University of Wisconsin Hematology

Aplastic anemia and related disorders

General; biology & pathophysiology

  1. Young NS. Aplastic anemia. NEJM 2018;379:1643
  2. Calado and Young. Telomere diseases. NEJM 2009;361:2353
  3. Niewisch et al. Disease progression and clinical outcomes in telomere biology disorders. Blood 2022;1807
  4. Gutierrez-Rodrigues et al. Clonal landscape and clinical outcomes of telomere biology disorders: somatic rescue and cancer mutations.  Blood 2024;144:2402
  5. Marsh J. Making Therapeutic Decisions in Adults with Aplastic Anemia. Hematology 2006;78-85
  6. Ogawa S. Clonal hematopoiesis in acquired aplastic anemia. Blood 2016;128:337
  7. Afable et al. Clonal evolution in aplastic anemia. Hematology 2011:90
  8. Yoshizato et al. Somatic mutations and clonal hematopoiesis in aplastic anemia. NEJM 2015;373:35(About half of patients have evidence of clonal hematopoiesis; biased mutation set consistent with Darwinian selection in marrow, correlated with outcome)
  9. Wu and Young. Single-cell genomics in acquired bone marrow failure syndromes. Blood 2023;142:1193
  10. Yamaguchi et al. Mutations in TERT, the Gene for Telomerase Reverse Transcriptase, in Aplastic Anemia. NEJM 2005;352:1413
  11. Calado and Young. Telomere maintenance and human bone marrow failure. Blood 2008;111:4446
  12. Scheinberg et al. Association of Telomere Length of Peripheral Blood Leukocytes With Hematopoietic Relapse, Malignant Transformation, and Survival in Severe Aplastic Anemia. JAMA 2010;304:1358(Shorter telomeres predicted risk of relapse, clonal evolution and overall survival)
  13. Gutierrez-Rodrigues et al. Differential diagnosis of bone marrow failure syndromes guided by machine learning. Blood 2023;141:2100
  14. Dumitriu et al. Telomere attrition and candidate gene mutations preceding monosomy 7 in aplastic anemia. Blood 2015;125:706
  15. Jerez et al. STAT3 mutations indicate the presence of subclinical T-cell clones in a subset of aplastic anemia and myelodysplastic syndrome patients. Blood 2013;122:2453(LGL clones with STAT3 mutations may cause marrow failure in some patients with AA and MDS)
  16. Seo et al. Bone marrow failure unresponsive to bone marrow transplant is caused by mutations in thrombopoietin. Blood 2017;130:875(Germ line biallelic THPO mutations cause marrow failure that responds to THPO receptor agonists)
  17. Dunn et al. Paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure syndromes. Ann Intern Med 1999;131:401
  18. Sugimori et al. Minor population of CD55-CD59- blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia. Blood 2006;107:1308z
  19. Baumelou et al. Epidemiology of aplastic anemia in France. Blood 1990; 75:1646
  20. Marsh et al. The hematopoietic defect in aplastic anemia assessed by long-term marrow culture. Blood 1990; 76:1748
  21. Nosticò and Young. Gamma-interferon gene expression in the bone marrow of patients with aplastic anemia. Ann Intern Med 1994;120:463
  22. Brown et al. Hepatitis-associated aplastic anemia. NEJM 1997;336:1059
  23. Dainiak et al. The Hematologist and Radiation Casualties.Hematology 2003:473-496
  24. Parry et al. Syndrome complex of bone marrow failure and pulmonary fibrosis predicts germline defects in telomerase. Blood 2011;117:5607
  25. Sun and Babushok. Secondary myelodysplastic syndrome and leukemia in acquired aplastic anemia and paroxysmal nocturnal hemoglobinuria. Blood 2020;136:36
  26. Zhu et al Single-cell transcriptomics dissects hematopoietic cell destruction and T-cell engagement in aplastic anemia. Blood 2021;138:23 (Stem cells in AA show defective DNA repair; possible link to MDS)

