Human leukocyte antigen supertype matching after myeloablative hematopoietic cell transplantation with 7/8 matched unrelated donor allografts: a report from the Center for International Blood and Marrow Transplant Research

Lazaryan, Aleksandr; Wang, Tao; Spellman, Stephen R.; Wang, Hailin; Pidala, Joseph; Nishihori, Taiga; Askar, Medhat; Olsson, Richard F.; Oudshoorn, Matchteld; Abdel‐Azim, Hisham; Yong, Agnes S. M.; Gandhi, Manish J.; Dandoy, Christopher E.; Savani, Bipin N.; Hale, Gregory A.; Page, Kristin; Bitan, Menachem; Reshef, Ran; Drobyski, William R.; Marsh, Steven G.E.; Schultz, Kirk R.; Müller, Carlheinz; Fernández-Viña, Marcelo; Verneris, Michael R.; Horowitz, Mary M.; Arora, Mukta; Weisdorf, Daniel J.; Lee, Stephanie J.

doi:10.3324/haematol.2016.143271

Cited by 20 publications

(19 citation statements)

References 35 publications

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“…However, use of these donors leads to rates of GVHD and TRM that are much higher than expected for fully-matched donor HCT. Multiple strategies have been sought to identify “permissible mismatches” associated with improved outcomes of a single-allele mismatched unrelated donor HCT [35]. Haploidentical transplantation, facilitated by the administration of cyclophosphamide after cellular infusion, has the advantages of following a logistical pattern similar to matched sibling transplantation, and a time to engraftment on par with matched related and unrelated donor transplants [36].…”

Section: Discussionmentioning

confidence: 99%

Outcomes after Umbilical Cord Blood Transplantation for Myelodysplastic Syndromes

Gerds

Ahn

et al. 2017

Biology of Blood and Marrow Transplantation

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For patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplantation, umbilical cord blood transplantation (UCBT) has become an acceptable alternative donor source in the absence of a matched sibling or unrelated donor. However, there have been few published series dedicated solely to describing the outcomes of adult patients with myelodysplastic syndrome (MDS) who have undergone UCBT. From 2004 to 2013, 176 adult MDS patients underwent UCBT as reported to the Center for International Blood and Marrow Transplant Research. Median age at the time of transplant was 56 years (range 18–73 years), with 10% having very low, 23% low, 19% intermediate, 19% high, and 13% very high-risk Revised International Prognostic Scoring System (IPSS-R) scores, respectively. The 100-day probability of Grade 2–4 acute graft-versus-host disease (GVHD) was 38%, and the 3-year probability of chronic GVHD was 28%. The probability of relapse and transplant-related mortality (TRM) at 3 years was 32% and 40%, respectively, leading to a 3-year, disease-free survival (DFS) of 28%, and overall survival (OS) of 31%. In multivariate analysis increasing IPSS-R score at time of HCT was associated with inferior TRM (P=.0056), DFS (P=.018), and OS (P=.0082), but not with GVHD or relapse. Pre-transplant comorbidities were associated with TRM (P=.001), DFS (P=.02), and OS (P=.001). Reduced conditioning intensity was associated with increased risk of relapse (RR 3.95; 95% CI 1.78–8.75, P<.001), and although a higher proportion of myeloablative UCBTs were done for those with high-risk disease, the effect of conditioning regimen intensity was the same regardless of IPSS-R score. For those who lack a matched sibling or unrelated donor, UCBT can result in long-term, disease-free survival for some patients. However, the success of UCBT in this population is hampered by a high rate of TRM.

