High-dose cyclophosphamide after allogeneic stem cell transplantation as a graft-versus-host-disease prophylactic agent in adult acute leukemia: Experience of two Mexican hospitals

Summary

Introduction

Usage of high-dose Cyclophosphamide (HDCY) after allogeneic stem cell transplantation (alloSCT) as a prophylactic agent against acute graft-versus-host-disease (aGVHD) has been widespread worldwide with good results. Our aim was to assess incidence of aGVHD when applying HDCY as a prophylaxis agent in our patients.

Materials and methods.

Forty-eight patients were allo-transplanted between January 2012 and January 2016 including 22 patients (46%) from fully HLA-matched related donors, and 26 (54%), from haploidentical donors. Their median age was 34 (2-65) years old. Acute lymphoblastic leukemia was the most common diagnosis (79% of patients). Twenty-nine (60%) patients received myeloablative conditioning (MAC), and 19 (40%) were administered a reduced intensity conditioning (RIC). In alloSCT from fully HLA-matched related donors, we used peripheral blood stem cells in 12 (54%) patiens, and bone marrow in 10 (46%) patients; in all haploSCT we used bone marrow as a source of stem cells. All the patients received aGVHD prophylaxis with HDCY (50 mg/kg) day+3 and +4, haploSCT patients received also Tacrolimus and Mycophenolate Mofetil.

Results

Median neutrophilic engraftment term was on the +15 (MAC) and +17 (RIC). Graft failure was observed in 6 patients (MAC) and 3 patients (RIC). Incidence of aGVHD in total group was 41.6% (n=20), including grade I (5 patients); grade II (8 cases); grade III (3 patients), and grade IV in 4 cases. Skin was the most affected organ (n=11). Four patients relapsed, with median time of relapse at 266 (108-756) days post-transplant. Conditioning regimen was not a risk factor for aGVHD (p=0.349). A special risk factor for aGVHD was a transplant from female donor to male recipient (p=0.019). The presence of aGVHD was not predictive for death (RR 2.110, 95% IC, 0.645-6.902, p= 0.214). Median follow-up terms were 108 (6-999) days for MAC regimen, and 240 (27-939) days for RIC patients. Median OS was 15 months for haplo-SCT and 18 months for alloSCT from related donors. Median disease free survival (DFS) for haploSCT and alloSCT from related donor was, respectively, 28 months and 27 months. OS value was 39% for haploSCT and 56% for alloSCT from related donor.

Conclusions

HDCY application for aGVHD prophylaxis is a feasible scheme to use in Mexico being cheaper tolerable and effective. In our study, no patient died for aGVHD. Among total group, only 14% (48) had grade III/IV aGVHD.

References

1. Kanakry CG, et al. Multi-institutional study of post-transplantation cyclophosphamide as single- agent graft-versushost disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning. J Clin Oncol. 2014; 32(31):3497–3505.

1. Luznik L, et al. High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft- versus-host disease. Blood. 2010; 115(16):3224–3230.

Keywords

High-dose cyclophosphamide, allogeneic stem cell transplantation, acute graft versus host disease