Research and publications from the Bone Marrow Transplant Unit

While the majority of bone marrow transplants (BMTs) are successful, there are four main reasons why a BMT may fail. Our research in the BMT Unit at Great Ormond Street Hospital (GOSH) centres on a number of areas, which are summarised below.

Toxicity from the chemotherapy and/or radiotherapy in preparation for BMT. GOSH has pioneered a number of reduced intensity transplants in an attempt to reduce both the early and late toxicity of BMT. GOSH is now recognised as world leaders in this field.

GOSH has a number of studies that allow the donor immune system to be specifically targeted to disease (tumour cells) or to viruses.

Adoptive immunotherapy (as described above) allows the benefit of the graft to be maximised while reducing one of the other complications of BMT: graft-versus-host disease (GVHD).

Cord blood transplantation which, because of less stringency for full tissue type matching, provides suitable donors when no bone marrow donor can be found. Cord blood also appears to provide a new immune system faster than other stem cell sources so helps to fight infection more rapidly.

Ozsahin H, Cavazzana-Calvo M, Notarangelo LD, Schulz A, Thrasher AJ, Mazzolari E, Slatter MA, Le Deist F, Blanche S, Veys P, Fasth A, Bredius R, Sedlacek P, Wulffraat N, Ortega J, Heilmann C, O'Meara A, Wachowiak J, Kalwak K, Matthes-Martin S, Gungor T, Ikinciogullari A, Landais P, Cant AJ, Friedrich W, Fischer A (2008) Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow Transplantation. Blood 111 (1): 439-45

Satwani P, Cooper N, Rao K, Veys P, Amrolia P (2008) Reduced intensity conditioning and allogeneic stem cell transplantation in childhood malignant and nonmalignant diseases. Bone Marrow Transplant 41 (2): 173-82

Thapar N, Lindley KJ, Kiparissi F, Elawad MA, Ashworth M, Veys P, Gaspar HB, Hill SM, Milla PJ, Shah N (2008) Treatment of intractable ulcerating enterocolitis of infancy by allogeneic bone marrow transplantation. Clin Gastroenterol Hepatol 6 (2): 248-50

Connor P, Khair K, Liesner R, Amrolia P, Veys P, Ancliff P, Mathias M (2008) Stem cell transplantation for children with Glanzmann thrombasthenia. Br J Haematol 140 (5): 568-71

Connor P, Veys P, Amrolia P, Haworth S, Ashworth M, Moledina S (2008) Pulmonary hypertension in children with Evans syndrome. Pediatr Hematol Oncol 25 (2): 93-8

Karlsson H, Samarasinghe S, Ball LM, Sundberg B, Lankester AC, Dazzi F, Uzunel M, Rao K, Veys P, Le Blanc K, Ringdén O, Amrolia PJ (2008) Mesenchymal stem cells exert differential effects on alloantigen and virus-specific T-cell responses. Blood 112 (3): 532-41

Greystoke B, Bonanomi S, Carr TF, Gharib M, Khalid T, Coussons M, Jagani M, Naik P, Rao K, Goulden N, Amrolia P, Wynn RF, Veys PA (2008) Treosulfan-containing regimens achieve high rates of engraftment associated with low transplant morbidity and mortality in children with non-malignant disease and significant co-morbidities. Br J Haematol 142 (2): 257-62

Bonanomi S, Connor P, Webb D, Ancliff P, Amrolia P, Rao K, McCloskey D, Hemmatpour S, Goulden N, Veys P (2008) Successful outcome of allo-SCT in high-risk pediatric AML using chemotherapy-only conditioning and post transplant immunotherapy. Bone Marrow Transplant 42 (4): 253-7

Titman P, Pink E, Skucek E, O'Hanlon K, Cole TJ, Gaspar J, Xu-Bayford J, Jones A, Thrasher AJ, Davies EG, Veys PA, Gaspar HB (2008) Cognitive and behavioral abnormalities in children after hematopoietic stem cell transplantation for severe congenital immunodeficiencies. Blood 112 (9): 3907-13

Cooper N, Rao K, Goulden N, Webb D, Amrolia P, Veys P (2008) The use of reduced-intensity stem cell transplantation in haemophagocytic lymphohistiocytosis and Langerhans cell histiocytosis. Bone Marrow Transplant 42 Suppl 2 (): S47-50

Shaw BE, Veys P, Pagliuca A, Addada J, Cook G, Craddock CF, Gennery AR, Goldman J, Mackinnon S, Madrigal JA, Marks DI, Navarrete C, Potter MN, Querol S, Regan F, Russell NH, Hough RE (2009) Recommendations for a standard UK approach to incorporating umbilical cord blood into clinical transplantation practice: conditioning protocols and donor selection algorithms. Bone Marrow Transplant 44 (1): 7-12

Daikeler T, Hügle T, Farge D, Andolina M, Gualandi F, Baldomero H, Bocelli-Tyndall C, Brune M, Dalle JH, Urban C, Ehninger G, Gibson B, Linder B, Lioure B, Marmont A, Matthes-Martin S, Nachbaur D, Schuetz P, Tyndall A, van Laar JM, Veys P, Saccardi R, Gratwohl A, Working Party Autoimmune Diseases of the EBMT (2009) Allogeneic hematopoietic SCT for patients with autoimmune diseases. Bone Marrow Transplant 44 (1): 27-33

