Peripheral-Blood Stem Cells versus Bone Marrow from Unrelated Donors

H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. .
New England Journal of Medicine (Impact Factor: 55.87). 10/2012; 367(16):1487-96. DOI: 10.1056/NEJMoa1203517
Source: PubMed


Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia.
We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37).
The overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P=0.29), with an absolute difference of 5 percentage points (95% CI, -3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P=0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P=0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse.
We did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute-National Cancer Institute and others; number, NCT00075816.).

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    • "The incidence of chronic graft-versus-host disease (cGVHD) continues to rise as the number of allogeneic stem cell transplants (allo-SCT) has increased to >25,000 annually worldwide. The utilization of peripheral blood as a preferred stem cell source for allografts may have led to an increased incidence of cGVHD [1]. Aside from being the leading cause of treatment-related mortality among long-term survivors of allo-SCT, it also has a significant impact on quality of life [2]. "
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    ABSTRACT: Background The safety of extracorporeal photopheresis (ECP) in steroid-refractory chronic graft-versus-host disease (SR-cGVHD) has been explored in multiple studies but reported response rates (RR) vary significantly across studies. Methods We conducted a meta-analysis to assess the efficacy of ECP for SR-cGVHD. A search of electronic databases for studies published between 1984 and 2012 was conducted. End points included RR: complete response (CR), overall response rates (ORR), and organ-specific RR. The initial search generated 312 studies, of which 18 met the selection criteria (N=595). A random effects model was used for pooled rates. Results Pooled CR rates and ORR were 29% (confidence interval [CI], 19-42%) and 64% (CI, 65-82%), respectively. One-year overall survival was available for 4 studies only and was 49% (CI, 29-70%). The pooled RR for skin, liver, ocular, oral, lung, gastrointestinal and musculoskeletal SR-cGVHD was 74%, 68%, 60%, 72%, 48%, 53%, and 64%, respectively. There was a significant heterogeneity among studies due to differences in ECP schedules and duration. No significant differences in responses to ECP for pediatric and adult populations were found. Sensitivity analysis could not be undertaken due to a limited number of prospective studies. Conclusion ECP is an effective therapy for oral, skin, and liver SR-cGVHD, with modest activity in lung and gastrointestinal SR-cGVHD.
    Blood Research 06/2014; 49(2):100-6. DOI:10.5045/br.2014.49.2.100
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    • "Allograft rejection occurs when donor cells fail to engraft initially, or when there is a loss of donor cells at a later time point following initial engraftment. While the overall frequency of graft failure in BMT is less than 5%, graft failure is still a major concern when the source of the allograft is a T cell depleted (TCD) human leukocyte antigen (HLA) – haploidentical donor, in cord blood transplants [1], in BM grafts from unrelated donors [2], or in patients where non-myeloablative conditioning is used. LeBlanc et al. examined patients with various hematological malignancies or solid tumors that had received non-myeloablative conditioning or a higher-intensity conditioning regimen followed by a hematopoietic stem cell transplant (HSCT) from either HLA-identical siblings or unrelated donors [3]. "
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    ABSTRACT: Donor cell engraftment is critical for the success of allogeneic bone marrow transplants. Graft failure is a result of donor cells either failing to engraft initially or being eliminated at later time points. Donor cell engraftment is facilitated by donor T cells, which eliminate residual host hemato-lymphoid effector cells such as NK cells and T cells. We aimed to explore the role of host hematopoietic cell derived IL-12 on donor cell engraftment in a murine model of BMT. We established radiation chimeras by transplanting C57BL6/J (B6) mice with BM from either congenic B6 mice or IL-12p40 KO mice. These WT [rightwards arrow] WT or IL-12 KO [rightwards arrow] WT chimeras then underwent a secondary transplant with allogeneic (FVB) BM. Survival, engraftment, donor T cell expansion, cytokine production by donor T cells, as well as expression of stimulatory markers on donor T cells was analyzed. Mice whose residual host hematopoietic cells were capable of producing IL-12 had modestly higher survival, and significantly higher donor T cell and erythroid engraftment. We have also found that an increased number of donor T cells in IL-12 KO [rightwards arrow] WT chimeras have a regulatory phenotype, expressing FoxP3, producing lower levels of TNF-alpha, higher levels of IL-10, and expressing higher levels of ICOS as well as PD-1 on CD4+ T cells. To our knowledge, this is the first report of a beneficial role of IL-12 production by host cells in the context of bone marrow engraftment in a murine model of BMT. These findings support the clinical use of exogenous IL-12 for use in settings where graft failure is of concern.
    Journal of Hematology & Oncology 02/2014; 7(1):16. DOI:10.1186/1756-8722-7-16 · 4.81 Impact Factor
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    • "In recent years, the use of G-CSF-mobilized peripheral blood progenitor cells (PBPC) has been favored because of more rapid engraftment, i.e. shorter duration of pancytopenia, in particular neutropenia, and a more potent anti-tumor (GVL) effect than observed with marrow cells. However, a randomized study in patients receiving unrelated donor transplants, similar to earlier studies with HLA-identical sibling transplants, showed a higher incidence of chronic GHVD with PBPC, even though this did not impact long-term survival.44 However, as stated above, long-term steroid use (for GVHD) will create new problems, particularly in these older patients and will affect the QOL. "
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    ABSTRACT: The incidence of myeloid malignancies, including myelodysplastic syndromes (MDS) increases with age. While several therapeutic modalities have been developed, for most of these patients the only treatment with curative potential is allogeneic hematopoietic cell transplantation (HCT). The development of reduced/low intensity transplant conditioning regimens allows to successfully transplant patients in their '60s and even '70s, although comorbidities may determine who does come to transplantation and who does not. Also, as many as half of the patients will develop graft versus host disease (GVHD), even with HLA matched donors, requiring therapy for extended periods of time, and GVHD and treatment with glucocorticoids is likely to impact the quality of life. Nevertheless, dependent upon disease stage at HCT, the presence of comorbidities and the regimen used, 30% to 50% of patients 60 years of age or older, may survive long-term cured of their disease. Future studies should focus on the incorporation of non-transplant modalities into the overall transplant approach, the prevention of GVHD, and the utilization of immunotherapy to reduce the incidence of relapse and GVHD and further improve overall transplant success.
    Mediterranean Journal of Hematology and Infectious Diseases 01/2014; 6(1):e2014056. DOI:10.4084/MJHID.2014.056
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