Abstract
Adolescent and young adult patient presentations of aplastic anemia require a particular perspective on both diagnosis and treatment. This unique age group necessitates a thorough diagnostic evaluation to ensure the etiology, acquired or inherited, is sufficiently determined. The treatment options include human leukocyte antigen-identical sibling hematopoietic cell transplantation or immunosuppressive therapy, and both require attention to the specific medical and social needs of these adolescents and young adults. Longitudinal surveillance throughout life for the development of late complications of the disease and treatment is mandatory.
References
1.
Brodsky RA, Jones RJ: Aplastic anaemia. Lancet 2005;365:1647-1656.
2.
Alter BP: Diagnosis, genetics, and management of inherited bone marrow failure syndromes. Hematology Am Soc Hematol Educ Program 2007, pp 29-39.
3.
Rozman C, Nomdedeu B, Marin P, Montserrat E: Criteria for severe aplastic-anemia. Lancet 1987;2:955-957.
4.
Marsh JC, Hows JM, Bryett KA, Al-Hashimi S, Fairhead SM, Gordon-Smith EC: Survival after antilymphocyte globulin therapy for aplastic anemia depends on disease severity. Blood 1987;70:1046-1052.
5.
Brock K, Goldenberg N, Graham DK, Liang X, Hays T: Moderate aplastic anemia in children: Preliminary outcomes for treatment versus observation from a single-institutional experience. J Pediatr Hematol Oncol 2013;35:148-152.
6.
Sugimori C, Chuhjo T, Feng X, Yamazaki H, Takami A, Teramura M, Mizoguchi H, Omine M, Nakao S: Minor population of cd55-cd59- blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia. Blood 2006;107:1308-1314.
7.
Socie G, Devergie A, Girinski T, Piel G, Ribaud P, Esperou H, Parquet N, Maarek O, Noguera MH, Richard P, Brison O, Gluckman E: Transplantation for Fanconi's anaemia: long-term follow-up of fifty patients transplanted from a sibling donor after low-dose cyclophosphamide and thoraco-abdominal irradiation for conditioning. Br J Haematol 1998;103:249-255.
8.
Rocha V, Devergie A, Socie G, Ribaud P, Esperou H, Parquet N, Gluckman E: Unusual complications after bone marrow transplantation for dyskeratosis congenita. Br J Haematol 1998;103:243-248.
9.
Locasciulli A, Oneto R, Bacigalupo A, Socie G, Korthof E, Bekassy A, Schrezenmeier H, Passweg J, Fuhrer M: Outcome of patients with acquired aplastic anemia given first line bone marrow transplantation or immunosuppressive treatment in the last decade: a report from the European Group for Blood and Marrow Transplantation (EBMT). Haematologica 2007;92:11-18.
10.
Schrezenmeier H, Passweg JR, Marsh JC, Bacigalupo A, Bredeson CN, Bullorsky E, Camitta BM, Champlin RE, Gale RP, Fuhrer M, Klein JP, Locasciulli A, Oneto R, Schattenberg AV, Socie G, Eapen M: Worse outcome and more chronic GVHD with peripheral blood progenitor cells than bone marrow in HLA-matched sibling donor transplants for young patients with severe acquired aplastic anemia. Blood 2007;110:1397-1400.
11.
Lawler M, McCann SR, Marsh JC, Ljungman P, Hows J, Vandenberghe E, O'Riordan J, Locasciulli A, Socie G, Kelly A, Schrezenmeier H, Marin P, Tichelli A, Passweg JR, Dickenson A, Ryan J, Bacigalupo A: Serial chimerism analyses indicate that mixed haemopoietic chimerism influences the probability of graft rejection and disease recurrence following allogeneic stem cell transplantation (SCT) for severe aplastic anaemia (SAA): indication for routine assessment of chimerism post SCT for SAA. Br J Haematol 2009;144:933-945.
12.
Im HJ, Koh KN, Choi ES, Jang S, Kwon SW, Park CJ, Chi HS, Seo JJ: Excellent outcome of haploidentical hematopoietic stem cell transplantation in children and adolescents with acquired severe aplastic anemia. Biol Blood Marrow Transplant 2013;19:754-759.
13.
Xu LP, Liu KY, Liu DH, Han W, Chen H, Chen YH, Zhang XH, Wang Y, Wang FR, Wang JZ, Huang XJ: A novel protocol for haploidentical hematopoietic SCT without in vitro T-cell depletion in the treatment of severe acquired aplastic anemia. Bone Marrow Transplant 2012;47:1507-1512.
