Hematopoietic cell transplantation for Diamond-Blackfan anemia and the myelodysplastic syndromes in children and adolescents
- Shakila Khan, MD
Shakila Khan, MD
- Associate Professor of Pediatrics
- Mayo Clinic College of Medicine
- Section Editors
- Donald H Mahoney, Jr, MD
Donald H Mahoney, Jr, MD
- Section Editor — Pediatric Hematology
- Professor of Pediatrics
- Baylor College of Medicine
- Robert S Negrin, MD
Robert S Negrin, MD
- Section Editor — Bone Marrow Transplantation
- Professor of Medicine
- Stanford University School of Medicine
Hematopoietic cell transplantation (HCT) is an accepted form of treatment for various hematologic disorders in children, such as aplastic anemia and beta thalassemia major. (See "Hematopoietic cell transplantation for aplastic anemia in adults" and "Hematopoietic cell transplantation for idiopathic severe aplastic anemia and Fanconi anemia in children and adolescents" and "Efficacy of hematopoietic cell transplantation in beta thalassemia major".)
The use in other hematologic disorders is not as well established. This topic review discusses the use of HCT in two pediatric disorders: Diamond-Blackfan anemia and the myelodysplastic syndromes. The use of HCT in patients with sickle cell anemia is discussed separately. (See "Hematopoietic cell transplantation in sickle cell disease".)
The term "hematopoietic cell transplantation" (HCT) will be used throughout this review as a general term to cover transplantation of progenitor cells from any source (eg, bone marrow, peripheral blood, cord blood). Otherwise, the source of such cells will be specified (eg, allogeneic peripheral blood progenitor cell transplantation). (See "Sources of hematopoietic stem cells".)
Diamond-Blackfan anemia (DBA) is a rare congenital hypoplastic anemia that usually presents early in infancy. It is characterized by macrocytic anemia, a normal or slightly reduced white blood cell count, and a normocellular bone marrow with erythroid hypoplasia. (See "Anemia in children due to decreased red blood cell production".)
Initial treatment — Approximately 20 to 30 percent of children with DBA recover spontaneously after initial supportive care. The mainstays of therapy of DBA are corticosteroids and blood transfusion. Infants are typically maintained with transfusions until they are 6 to 12 months old, then a trial of corticosteroids is given and has a 60 to 70 percent response rate. This is discussed in more detail separately. (See "Anemia in children due to decreased red blood cell production", section on 'Diamond-Blackfan anemia'.)
- August CS, King E, Githens JH, et al. Establishment of erythropoiesis following bone marrow transplantation in a patient with congenital hypoplastic anemia (Diamond-Blackfan syndrome). Blood 1976; 48:491.
- Roy V, Pérez WS, Eapen M, et al. Bone marrow transplantation for diamond-blackfan anemia. Biol Blood Marrow Transplant 2005; 11:600.
- Mugishima H, Ohga S, Ohara A, et al. Hematopoietic stem cell transplantation for Diamond-Blackfan anemia: a report from the Aplastic Anemia Committee of the Japanese Society of Pediatric Hematology. Pediatr Transplant 2007; 11:601.
- Lipton JM, Atsidaftos E, Zyskind I, Vlachos A. Improving clinical care and elucidating the pathophysiology of Diamond Blackfan anemia: an update from the Diamond Blackfan Anemia Registry. Pediatr Blood Cancer 2006; 46:558.
- Fagioli F, Quarello P, Zecca M, et al. Haematopoietic stem cell transplantation for Diamond Blackfan anaemia: a report from the Italian Association of Paediatric Haematology and Oncology Registry. Br J Haematol 2014; 165:673.
- Vlachos A, Muir E. How I treat Diamond-Blackfan anemia. Blood 2010; 116:3715.
- Narla A, Vlachos A, Nathan DG. Diamond Blackfan anemia treatment: past, present, and future. Semin Hematol 2011; 48:117.
- Aghalar J, Atsidaftos E, Lipton JM, Vlachos A. Improved outcomes in Diamond Blackfan anemia treated via stem cell transplantation since the year 2000 (abstract). Blood 2009; 114:3202.
- Wagner JE, Rosenthal J, Sweetman R, et al. Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease. Blood 1996; 88:795.