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Section: Discussionmentioning

confidence: 99%

Outcomes after Umbilical Cord Blood Transplantation for Myelodysplastic Syndromes

Gerds

Ahn

et al. 2017

Biology of Blood and Marrow Transplantation

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“…Pharmacokinetic modelling showed that 1000mg on days 1, 8 and 15 of cycle 1 could achieve similar exposures. 123 A simplified fixed dose schedule of obinutuzumab 1000mg on days 1, 8 and 15 of the first 21-day cycle and day 1 of subsequent 21-day cycles was selected to achieve adequate exposure levels in subsequent phase II and III trials. Pharmacokinetic studies showed that the flat-dose schedule rapidly achieved CD20 target saturation and serum drug concentrations were maintained at the therapeutic level throughout the treatment course.…”

Section: Indolent Hematological Malignanciesmentioning

confidence: 99%

Anti-CD20 monoclonal antibodies: reviewing a revolution

Casan

Wong

Northcott

et al. 2018

Human Vaccines & Immunotherapeutics

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Since the inception of rituximab in the 1990s, anti-CD20 monoclonal antibodies have revolutionised the treatment of B cell hematological malignancies and have become a cornerstone of modern gold-standard practice. Additionally, the potent efficacy of these agents in depleting the B cell compartment has been used in the management of a broad array of autoimmune diseases. Multiple iterations of these agents have been investigated and are routinely used in clinical practice. In this review, we will discuss the physiology of CD20 and its attractiveness as a therapeutic target, as well as the pharmacology, pre-clinical and clinical data for the major anti-CD20 monoclonal antibodies: rituximab, obinutuzumab and ofatumumab.

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“…In particular, determining the MHC-binding peptide motif is now widely accessible as an important approach of MHC I allele classification (4). Twelve HLA supertypes (A1, A1A3, A1A24, A2, A3, A24, B7, B8, B27, B44, B58, and B62) have thus far been reported, based on their binding motifs (4)(5)(6)(7)(8). Alleles of the same supertype have similar binding motifs, which is very useful for screening special peptides presented by certain MHC I molecules and would benefit subsequent T-cell recognition and vaccine development studies.…”

Section: Introductionmentioning

confidence: 99%

Divergent Peptide Presentations of HLA-A*30 Alleles Revealed by Structures With Pathogen Peptides

et al. 2019

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Human leukocyte antigen (HLA) alleles have a high degree of polymorphism, which determines their peptide-binding motifs and subsequent T-cell receptor recognition. The simplest way to understand the cross-presentation of peptides by different alleles is to classify these alleles into supertypes. A1 and A3 HLA supertypes are widely distributed in humans. However, direct structural and functional evidence for peptide presentation features of key alleles (e.g., HLA-A * 30:01 and -A * 30:03) are lacking. Herein, the molecular basis of peptide presentation of HLA-A * 30:01 and -A * 30:03 was demonstrated by crystal structure determination and thermostability measurements of complexes with T-cell epitopes from influenza virus (NP44), human immunodeficiency virus (RT313), and Mycobacterium tuberculosis (MTB). When binding to the HIV peptide, RT313, the PΩ-Lys anchoring modes of HLA-A * 30:01, and -A * 30:03 were similar to those of HLA-A * 11:01 in the A3 supertype. However, HLA-A * 30:03, but not -A * 30:01, also showed binding with the HLA * 01:01-favored peptide, NP44, but with a specific structural conformation. Thus, different from our previous understanding, HLA-A * 30:01 and -A * 30:03 have specific peptide-binding characteristics that may lead to their distinct supertype-featured binding peptide motifs. Moreover, we also found that residue 77 in the F pocket was one of the key residues for the divergent peptide presentation characteristics of HLA-A * 30:01 and -A * 30:03. Interchanging residue 77 between HLA-A * 30:01 and HLA-A * 30:03 switched their presented peptide profiles. Our results provide important recommendations for screening virus and tumor-specific peptides among the population with prevalent HLA supertypes for vaccine development and immune interventions.

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Human leukocyte antigen supertype matching after myeloablative hematopoietic cell transplantation with 7/8 matched unrelated donor allografts: a report from the Center for International Blood and Marrow Transplant Research

Cited by 20 publications

References 35 publications

Outcomes after Umbilical Cord Blood Transplantation for Myelodysplastic Syndromes

Outcomes after Umbilical Cord Blood Transplantation for Myelodysplastic Syndromes

Anti-CD20 monoclonal antibodies: reviewing a revolution

Divergent Peptide Presentations of HLA-A*30 Alleles Revealed by Structures With Pathogen Peptides

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