scholarly journals Refined HLA-DPB1 mismatch with molecular algorithms predicts outcomes in hematopoietic stem cell transplantation

Haematologica ◽  
2021 ◽  
Author(s):  
Jun Zou ◽  
Piyanuch Kongtim ◽  
Betül Oran ◽  
Vasilis Kosmoliaptsis ◽  
Yudith Carmazzi ◽  
...  

HLA-DPB1 mismatches between donor and recipient are commonly seen in allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated donor. HLA-DPB1 mismatch, conventionally determined by the similarity of the T-cell epitope (TCE), is associated with an increased risk of acute graft-versus-host disease (aGVHD) and a decreased risk of disease relapse. We investigated the clinical impact of HLA-DPB1 molecular mismatch quantified by mismatched eplets (ME) and Predicted Indirectly Recognizable HLA Epitopes score (PS) in a cohort of 1,514 patients receiving HSCT from unrelated donors matched at HLA-A, -B, -C, -DRB1/3/4/5, and -DQB1 loci. HLA-DPB1 alloimmunity in the GVH direction determined by high GVH ME/PS was associated with a reduced risk of relapse (HR 0.83, P= .05 for ME) and increased risk of grade 2-4 aGVHD (HR 1.44, P< .001 for ME), whereas high HVG ME/PS was only associated with an increased risk of grade 2-4 aGVHD (HR 1.26, P= .004 for ME). Notably, in the permissive mismatch subgroup classified by TCE grouping, high HVG ME/PS was associated with an increased risk of relapse (HR 1.36, P= .026 for ME) and grade 2-4 aGVHD (HR 1.43, P= .003 for PS-II). Decision curve analysis showed GVH ME outperformed other models and provided the best clinical net benefit for the modification of aGVHD prophylaxis regimen in patients with high risk of developing clinically significant aGVHD. In conclusion, molecular assessment of HLA-DPB1 mismatch enables separate prediction of HVG or GVH alloresponse quantitatively and allows further refinement of HLA-DPB1 permissiveness as defined by conventional TCE grouping.

Blood ◽  
2011 ◽  
Vol 117 (1) ◽  
pp. 21-25 ◽  
Author(s):  
Michael Boo ◽  
Suzanna M. van Walraven ◽  
Jeremy Chapman ◽  
Brian Lindberg ◽  
Alexander H. Schmidt ◽  
...  

Abstract Hematopoietic stem cell transplantation is a curative procedure for life-threatening hematologic diseases. Donation of hematopoietic stem cells (HSCs) from an unrelated donor, frequently residing in another country, may be the only option for 70% of those in need of unrelated hematopoietic stem cell transplantation. To maximize the opportunity to find the best available donor, individual donor registries collaborate internationally. To provide homogeneity of practice among registries, the World Marrow Donor Association (WMDA) sets standards against which registries are accredited and provides guidance and regulations about unrelated donor safety and care. A basic tenet of the donor registries is that unrelated HSC donation is an altruistic act; nonpayment of donors is entrenched in the WMDA standards and in international practice. In the United States, the prohibition against remuneration of donors has recently been challenged. Here, we describe the reasons that the WMDA continues to believe that HSC donors should not be paid because of ethical concerns raised by remuneration, potential to damage the public will to act altruistically, the potential for coercion and exploitation of donors, increased risk to patients, harm to local transplantation programs and international stem cell exchange, and the possibility of benefiting some patients while disadvantaging others.


2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Salem Alshemmari ◽  
Reem Ameen ◽  
Javid Gaziev

Haploidentical hematopoietic stem-cell transplantation is an alternative transplant strategy for patients without an HLA-matched donor. Still, only half of patients who might benefit from transplantation are able to find an HLA-matched related or unrelated donor. Haploidentical donor is readily available for many patients in need of immediate stem-cell transplantation. Historical experience with haploidentical stem-cell transplantation has been characterised by a high rejection rate, graft-versus-host disease, and transplant-related mortality. Important advances have been made in this field during the last 20 years. Many drawbacks of haploidentical transplants such as graft failure and significant GVHD have been overcome due to the development of new extensive T cell depletion methods with mega dose stem-cell administration. However, prolonged immune deficiency and an increased relapse rate remain unresolved problems of T cell depletion. New approaches such as partial ex vivo or in vivo alloreactive T cell depletion and posttransplant cell therapy will allow to improve immune reconstitution in haploidentical transplants. Results of unmanipulated stem-cell transplantation with using ATG and combined immunosuppression in mismatched/haploidentical transplant setting are promising. This paper focuses on recent advances in haploidentical hematopoietic stem-cell transplantation for hematologic malignancies.


Blood ◽  
2020 ◽  
Vol 135 (18) ◽  
pp. 1548-1559 ◽  
Author(s):  
Steffen Boettcher ◽  
C. Matthias Wilk ◽  
Jochen Singer ◽  
Fabian Beier ◽  
Elodie Burcklen ◽  
...  

