Pre-transplant prognostic factors of long-term survival after allogeneic peripheral blood stem cell transplantation with matched related/unrelated donors

Abstract

Mobilized peripheral blood has become the predominant stem cell source for allogeneic hematopoietic cell transplantation. In this retrospective single center study of 442 patients with hematologic malignancies, we analyzed prognostic factors for long-term survival after peripheral blood stem cell transplantation from HLA-matched related or unrelated donors. To account for disease/status heterogeneity, patients were risk-stratified according to the Disease Risk Index. Five-year overall survival was similar after transplants with matched related and unrelated donors (45% and 46%, respectively; P=0.49). Because donor age ≥60 years impacted outcome during model building, we further considered 3 groups of donors: matched unrelated (aged <60 years by definition), matched related aged <60 years and matched related aged ≥60 years. In multivariate analysis, the donor type/age group and the graft CD34+ and CD3 + cell doses impacted long-term survival. Compared with matched unrelated donor transplant, transplant from matched related donor <60 years resulted in similar long-term survival (P=0.67) while transplant from matched related donor ≥60 years was associated with higher risks for late mortality (hazard ratio (HR) 4.41; P=0.006) and treatment failure (HR: 6.33; P=0.009). Lower mortality risks were observed after transplant with CD34 + cell dose more than 4.5x10 6 /kg (HR: 0.56; P=0.002) and CD3 + cell dose more than 3x10 8 /kg (HR: 0.61; P=0.01). The Disease Risk Index failed to predict survival. We built an "adapted Disease Risk Index" by modifying risks for myeloproliferative neoplasms and multiple myeloma that improved stratification ability for progressionfree survival (P=0.04) but not for overall survival (P=0.82). Pre-transplant prognostic factors of long-term survival after allogeneic peripheral blood stem cell transplantation with matched related/unrelated donors ABSTRACT © F e r r a t a S t o r t i F o u n d a t i o nHere, we report a large single center retrospective study of PB-HSCT with MRD or 10/10 MUD in patients with hematologic malignancies. To account for disease/status heterogeneity, patients were stratified for disease risk according to the DRI. The aims of this study were: 1) to evaluate how donor type (MRD vs. MUD) and other pretransplant factors may predict for long-term OS and PFS after PB-HSCT; and 2) to evaluate DRI as a predictor for OS and PFS. Methods PatientsWe performed a retrospective analysis of all consecutive patients with hematologic malignancies who underwent a first PB-HSCT from either MRD or MUD at Saint-Louis Hospital (Paris, France) between January 2000 and December 2010. According to institutional guidelines, MRD was considered as the first donor choice and search for MUD was only undertaken if no suitable MRD was identified. For MUD PB-HSCT, only donor/recipient pairs matched at the allelic level at HLA-A, -B, -C, -DRB1 and -DQB1 loci (10/10 HLA-matched) were included. Data concerning pre-transplant characteristics and transplant outcomes were extracted from our transplantatio...

In patients older than 55 years with AML in first CR, should we search for a matched unrelated donor when an old sibling donor is available?

“…Consequently, half of the patients published previously were transplanted with a standard conditioning regimen and 20% with bone marrow as the source of stem cells 7,9,17 except one study that included only PBSCs. 8 All our patients received only RIC regimen and PBSC, which may explain the disparity of the results. Finally, all our patients were transplanted in a recent period (2005 or after) to avoid as much as possible the bias of practice changing during time, whereas the other studies included patients transplanted before this date.…”

“…[7][8][9][10]17 Two studies did not find any difference between old MSD and MUD, 9,10 whereas the three others favored a MUD over a MSD. 7,8,17 It is important to note that the population being studied strongly influences the results.…”

“…[7][8][9][10]17 Two studies did not find any difference between old MSD and MUD, 9,10 whereas the three others favored a MUD over a MSD. 7,8,17 It is important to note that the population being studied strongly influences the results. One report addressed patients with AML only but in a small group of patients, 7 one study included patients who were transplanted only with PBSCs, 8 another one, patients with MDS only, 17 whereas the final two included various hematological malignancies.…”

“…7,8,17 It is important to note that the population being studied strongly influences the results. One report addressed patients with AML only but in a small group of patients, 7 one study included patients who were transplanted only with PBSCs, 8 another one, patients with MDS only, 17 whereas the final two included various hematological malignancies. 9,10 One other important factor is the age limit of the selected populations.…”

“…7 Similar results were published by another single-center study of 442 patients, which included various hematological malignancies but only PBSC as the source of stem cells. 8 Conversely, another study from the Center for International Bone and Marrow Transplant Research (CIBMTR) including more than 2000 patients older than 50 years with different hematological malignancies (patients with AML, n = 904) did not suggest such an advantage, 9 in line with the Fred Hutchinson Cancer Research Center experience published recently. 10 In daily practice, the use of unrelated donors implies less convenience, longer delay between CR1 to HCT and also less availability of donor lymphocyte infusions.…”