Molecular basis for stem cell transplantation in indolent lymphomas

To assess the role of bone marrow transplantation in indolent lymphomas.

Autologous and allogeneic stem cell transplantations (SCTs) are performed routinely for a number of hematologic malignancies; however, few patients with indolent lymphoma have been treated with SCT. The high incidence of bone marrow infiltration in the indolent lymphomas has made it difficult to perform autologous SCT. In addition, although indolent lymphomas are initially responsive to chemotherapy, many patients have been heavily pretreated, have become chemotherapy resistant, and have a decreased marrow reserve by the time they are considered for high-dose myeloablative therapy. An advantage of studying the indolent lymphomas is that they are characterized by nonrandom chromosomal translocations and/or clonal rearrangements of the immunoglobulin heavy-chain locus. These translocations and unique immunoglobulin rearrangements provide clonal markers of disease that can be amplified with the polymerase chain reaction (PCR), allowing detection and assessment of the clinical significance of minimal residual disease (MRD) after SCT.

Studies demonstrate that SCT can be performed safely in patients with indolent lymphomas. Although standard-dose therapy rarely eradicates MRD, high-dose therapy and SCT result in eradication of PCR-detectable MRD in a significant number of patients. Furthermore, eradication of MRD is associated with greatly prolonged disease-free survival.

These results suggest that our therapeutic goal should be attainment of a "molecular complete remission" for cure in these malignancies.