Trisomy 5 in acute lymphoblastic leukaemia

Sir, Trisomy 5 ( 5) is extremely rare as the sole cytogenetic abnormality in acute lymphoblastic leukaemia (ALL). So far, only five cases have been reported in the literature (1–5). Owing to this limited number of cases identified, the clinical significance of 5 as the sole cytogenetic aberration in ALL is not fully appreciated. We report here, a case of 5 as the sole cytogenetic abnormality in precursor-B-ALL. The patient is a 22mo-old, previously healthy, Jordanian boy who was admitted to the paediatric casualty department presenting a 3-d history of purpuric rash and spontaneous bruising all over his body. Examination of the abdomen revealed an enlarged spleen of 6 cm and enlarged liver of 4 cm. Laboratory investigations showed that the patient had anaemia, haemoglobin was 9.2 g/dL, with a microcytic hypochromic picture, thrombocytopenia, platelets were 15000/mm and leukocytosis, total WBC count was 54500/mm and ESR was 25 mmHg/ h. Examination of the blood film showed lymphoblasts comprising 80% of the total WBC count. A biochemical analysis showed normal renal function and a raised serum LDH level (598 IU/L). Serum uric acid was normal. The coagulation profile (PT, APTT) was also normal. The presence of 85% lymphoblasts with depressed erythropoeisis and megakaryopoeisis found during bone marrow examination confirmed the diagnosis of ALL. The lymphoblasts were of L1 morphology according to the FAB classification. Immunophenotyping, done by flow cytometry, revealed CD19, CD22 and CD20 expression, (78.9%, 77.5% and 20.7%, respectively); CD10, however, was not expressed (0.2%). CD2 was 16.1%, CD5 17.1% and CD7 was 18.1%; CD33 was 2.2%, CD34 was 0.8% and HLA-DR was 67% (which is associated with a good prognosis in ALL). Based on the results of the immunophenotyping, the leukaemia was thus subtyped as a precursor to BALL. There was no evidence of either testicular or neurological involvement. The induction chemotherapy was completed with complete haematological and cytogenetic remission, as confirmed by bone marrow examination. The cytogenetic studies of the marrow aspiration specimen showed the presence of two clones: 47,XY, 5[10]/46,XY[13]. The Fluorescence in situ hybridization (FISH) analysis with the chromosome 5 probe, D5S23 (Oncor-Appligene, Illkirch, France) showed 60% of interphase with 5 (120 out of 200 scored interphase cells). Currently, theclinical significance of the 5 is not clear. The patient described by Sandberg et al. (1) was a 26-y-old Jamaican male with a B-cell precursor leukaemia that was refractory to therapy. Although the leukaemia went into remission, the duration was brief and the patient died after 4 mo of intensive chemotherapy. The discovery of the 5 in this patient was made on a bone marrow specimen taken from the patient after relapse (nearly 5 mo after ALL was diagnosed and after a long period of chemotherapy). As for the case reported by Rao et al. (2), the patient was a 24-y-old Caucasian female. The investigators did not mention the period at which the 5 was discovered and it was not clear if the 5 was seen at early diagnosis or after chemotherapy. The patient had a massive mediastinal mass and a T-cell phenotype with coexpression of CD4 and CD8. The leukaemia went into remission after induction chemotherapy, and the patient survived for 4 y. Sandoval et al. (3) recently reported the third case of 5 as a sole chromosomal abnormality in ALL, in a 12-y-old Caucasian female. This case was classified as pre-B-ALL and designated as a high risk. Despiteclinical and cytogenetic remission at the end of induction chemotherapy, the patient showed evidence of minimal residual disease (detected by PCR) and the leukaemia relapsed after 6 wk in remission; the patient died after three unsuccessful attempts at reinduction chemotherapy. The cytogenetic study for this patient was performed at diagnosis and showed a low grade of 5 karyotype: 47,XX, 5[5]/46,XX[19]. After the second course of reinduction chemotherapy, bone marrow cytogenetics showed trisomy 5 along with other aberrations in only one metaphase out of 20 metaphases analysed. Abshire et al. (4) described one case of 5 in a pre-B-ALL male patient and Lampert et al. (5) reported a 4-y-old Down syndrome female with 5 as the only acquired abnormality. Theclinical and prognostic features of these two patients were not provided in their case sheets. It should be noted that 5 as the single aberration also has been reported in acute myeloid leukaemia and hence is not specific for ALL (6). To our knowledge, our patient is the youngest child described with precursor-B-ALL and 5, which was identified at diagnosis and before the start of chemotherapy. After one year of induction chemotherapy, both clinical and cytogenetic remissions were observed. The follow-up of our patient is important and will help to evaluate the biological and prognostic significance of 5 in ALL. Because of its rarity in ALL, further identification and comparison of additional cases of 5 need to be analysed before theclinical importance of this cytogenetic aberration is fully understood.