Haploidentical Bone Marrow Transplantation Without T-Cell Depletion

Chang, Ying‐Jun; Huang, Xiao‐Jun

doi:10.1053/j.seminoncol.2012.09.003

Cited by 30 publications

(23 citation statements)

References 70 publications

(79 reference statements)

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“…36 Ciurea et al 37 compared TCR and TCD haploidentical HSCT and found that TCR protocol had a fast immune recovery. This result is in accordance with our data, 7,38 suggesting that a rapid immune reconstitution may contribute to a superior outcome as reported by Ciurea et al 37 Interestingly, healthrelated quality of life in unmanipulated HBMT at our centre is comparable to that in patients receiving HLA-identical sibling allo-HSCT. 39 Furthermore, other factors such as donor age can also be a useful predictive factor.…”

Section: Discussionsupporting

confidence: 93%

“…The approach to include haploidentical transplants in the 'non-HLA identical sibling donor' category is not precise, and the significance of the EBMT risk score is unclear in haploidentical transplantation. In our centre, we used a uniform regimen that includes the transplantation of G-CSF-mobilised PBSCs (G-PBSCs) and G-CSF-primed BM (G-BM) from HLA-mismatched/ haploidentical related donors without in vitro T-cell depletion, and we name this transplant protocol as unmanipulated haploidentical blood and marrow transplantation (HBMT) 6,7 . This protocol was reliable for leukaemia patients with similar GVHD, NRM, relapse and survival.…”

Section: Introductionmentioning

confidence: 99%

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EBMT risk score can predict the outcome of leukaemia after unmanipulated haploidentical blood and marrow transplantation

et al. 2014

Bone Marrow Transplant

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Systematic, standardised pretransplant risk assessment is an important tool for predicting patient outcomes following allogeneic haematopoietic SCT (HSCT). To assess the European Group for Blood and Marrow Transplantation (EBMT) risk score capacities for predicting patient outcomes following unmanipulated haploidentical blood and marrow transplantation (HBMT), we analysed 502 leukaemia patients who received transplants at our centre between 2008 and 2010. The cohort OS and leukaemia-free survival (LFS) were 72.1% and 68.1%, whereas the cumulative non-relapse mortality (NRM) and relapse incidences were 16.5% and 16.1%. According to univariate analysis, the values for OS, LFS and NRM were worse for an EBMT risk score of 6 (40.0, 40.0, 50.0%) than a score of 1 (83.1, 78.3, 8.4%). Hazard ratios steadily increased for each additional score point. Likewise, a higher EBMT risk score was associated with an increased relapse incidence. Importantly, the EBMT risk score prognostic value regarding OS, LFS, NRM and relapse was maintained in the multivariate analysis. Moreover, we also made a haploidentical EBMT (haplo-EBMT) risk score, which used number of HLA disparity instead of donor type, and the haplo-EBMT risk scores can also be used to predict patient outcomes following unmanipulated HBMT.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

EBMT risk score can predict the outcome of leukaemia after unmanipulated haploidentical blood and marrow transplantation

et al. 2014

Bone Marrow Transplant

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“…High T-cell content of allografts without TCD potentially enhances the GVL effect compared with CD34-selected haplo-HSCT. 38 In addition, we were able to decrease the occurrence of severe GVHD with our protocol, which included a combination of the G-PB/G-BM mixed harvest as the source of stem cell grafts as well as the addition of ATG to the conditioning regimen as prophylaxis for GVHD. 33 On the other hand, we could not completely exclude the influence of race and ethnicity on the clinical outcomes.…”

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confidence: 99%

Haploidentical hematopoietic stem cell transplantation in adults with Philadelphia‐negative acute lymphoblastic leukemia: No difference in the high‐ and low‐risk groups

