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Cord Blood Stem Cells

High-resolution HLA typing by sequencing for HLA-A, -B, -C, -DR, -DQ in 122 unrelated cord blood/patient pair transplants hardly improves long-term clinical outcome

Summary:

To determine the impact of high-resolution (HR) HLA typing with outcomes after UCBT, DNAs of 122 pairs were analysed for HLA class I and class II mismatches (MM) based on HR typing. For HLA-A, -B on low-resolution typing and -DRB1 on HR typing, the following MM situation resulted: no MM (13%), one MM (40%), two MM (36%), three MM (8%), four MM (3%). For A, B, C, DR and DQ based on HR typing the following MM occurred: No MM (4%), one MM (10%), two MM (15%), three MM (22%), four MM (25%), five MM (12%), six MM (6%), seven MM (3%), eight MM (2%). There was no significant association between number of MM (HR) for both HLA-A, -B and -DRB1 and HLA-A, -B, -C, -DRB1 and DQB1 and aGvHD grade II–IV. There was a trend that MM in class I HR were associated with neutrophil recovery; HLA-A locus typing analysed in HvG direction was associated with reduced cumulative incidence of engraftment (P=0.04), the same for C-KIR in HvG direction (P=0.01). No significant correlation was found between numbers of HLA-MM on the HR level with 2-year survival. The analysis shows that the degree of mismatching in UCBT is even higher than expected.

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Acknowledgements

This work was supported by grants from EUROBANK and EUROCORD III of the EU as well as the German José Carreras Leukaemia Foundation.

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Correspondence to G Kögler.

Appendix

Appendix

The authors thank the collaboration of Frederico Garnier and Irina Ionescu from the Eurocord registry and the clinicians and transplant centers that performed the CBT and reported the data:

The Eurocord-EBMT transplant centers: Hospital de Clinicas, Pr R Pasquini, Curitiba, Brasil; MD Anderson Cancer Center (adults), Dr S Giralt, Houston, USA; UCLA Medical Center, Mrs S Fischer, RN, Los Angeles, USA; Children's Hospital Medical Center, Dr A Filipovich, Cincinnati, USA; MD Anderson Cancer Center (Pediatrics), Dr Ka Wah Chan, Houston, USA; Hôpital Pédiatrique de ‘La Timone’, Pr G Michel, Marseille, France; Oregon Health Sciences University, Dr T Moore, Portland, USA; Sydney Children's Hospital, Dr M Vowels, Randwick, Australia; Medical City Dallas Hospital, Mrs Hooker, RN, Dallas, USA; Prince of Wales Hospital, Dr Chi Kong Li, Hong Kong, China; Fairview University of Minesota, Dr J Wagner, Minneapolis, USA; FLENI, Dr B Diez, Buenos Aires, Argentina; Emory University School of Medecine, Dr Angela Ogden, Atlanta, USA; University Medical Center, Dr Michael Graham, Tucson, USA; Startship Hospital, Dr L Teague, Auckland, New Zealand; Hackensack University Medical Center, Dr S Goldberg, Hackensack, USA; iLoyola University Medical Center, Dr Patrick J Stiff, Maywood, USA; CETRAMOR, Dr Jorge Saslavsky, Rosario, Argentina; University Hospital, Dr Lin Hai Peng, Kuala Lumpur, Malaysia; Leiden University Hospital, Dr W Fibbe, Leiden, The Netherlands; Universitätskinderklinik, Dr W Friedrich, Ulm, Germany; Rigshospitalet, Dr N Jacobsen, Copenhagen, Denmark; Hôpital Saint Louis, Pr E Gluckman, Paris, France; Hospital for Children and Adolescents, Dr K Vetteranta, Helsinki, Finland; Institut Paoli Calmettes, Dr D Blaise, Marseille, France; Azienda Ospedaliera S Giovanni, Dr M Falda, Torino, Italy; E Ematologia, University of La Sapienza, Dr W Arcese, Rome, Italy; Hôpital Jean Minjos, Dr J-Y Cahn, Besançon, France; Cliniques Universitaires St Luc, Dr B Brichard, Brussels, Belgium; Hospital Santa Creu i Sant Pau, Dr I Badell Serra, Barcelona, Spain; Ospedale Maggiore di Milano, IRCCS, Dr G Lambertenghi Deliliers, Milano, Italie; Hôpital Claude Huriez, Dr JP Jouet, Lille, France; Clinica di Oncoematologia Pediatrica, Dr C Messina, Padova, Italy; Inst Portugues Oncologia, Dr P Pimentel, Porto, Portugal; Medical School of Hannover, Dr A Ganser, Hannover, Germany; Inst Portugues Oncologia, Dr M Abecasis, Lisboa, Portugal; Ospedale Regina Margherita, Dr F Fagioli, Torino, Italy; Charité-Virchow Klinikum, Dr W Ebell, Berlin, Germany; Royal Manchester Children's Hospital, Dr A Will, Pendlebury, UK; Hôpital de l’Archet, Dr A Sirvent, Nice, France; Hospital M. Infantil Vall d’Hebron, Dr J Ortega, Barcelona, Spain; Lower Silesian Centre for Cellular Transplantation, Dr A Lange, Wroclaw, Poland; IRCCS Policlinico San Matteo, Dr F Locatelli, Pavia, Italy; University Children's Hospital, Dr C Urban, Graz, Austria; Hospital Ramon y Cajal, Dr A Munoz Villa, Madrid, Spain; Hôpital R. Debré, Dr E Vilmer, Paris, France; Universitätsklinikum, Dr G Ulrich, Düsseldorf, Germany; Hospital Infantil ‘La Fe’, Dr V Castel, Valencia, Spain; Klinik für Kinder und Jugendmedizin, Dr S Burdach, Halle, Germany; Hospital Universitario ‘La Fe’, Dr G Sanz, Valencia, Spain; Hôpital d’ Enfants, Dr P Bordigoni, Vandoeuvre, France; The Children's Hospital at Westmead, Dr P Shaw, Sydney, Australia; Clinica Puerta de Hierro, Dr MN Fernandez, Madrid, Spain; Hospital Nino Jesus, Dr MA Diaz, Madrid, Spain; Hospital Infantil La Paz, Dr AM Martinez Rubio, Madrid, Spain; University Hospital Gent, Dr LA Noens, Gent, Belgium; Schneider Children's Medical Center, Dr I Yaniv, Petach-Tikva, Israel; University Tor Vergata, St Eugenio Hospital, Dr S Amadori, Rome, Italy; University of Bologna, Dr A Pession, Bologna, Italy.

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Kögler, G., Enczmann, J., Rocha, V. et al. High-resolution HLA typing by sequencing for HLA-A, -B, -C, -DR, -DQ in 122 unrelated cord blood/patient pair transplants hardly improves long-term clinical outcome. Bone Marrow Transplant 36, 1033–1041 (2005). https://doi.org/10.1038/sj.bmt.1705189

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