Blood Journal
Leading the way in experimental and clinical research in hematology

Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo–purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group

  1. Christian H. Geisler1,
  2. Arne Kolstad2,
  3. Anna Laurell3,
  4. Niels S. Andersen1,
  5. Lone B. Pedersen1,
  6. Mats Jerkeman4,
  7. Mikael Eriksson4,
  8. Marie Nordström5,
  9. Eva Kimby5,
  10. Anne Marie Boesen6,
  11. Outi Kuittinen7,
  12. Grete F. Lauritzsen2,
  13. Herman Nilsson-Ehle8,
  14. Elisabeth Ralfkiær1,
  15. Måns Åkerman4,
  16. Mats Ehinger4,
  17. Christer Sundström3,
  18. Ruth Langholm2,
  19. Jan Delabie2,
  20. Marja-Liisa Karjalainen-Lindsberg9,
  21. Peter Brown1,
  22. Erkki Elonen9, and
  23. for the Nordic Lymphoma Group
  1. 1Rigshospitalet, Copenhagen, Denmark;
  2. 2Norwegian Radium Hospital, Oslo, Norway;
  3. 3Uppsala University Hospital, Uppsala, Sweden;
  4. 4Lund University Hospital, Lund, Sweden;
  5. 5Karolinska Institute, Stockholm, Sweden;
  6. 6Aarhus University Hospital, Aarhus, Denmark;
  7. 7Oulu University Hospital, Oulu, Finland;
  8. 8Sahlgrenska Hospital, Gothenburg, Sweden; and
  9. 9Helsinki University Central Hospital, Helsinki, Finland
  1. Presented in part at the 49th Annual Meeting of the American Society of Hematology, December 11, 2007, Atlanta, GA.

Abstract

Mantle cell lymphoma (MCL) is considered incurable. Intensive immunochemotherapy with stem cell support has not been tested in large, prospective series. In the 2nd Nordic MCL trial, we treated 160 consecutive, untreated patients younger than 66 years in a phase 2 protocol with dose-intensified induction immunochemotherapy with rituximab (R) + cyclophosphamide, vincristine, doxorubicin, prednisone (maxi-CHOP), alternating with R + high-dose cytarabine. Responders received high-dose chemotherapy with BEAM or BEAC (carmustine, etoposide, cytarabine, and melphalan/cyclophosphamide) with R-in vivo purged autologous stem cell support. Overall and complete response was achieved in 96% and 54%, respectively. The 6-year overall, event-free, and progression-free survival were 70%, 56%, and 66%, respectively, with no relapses occurring after 5 years. Multivariate analysis showed Ki-67 to be the sole independent predictor of event-free survival. The nonrelapse mortality was 5%. The majority of stem cell products and patients assessed with polymerase chain reaction (PCR) after transplantation were negative. Compared with our historical control, the Nordic MCL-1 trial, the event-free, overall, and progression-free survival, the duration of molecular remission, and the proportion of PCR-negative stem cell products were significantly increased (P < .001). Intensive immunochemotherapy with in vivo purged stem cell support can lead to long-term progression-free survival of MCL and perhaps cure. Registered at www.isrctn.org as #ISRCTN 87866680.

  • Submitted March 21, 2008.
  • Accepted June 14, 2008.
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