Browsing by Author "Paviglianiti, Annalisa"

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    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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    Early and late outcomes after cord blood transplantation for pediatric patients with inherited leukodystrophies.
    (Blood Adv, 2018-01-09) van den Broek, Brigitte TA; Page, Kristin; Paviglianiti, Annalisa; Hol, Janna; Allewelt, Heather; Volt, Fernanda; Michel, Gerard; Diaz, Miguel Angel; Bordon, Victoria; O'Brien, Tracey; Shaw, Peter J; Kenzey, Chantal; Al-Seraihy, Amal; van Hasselt, Peter M; Gennery, Andrew R; Gluckman, Eliane; Rocha, Vanderson; Ruggeri, Annalisa; Kurtzberg, Joanne; Boelens, Jaap Jan
    Leukodystrophies (LD) are devastating inherited disorders leading to rapid neurological deterioration and premature death. Hematopoietic stem cell transplantation (HSCT) can halt disease progression for selected LD. Cord blood is a common donor source for transplantation of these patients because it is rapidly available and can be used without full HLA matching. However, precise recommendations allowing care providers to identify patients who benefit from HSCT are lacking. In this study, we define risk factors and describe the early and late outcomes of 169 patients with globoid cell leukodystrophy, X-linked adrenoleukodystrophy, and metachromatic leukodystrophy undergoing cord blood transplantation (CBT) at an European Society for Blood and Marrow Transplantation center or at Duke University Medical Center from 1996 to 2013. Factors associated with higher overall survival (OS) included presymptomatic status (77% vs 49%;P= .006), well-matched (≤1 HLA mismatch) CB units (71% vs 54%;P= .009), and performance status (PS) of >80 vs <60 or 60 to 80 (69% vs 32% and 55%, respectively;P= .003). For patients with PS≤60 (n = 20) or 60 to 80 (n = 24) pre-CBT, only 4 (9%) showed improvement. Of the survivors with PS >80 pre-CBT, 50% remained stable, 20% declined to 60 to 80, and 30% to <60. Overall, an encouraging OS was found for LD patients after CBT, especially for those who are presymptomatic before CBT and received adequately dosed grafts. Early identification and fast referral to a specialized center may lead to earlier treatment and, subsequently, to improved outcomes.