Purging in Vivo and Auto-Transplantation in Patients with Poor Prognosis Lymphoproliferative Disease

Autologous stem cell transplantation is an efficacy therapy for limphoproliferative disease. However a concern with the procedure is the potential of malignant cells to reinfuse with stem-cell graft. In the past five year, investigators have used rituximab to purge malignant cells in vivo without any manipulation in vitro. From April 2003 to June 2008 we have treated with Autologous stem cell transplantation, purged in vivo with monoclonal antibodies, 24 patients (8 F; 16 M median age: 55 years) with limphoproliferative diseases to poor prognosis (2 Burkitt lymphoma; 3 Burkitt like lymphoma; 4 mantle cells; 3 CLL; 3 NHL-T cells (1 peripheral and 2 lymphoblastic); 2 follicular and 7 large cells) and we have evaluated the results and the feasibility. In all patients, the purged in vivo, has been effected administering a dose of monoclonal antibodies (anti CD20 in B-NHL and anti CD52 in CLL and T-NHL) before the harvest and after the infusion of the stem-cells. To the transplantation 10 patients were in CR (2 Burkitt lymphoma; 3 Burkitt like lymphoma; 2 large cells; 2 NHL-T lymphoblastic and 1 mantle cells) 9 in PR (1 CLL; 3 mantle cells; 2 follicular and 4 large cells lymphoma) and 5 in resistant disease (2 CLL; 2 large cells and 1 NHL peripheral T cells). All patients have harvest (median CD34:4 ×10⁶/Kg) and median minimal residual disease in the harvest has been < to 2%. All the patients have been conditioned with BEAM and the graft are documented in 22/24 patients (2 patients are dead to the day +4 and +10 for gastric haemorrhage and septic shock respectively) with neutrophils> 1000 in media to day + 11 (range 10–19 days). After transplantation 20/22 patients were in CR, a day +60 the MMR in bone marrow was <0, 5% (range 0–0, 3%). With a median follow-up of 18 months after transplantation (range 2–64) 12/22 (54,5%) patients are in CR (8 patients have relapsed: 1 burkitt lymphoma (is relapsed extra-nodular at months +3 and died for disease a months + 5 after transplantation); 1 mantle cells (month +11); 2 follicular (months +21; +23); 1 large cells (month +14);1 NHL-peripheral T-cells (month +13); 1 NHL-T lymphoblastic (month +7) and 1 CLL (month +53). Two patients are results to be resistant to the treatment (2 large cells B lymphoma). Two patients (1 large cells and 1 CLL) are died in remission at months +3 and + 7 for CMV reactivation and interstitial pneumonia respectively. The EFS and OS projected at 50 months are of the 50% and 63% respectively. In conclusion the purging in vivo with antibodies monoclonal, effected during the harvest that immediately after the infusion of the stem-cells, allows to get besides a graft with least residual disease in this cohort (patients with poor prognosis) and the preliminary results they are interesting. The principal problem in these patients have been primarily the infectious and gastro-intestinal complications, these has been correlated to patients over treated and in disease. These data suggest treating in first line, with transplantation of stem-cells purged in vivo with monoclonal antibodies to eradicate the MRD, patients to poor prognosis or with chronic limphoproliferative disease.