Pediatric Hematology and Oncology, 31:178–180, 2014Copyright C© Informa Healthcare USA, Inc.ISSN: 0888-0018 print / 1521-0669 onlineDOI: 10.3109/08880018.2013.838813

LETTER TO THE EDITORAcute Lymphoblastic Leukemias

Congenital Acute Lymphoblastic Leukemia Casewith a Novel t(2:4:11) (p21:q21:q23) Translocation

Emmanuel Hatzipantelis, MD, PhD,1 Zoe Dorothea Pana, MD, MSc,1

Theodotis Papageorgiou, MD, PhD,1 Maria Hatzistilianou, MD, PhD,1

Anastasia Athanasiadou, MD, PhD,2 Kosmas Sarafidis, MD, PhD,3

Vasiliki Tsotoulidou, MD,1 George Papaioannou, MD,2 andFani Athanassiadou, MD, PhD1

1Pediatric Hematology Oncology Unit, 2nd Pediatric Department of Aristotle University,AHEPA General Hospital, Thessaloniki, Greece; 2Hematology Department and BMT Unit,General Hospital of Papanicolaou, Thessaloniki, Greece; 31st Department of Neonatologyof Aristotle University, Hippokration General Hospital, Thessaloniki, Greece

Keywords 11q23 translocation, congenital leukemia, three-way novel translocations

Herewith, we present a rare case of a 6-day-old male neonate, born at 40 weeks’ ges-tation, in whom the diagnosis of congenital acute lymphoblastic leukemia (cALL) wasestablished, characterized by the immunophenotype of the most immature B-cell pre-cursors (pro pro-B-ALL). The initial clinical/laboratory manifestations were leucocy-tosis, hepatosplenomegaly, anemia, thrombocytopenia, cutaneous lesions known as“leukemia cutis,” and CNS involvement. Cytogenetic testing revealed an extremely rarenovel complex chromosomal translocation t(2:4:11) (p21:q21:q23) associated with therearrangement of MLL gene. The child was treated with the chemotherapy protocolINTERFANT ‘99 but one month after birth developed multiple organ failure and died.

The cutaneous lesions were located on the right cheek and left forearm and in-cluded nontender, magenta tan papules and nodules with sizes ranging from 3.5 to1.7 cm (Figure 1). The liver was palpable 4 cm while the spleen 5 cm below the costalmargins. The history of the child during the antenatal period was uneventful. Themother first trimester TORCH results were negative and there was no history of ex-posure to radiation or drugs during pregnancy.

Laboratory investigations were: hb 13.5 g/dL, hct 40.2%, WBC 169.000/mm3 (89%lymphoblasts, 5% neutrophils, 6% lymphocytes), and PLT 42.000/mm3. The retic-ulocyte count was 2.5%, and LDH was 2.265 U/L. Blood and urine culture werenegative and serologic testing was not indicative of congenital infection with toxo-plasma, rubella, CMV, HSV, syphilis, Epstein Barr, HIV, HAV, HBV, and HCV. Chestradiograph and cranial ultrasound were normal. Bone marrow aspiration revealed

Received 19 July 2013; accepted 25 August 2013.Address correspondence to Zoe Dorothea Pana, Pediatric Hematology Oncology Unit, 2ndPediatric Department, AHEPA General Hospital, St. Kyriakidi 1, 54636, Thessaloniki, Greece.E-mail: panazoi@gmail.com

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cALL with Novel Three Way Translocation

FIGURE 1 (A) The cutaneous lesions located on the right cheek of the baby. The lesion was a non-tender, freely moved over the subcutaneous tissue magenta tan nodule 3.5 cm in size. (B) The kary-otype with a novel complex three way t(2:4:11) (p21:q21:q23) translocation.

90–95% blasts and immunophenotyping test showed that the blasts were positive forHLA DR (96.1%), cCD79a (87,7%), and CD19 (89%). Cerebrospinal fluid cytopatho-logic studies revealed leukemic infiltration (>2.000 cells/μL). A diagnosis of a pre-preB ALL, French-American- British (FAB) type L1 was made. Further cytogenetic inves-tigation revealed a karyotype with a novel complex three way t(2:4:11) (p21:q21:q23)translocation and the INTERFANT 99 treatment protocol was immediately started(Figure 1).

Nine days later, the child presented respiratory distress, fever, jaundice, and hy-potension. Due to the progression of his condition, the child was referred to the in-tensive neonatal care unit, where he stayed and treated properly for 13 days and thenreturned in good general condition. The neonate continued the chemotherapy pro-tocol and 14 days later, the child presented with decerebrate rigidity due to massiveintracranial cerebral hemorrhage and was again referred to the ICU where he died af-ter 3 days. During this period leukemia remission was not achieved.

The 2-year event-free survival rate of congenital ALL treated with the uniformInterfant-99 protocol is 20% [1]. Congenital ALL seems to have a rather variable clinicalpresentation with rapid progression and poor prognosis, although cases with spon-taneous remission have also been reported [2]. The most common chromosome in-volved in translocation of infantile ALL is the 11q23 found in at least 50% of infantleukemia cases [3]. According to Tauchi et al., complex chromosomal rearrangementsare in general indicative of poor prognosis though data are lacking [4–8]. The true in-fluence of genetics on the prognosis of infant leukemia remains to be established.

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for thecontent and writing of the paper.

REFERENCES

[1] Van der Linden MH, Valsecchi MG, Lorenzo PD, et al. Outcome of congenital acute lymphoblasticleukemia treated on the Interfant-99 protocol. Blood. 2009;114:3764–3768.

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E. Hatzipantelis et al.

[2] Wu X, Sulavik D, Roulston D, Lim MS. Spontaneous remission of congenital acute myeloid leukemiawith t(8;16)(p11;13). Br J Haematol. 2002;117:513–524.

[3] Isaacs H Jr. Fetal and neonatal leukemia. J Pediatr Hematol Oncol. 2003;25:348–361.[4] Bas Suarez MP, Lopez Brito J, Santana Reyes C, et al. Congenital acute lymphoblastic leukemia: a two-

case report and a review of the literature. Eur J Pediatr. 2011;170:531–534.[5] Pui CH, Behm FG, Downing JR, et al. 11q23/MLL rearrangement confers a poor prognosis in infants

with acute lymphoblastic leukemia. J Clin Oncol. 1994;12:909–915.[6] Tauchi H, Tomizawa D, Eguchi M, et al. Clinical features and outcome of MLL gene rearranged acute

lymphoblastic leukemia in infants with additional chromosomal abnormalities other than 11q23translocation. Leukemia Res. 2008;32:1523–1529.

[7] Kowarz E, Burmeister T, Lo Nigro L, et al. Complex MLL rearrangements in t(4;11) leukemia patientswith absent AF4.MLL fusion allele. Leukemia. 2007;21:1232–1238.

[8] Coenen EA, Raimondi SC, Harbott J, et al. Prognostic significance of additional cytogenetic aberra-tions in 733 de novo pediatric 11q23/MLL-rearranged AML patients: results of an international study.Blood. 2011;117:7102–7111.

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