Moderate increase of secondary hematologic malignancies after myeloablative radiochemotherapy and autologous stem-cell transplantation in patients with indolent lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group.

Abstract

PURPOSE:

An increased risk of therapy-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML) after high-dose therapy and autologous stem-cell transplantation (ASCT) for malignant lymphoma has been described by several studies, reporting a highly variable incidence ranging from 1% to 12%. To assess this risk more precisely, the German Low Grade Lymphoma Study Group investigated the incidence of t-MDS/t-AML after ASCT on the basis of a randomized comparison of ASCT versus interferon alfa (IFN-alpha) maintenance in indolent lymphoma.

PATIENTS AND METHODS:

Between 1996 and 2002, 440 patients with indolent lymphoma were randomly assigned after a cyclophosphamide, doxorubicin, vincristine, and prednisone-like induction therapy regimen to myeloablative radiochemotherapy followed by ASCT or IFN-alpha. The incidence of secondary hematologic malignancies was determined by standardized follow-up of all study patients. Bone marrow samples from patients with proven or suspected t-MDS/t-AML were centrally reviewed.

RESULTS:

After a median follow-up of 44 months, 431 patients were assessable. Five of 195 patients developed a secondary hematologic malignancy after ASCT. Two of these patients developed a secondary AML. Accordingly, the estimated 5-year risk for secondary hematologic neoplasias after ASCT was 3.8%. In contrast, in the IFN-alpha arm, the 5-year risk of hematologic neoplasias was 0.0% (P = .0248).

CONCLUSION:

The data of this randomized trial demonstrate an increased risk of secondary hematologic malignancies after myeloablative radiochemotherapy and ASCT compared with conventional chemotherapy. However, as ASCT significantly improves progression-free survival, it is currently not evident to what extent the higher rate of t-MDS/t-AML will diminish the benefit of ASCT in indolent lymphoma.

• Authors: Georg Lenz, Martin Dreyling, Eva Schiegnitz, Torsten Haferlach, Joerg Hasford, Michael Unterhalt, Wolfgang Hiddemann
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 22 Issue 24 Pg. 4926-33 (Dec 15 2004) ISSN: 0732-183X [Print] United States
• PMID: 15611507 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Vincristine
• Doxorubicin
• Cyclophosphamide
• Prednisone

Topics

• Acute Disease
• Adult
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Combined Modality Therapy
• Cyclophosphamide (administration & dosage)
• Doxorubicin (administration & dosage)
• Female
• Follow-Up Studies
• Humans
• Incidence
• Leukemia, Myeloid (epidemiology, etiology)
• Lymphoma, Non-Hodgkin (drug therapy, radiotherapy)
• Male
• Middle Aged
• Myelodysplastic Syndromes (epidemiology, etiology)
• Neoplasms, Second Primary (epidemiology, etiology)
• Prednisone (administration & dosage)
• Prospective Studies
• Radiotherapy
• Risk Factors
• Stem Cell Transplantation
• Transplantation, Autologous
• Vincristine (administration & dosage)