Zhang

et al. 2014

Intl Journal of Cancer

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Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective post-consolidation therapy and curative option for adult patients with Philadelphia chromosome-negative (Ph-negative) acute lymphoblastic leukemia (ALL) in first complete remission (CR1). A human leukocyte antigen (HLA)-haploidentical related donor (haplo-RD) is one of the most important alternative sources for those without HLA-identical sibling donor (ISD). The present study aimed to evaluate the outcomes of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in adult Ph-negative ALL CR1 patients (n 5 183). We produced an unmanipulated haplo-HSCT protocol including granulocyte colony stimulating factor (G-CSF) for all donors, intensive immune suppression, anti-thymocyte globulin, and combination of G-CSF-primed bone marrow harvest and G-CSF-mobilized peripheral blood stem cells harvest as the source of stem cell grafts. The median age for high-risk versus low-risk groups were 29 versus 23 years. Three-year incidences of relapse mortality and nonrelapse mortality for high-risk versus low-risk groups were 7.1% versus 11.1% (p 5 0.498) and 18.0% versus 16.2% (p 5 0.717), respectively. Three-year probabilities of disease-free survival and overall survival for high-risk versus low-risk groups were 67.6% versus 68.2% (p 5 0.896) and 74.9% versus 72.7% (p 5 0.981), respectively. Multivariate analysis showed that limited cGVHD and a lower pre-HSCT comorbidity burden were associated with better outcomes. In summary, comparable outcomes were observed among high-and lowrisk Ph-negative ALL CR1 patients after haplo-HSCT. Haplo-RD could be considered for adults with Ph-negative ALL in CR1 as an important alternative source of donors in cases when no ISD is available.

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“…1,3,4,66,99 However, currently, there is no well-recognized standard haploidentical transplant protocol because each is based on the combination of different strategies with unique advantages and disadvantages (Tables 1 and 2; Figure 1). 3,8,12,24,64 Therefore, investigating novel combinations of strategies that can be used to overcome HLA barriers is a necessary future research direction to establish improved haploidentical protocols. The best combination may rely on a variety of factors including disease subgroup, disease status pretransplantation and the goal of transplantation.…”

Section: Future Perspectivesmentioning

confidence: 99%

“…[1][2][3][4][5][6][7] However, the success of haploidentical SCT is hindered by the host and donor T-cell response to allogeneic HLA molecules resulting in unacceptably high incidences of GVHD and graft rejection. The questions of how allografts can avoid rejection from a haploidentical recipient immune system and how normal host tissues can avoid attack by donor alloreactive immune cells have intrigued immunologists and hematologists alike for nearly 30 years.…”

Section: Introductionmentioning

confidence: 99%

Haploidentical SCT: the mechanisms underlying the crossing of HLA barriers

Huang

2014

Bone Marrow Transplant

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Research on the different mechanisms for crossing HLA barriers has progressed over the past 10 years. General outlines have come into view for a solution to this issue and are often presented as 'haploidentical SCT' immunology. In this review, we discuss several mechanisms that have recently been described in ex vivo and in vivo settings that can either avoid GVHD or promote hematopoietic reconstitution in haploidentical settings. The host and donor T-cell responses to allogeneic HLA molecules are a fundamental obstacle to the successful application of haploidentical transplantation, which results in unacceptably high incidences of GVHD and graft rejection. Thus, the T-cell response is a central factor in the establishment of a novel haploidentical transplant protocol with superior outcomes.

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Haploidentical Bone Marrow Transplantation Without T-Cell Depletion

Cited by 30 publications

References 70 publications

EBMT risk score can predict the outcome of leukaemia after unmanipulated haploidentical blood and marrow transplantation

EBMT risk score can predict the outcome of leukaemia after unmanipulated haploidentical blood and marrow transplantation

Haploidentical hematopoietic stem cell transplantation in adults with Philadelphia‐negative acute lymphoblastic leukemia: No difference in the high‐ and low‐risk groups

Haploidentical SCT: the mechanisms underlying the crossing of HLA barriers

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