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 (

Schultz et al.
BMT
1995
:
16
:
289
–289
). More recently, we observed a lower incidence of chronic (and to a lesser extent acute GVHD) in patients with CLL who received an allogeneic stem cell transplantation after a non-myeloablative conditioning regimen containing rituximab (
Exp Hematol
32
:
28
–35,
2004
). The purpose of this study is to investigate the effect of rituximab on GVHD in the setting of a more intense chemotherapy with BEAM, in patients who received an allogeneic peripheral blood stem cell from HLA-identical siblings.

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 GroupControl 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 GroupControl 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 
View Large

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.

Topics:
allogeneic stem cell transplant, conditioning (psychology), graft-versus-host disease, lymphoma, rituximab, graft-versus-host disease, acute, cd34 antigens, chemotherapy regimen, cytokine, follow-up

Author notes

Corresponding author

2005, The American Society of Hematology
2004
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