Abstract
It has been postulated that B cells functioning as antigen-presenting cells may have an important role in the pathogenesis of GVHD. Depletion of donor cells from B-cells resulted in a low incidence of GVHD in mouse model (
To test this hypothesis, we retrospectively studied 11 consecutive patients with non-Hodgkin’s lymphoma who received BEAM/Rituximab at the M. D. Anderson Cancer Center. We attempted to match these patients by age, donor-recipient gender, and donor-recipient CMV reactivity to a historical control of 44 patients with lymphoma, who received BEAM alone as a conditioning regimen, without the Rituximab. Tacrolimus and methotrexate were used for GVHD prophylaxis in both groups. A total of 10 patients in the study group, could be matched with 19 patients in the control group and were included in the final analysis. The outcome of the 2 groups is shown below:
| . | Rituximab-Study Group . | Control Group . | -value P . |
|---|---|---|---|
| No. of patients | 10 | 19 | |
| Median age | 41 | 44 | 0.4 |
| (range) | (19–55) | (19–60) | |
| Patient-Donor sex-matched | 9(82%) | 18(95%) | 0.6 |
| Median # CD34 + cells infused (106/kg) | 5.1 | 4.73 | 0.1 |
| Patient or Donor CMV+ | 9(82%) | 18(95%) | 0.6 |
| Patient and Donor CMV − | 1(10%) | 1(5%) | |
| Median # prior chemoregimens | 3 | 3 | 0.9 |
| range | (1–8) | (1–9) | |
| Median follow-up | 17 | 38 | |
| range | (8–48) | (27–77) | |
| Acute GVHD 2–4 (n,%) | 5(50%) | 7(37%) | 0.5 |
| Acute GVHD 3–4 (n,%) | 3(30%) | 5(26%) | 0.6 |
| Chronic GVHD (n, % cumulative incidence) | 8 (90% + 15) | 10 (53% + 12 | 0.01 |
| . | Rituximab-Study Group . | Control Group . | -value P . |
|---|---|---|---|
| No. of patients | 10 | 19 | |
| Median age | 41 | 44 | 0.4 |
| (range) | (19–55) | (19–60) | |
| Patient-Donor sex-matched | 9(82%) | 18(95%) | 0.6 |
| Median # CD34 + cells infused (106/kg) | 5.1 | 4.73 | 0.1 |
| Patient or Donor CMV+ | 9(82%) | 18(95%) | 0.6 |
| Patient and Donor CMV − | 1(10%) | 1(5%) | |
| Median # prior chemoregimens | 3 | 3 | 0.9 |
| range | (1–8) | (1–9) | |
| Median follow-up | 17 | 38 | |
| range | (8–48) | (27–77) | |
| Acute GVHD 2–4 (n,%) | 5(50%) | 7(37%) | 0.5 |
| Acute GVHD 3–4 (n,%) | 3(30%) | 5(26%) | 0.6 |
| Chronic GVHD (n, % cumulative incidence) | 8 (90% + 15) | 10 (53% + 12 | 0.01 |
Our data suggest that the described protective effect of Rituximab against GVHD in mouse models or in the setting of non-myeloablative allogeneic transplantation, may be overcome by the BEAM. This more intense conditioning regimen may induce more GVHD by enhancing T-cell cytokines release and by causing more gastrointestinal toxicity, thus allowing for a greater antigen presentation.
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