Pediatric Hematology and Oncology, 31:178–180, 2014 C Informa Healthcare USA, Inc. Copyright ISSN: 0888-0018 print / 1521-0669 online DOI: 10.3109/08880018.2013.838813
LETTER TO THE EDITOR Acute Lymphoblastic Leukemias
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Bath on 10/04/14 For personal use only.
Congenital Acute Lymphoblastic Leukemia Case with 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 and Fani Athanassiadou, MD, PhD1 1
Pediatric Hematology Oncology Unit, 2nd Pediatric Department of Aristotle University, AHEPA General Hospital, Thessaloniki, Greece; 2 Hematology Department and BMT Unit, General Hospital of Papanicolaou, Thessaloniki, Greece; 3 1st Department of Neonatology of 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’ gestation, in whom the diagnosis of congenital acute lymphoblastic leukemia (cALL) was established, characterized by the immunophenotype of the most immature B-cell precursors (pro pro-B-ALL). The initial clinical/laboratory manifestations were leucocytosis, hepatosplenomegaly, anemia, thrombocytopenia, cutaneous lesions known as “leukemia cutis,” and CNS involvement. Cytogenetic testing revealed an extremely rare novel complex chromosomal translocation t(2:4:11) (p21:q21:q23) associated with the rearrangement of MLL gene. The child was treated with the chemotherapy protocol INTERFANT ‘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 included nontender, magenta tan papules and nodules with sizes ranging from 3.5 to 1.7 cm (Figure 1). The liver was palpable 4 cm while the spleen 5 cm below the costal margins. The history of the child during the antenatal period was uneventful. The mother first trimester TORCH results were negative and there was no history of exposure 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 reticulocyte count was 2.5%, and LDH was 2.265 U/L. Blood and urine culture were negative and serologic testing was not indicative of congenital infection with toxoplasma, rubella, CMV, HSV, syphilis, Epstein Barr, HIV, HAV, HBV, and HCV. Chest radiograph 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, 2nd Pediatric Department, AHEPA General Hospital, St. Kyriakidi 1, 54636, Thessaloniki, Greece. E-mail: [email protected]
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Bath on 10/04/14 For personal use only.
cALL with Novel Three Way Translocation
FIGURE 1 (A) The cutaneous lesions located on the right cheek of the baby. The lesion was a nontender, freely moved over the subcutaneous tissue magenta tan nodule 3.5 cm in size. (B) The karyotype 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 for HLA DR (96.1%), cCD79a (87,7%), and CD19 (89%). Cerebrospinal fluid cytopathologic studies revealed leukemic infiltration (>2.000 cells/μL). A diagnosis of a pre-pre B ALL, French-American- British (FAB) type L1 was made. Further cytogenetic investigation 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 hypotension. Due to the progression of his condition, the child was referred to the intensive neonatal care unit, where he stayed and treated properly for 13 days and then returned in good general condition. The neonate continued the chemotherapy protocol and 14 days later, the child presented with decerebrate rigidity due to massive intracranial cerebral hemorrhage and was again referred to the ICU where he died after 3 days. During this period leukemia remission was not achieved. The 2-year event-free survival rate of congenital ALL treated with the uniform Interfant-99 protocol is 20% [1]. Congenital ALL seems to have a rather variable clinical presentation with rapid progression and poor prognosis, although cases with spontaneous remission have also been reported [2]. The most common chromosome involved in translocation of infantile ALL is the 11q23 found in at least 50% of infant leukemia cases [3]. According to Tauchi et al., complex chromosomal rearrangements are in general indicative of poor prognosis though data are lacking [4–8]. The true influence 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 the content and writing of the paper. REFERENCES [1] Van der Linden MH, Valsecchi MG, Lorenzo PD, et al. Outcome of congenital acute lymphoblastic leukemia treated on the Interfant-99 protocol. Blood. 2009;114:3764–3768. C Informa Healthcare USA, Inc. Copyright
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Bath on 10/04/14 For personal use only.
