Retinal abnormalities (RA) are very frequently observed in adult patients with acute myeloid leukemia (AML), but the clinical significance of these findings has not been fully investigated. We examined the fundus oculi in a cohort of 122 adult patients with AML at presentation and analyzed some clinical and biological features to assess whether there was any association with RA. For this purpose, we subdivided the patients into two groups according to the presence or absence of RA (groups 1 and 2, respectively). We considered current laboratory parameters such as white blood cell (WBC) count, hemoglobin (Hb), platelets and serum lactate dehydrogenase (LDH). Moreover, we subdivided the patients into two groups according to age <60 (group A) or ≧60 years (group B) to evaluate a possible association between RA and response to treatment and/or overall survival (OS). In our series, a higher median age and a lower Hb value were associated with group 1 (p = 0.001 and p = 0.04, respectively); the median LDH value was 812 U/l (range 224–5,551) and 607 (range 181–5,244) for groups 1 and 2, respectively (p = 0.02). There was no association between RA and karyotypic alterations. In terms of outcome, in group A (<60 years), 80% patients who achieved complete remission (CR) were in group 2 vs. 13% nonresponders (NR) (p < 0.0001). Median OS of group 2 patients was 49.7 months compared with 7.2 months for those in group 1 (p = 0.002). In group B, 58% patients who achieved CR were in group 1 vs. 15% NR (p < 0.006). Median OS of patients in group 2 was 14.6 months compared with 2.9 months in group 1 (p = 0.02). Our data show that RA are significantly associated with some biological features and with shorter OS in AML patients and this parameter seems to be an effective clinical sign of poor prognosis in terms of CR.

Keywords:
Acute myeloid leukemia, Retinal abnormalities, Prognostic factors
1.
Guyer DR, Schachat AP, Vitale S, Markowitz JA, Braine H, Burke PJ, Karp JE, Graham M: Relationship between fundus lesions and hematologic parameters at diagnosis. Opthalmology 1989;96:860–864.
2.
Abu E-Asrar AM, Al-Momen AK, Kangave D, Harakati MS, Ajarim DS: Correlation of fundus lesions and hematologic findings in leukemic retinopathy. Eur J Ophthalmol 1996;6:166–172.
3.
Reddy SC, Quah SH, Low HC, Jackson N: Prognostic significance of retinopathy at presentation in adult acute leukemia. Ann Hematol 1998;76:15–18.
4.
Liu Yin JA, Johnson PRE: Acute myeloid leukaemia in elderly: Biology and treatment (annotation). Br J Haematol 1993;83:1–6.
5.
Giannoulis N, Ogier C, Hast R, Lindblom B, Sjögren AM, Reizenstein P: Difference between young and old patients in characteristics of leukemic cells: Older patients have cells growing excessively in vitro, with low antigenicity despite high HLA-DR antigens. Am J Hematol 1984;16:113–121.
6.
Johnson PRE, Liu Yin AL: Prognostic factors in elderly patients with acute myeloid leukaemia: Development of a model to predict survival. Br J Haematol 1993;85:300–306.
7.
Smith GA, Damon LE, Rugo HS, Ries CA, Linker CA: High-dose cytarabine dose modification reduces the incidence of neurotoxicity in patients with renal insufficiency. J Clin Oncol 1997;15:833–839.
8.
Leith CP, Kopecky KJ, Godwin J, McConnell T, Slovak ML, Chen IM, Head DR, Appelbaum FR, Willman CL: Acute myeloid leukemia in the elderly: Assessment of multidrug resistance (MDR) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study. Blood 1997;89:3323–3329.
9.
Zhu YM, Das-Gupta EP, Russel NH: Microsatellite instability and p53 mutations are associated with abnormal expression of the MSH2 gene in adult acute leukemia. Blood 1999;94:733–740.
10.
Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, Rees J, Hann I, Stevens R, Burnett A, Goldstone A: The importance of diagnostic cytogenetics on outcome in AML: Analysis of 1,612 patients entered into the MRC AML 10 trial. Blood 1998;92:2322–2333.
11.
Bennet JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C: Proposals for the classification of the acute leukaemias. French-American-British (FAB) cooperative group. Br J Haematol 1976;33:451–458.
12.
