Abstract
Introduction: Peripheral blood stem cells (PBSC) are increasingly used for unrelated donor (UD) hematopoietic stem cell transplantation (HSCT). A recent randomized prospective trial did not detect significant survival differences between PBSC and bone marrow (BM) transplantation from a UD. The use of PBSC reduced the risk of graft failure, whereas BM reduced the risk of chronic graft versus host disease (GVHD) (Anasetti & al, NEJM 2012). However, HLA matching was based on HLA-A, HLA-B, HLA-C &HLA-DRB1 (8/8 but also 7/8), some of the patients (pts) received a reduced intensity conditioning regimen (22%) and diseases consisted of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), but also other hematological malignancies. We thus conducted this study to compare mobilized PBSC with BM for matched 10/10 UD HSCT after standard conditioning regimen (MAC) in pts with AML and MDS only.
Patients and methods: We included all consecutive pts in France who received a first HSCT for AML or MDS with PBSC or BM from a matched 10/10 UD after a MAC (fractionated total body irradiation (TBI)-Cyclophosphamide(Cy), n=165 or Endoxan-Cy, n=203) between 2000 and 2013. Clinical data were prospectively collected using ProMISe (Project Manager Internet Server), an internet-based data registry system shared by all centers of the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC). HLA typing data were collected from the SFHI (French Society of Histocompatibility and Immunogenetic) and the ABM (French Biomedical Agency). This study is in accordance with Helsinki declaration for clinical research.
Results: We included368 adults pts (221 [60%] received BM; 147 [40%] received PBSC). Median follow-up was of 16.5 months [0-156]. The BM and PBSC groups were well balanced with respect to age, diagnosis, disease risk, use of antithymocyte globulins (ATG) (67 [30%] BM and 52 [35%] PBSC recipients,) and cytomegalovirus (CMV) recipient and donor status. PBSC recipients were more likely to be male and received less TBI-based regimen. GVHD prophylaxis mainly combined cyclosporine A (CSA) and methotrexate (MTX) (82%).
The median number of nucleated cell dose infused was higher in the PBSC group compared with the BM group: CD34+ cells, 6.96 x10⁶/kg [1.2-37.8] vs 2,78 x10⁶/kg [0.6-89] p<0.01) and total nucleated cells, 9.8 x10⁸/kg [1.3-663] vs 2.3 x10⁸/kg [0.3-305.3] p<0.01).
Two hundred and seven (90%) pts engrafted after BM and 144 (99.3%) after PBSC HSCT (p=0.1). Among pts who received PBSC as compared with those who received BM, the median time to neutrophils engraftment (> 0.5 x 109 /L) was 6 days shorter and 8 days shorter to platelets engraftment (>20x109 /L) (p<0.01).
The cumulative incidence (CI) for severe acute GVHD III-IV was 21.1% and 16.3% in the PBSC and the BM group, respectively (p=0.18).
CI of chronic GVHD was higher after PBSC (47.1% vs 34.3% for BM, p=0.05). By multivariate analysis, the absence of ATG in the conditioning regimen (HR 0.4 95%CI [0.22-0.72] p<0.01) and PBSC as stem cells source (HR 0.6 95%CI [0.34-0.97] p=0.04) were associated with an increased chronic GVHD.
At 2-years, the CI of non relapse related mortality (NRM), relapse as well as disease free survival (DFS) and overall survival (OS) were similar between the 2 groups (Table 1).
In multivariate analysis, better OS was associated with complete remission (CR) disease status (HR 0.5 95%CI [0.32-0.69] p<0.01) and pts’s age<38.1 years (HR 0.67 95%CI [0.48-0.93] p=0.02) at time of HSCT, and the use of CSA-MTX as GVHD prophylaxis (HR 0.6 95%CI [0.41-0.95] p=0.03).
Conclusion: OS, NRM and relapse rates are similar with PBSC and BM after HLA 10/10 matched UD for AML or MDS using MAC, but engraftment is better with PBSC and the CI of chronic GVHD is lower with BM. Better results are obtained for pts <38 years old with a disease in CR at time of HSCT using CSA-MTX as GVHD prophylaxis. The absence of ATG with PBSC was associated with chronic GVHD. This study thus favors the use of ATG in the setting of matched 10/10 PBSC. However, the role of ATG in the context of BM after HLA 10/10 matched UD MAC HSCT remains unclear and warrants further investigation.
Table 1: 2-year CI of NRM*, relapse, DFS** and OS*** Parameters BM % (95% CI) PBSC % (95%CI) p value NRM 23 (20-26) 18 (15-21) 0.8 Relapse 30 (27-33) 28 (25-31) 0.83 DFS 47.1 (44-51) 54.4 (50-58) 0.2 OS 54 .4 (50.8-57.9) 60.2 (55.7-64.6) 0.31
*NRM: non-relapse mortality
**DFS: disease free survival
***OS: overall survival
Disclosures
No relevant conflicts of interest to declare.
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