Treatment of aplastic anemia

  1. Guinan EC. Diagnosis and management of aplastic anemia. Hematology 2011:76
  2. Bacigalupo A. How I treat acquired aplastic anemia. Blood 2017;129:1428
  3. Young et al. A multicenter trial of antithymocyte globulin in aplastic anemia and related diseases. Blood 1988; 72:1861
  4. Frickhofen et al.  Antithymocyte globulin with or without cyclosporin A: 11-year follow-up of a randomized trial comparing treatments of aplastic anemia.  Blood 2003;101:1236
  5. Scheinberg et al. Treatment of severe aplastic anaemia with combined immunosuppression: anti-thymocyte globulin, ciclosporin and mycophenolate mofetil. Br J Haematol 2006;133:606 (no benefit from adding mycophenolate)
  6. Scheinberg et al. Retreatment with rabbit anti-thymocyte globulin and ciclosporin for patients with relapsed or refractory severe aplastic anaemia. Br J Haematol 2006;133:622 (30% response rate in patients who were refractory to horse ATG or who relapsed after treatment)
  7. Scheinberg et al. Horse versus rabbit antithymocyte globulin in acquired aplastic anemia. NEJM 2011;365:430(Horse ATG superior)
  8. Marsh et al. Prospective study of rabbit antithymocyte globulin and cyclosporine for aplastic anemia from the EBMT Severe Aplastic Anaemia Working Party. Blood 2012;119:5391(Response rates and OS lower than achieved with horse ATG)
  9. Teramura et al. Treatment of severe aplastic anemia with antithymocyte globulin and cyclosporin A with or without G-CSF in adults: a multicenter randomized study in Japan. Blood 2007;110:1756
  10. Brodsky et al. High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up. Blood 2010;115:2136(88% overall survival, 58% event-free survival at 10 years)
  11. Tichelli et al. A randomized controlled study in patients with newly diagnosed severe aplastic anemia receiving antithymocyte globulin (ATG), cyclosporine, with or without G-CSF: a study of the SAA Working Party of the European Group for Blood and Marrow Transplantation. Blood 2011;117:4434(OS at 6 years 76%; no survival benefit from adding G-CSF but fewer infections)
  12. Marsh and Kulasekararaj. Management of the refractory aplastic anemia patient: what are the options? Hematology 2013:87
  13. Socié et al. Malignant tumors occurring after treatment of aplastic anemia. NEJM 1993;329:1152
  14. Scheinberg et al. Activity of alemtuzumab monotherapy in treatment-naive, relapsed, and refractory severe acquired aplastic anemia. Blood 2012;119:345(Best results in relapsed and refractory patients; ATG preferable for treatment-naive patients)
  15. Olnes et al. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. NEJM 2012;367:11(44% of patients had a hematologic response; minimal toxicity)
  16. Desmond et al. Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug. Blood 2014;123:1818(40% OR rate)
  17. Townsley et al. Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia. NEJM 2017;376:1540(Treatment markedly improved response rates vs historical controls)
  18. Winkler et al. Treatment optimization and genomic outcomes in refractory severe aplastic anemia treated with eltrombopag. Blood 2019;133:2575(At least 24 weeks of treatment needed to determine responsiveness to eltrombopag)
  19. Patel et al. Long-term outcomes in patients with severe aplastic anemia treated with immunosuppression and eltrombopag: a phase 2 study. Blood 2022;139:34
  20. Townsley et al. Danazol treatment for telomere diseases. NEJM 2016;374:1922(Drug was effective in reducing rate of telomere attrition – almost all patients had telomere elongation – and improving hematopoietic function; with editorial)

Aplastic anemia: stem cell transplantation

Pure red cell aplasia

  1. Gurnari and Maciejewski. How I manage acquired pure red cell aplasia in adults. Blood 2021;137:2001
  2. Means RT. Pure red cell aplasia. Blood 2016;128:2504
  3. Sloand et al. Successful Treatment of Pure Red-Cell Aplasia with an Anti�Interleukin-2 Receptor Antibody (Daclizumab). Ann Intern Med 2006;144:181
  4. Macdougall et al. A Peptide-Based Erythropoietin-Receptor Agonist for Pure Red-Cell Aplasia. NEJM 2009;361:1848
  5. Young and Brown.  Parvovirus B-19.  NEJM 2004;350:586

