Graft-versus-host disease prophylaxis with post-transplantation cyclophosphamide
Olga V. Pirogova, Ivan S. Moiseev, Elena I. Darskaya, Sergej N. Bondarenko, Elena V. Babenko, Alexander L. Alyanskiy, Boris V. Afanasyev
R. M. Gorbacheva Memorial Institute of Children Hematology, Oncology and Transplantation, First I. Pavlov St. Petersburg State Medical University, St. Petersburg, Russia
Summary
Introduction
Improvement of current graft-versus-host disease (GVHD) treatment remains the important goal in allogeneic hematopoietic stem cell transplantation (alloHSCT). Following impressive results of high-dose posttransplant cyclophosphamide GVHD prophylaxis presented by the research team from Johns Hopkins University [1] we performed a pilot study with this prophylaxis after alloHSCT.
Methods
111 adult patients undergoing alloHSCT from matched unrelated donors (MUD) (69 pts), mismatched unrelated (MMUD) (28 pts) and haploidentical donors (Haplo) (14 pts) were included in the analysis. GVHD prophylaxis consisted of Cy 50 mg/kg/day on day +3 and +4, tacrolimus starting on day +5 and mycophenolate mofetil from day +5 until day +35. Detailed patients’ characteristics and analysis of groups’ differences are presented in table 1.
Results
Cumulative incidences of the grades II to IV acute GVHD were not significantly different between the groups: 15,9% vs 17,9% vs 14,3% (p>0,05) for MUD, MMUD and Haplo, respectively. The cumulative incidence of chronic GVHD was 11,6% vs 21,4% vs 14,4% (p>0,05) for MUD, MMUD and Haplo, respectively. One-year GVHD – and relapse-free survival was 65,2 % vs 60,7% vs 28,6% (p<0,001) for MUD, MMUD and Haplo, respectively. One-year non-relapse mortality (7,4% vs 0% vs 28,6%, p=0,004) was higher, and 1-year overall survival (78,3% vs 75,0% vs 35,7%, p<0,001) and event-free survival (68,1% vs 67,9% vs 28,6, p<0,001) were lower in Haplo-group.
Conclusion
This new regimen of GVHD prophylaxis demonstrates lower levels of acute GVHD for all types of donors. Poor overall survival and high non-relapse mortality in Haplo-group were due to the predominance of salvage patients, but not due to GVHD.
References
1. Luznik L at al. Biol Blood Marrow Transplant.
2008; 14 (6): 641–650.
|
Characteristics |
MUD (N=69) |
MMUD (N=28) |
Haplo (N=14) |
|
Median follow-up (days) |
243 |
304 |
125 |
|
Disease status Active disease at transplantation |
14 (20,2%) |
6 (21,4%) |
8 (57%) |
|
Age at transplantation Median (range) |
34 (18–59) |
32 (19–58) |
27 (20–51) |
|
Sex, female |
31 (45%) |
9 (32%) |
8 (57%) |
|
Diagnosis AML ALL MDS CML |
36 (52,7%) 23 (33,3%) 4 (5,8%) 6 (8,2%) |
11 (39,3%) 10 (35,7%) 1 (3,5%) 6 (21,5%) |
10 (78,5%) 2 (14,2%) 0 (0%) 1 (7,3%) |
|
Conditioning Myeloablative Reduced-intensity |
18 (26%) 51 (74%) |
3 (10,7%) 25 (89,3%) |
2 (14,2%) 12 (85,8%) |
Table 1. Detailed characteristics of the patients and analysis of the inter-group differences
Keywords
Host-versus-gra disease, acute, posttransplant prophylaxis, cyclophosphamide
