Significance of detection of occult non-Hodgkin's lymphoma in histologically uninvolved bone marrow by a culture technique

Abstract

Prolonged disease-free survival of patients with recurrent or resistant non-Hodgkin's lymphoma (NHL) has been achieved with high-dose therapy followed by autologous bone marrow transplantation (ABMT). A concern with the use of ABMT is that the marrow that is reinfused may contain undetected NHL cells with the potential to reestablish metastatic disease in the recipient. Using a culture technique that is sensitive for detecting occult lymphoma cells in BM, we analyzed histologically normal marrow harvests from 59 consecutive patients with intermediate- or high-grade NHL who were candidates for high-dose therapy and ABMT. The culture results indicated that 22 of the patients had occult lymphoma in their marrow. Forty-three patients underwent high-dose therapy followed by ABMT. Twenty-four achieved a complete clinical remission. Those with occult lymphoma in their harvests (11 patients) continued to relapse for up to 3 years, whereas no relapses were observed beyond 8 months in 13 patients receiving marrow that did not contain detectable lymphoma cells using the culture technique. The relapses in the patients who achieved a complete remission occurred at sites of prior bulky disease rather than at new sites, suggesting that the ability to detect occult lymphoma cells in marrow is a marker of biologic aggressiveness and/or resistance to therapy, or that the reinfused cells could only grow in previously involved sites. The detection of lymphoma cells in marrow used for ABMT is an important adverse prognostic factor, and appears to be independent of other clinical predictors of outcome such as sensitivity or resistance of disease to prior chemotherapy.

Infused CD34+ cell dose, but not tumour cell content of peripheral blood progenitor cell grafts, predicts clinical outcome in patients with diffuse large B‐cell lymphoma and follicular lymphoma grade 3 treated with high‐dose therapy

“…Several studies have shown a relationship between tumour cell contamination of BM autografts and relapse in lymphoma patients (Gribben et al, 1991;Sharp et al, 1992;Blystad et al, 1999;Sharp & Chan, 1999). Only smaller studies have been performed for patients with DLBCL given PBPC grafts.…”

“…This might be the result of residual tumour cells in the patient and/or infusion of contaminating tumour cells with the stem cell graft. The latter is supported by the fact that lymphoma patients receiving contaminated bone marrow (BM) grafts have shorter disease-free survival (DFS) (Gribben et al, 1991;Sharp et al, 1992) (Sharp et al, 1996). In line with this, we have previously found that patients with DLBCL receiving tumour-free, purged BM grafts had a favourable outcome (Blystad et al, 1999).…”

“Less is More”: The Role of Purging in Hematopoietic Stem Cell Transplantation

“…Several investigations have demonstrated tumor cell contamination of 10% to 30% of leukapheresis products used for transplants [7], and, in patients with neuroblastoma, stem cell harvests have been shown to contain contaminating tumor cells irrespective of marrow involvement [9]. In other studies in patients with breast cancer or lymphoma, tumor-contaminated peripheral blood stem cell collections resulted in a poor clinical outcome [10,11].…”

High‐Dose Chemotherapy with Autologous Stem Cell Rescue for Breast Cancer: Yesterday, Today and Tomorrow

“…These patients do not all relapse, and several studies looking at outcome disagree as to whether these cells are correlated with worsened outcome [27][28][29][30][31]. Recently several publications have shown that the presence of tumor cells in stem cell harvests may mark for, or have a direct deleterious effect on outcome in leukemia [32], lymphoma [33], neuroblastoma [34] and breast cancer (Brockstein, submitted for publication).…”