:Molecular Sequence Data; D017713:Platelet Transfusion; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins; D014178:Translocation, Genetic; D014182:Transplantation, Autologous; D014916:Whole-Body Irradiation
chemical_list: D011994:Recombinant Proteins; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D008942:Mitoxantrone; D000069585:Filgrastim