Reduced-dose methotrexate in combination with tacrolimus was associated with rapid engraftment and recovery from oral mucositis without affecting the incidence of GVHD

Abstract

Allogeneic hematopoietic stem cell transplantation is a curable treatment for hematological diseases. Graft-versus-host disease (GVHD) causes morbidity and mortality after HSCT.Methotrexate (MTX) is used for GVHD prophylaxis, but its appropriate dose remains unclear. In the present study, we compared the efficacy and toxicity of 15-10-10 MTX (day +1: 15 mg/m 2 ; days +3 and +6: 10 mg/m 2 ) with 10-7-7 MTX (day +1: 10 mg/m 2 ; day +3and +6: 7 mg/m 2 ) in combination with tacrolimus. The cumulative incidences rates of grades Ⅱ-Ⅳ acute GVHD and grades Ⅲ-Ⅳ acute GVHD and chronic GVHD in the 15-10-10 MTX and 10-7-7 MTX groups did not differ to a statistically significant extent.The median time for neutrophil engraftment in the 15-10-10 MTX group was 16 days (range, 11-31 days), while that in the 10-7-7 group was 15 days (range, 12-19 days) (P=0.024). Moreover, the median time for platelet recovery was significantly shorter in the 10-7-7 MTX group (22 days; range, 13-49 days) than that in the 15-10-10 MTX group (27 days; range, 9-405 days) (P=0.027). The duration of oral mucositis was significantly shorter in the patients who received a reduced dose of MTX (median, 4.5 vs 13.0 days; P=0.013). In conclusion, GVHD prophylaxis with a reduced dose of MTX was associated with earlier engraftment and earlier recovery from mucositis in comparison to a standard dose of MTX, without affecting the incidence of GVHD.

Female sex as an independent prognostic factor in the development of oral mucositis during autologous peripheral stem cell transplantation

“…Timely insertion and proliferation of stem cells in neutrophil and thrombocyte engraftments are essential in reducing risk and severity of OM. Earlier studies have reported at length on the relationship between neutrophil engraftment and OM, and the positive correlation has also been confirmed between the duration of mucositis and neutrophil engraftment 19 . Reduced as opposed to standard dose MTX in allogeneic HSCT patients resulted in shorter neutrophil engraftment time and faster recovery from mucositis 19 .…”

“…Earlier studies have reported at length on the relationship between neutrophil engraftment and OM, and the positive correlation has also been confirmed between the duration of mucositis and neutrophil engraftment 19 . Reduced as opposed to standard dose MTX in allogeneic HSCT patients resulted in shorter neutrophil engraftment time and faster recovery from mucositis 19 . The anti-inflammatory, antioxidant and wound-healing promoting effects of erythropoietin containing mouthwash in patients who underwent APSCT, reducing severity and incidence of OM without significant effect on blood neutrophil and thrombocyte engraftment 12 , further supports the role of local factors in the aetiology and therapy of OM.…”

Evaluación longitudinal de la mucositis oral en el trasplante de células madre hematopoyéticas: un estudio piloto

“…The use of MTX as immunoprophylaxis may also have been a contributing factor to OM high incidence due to its high cytotoxic potential in cells with rapid multiplication. In addition, MTX is responsible for the delay of repair of the tissue damaged by chemotherapeutic conditioning (Ahmed et al, 2017;Cutler et al, 2005;Knoll et al, 2016;Matsukawa et al, 2016;Ramírez-amador et al, 2010;Small et al, 2007).…”

The effect of granulocyte colony‐stimulating factor dose and administration interval after allogeneic hematopoietic cell transplantation on early engraftment of neutrophil and platelet

“…Efficient engraftment occurs through three steps: i) migration of infused HSCs toward bone marrow microvessels through adhesion molecules and their expression on the surface of endothelial cells; ii) stem cells homing to the bone marrow niche via interactions with homing receptors; iii) proliferation and differentiation of HSCs to various blood cells 5 . Many factors may influence the kinetics of engraftment after allo‐HSCT, including the number of HSCs and T cells, subset of T cells, infections, graft‐versus‐host disease (GVHD) prophylaxis, post‐transplant granulocyte colony‐stimulating factor (G‐CSF) administration, and the disease status 4,6‐8 . Cancer therapy‐related neutropenia is the most common complication resulting from chemotherapy toxicity 9 .…”

“… 5 Many factors may influence the kinetics of engraftment after allo‐HSCT, including the number of HSCs and T cells, subset of T cells, infections, graft‐versus‐host disease (GVHD) prophylaxis, post‐transplant granulocyte colony‐stimulating factor (G‐CSF) administration, and the disease status. 4 , 6 , 7 , 8 Cancer therapy‐related neutropenia is the most common complication resulting from chemotherapy toxicity. 9 Before the HSCT, patients receive high‐dose chemotherapy regimens, which have myelosuppressive effects.…”