Zittoun R, Suciu S, De Witte T, Resegotti L, Liso V, Willemze R, Belhabri A, Amadori S, Giustolisi R, Labar B, Fioritoni G, Rossi Ferrini P, Leone G,Jehn U, Keating S, Fazi P, Dardenne M, Solbu G, Mandelli F: Comparison of three intercalating agent induction and consolidation in acute myeloid leukemia (AML) followed by autologous or allogeneic transplantation: Preliminary results of the EORTC- GIMEMA AML-10 randomized trial. Blood 1999;94:658a.
13.
De Witte T, Suciu S, Zittoun R, Resegotti L, Liso V, Willemze R, Belhabri A, Amadori S, Giustolisi R, Labar B, Fioritoni G, Rossi-Ferrini G, Leone G, Jehn U, Keating S, Fazi P, Rodts P, Solbu G, Mandelli F: The type of antracycline administered during remission induction and consolidation therapy of AML has an impact factor on feasibility of subsequent autologous or allogeneic transplantation and induced marrow toxicity: Preliminary results of the EORTC-GIMEMA AML-10 randomized trial. Blood 2000;96:503a.
14.
Avvisati G, Lo Coco F, Diverio D, Falda M, Ferrara F, Lazzarino M, Russo D, Petti MC, Mandelli F: AIDA (all-trans retinoic acid + idarubicin) in newly diagnosed acute promyelocytic leukemia: A Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto (GIMEMA) pilot study. Blood 1996;88:1390–1398.
15.
Schepens CL, Reagan CDJ (eds): Controversial Aspects of the Management of Retinal Detachment. Boston, Little, Brown, 1965, pp 6–7.
16.
Mitelman F (ed): International System for Human Cytogenetic Nomenclature (1995). Recommendations of the International Standing Committee on Human Cytogenetic Nomenclature. Memphis, October 1994. Basel, Karger, 1995.
17.
Aisen ML, Bacon BR, Goodman AM, Chester EM: Retinal abnormalities associated with anemia. Arch Ophthalmol 1983;101:1049–1052.
18.
Culler AM: Fundus changes in leukemia. Trans Am Ophthalmol Soc 1951;49:445–473.
19.
Schachat AP, Markowitz JA, Guyer DR, Burke PJ, Karp JE, Graham ML: Ophthalmic manifestations of leukemia. Arch Ophthalmol 1989;107:697–700.
20.
Jackseon N, Reddy SC, Harun MH, Quah SH, Low HC: Macular haemorrhage in adult leukaemia patients at presentation and the risk of subsequent intracranial haemorrhage. Br J Haematol 1997;98:204–249.
21.
Jackson N, Reddy SC, Hishamuddin MD, Quah SH, Low HC: Retinal findings in adult acute leukaemia: Correlation with leukocytosis. Clin Lab Haematol1996;18:105–109.
22.
Rubenstein RA, Yanoff M, Albert DM: Thrombocytopenia, anemia and retinal hemorrhages. Am J Ophthalmol 1968;65:435–439.
23.
Robb RM, Ervin LD, Sallan SE: A pathological study of eye involvement in acute leukemia of childhood. Trans Am Ophthalmol Soc 1978;76:90–101.
24.
Karesh JW, Golman EJ, Reck K, Kelman SE, Lee EJ, Schiffer CA: A prospective ophthalmic evaluation of patients with acute myeloid leukemia: Correlation of ocular and hematologic findings. J Clin Oncol 1989;7:1528–1532.
25.
Boneu B, Fernandez F: The role of hematocrit in bleeding. Transfusion Med Rev 1987;1:182–185.
26.
Ferrara F, Mirto S: Serum LDH value as a predictor of clinical outcome in acute myelogenous leukaemia of the elderly. Br J Haematol 1996;92:627–631.
27.
Baer MR, Barcos M, Farrell H, Raza A, Preisler HD: Acute myelogenous leukemia with leukemia cutis. Cancer 1989;63:2192–2200.
28.
Longacre T, Smoller B: Leukemia cutis. Am J Clin Pathol 1993;100:276–284.
29.
Holt JM, Gordon-Smith EC: Retinal abnormalities in diseases of the blood. Br J Ophthalmol 1969;53:145–160.
30.
Loewenstein JL: Retinopathy associated with blood anomalies; in Albert DM, Jakobiec FA: Principles and Practice of Ophthalmology. Philadelphia, Saunders, 1994, vol 2, pp 995–1000.
© 2001 S. Karger AG, Basel
2001
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.