Ochs HD, Filipovich AH, Veys P, Cowan MJ, Kapoor N (2009) Wiskott-Aldrich syndrome: diagnosis, clinical and laboratory manifestations, and treatment. Biol Blood Marrow Transplant 15 (1 Suppl): 84-90

Abinun M, Flood TJ, Cant AJ, Veys P, Gennery AR, Foster HE, Friswell M, Baildam E, Davidson J, Southwood TR, Livermore P, Wedderburn LR (2009) Autologous T cell depleted haematopoietic stem cell transplantation in children with severe juvenile idiopathic arthritis in the UK (2000-2007). Mol Immunol 47 (1): 46-51

Qasim W, Cavazzana-Calvo M, Davies EG, Davis J, Duval M, Eames G, Farinha N, Filopovich A, Fischer A, Friedrich W, Gennery A, Heilmann C, Landais P, Horwitz M, Porta F, Sedlacek P, Seger R, Slatter M, Teague L, Eapen M, Veys P (2009) Allogeneic hematopoietic stem-cell transplantation for leukocyte adhesion deficiency. Pediatrics 123 (3): 836-40

Rao K, Rao A, Karlsson H, Jagani M, Veys P, Amrolia PJ (2009) Improved survival and preserved antiviral responses after combination therapy with daclizumab and infliximab in steroid-refractory graft-versus-host disease. J Pediatr Hematol Oncol 31 (6): 456-61

Hough R, Cooper N, Veys P (2009) Allogeneic haemopoietic stem cell transplantation in children: what alternative donor should we choose when no matched sibling is available?. Br J Haematol 147 (5): 593-613

Straathof KC, Rao K, Eyrich M, Hale G, Bird P, Berrie E, Brown L, Adams S, Schlegel PG, Goulden N, Gaspar HB, Gennery AR, Landais P, Davies EG, Brenner MK, Veys PA, Amrolia PJ (2009) Haemopoietic stem-cell transplantation with antibody-based minimal-intensity conditioning: a phase 1/2 study. Lancet 374 (9693): 912-20

Samarasinghe S, Mancao C, Pule M, Nawroly N, Karlsson H, Brewin J, Openshaw P, Gaspar HB, Veys P, Amrolia PJ (2010) Functional characterization of alloreactive T cells identifies CD25 and CD71 as optimal targets for a clinically applicable allodepletion strategy. Blood 115 (2): 396-407

Veys P (2010) Reduced intensity transplantation for primary immunodeficiency disorders. Immunol Allergy Clin North Am 30 (1): 103-24

Szabolcs P, Cavazzana-Calvo M, Fischer A, Veys P (2010) Bone marrow transplantation for primary immunodeficiency diseases. Pediatr Clin North Am 57 (1): 207-37

Bordon V, Gennery AR, Slatter MA, Vandecruys E, Laureys G, Veys P, Qasim W, Friedrich W, Wulfraat NM, Scherer F, Cant AJ, Fischer A, Cavazzana-Calvo M, Bredius RG, Notarangelo LD, Mazzolari E, Neven B, Güngör T, Inborn Error Working Party of the European Bone Marrow Transplantation (EBMT) group (2010) Clinical and immunologic outcome of patients with cartilage hair hypoplasia after hematopoietic stem cell transplantation. Blood 116 (1): 27-35

Gennery AR, Slatter MA, Grandin L, Taupin P, Cant AJ, Veys P, Amrolia PJ, Gaspar HB, Davies EG, Friedrich W, Hoenig M, Notarangelo LD, Mazzolari E, Porta F, Bredius RG, Lankester AC, Wulffraat NM, Seger R, Güngör T, Fasth A, Sedlacek P, Neven B, Blanche S, Fischer A, Cavazzana-Calvo M, Landais P, Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation, European Society for Immunodeficiency (2010) Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: entering a new century, do we do better?. J Allergy Clin Immunol 126 (3): 602-10.e1-11

Booth C, Gilmour KC, Veys P, Gennery AR, Slatter MA, Chapel H, Heath PT, Steward CG, Smith O, O'Meara A, Kerrigan H, Mahlaoui N, Cavazzana-Calvo M, Fischer A, Moshous D, Blanche S, Pachlopnick-Schmid J, Latour S, de Saint-Basile G, Albert M, Notheis G, Rieber N, Strahm B, Ritterbusch H, Lankester A, Hartwig NG, Meyts I, Plebani A, Soresina A, Finocchi A, Pignata C, Cirillo E, Bonanomi S, Peters C, Kalwak K, Pasic S, Sedlacek P, Jazbec J, Kanegane H, Nichols KE, Hanson IC, Kapoor N, Haddad E, Cowan M, Choo S, Smart J, Arkwright PD, Gaspar HB (2011) X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease. Blood 117 (1): 53-62

Brown L, Xu-Bayford J, Allwood Z, Slatter M, Cant A, Davies EG, Veys P, Gennery AR, Gaspar HB (2011) Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screening. Blood 117 (11): 3243-6

Segal BH, Veys P, Malech H, Cowan MJ (2011) Chronic granulomatous disease: lessons from a rare disorder. Biol Blood Marrow Transplant 17 (1 Suppl): S123-31

Slatter MA, Rao K, Amrolia P, Flood T, Abinun M, Hambleton S, Nademi Z, Goulden N, Davies G, Qasim W, Gaspar HB, Cant A, Gennery AR, Veys P (2011) Treosulfan-based conditioning regimens for hematopoietic stem cell transplantation in children with primary immunodeficiency: United Kingdom experience. Blood 117 (16): 4367-75