Abstract Clonal hematopoiesis (CH) is associated with age and an increased risk of myeloid malignancies, cardiovascular risk, and all-cause mortality. We tested for CH in a setting where hematopoietic stem cells (HSCs) of the same individual are exposed to different degrees of proliferative stress and environments, ie, in long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their respective related donors (n = 42 donor-recipient pairs). With a median follow-up time since allo-HSCT of 16 years (range, 10-32 years), we found a total of 35 mutations in 23 out of 84 (27.4%) study participants. Ten out of 42 donors (23.8%) and 13 out of 42 recipients (31%) had CH. CH was associated with older donor and recipient age. We identified 5 cases of donor-engrafted CH, with 1 case progressing into myelodysplastic syndrome in both donor and recipient. Four out of 5 cases showed increased clone size in recipients compared with donors. We further characterized the hematopoietic system in individuals with CH as follows: (1) CH was consistently present in myeloid cells but varied in penetrance in B and T cells; (2) colony-forming units (CFUs) revealed clonal evolution or multiple independent clones in individuals with multiple CH mutations; and (3) telomere shortening determined in granulocytes suggested ∼20 years of added proliferative history of HSCs in recipients compared with their donors, with telomere length in CH vs non-CH CFUs showing varying patterns. This study provides insight into the long-term behavior of the same human HSCs and respective CH development under different proliferative conditions.


Blood ◽  
2012 ◽  
Vol 120 (2) ◽  
pp. 473-476 ◽  
Author(s):  
Maria Ester Bernardo ◽  
Eugenia Piras ◽  
Adriana Vacca ◽  
Giovanna Giorgiani ◽  
Marco Zecca ◽  
...  

Abstract Sixty thalassemia patients (median age, 7 years; range, 1-37) underwent allogeneic hematopoietic stem cell transplantation (HSCT) after a preparation combining thiotepa, treosulfan, and fludarabine. Before HSCT, 27 children were assigned to risk class 1 of the Pesaro classification, 17 to class 2, and 4 to class 3; 12 patients were adults. Twenty patients were transplanted from an HLA-identical sibling and 40 from an unrelated donor. The cumulative incidence of graft failure and transplantation-related mortality was 9% and 7%, respectively. Eight patients experienced grade II-IV acute GVHD, the cumulative incidence being 14%. Among 56 patients at risk, 1 developed limited chronic GVHD. With a median follow-up of 36 months (range, 4-72), the 5-year probability of survival and thalassemia-free survival are 93% and 84%, respectively. Neither the class of risk nor the donor used influenced outcome. This treosulfan-based preparation proved to be safe and effective for thalassemia patients given allogeneic HSCT.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3517-3517
Author(s):  
Sebastian Giebel ◽  
Myriam Labopin ◽  
Mohamad Mohty ◽  
Didier Blaise ◽  
Charles Craddock ◽  
...  

Abstract Abstract 3517 Allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning (RIC-HSCT) is increasingly applied for the treatment of patients with acute myeloid leukemia. However, the procedure is heterogeneous with no standards based on randomized trials being elaborated so far. Hence, particular therapeutic decisions are in major part based on individual experience. The goal of this study was to evaluate the impact of center experience on outcome of RIC-HSCT. Based on the registry of ALWP of the EBMT, we analyzed results of 1413 HLA-matched related (n=1058) or unrelated (n=355) transplantations performed in 203 European centers between 2001 and 2007. Only patients with AML in first complete remission were included. Median recipient age was 55 years (range, 18–77 y.). Centers were categorized by quintiles according to the number of RIC-HSCT procedures in a study period. The 2 years probability of leukemia-free survival (LFS) after RIC-HSCT performed in centers with the lowest activity (1st quintile, ≤ 15 procedures/7 years) equaled 43% compared to 55% in the remaining ones (p<0.001). The incidence of non-relapse mortality (NRM) was 24% and 15%, respectively (p=0.004). In a multivariate model adjusted for other potential prognostic factors low RIC-HSCT activity was associated with decreased chance of LFS (HR=0.69, p<0.001) as well as increased risk of NRM (HR=1.69, p=0.001) and relapse (HR=1.37, p=0.01). No significant differences were found between centers belonging to the 2nd -5th quintile. We conclude that center experience is a strong predictor of outcome and should be considered for future analyses evaluating results of RIC-HSCT. Disclosures: Off Label Use: Dasatinib as first line therapy in Ph ALL.


2009 ◽  
Vol 02 ◽  
pp. 49
Author(s):  
Angela Susanne Punnett ◽  

There is a growing appreciation of the increased risk for malignancy following solid organ and hematopoietic stem cell transplantation as the survival of these patient populations increases overall. The risk for malignancy is related to a complex interaction of type, degree, and duration of immunosuppression, viral status, and recipient age. Most of the malignancies documented are common in the general population but occur with increasing incidence and have significant implications for post-transplant surveillance. Post-transplant lymphoproliferative disorder is specific to the transplant population and remains a treatment challenge. The development of novel immunosuppressive agents, the use of individualized immunosuppressive regimens, and collaborative therapeutic trials are necessary to advance clinical care for these patients. This article will review the current issues around malignancy in the post-transplant patient population.


Sign in / Sign up

Export Citation Format

Share Document