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Introduction: Acute graft-versus-host-disease (aGVHD) is a frequent and lethal complication of HSCT despite current prophylaxis. Release of pro-inflammatory cytokines lead to damage of host tissues. Statins have been shown to reduce pro-inflammatory cytokines while increasing the migration of anti-inflammatory cytokines, especially when donor and recipient are exposed to it, thus reducing aGVHD. We present data on 14 patients enrolled in an ongoing phase II study evaluating the efficacy of atorvastatin as aGVHD prophylaxis in patients undergoing matched-related donor AHSCT. Method: In this phase II study donors receive atorvastatin 40 mg daily for at least 14 days before leukapheresis. Recipient patients receive Atorvastatin 40mg daily starting at least 7 days before initiation of transplant conditioning regimen in addition to standard approved GVHD prophylaxis with tacrolimus and methotrexate. Atorvastatin is continued until development of grade II or higher aGVHD, cessation of aGVHD prophylaxis and or adverse event. We compared the immune reconstitution pattern of patients on statin to those of historic control patients not on statin matched to age, sex, type of AHSCT and intensity of regimen. Result: Median age of patients is 47(range 27-67) and of donor 46.5 (29-64). Ten patients received reduced intensity AHSCT. Median neutrophil and platelets engraftment were 18.9 and 12.9 days. With a median follow up of 120 days (23-287), two patients have relapsed one of whom died due to disease. The median day 30 CD3 and CD34 chimerism were 81% and 100%. Two patients (14%) have developed grade II aGVHD with no patients developing grade III or IV aGVHD. Two patients developed chronic GVHD both mild and limited. At day 30 post HSCT, compared to historic control, patients exposed to statin had no difference in B cells(CD19+) or total T cells (CD3+/DR+; CD3+/DR-), but a significant decline in NK cells, including total NK cells and NK cells positive for CD314(Table 1).Conclusion: While this is a small sample, and no conclusion can be deduced, it is interesting to note the significant difference in the number of NK cells in patients exposed to statin as compared to historic control.
Statin vs. non-statin D30 (%)
| p-value
| Median(Range) Non-statin exposed
| Median(Range) Statin exposed
|
Absolute Lymphocyte count
| 0.04688 | 850 (100-1300) | 774.8 (109-2120) |
DR+/14+ (absolute)
| 0.375 | 77.6 (43.1-86.3) | 69.3 (19.2-92.1) |
DR-/14+ (absolute)
| 0.1094 | 12.5 (2.7-34.4) | 25.4 (1.8-78.6) |
CD3+/56-/16-
| 0.04688 | 55 (15.4-78.2) | 78.7 (52.5-95.8) |
CD19+
| 1 | 1 (0.2-2.0) | 0.7 (0-39.4) |
CD69 + / CD3+
| 0.8655 | 3.2 (0.7-4.7) | 2.7 (1.1-4.4) |
CD3+ /DR+
| 1 | 5 (1.4-30.1) | 5.1 (0.4-13.7) |
CD3+ / DR -
| 0.1563 | 48 (17.5-77.1) | 70.1 (52.9-85.1) |
CD3-/56+/16+
| 0.03125 | 33.5 (16.5-42.2) | 7.9 (2.7-21.0) |
CD3-/56+/16+/314+
| 0.03125 | 18.1 (6.5-34.0) | 4.6 (0.7-10) |
CD3-/56+/16+/117-
| 0.03125 | 22.4 (11.8-36.4) | 6.3 (0.9-12.9) |
Table 1: Effect of Statin on Immunomes