**Part 3**

**Clinical Manifestations of Acute Lymphoblastic Leukemia** 

50 Novel Aspects in Acute Lymphoblastic Leukemia

Swerdlow SH, et al. (2008) WHO classification of tumours of haematopoietic and lymphoid tissues. Fourth edition, Lyon, IARC Press. *Ann Oncol.* Vol.21. No.5. pp.1032-40. Takeuchi K, Yokoyama M, Ishizawa S, et al. Lymphomatoid gastropathy: a distinct

Tang G, Truong F, Fadare O. et.al (2008) Diagnostic challenges related to myeloid/natural killer cells, a variant of myeloblasts. *Int J Clin Exp Pathol. Vol* 1. No.6. pp544-9. Tsukune Y, Isobe Y, Yasuda H, et al.(2010) Activity and safety of combination chemotherapy

Yamaguchi M, Suzuki R, Kwong YL, et al.(2008) Phase I study of dexamethasone,

Yok-Lam K.(2011) The Diagnosis and Management of Extranodal NK/T-Cell Lymphoma,

Yong W, Zheng W, Zhu J, Zhang Y, Wei Y, Wang X, et al.(2006) Midline NK/T-cell

regimen, and prognostic factors.*Hematol Oncol.* Vol 24, No.1. pp.28-32. Zhang L, Anglesio MS, O'Sullivan M, Zhang F, Yang G, Sarao R, et al.(2007) The E3 ligase

lymphoma and leukemia.*Cancer Sci. Vol* 99. No.5. pp.1016-20.

*Blood.* Vol.116, No.25. pp.5631-7.

cancers.*Nat Med.* Vol.13. No.9. pp1060-9.

pp.310-5.

pp.21-8.

clinicopathologic entity of self-limited pseudomalignant NK-cell proliferation.

with methotrexate, ifosfamide, l-asparaginase and dexamethasone (MILD) for refractory lymphoid malignancies: a pilot study.*Eur J Haematol.* Vol.84. No.4.

methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell

Nasal-Type and Aggressive NK-Cell Leukemia.*J Clin Exp Hematop.* Vol.51, No.1,

lymphoma nasal-type: treatment outcome, the effect of L-asparaginase based

HACE1 is a critical chromosome 6q21 tumor suppressor involved in multiple

**3** 

*Spain* 

**Ophthalmological Manifestations** 

**in Acute Lymphoblastic Leukemia** 

*2Department of Pediatrics, "Lozano Blesa" University Clinic Hospital, Zaragoza* 

The aim of the present chapter is to review the different ophthalmological signs and symptoms that can be observed in acute lymphoblastic leukemia and the importance of the examination of these patients by an ophthalmologist whenever an ocular affectation is

Acute lymphoblastic leukemia is a malignant neoplasm caused by the proliferation of poorly differenciated precursors of the lymphoid cells, which are known as blast cells. Blast cells replace the normal elements of the bone marrow, decreasing the production of normal blood cells and, therefore, causing anemia, thrombocytopenia and neutropenia. They can also infiltrate other organs, such as liver, spleen, lymph nodes or, less frequently, central

Acute lymphoblastic leukemia is the most common type of leukemia in children, although it is also seen in adult patients. If blood test results are abnormal or the doctor suspects leukemia despite normal cell counts, a bone marrow aspiration and biopsy are the next steps. Treatment is based on chemotherapy, radiotherapy and bone marrow transplantation.

The dominant clinical feature of these diseases is usually bone marrow failure caused by accumulation of blast cells although any organ can be infiltrated. Furthermore, signs and symptoms of acute lymphoblastic leukemia can be secondary to the toxicity of chemotherapy and/or radiotherapy, graft versus host reaction following bone marrow transplantation, or infections due to immunosuppression. They can include fever, weakness, fatigue, breathlessness, opportunistic infections, weight loss, anorexia, easy bruising and bleeding, thrombosis, edema of the lower limbs and the abdomen, swollen liver or spleen, lymphadenopathy, or bone pain. (Florensa et al, 2006; Ribera & Ortega, 2003; Ortega, 2006) Ophthalmological signs in patients suffering from leukemia were first described as "leukemic retinopathy" by Liebreich in 1863. (Campos-Campos et al, 2004; Guyer et al, 1989) Reports of patients with acute lymphoblastic leukemia presenting with visual symptoms as the initial sign of the disease are rare (Kim et al, 2010). However, ocular changes in acute lymphoblastic leukemia are common. They have been reported to occur in up to 90% of

nervous system. (Florensa et al, 2006; Ribera & Ortega, 2003; Sharma et al, 2004)

(Ribera & Ortega, 2003; Ortega, 2006; Ribera, 2006)

patients with this disease (Kincaid & Green, 1983; Mesa, 2003).

**1. Introduction** 

suspected.

Javier Mateo1, Francisco J. Ascaso1, Esther Núñez1, Carlos Peiro1, Gonzalo González2 and José A. Cristóbal1

*1Department of Ophthalmology,* 