14.
Yamamoto H, Kato D, Uchida N, Ishiwata K, Araoka H, Takagi S, Nakano N, Tsuji M, Asano-Mori Y, Matsuno N, Masuoka K, Izutsu K, Wake A, Yoneyama A, Makino S, Taniguchi S: Successful sustained engraftment after reduced-intensity umbilical cord blood transplantation for adult patients with severe aplastic anemia. Blood 2011;117:3240-3242.
15.
Peffault de Latour R, Rocha V, Socie G: Cord blood transplantation in aplastic anemia. Bone Marrow Transplant 2013;48:201-202.
16.
Marsh JC, Ball SE, Cavenagh J, Darbyshire P, Dokal I, Gordon-Smith EC, Keidan J, Laurie A, Martin A, Mercieca J, Killick SB, Stewart R, Yin JA: Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol 2009;147:43-70.
17.
Gafter-Gvili A, Ram R, Gurion R, Paul M, Yeshurun M, Raanani P, Shpilberg O: ATG plus cyclosporine reduces all-cause mortality in patients with severe aplastic anemia - systematic review and meta-analysis. Acta Haematol 2008;120:237-243.
18.
Scheinberg P, Nunez O, Weinstein B, Scheinberg P, Wu CO, Young NS: Activity of alemtuzumab monotherapy in treatment-naive, relapsed, and refractory severe acquired aplastic anemia. Blood 2012;119:345-354.
19.
Scheinberg P, Nunez O, Wu C, Young NS: Treatment of severe aplastic anaemia with combined immunosuppression: anti-thymocyte globulin, ciclosporin and mycophenolate mofetil. Br J Haematol 2006;133:606-611.
20.
Alsultan A, Goldenberg NA, Kaiser N, Graham DK, Hays T: Tacrolimus as an alternative to cyclosporine in the maintenance phase of immunosuppressive therapy for severe aplastic anemia in children. Pediatr Blood Cancer 2009;52:626-630.
21.
Tisdale JF, Dunn DE, Geller N, Plante M, Nunez O, Dunbar CE, Barrett AJ, Walsh TJ, Rosenfeld SJ, Young NS: High-dose cyclophosphamide in severe aplastic anaemia: a randomised trial. Lancet 2000;356:1554-1559.
22.
Brodsky RA, Chen AR, Dorr D, Fuchs EJ, Huff CA, Luznik L, Smith BD, Matsui WH, Goodman SN, Ambinder RF, Jones RJ: High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up. Blood 2010;115:2136-2141.
23.
Eapen M, Ramsay NK, Mertens AC, Robison LL, DeFor T, Davies SM: Late outcomes after bone marrow transplant for aplastic anaemia. Br J Haematol 2000;111:754-760.
24.
Loren AW, Chow E, Jacobsohn DA, Gilleece M, Halter J, Joshi S, Wang Z, Sobocinski KA, Gupta V, Hale GA, Marks DI, Stadtmauer EA, Apperley J, Cahn JY, Schouten HC, Lazarus HM, Savani BN, McCarthy PL, Jakubowski AA, Kamani NR, Hayes-Lattin B, Maziarz RT, Warwick AB, Sorror ML, Bolwell BJ, Socie G, Wingard JR, Rizzo JD, Majhail NS: Pregnancy after hematopoietic cell transplantation: a report from the late effects working committee of the center for international blood and marrow transplant research (CIBMTR). Biol Blood Marrow Transplant 2011;17:157-166.
25.
Sanders JE: The impact of marrow transplant preparative regimens on subsequent growth and development. The Seattle Marrow Transplant Team. Semin Hematol 1991;28:244-249.
26.
Konopacki J, Porcher R, Robin M, Bieri S, Cayuela JM, Larghero J, Xhaard A, Andreoli AL, Dhedin N, Petropoulou A, Rodriguez-Otero P, Ribaud P, Moins-Teisserenc H, Carmagnat M, Toubert A, Chalandon Y, Socie G, Peffault de Latour R: Long-term follow up after allogeneic stem cell transplantation in patients with severe aplastic anemia after cyclophosphamide plus antithymocyte globulin conditioning. Haematologica 2012;97:710-716.
27.
Laundy GJ, Bradley BA, Rees BM, Younie M, Hows JM: Incidence and specificity of HLA antibodies in multitransfused patients with acquired aplastic anemia. Transfusion 2004;44:814-825.
28.
