Rituximab Plus Donor Lymphocyte Infusion (DLI) to Prevent or Treat Relapse for B Cell Malignancies after Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT)

Dose-reduced conditioning followed by allogeneic stem cell transplantation (HSCT) is a potentially curative therapy in B non Hodgkin lymphomas (NHL). However, the number of patients who experienced an early relapse is significant, and the achievement of a prolonged second remission is usually a rare event.

Posttransplant immunotherapy with DLI to induce graft versus lymphoma (GVL) effect is a reasonable option to prevent or treat relapse, however the risk of graft versus host disease (GvHD) is high. Since B-cells might serve as antigen presenting cells to induce GvHD, additional B-cell depleting therapy with monoclonal antibody (anti CD20) might reduce the risk of GvHD while inducing additional cytotoxicity to B-cells originating from B-cell lymphoma. In the current pilot study we investigated the feasibility of a combined rituximab (Rtx) plus DLI therapy in B-cell malignancies after allogeneic stem cell transplantation to prevent (n=10) or treat relapse (n=2).

Twelve consecutive patients, 8 male and 4 female, affected by B cell malignancies and transplanted between July 2002 and February 2007, were included in this study. The median age at alloHSCT was 58 ys (range 27–64). The conditioning regimen consisted of melphalan (140 mg/m²), fludarabine (150 mg/m²) and ATG–Fresenius (30–60 mg/kg) (n=9) or busulfan (8–10 mg/kg), fludarabine (150 mg/kg) (n=3), donors were HLA identical sibling in the half of the group, with one HLA mismatched-unrelated donor. The source of stem cell was peripheral blood in all patients. Seven patients were not in disease remission at the time of HSCT. The indication of Rtx-DLI administration was prophylaxis of relapse in all but two patients. The schedule of this approach was: Rtx (375 mg/mq, in 4 consecutive weekly infusions), started at a median time of 194 dy from HSCT (range 77–895). DLI, in a single dose, was administered from a minimum of 1×10⁵/Kg up to 5×10⁶/Kg, after discontinuation of immuno-suppression, without signs of GvHD.

Three patients developed acute GvHD after DLI, two with gastro-intestinal and one with cutaneous involvement, whereas 6/12 patients experienced chronic GvHD, limited in all but two. Two cases of bacterial and one case of Pneumocystis jirovecij pneumonia were diagnosed after the treatment, in 3 different patients. Two patients died in complete remission due to infectious complications.

The median number of B-circulating lymphocytes before and after Rtx was 42/μL (range 0–477) and 4 (range 0–226) respectively, and the difference is not statistically significant in terms of incidence of infection in our group (χ² test).

After a median follow up of 21 mo (range 4–37) from the 1^st Rtx infusion, 8/12 patients are alive at the last follow-up, six of them without disease, whereas 2 patients died due to progressive disease(table1).

Rituximab and DLI post allogeneic HSCT seems to be a safe and effective approach to prevent early relapse in B malignancies in complete remission after allogeneic stem cell transplantation.

Table 1