Szczepański Tomasz, de Vaan Gerard A M, Beishuizen Auke, Bogman José, Jansen Mieke W J C, van Wering Elisabeth R, van Dongen Jacques J M
Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Pediatr Blood Cancer. 2004 Apr;42(4):343-9. doi: 10.1002/pbc.10466.
Complicating malignant hematopoietic proliferations might severely hamper the course of acute lymphoblastic leukemia (ALL) in patients with an otherwise good prognosis. It is important to distinguish whether such neoplastic proliferations represent ALL relapses or secondary treatment-related malignancies.
We present an 11-year-old girl with precursor-B-ALL in whom maintenance treatment was complicated by an isolated ALL relapse in the brain, nodular lymphoproliferations in the liver, and an isolated myelo-monocytic leukemia cutis. All these hemato-oncologic malignancies occurred in the background of a secondary immunodeficiency, most likely caused by cytotoxic treatment.
Using a stepwise molecular approach, we were able to demonstrate that the liver infiltrates were Epstein-Barr virus (EBV)-positive, contained monoclonal mature B-cells with immunoglobulin heavy chain gene (IGH) gene rearrangements unrelated to the primary ALL, and thus represented a true secondary non-Hodgkin lymphoma (NHL). In contrast, the skin infiltrates consisted of myelo-monocytic cells with clonal IGH and T-cell receptor gamma gene rearrangements, identical to the precursor-B-ALL blasts at diagnosis. Thus, the disease course of the precursor-B-ALL patient was complicated by two different isolated extramedullary relapses (brain and skin) and a secondary EBV(+) B-NHL.
复杂的恶性造血增殖可能严重妨碍预后原本良好的急性淋巴细胞白血病（ALL）患者的病程。区分此类肿瘤增殖是代表ALL复发还是继发的与治疗相关的恶性肿瘤很重要。
我们报告一名11岁患前体B-ALL的女孩，其维持治疗因脑部孤立的ALL复发、肝脏结节性淋巴细胞增殖以及孤立的皮肤骨髓单核细胞白血病而变得复杂。所有这些血液肿瘤恶性疾病均发生在继发免疫缺陷的背景下，很可能是由细胞毒性治疗引起的。
采用逐步分子方法，我们能够证明肝脏浸润细胞为EB病毒（EBV）阳性，含有单克隆成熟B细胞，其免疫球蛋白重链基因（IGH）基因重排与原发性ALL无关，因此代表真正的继发性非霍奇金淋巴瘤（NHL）。相比之下，皮肤浸润由骨髓单核细胞组成，具有克隆性IGH和T细胞受体γ基因重排，与诊断时的前体B-ALL原始细胞相同。因此，该前体B-ALL患者的病程因两种不同的孤立髓外复发（脑部和皮肤）以及继发性EBV（+）B-NHL而变得复杂。
