Successful neutrophil engraftment by reduced use of granulocyte colony-stimulating factor after allogeneic hematopoietic stem cell transplantation with mycophenolate mofetil for graft-versus-host disease prophylaxis

Abstract

In allogeneic hematopoietic stem cell transplantation (allo-SCT), most physicians in Japan utilize granulocyte colony-stimulating factor (G-CSF) at a high dose (HD) of 300 μg/m(2) per day for filgrastim to promote faster neutrophil engraftment. However, the necessity of the HD has not been validated under graft-versus-host disease (GVHD) prophylaxis by mycophenolate mofetil (MMF), which can also be expected to facilitate engraftment. In a total of 51 patients, we compared the clinical outcomes between a standard dose (SD) fixed at 300 μg per day and a HD of G-CSF. While time to neutrophil engraftment was not different in the HD and SD groups in patients receiving cord blood transplantation (CBT, 20 vs. 17.5 days, P = 0.243) or bone marrow transplantation (BMT, 11 vs. 10 days, P = 0.227), there seemed to be an increased risk of developing acute GVHD in the HD group with CBT (20 vs. 0%, P = 0.073) and BMT (57 vs. 24%, P = 0.165). Progression-free survival of patients in the HD group was likely to be worse compared with that of the SD group with CBT (P = 0.099). In this study, the clinical benefits of a HD of G-CSF could not be documented, and we find that the use of G-CSF at a SD after allo-SCT with MMF should be prospectively evaluated.

Histologic Features in Colon Biopsies Can Discriminate Mycophenolate From GVHD-induced Colitis

“…[9][10][11] The exact mechanism of MMF GI toxicity is unknown. 20 Thus, bone marrow transplant (BMT) patients who receive MMF for prophylaxis of GVHD 19,21,22 are at risk for both GVHD and MMF-induced colitis. [12][13][14][15] For instance, in 1 study by Papadimitriou et al 13 significant differences were observed in the degree of crypt cell apoptosis, gland distortion, epithelial cell atypia, quantity of neuroendocrine cells, and lamina propria inflammation, all of which are features of GVHD, in MMF-toxicity patients in comparison with matched controls.…”