Inherited marrow failure syndromes

  1. Niewisch et al. Clinical manifestations of telomere biology disorders in adults. Hematology Am Soc Hematol Educ Program (2023): 563
  2. Alter BP. Inherited bone marrow failure syndromes: considerations pre- and posttransplant. Blood 2017;130:2257
  3. Cull et al. Emerging genetic technologies informing personalized medicine in Shwachman-Diamond syndrome and other inherited BMF disorders. Blood 2024;144:931
  4. Townsley et al. Bone marrow failure and the telomeropathies. Blood 2014;124:2775
  5. Narla and Ebert. Ribosomopathies: human disorders of ribosome function. Blood 2010;115:3196(Mutations involved in several marrow failure syndromes)
  6. De Keersmaecker et al. Ribosomopathies and the paradox of cellular hypo- to hyperproliferation. Blood 2015;125:1377
  7. Ruggero and Shimamura. Marrow failure: a window in to ribosome biology. Blood 2014;124:2784
  8. Bluteau et al. A landscape of germ line mutations in a cohort of inherited bone marrow failure patients. Blood 2018;131:717
  9. Longerich et al. Stress and DNA repair biology of the Fanconi anemia pathway. Blood 2014;124:2812
  10. Olson T. Management of Fanconi anemia beyond childhood. Hematology Am Soc Hematol Educ Program (2023): 556
  11. Wang et al. Genotoxic aldehydes in the hematopoietic system. Blood 2022;139:2119 (Pathogenesis of Fanconi anemia)
  12. Garaycoechea and Patel. Why does the bone marrow fail in Fanconi anemia? Blood 2014;123:26
  13. D’Andrea A. Susceptibiity pathways in Fanconi’s anemia and breast cancer. NEJM 2010;362:1909
  14. Kutler et al.  A 20-year perspective on the International Fanconi Anemia Registry (IFAR).  Blood 2003;101:1249
  15. Peffault de Latour and Soulier. How I treat MDS and AML in Fanconi anemia. Blood 2016;127:2971
  16. Crispino and Horwitz. GATA factor mutations in hematologic disease. Blood 2017;129:2103
  17. Wong et al. Defective ribosome assembly in Schwachman-Diamond syndrome. Blood 2011;118:4305
  18. Dokal I. Dyskeratosis Congenita. Hematology 2011:480
  19. Seo et al. Bone marrow failure unresponsive to bone marrow transplant is caused by mutations in thrombopoietin. Blood 2017;130:875
  20. Tsai and Lindsley. Clonal hematopoiesis in the inherited bone marrow failure syndromes. Blood 2020;136:1615

Diamond-Blackfan anemia

  1. Da Costa et al. Diamond-Blackfan anemia. BLood 2020;136:1282
  2. Flygare and Karlsson. Diamond-Blackfan anemia: erythropoiesis lost in translation. Blood 2007;109:3152
  3. Vlachos and Muir. How I treat Diamond-Blackfan anemia. Blood 2010;116:3715
  4. Farrar et al. Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan anemia. Blood 2008;112:1582
  5. Vlachos et al. Incidence of neoplasia in Diamond Blackfan anemia: a report from the Diamond Blackfan Anemia Registry. Blood 2012;119:3815(5.4-fold increased cancer risk; risk of MDS increased 287-fold)
  6. Gagne et al. Pearson marrow pancreas syndrome in patients suspected to have Diamond-Blackfan anemia. Blood 2014;124:437
  7. Ludwig et al. Altered translation of GATA1 in Diamond-Blackfan anemia. Nat Med 2014;20:748(with editorial)
  8. O’Donohue et al. HEATR3 variants impair nuclear import of uL18 (RPL5) and drive Diamond-Blackfan anemia. Blood 2022;139:3111

Congenital dyserythropoietic anemia

  1. Iolascon et al. Congenital dyserythropoietic anemias. Blood 2020;136:1274
  2. Iolascon et al. Congenital dyserythropoietic anemias: molecular insights and diagnostic approach. Blood 2013;122:2162
  3. Heimpel et al. Congenital dyserythropoietic anemia type I (CDA I): molecular genetics, clinical appearance, and prognosis based on long-term observation. Blood 2006;107:334
  4. Heimpel et al.  Congenital dyserythropoietic anemia type II: epidemiology, clinical appearance, and prognosis based on long-term observation.  Blood 2003;102:4576

Other inherited anemias

  1. Donker et al. Practice guidelines for the diagnosis and management of microcytic anemias due to genetic disorders of iron metabolism or heme synthesis. Blood 2014;123:3873
  2. Schmitz-Abe et al. Congenital sideroblastic anemia due to mutations in the mitochondrial HSP70 homologue HSPA9. Blood 2015;126:2734(Mild anemia, dominant inheritance)
  3. Ducamp and Fleming. The molecular genetics of sideroblastic anemia. Blood 2019;133:59
  4. Fleming MD. Congenital Sideroblastic Anemias: Iron and Heme Lost in Mitochondrial Translation. Hematology 2011:525
  5. Van Dijck et al. Luspatercept as Potential Treatment for Congenital Sideroblastic Anemia. NEJM 2023;388:1435