- Vettenranta K, Saarinen UM. Cord blood stem cell transplantation for Diamond-Blackfan anemia. Bone Marrow Transplant 1997; 19:507.
- Bonno M, Azuma E, Nakano T, et al. Successful hematopoietic reconstitution by transplantation of umbilical cord blood cells in a transfusion-dependent child with Diamond-Blackfan anemia. Bone Marrow Transplant 1997; 19:83.
- Gluckman E, Rocha V, Boyer-Chammard A, et al. Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group. N Engl J Med 1997; 337:373.
- Bizzetto R, Bonfim C, Rocha V, et al. Outcomes after related and unrelated umbilical cord blood transplantation for hereditary bone marrow failure syndromes other than Fanconi anemia. Haematologica 2011; 96:134.
- Blank J, Lange B. Preleukemia in children. J Pediatr 1981; 98:565.
- Swerdlow SH, Campo E, Harris NL, et al. WHO classification of Tumors of Haematopoietic and Lymphoid Tissues, IARC Press, Lyon 2008.
- Luna-Fineman S, Shannon KM, Atwater SK, et al. Myelodysplastic and myeloproliferative disorders of childhood: a study of 167 patients. Blood 1999; 93:459.
- Passmore SJ, Hann IM, Stiller CA, et al. Pediatric myelodysplasia: a study of 68 children and a new prognostic scoring system. Blood 1995; 85:1742.
- Bader-Meunier B, Miélot F, Tchernia G, et al. Myelodysplastic syndromes in childhood: report of 49 patients from a French multicentre study. French Society of Paediatric Haematology and Immunology. Br J Haematol 1996; 92:344.
- Muñoz A, Díaz-Heredia C, Badell I, et al. Allogeneic stem cell transplantation for myelodysplastic syndromes in children: a report from the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON). Pediatr Hematol Oncol 2009; 26:345.
- Andolina JR, Kletzel M, Tse WT, et al. Allogeneic hematopoetic stem cell transplantation in pediatric myelodysplastic syndromes: improved outcomes for de novo disease. Pediatr Transplant 2011; 15:334.
- Guinan EC, Tarbell NJ, Tantravahi R, Weinstein HJ. Bone marrow transplantation for children with myelodysplastic syndromes. Blood 1989; 73:619.
- Rubie H, Attal M, Demur C, et al. Intensified conditioning regimen with busulfan followed by allogeneic BMT in children with myelodysplastic syndromes. Bone Marrow Transplant 1994; 13:759.
- Locatelli F, Niemeyer C, Angelucci E, et al. Allogeneic bone marrow transplantation for chronic myelomonocytic leukemia in childhood: a report from the European Working Group on Myelodysplastic Syndrome in Childhood. J Clin Oncol 1997; 15:566.
- Woolfrey AE, Gooley TA, Sievers EL, et al. Bone marrow transplantation for children less than 2 years of age with acute myelogenous leukemia or myelodysplastic syndrome. Blood 1998; 92:3546.
- Yusuf U, Frangoul HA, Gooley TA, et al. Allogeneic bone marrow transplantation in children with myelodysplastic syndrome or juvenile myelomonocytic leukemia: the Seattle experience. Bone Marrow Transplant 2004; 33:805.
- Basquiera AL, Pizzi S, Correas AG, et al. Allogeneic hematopoietic stem cell transplantation in pediatric myelodysplastic syndromes: a multicenter experience from Argentina. Pediatr Blood Cancer 2015; 62:153.
- Woodard P, Carpenter PA, Davies SM, et al. Unrelated donor bone marrow transplantation for myelodysplastic syndrome in children. Biol Blood Marrow Transplant 2011; 17:723.
- Strahm B, Nöllke P, Zecca M, et al. Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome in children: results of the EWOG-MDS 98 study. Leukemia 2011; 25:455.
- de Witte T, Brand R, van Biezen A, et al. Allogeneic stem cell transplantation for patients with refractory anaemia with matched related and unrelated donors: delay of the transplant is associated with inferior survival. Br J Haematol 2009; 146:627.
- Leahey AM, Friedman DL, Bunin NJ. Bone marrow transplantation in pediatric patients with therapy-related myelodysplasia and leukemia. Bone Marrow Transplant 1999; 23:21.