Marsh J, Socie G, Tichelli A, Schrezenmeier H, Hochsmann B, Risitano AM, Fuehrer M, Bekassy AN, Korthof ET, Locasciulli A, Ljungman P, Bacigalupo A, Camitta B, Young NS, Passweg J: Should irradiated blood products be given routinely to all patients with aplastic anaemia undergoing immunosuppressive therapy with antithymocyte globulin (ATG)? A survey from the European Group for Blood and Marrow Transplantation severe aplastic anaemia working party. Br J Haematol 2010;150:377-379.
29.
Quillen K, Wong E, Scheinberg P, Young NS, Walsh TJ, Wu CO, Leitman SF: Granulocyte transfusions in severe aplastic anemia: An eleven-year experience. Haematologica 2009;94:1661-1668.
30.
Marsh JC, Ganser A, Stadler M: Hematopoietic growth factors in the treatment of acquired bone marrow failure states. Semin Hematol 2007;44:138-147.
31.
Tichelli A, Schrezenmeier H, Socie G, Marsh J, Bacigalupo A, Duhrsen U, Franzke A, Hallek M, Thiel E, Wilhelm M, Hochsmann B, Barrois A, Champion K, Passweg JR: 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;117:4434-4441.
32.
Gluckman E, Rokicka-Milewska R, Hann I, Nikiforakis E, Tavakoli F, Cohen-Scali S, Bacigalupo A: Results and follow-up of a phase III randomized study of recombinant human-granulocyte stimulating factor as support for immunosuppressive therapy in patients with severe aplastic anaemia. Br J Haematol 2002;119:1075-1082.
33.
Socie G, Mary JY, Schrezenmeier H, Marsh J, Bacigalupo A, Locasciulli A, Fuehrer M, Bekassy A, Tichelli A, Passweg J: Granulocyte-stimulating factor and severe aplastic anemia: a survey by the European Group for Blood and Marrow Transplantation (EBMT). Blood 2007;109:2794-2796.
34.
Aytac S, Yildirim I, Ceyhan M, Cetin M, Tuncer M, Kara A, Cengiz AB, Secmeer G, Yetgin S: Risks and outcome of fungal infection in neutropenic children with hematologic diseases. Turk J Pediatr 2010;52:121-125.
35.
Aki ZS, Sucak GT, Yegin ZA, Guzel O, Erbas G, Senol E: Hematopoietic stem cell transplantation in patients with active fungal infection: not a contraindication for transplantation. Transplant Proc 2008;40:1579-1585.
36.
Verweij PE, Kerremans JJ, Voss A, Meis JF: Fungal contamination of tobacco and marijuana. JAMA 2000;284:2875.
37.
Valdez JM, Scheinberg P, Nunez O, Wu CO, Young NS, Walsh TJ: Decreased infection-related mortality and improved survival in severe aplastic anemia in the past two decades. Clin Infect Dis 2011;52:726-735.
38.
Cappellini MD, Porter J, El-Beshlawy A, Li CK, Seymour JF, Elalfy M, Gattermann N, Giraudier S, Lee JW, Chan LL, Lin KH, Rose C, Taher A, Thein SL, Viprakasit V, Habr D, Domokos G, Roubert B, Kattamis A, Investigators ES: Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1,744 patients with transfusion-dependent anemias. Haematologica 2010;95:557-566.
39.
Lee JW, Yoon SS, Shen ZX, Ganser A, Hsu HC, El-Ali A, Habr D, Martin N, Porter J: Hematologic responses in patients with aplastic anemia treated with deferasirox: a post-hoc analysis from the EPIC study. Haematologica 2013;98:1045-1048.
40.
Tichelli A, Socie G, Marsh J, Barge R, Frickhofen N, McCann S, Bacigalupo A, Hows J, Marin P, Nachbaur D, Symeonidis A, Passweg J, Schrezenmeier H: Outcome of pregnancy and disease course among women with aplastic anemia treated with immunosuppression. Ann Intern Med 2002;137:164-172.
41.
Van Staa A, van der Stege HA, Jedeloo S, Moll HA, Hilberink SR: Readiness to transfer to adult care of adolescents with chronic conditions: exploration of associated factors. J Adolesc Health 2011;48:295-302.
42.
Bryant R, Young A, Cesario S, Binder B: Transition of chronically ill youth to adult health care: experience of youth with hemoglobinopathy. J Pediatr Health Care 2011;25:275-283.
© 2014 S. Karger AG, Basel
2014
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.