Browsing by Author "Wang, Tao"

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    ItemOpen Access
    Allele-level HLA matching for umbilical cord blood transplantation for non-malignant diseases in children: a retrospective analysis.
    (The Lancet. Haematology, 2017-07) Eapen, Mary; Wang, Tao; Veys, Paul A; Boelens, Jaap J; St Martin, Andrew; Spellman, Stephen; Bonfim, Carmem Sales; Brady, Colleen; Cant, Andrew J; Dalle, Jean-Hugues; Davies, Stella M; Freeman, John; Hsu, Katherine C; Fleischhauer, Katharina; Kenzey, Chantal; Kurtzberg, Joanne; Michel, Gerard; Orchard, Paul J; Paviglianiti, Annalisa; Rocha, Vanderson; Veneris, Michael R; Volt, Fernanda; Wynn, Robert; Lee, Stephanie J; Horowitz, Mary M; Gluckman, Eliane; Ruggeri, Annalisa

    Background

    The standard for selecting unrelated umbilical cord blood units for transplantation for non-malignant diseases relies on antigen-level (lower resolution) HLA typing for HLA-A and HLA-B, and allele-level for HLA-DRB1. We aimed to study the effects of allele-level matching at a higher resolution-HLA-A, HLA-B, HLA-C, and HLA-DRB1, which is the standard used for adult unrelated volunteer donor transplantation for non-malignant diseases-for umbilical cord blood transplantation.

    Methods

    We retrospectively studied 1199 paediatric donor-recipient pairs with allele-level HLA matching who received a single unit umbilical cord blood transplantation for non-malignant diseases reported to the Center for International Blood and Marrow Transplant Research or Eurocord and European Group for Blood and Marrow Transplant. Transplantations occurred between Jan 1, 2000, and Dec 31, 2012. The primary outcome was overall survival. The effect of HLA matching on survival was studied using a Cox regression model.

    Findings

    Compared with HLA-matched transplantations, mortality was higher with transplantations mismatched at two (hazard ratio [HR] 1·55, 95% CI 1·08-2·21, p=0·018), three (2·04, 1·44-2·89, p=0·0001), and four or more alleles (3·15, 2·16-4·58, p<0·0001). There were no significant differences in mortality between transplantations that were matched and mismatched at one allele (HR 1·18, 95% CI 0·80-1·72, p=0·39). Other factors associated with higher mortality included recipient cytomegalovirus seropositivity (HR 1·40, 95% CI 1·13-1·74, p=0·0020), reduced intensity compared with myeloablative conditioning regimens (HR 1·36, 1·10-1·68, p=0·0041), transplantation of units with total nucleated cell dose of more than 21 × 107 cells per kg compared with 21 × 107 cells per kg or less (HR 1·47, 1·11-1·95, p=0·0076), and transplantations done in 2000-05 compared with those done in 2006-12 (HR 1·64, 1·31-2·04, p<0·0001). The 5-year overall survival adjusted for recipient cytomegalovirus serostatus, conditioning regimen intensity, total nucleated cell dose, and transplantation period was 79% (95% CI 74-85) after HLA matched, 76% (71-81) after one allele mismatched, 70% (65-75) after two alleles mismatched, 62% (57-68) after three alleles mismatched, and 49% (41-57) after four or more alleles mismatched transplantations. Graft failure was the predominant cause of mortality.

    Interpretation

    These data support a change from current practice in that selection of unrelated umbilical cord blood units for transplantation for non-malignant diseases should consider allele-level HLA matching at HLA-A, HLA-B, HLA-C, and HLA-DRB1.

    Funding

    National Cancer Institute; National Heart, Lung, and Blood Institute; National Institute for Allergy and Infectious Diseases; US Department of Health and Human Services-Health Resources and Services Administration; and US Department of Navy.
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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.
    (Haematologica, 2016-10) Lazaryan, Aleksandr; Wang, Tao; Spellman, Stephen R; Wang, Hai-Lin; Pidala, Joseph; Nishihori, Taiga; Askar, Medhat; Olsson, Richard; Oudshoorn, Machteld; Abdel-Azim, Hisham; Yong, Agnes; Gandhi, Manish; Dandoy, Christopher; Savani, Bipin; Hale, Gregory; Page, Kristin; Bitan, Menachem; Reshef, Ran; Drobyski, William; Marsh, Steven Ge; Schultz, Kirk; Müller, Carlheinz R; Fernandez-Viña, Marcelo A; Verneris, Michael R; Horowitz, Mary M; Arora, Mukta; Weisdorf, Daniel J; Lee, Stephanie J
    The diversity of the human leukocyte antigen (HLA) class I and II alleles can be simplified by consolidating them into fewer supertypes based on functional or predicted structural similarities in epitope-binding grooves of HLA molecules. We studied the impact of matched and mismatched HLA-A (265 versus 429), -B (230 versus 92), -C (365 versus 349), and -DRB1 (153 versus 51) supertypes on clinical outcomes of 1934 patients with acute leukemias or myelodysplasia/myeloproliferative disorders. All patients were reported to the Center for International Blood and Marrow Transplant Research following single-allele mismatched unrelated donor myeloablative conditioning hematopoietic cell transplantation. Single mismatched alleles were categorized into six HLA-A (A01, A01A03, A01A24, A02, A03, A24), six HLA-B (B07, B08, B27, B44, B58, B62), two HLA-C (C1, C2), and five HLA-DRB1 (DR1, DR3, DR4, DR5, DR9) supertypes. Supertype B mismatch was associated with increased risk of grade II-IV acute graft-versus-host disease (hazard ratio =1.78, P=0.0025) compared to supertype B match. Supertype B07-B44 mismatch was associated with a higher incidence of both grade II-IV (hazard ratio=3.11, P=0.002) and III-IV (hazard ratio=3.15, P=0.01) acute graft-versus-host disease. No significant associations were detected between supertype-matched versus -mismatched groups at other HLA loci. These data suggest that avoiding HLA-B supertype mismatches can mitigate the risk of grade II-IV acute graft-versus-host disease in 7/8-mismatched unrelated donor hematopoietic cell transplantation when multiple HLA-B supertype-matched donors are available. Future studies are needed to define the mechanisms by which supertype mismatching affects outcomes after alternative donor hematopoietic cell transplantation.
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    ItemOpen Access
    In Vitro Differentiation of Tumor- Associated Macrophages from Monocyte Precursors with Modi
    (2021) Kaufman, Russel; Wang, Tao
    Tumor-associated macrophages (TAMs) are one of most important components of the tumor microenvironment. Although many assays have been developed to differentiate monocytes into macrophages (Mϕ) for studying the biology of TAMs in vitro, little is known whether the macrophages induced by these approaches can recapitulate the biology of TAMs present in the tumor microenvironment. We have developed a novel assay to differentiate human monocytes into TAMs using modified melanoma-conditioned medium, which is derived from the concentrated tumor cell culture medium. Characterization of these modified melanoma-conditioned medium-induced macrophages (MCMI-Mϕ) by multiple flow cytometry, Luminex, microarray, and immunohistochemistry analyses indicates that MCMI-Mϕ are phenotypically and functionally highly similar to the TAMs present in the tumor microenvironment.