This report updates a retrospective study from SFGM-TC registry concerning 738 patients who underwent RIC HSCT for hematological malignancies [280 F, 458 M, median age: 51 years (1–72)] between 1997 and 2004. The diagnosis were 173 AML, 40 ALL, 68 MDS, 152 NHL, 36 HD, 45 CLL, 70 CML, 154 MM; 332 patients have been previously transplanted. At time of conditioning, 261 patients were in CR, 224 in PR and 253 in progressive disease (PD). Peripheral blood stem cells (PBSC) were used in 574 patients and bone marrow in 164 patients from 655 HLA related donors and 83 unrelated donors. As conditioning, 152 patients received fludarabine and TBI (2 grays), 300 patients fludarabine, busulfan and anti-thymocyte globulins (FBS) (ATG 1d: 57, 2 d: 84, 3 d: 58, 4 d: 18, 5 d: 83) and 286 patients an other regimen. As GVHD prophylaxis, 722 patients received a cyclosporine A (CsA) based regimen. After transplant, 252 patients (35%) in the global population developed an acute GVHD ≥ grade II (grades III and IV: 116) and 208 patients (37%) in the PBSCT population (grades III and IV: 100). A chronic GVHD was present in 258 patients (38%) in the global population (115 limited and 143 extensive) and 221 patients (42%) in the PBSCT population (95 limited and 126 extensive). With a median follow-up of 27 months, the 3-year probability of overall survival (OS) and event-free survival (EFS) for the global population was 38% (33–44) and 28%(24–34) and for PBSC SCT patients 39%(33–46) and 32%(27–39) respectively. The 3-year probability of OS varied according to diagnosis (CLL: 62%, NHL:50%, CML:44%, MM:41%, MDS:37%, AML:26%, ALL:20%) and cGVHD (no:28%, yes:61%). The cumulative TRM incidence was 12% at 1 year and 13% at 3 years. A multivariate analysis was performed studying pre and post transplant factors for OS, EFS and GVHD:. Table 1 summarizes all variables showing a significant impact on OS and EFS. Furthermore, analyses showed the impact of one variable on AGVHD and cGVHD for PBSCT population: FBS with ATG 1day vs 2 days [HR:1.56(1.19–2.04) p=0.001, HR:1.50(1.14–1.97) p=0.003]. In conclusion, besides the influence of known factors on OS and EFS after RIC HSCT, this study pointed out, on a large series with a long-term follow-up, the major impact of disease status, acute and chronic GVHD and demonstrated the important role of ATG duration on GVHD incidence.

Table 1:

Multivariate analyses OS/EFS

VariablesOS (HR)pEFS (HR)p
Conditionning :FBS ATG 1d vs 2 d Global 1.47 (1–2.2) 0,05  NS 
 PBSC 1.6 (1.03–2.49) 0,04  NS 
FBS ATG 5d vs 2 d PBSC  NS 1.13(1.04–1,24) < 0.01 
PD vs CR Global 1.22 (1.1–1.32) < 0.01 1.15 (1.07–1.25) < 0.01 
 PBSC 1.2 (1.1–1,3) < 0.01 1.14 (1.05–1.24) < 0.01 
Previous HSCT: yes vs no Global 1.27 (1.02–1,59) 0,04 1.25 (1.01–1.55) 0.04 
AGVHD : Grade II vs 0-I PBSC 1.21 (1–1.47) 0,05  NS 
AGVHD : Grade III-IV vs 0-I Global 1,28 (1,14–1,43) < 0.01 1.12 (1–1.25) 0.04 
 PBSC 1.3 (1.14–1.47) < 0.01 1.13 (1–1.28) 0.05 
cGVHD : yes vs no Global 0.2 (0.14–0.28) < 0.01 0.25 (0.19–0.35) < 0.01 
 PBSC 0.19 (0.13–0.28) < 0.01 0.25 (0.18–0.34) < 0.01 
VariablesOS (HR)pEFS (HR)p
Conditionning :FBS ATG 1d vs 2 d Global 1.47 (1–2.2) 0,05  NS 
 PBSC 1.6 (1.03–2.49) 0,04  NS 
FBS ATG 5d vs 2 d PBSC  NS 1.13(1.04–1,24) < 0.01 
PD vs CR Global 1.22 (1.1–1.32) < 0.01 1.15 (1.07–1.25) < 0.01 
 PBSC 1.2 (1.1–1,3) < 0.01 1.14 (1.05–1.24) < 0.01 
Previous HSCT: yes vs no Global 1.27 (1.02–1,59) 0,04 1.25 (1.01–1.55) 0.04 
AGVHD : Grade II vs 0-I PBSC 1.21 (1–1.47) 0,05  NS 
AGVHD : Grade III-IV vs 0-I Global 1,28 (1,14–1,43) < 0.01 1.12 (1–1.25) 0.04 
 PBSC 1.3 (1.14–1.47) < 0.01 1.13 (1–1.28) 0.05 
cGVHD : yes vs no Global 0.2 (0.14–0.28) < 0.01 0.25 (0.19–0.35) < 0.01 
 PBSC 0.19 (0.13–0.28) < 0.01 0.25 (0.18–0.34) < 0.01 
View Large

Topics:
conditioning (psychology), hematologic neoplasms, hematopoietic stem cell transplantation, hematopoietic stem cells, transplantation, graft-versus-host disease, chronic, graft-versus-host disease, cyclosporine, fludarabine, follow-up

Author notes

Corresponding author

2005, The American Society of Hematology
2005
Sign in via your Institution