E. Hatzipantelis et al.
[2] Wu X, Sulavik D, Roulston D, Lim MS. Spontaneous remission of congenital acute myeloid leukemia with 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 Su´arez MP, L´opez Brito J, Santana Reyes C, et al. Congenital acute lymphoblastic leukemia: a twocase 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 11q23 translocation. Leukemia Res. 2008;32:1523–1529. [7] Kowarz E, Burmeister T, Lo Nigro L, et al. Complex MLL rearrangements in t(4;11) leukemia patients with absent AF4.MLL fusion allele. Leukemia. 2007;21:1232–1238. [8] Coenen EA, Raimondi SC, Harbott J, et al. Prognostic significance of additional cytogenetic aberrations in 733 de novo pediatric 11q23/MLL-rearranged AML patients: results of an international study. Blood. 2011;117:7102–7111.
Pediatric Hematology and Oncology
LETTER TO THE EDITOR Acute Lymphoblastic Leukemias
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Bath on 10/04/14 For personal use only.
Congenital Acute Lymphoblastic Leukemia Case with 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 and Fani Athanassiadou, MD, PhD1 1
Pediatric Hematology Oncology Unit, 2nd Pediatric Department of Aristotle University, AHEPA General Hospital, Thessaloniki, Greece; 2 Hematology Department and BMT Unit, General Hospital of Papanicolaou, Thessaloniki, Greece; 3 1st Department of Neonatology of 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’ gestation, in whom the diagnosis of congenital acute lymphoblastic leukemia (cALL) was established, characterized by the immunophenotype of the most immature B-cell precursors (pro pro-B-ALL). The initial clinical/laboratory manifestations were leucocytosis, hepatosplenomegaly, anemia, thrombocytopenia, cutaneous lesions known as “leukemia cutis,” and CNS involvement. Cytogenetic testing revealed an extremely rare novel complex chromosomal translocation t(2:4:11) (p21:q21:q23) associated with the rearrangement of MLL gene. The child was treated with the chemotherapy protocol INTERFANT ‘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 included nontender, magenta tan papules and nodules with sizes ranging from 3.5 to 1.7 cm (Figure 1). The liver was palpable 4 cm while the spleen 5 cm below the costal margins. The history of the child during the antenatal period was uneventful. The mother first trimester TORCH results were negative and there was no history of exposure 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 reticulocyte count was 2.5%, and LDH was 2.265 U/L. Blood and urine culture were negative and serologic testing was not indicative of congenital infection with toxoplasma, rubella, CMV, HSV, syphilis, Epstein Barr, HIV, HAV, HBV, and HCV. Chest radiograph 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, 2nd Pediatric Department, AHEPA General Hospital, St. Kyriakidi 1, 54636, Thessaloniki, Greece. E-mail: [email protected]
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Bath on 10/04/14 For personal use only.
cALL with Novel Three Way Translocation
FIGURE 1 (A) The cutaneous lesions located on the right cheek of the baby. The lesion was a nontender, freely moved over the subcutaneous tissue magenta tan nodule 3.5 cm in size. (B) The karyotype 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 for HLA DR (96.1%), cCD79a (87,7%), and CD19 (89%). Cerebrospinal fluid cytopathologic studies revealed leukemic infiltration (>2.000 cells/μL). A diagnosis of a pre-pre B ALL, French-American- British (FAB) type L1 was made. Further cytogenetic investigation 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 hypotension. Due to the progression of his condition, the child was referred to the intensive neonatal care unit, where he stayed and treated properly for 13 days and then returned in good general condition. The neonate continued the chemotherapy protocol and 14 days later, the child presented with decerebrate rigidity due to massive intracranial cerebral hemorrhage and was again referred to the ICU where he died after 3 days. During this period leukemia remission was not achieved. The 2-year event-free survival rate of congenital ALL treated with the uniform Interfant-99 protocol is 20% [1]. Congenital ALL seems to have a rather variable clinical presentation with rapid progression and poor prognosis, although cases with spontaneous remission have also been reported [2]. The most common chromosome involved in translocation of infantile ALL is the 11q23 found in at least 50% of infant leukemia cases [3]. According to Tauchi et al., complex chromosomal rearrangements are in general indicative of poor prognosis though data are lacking [4–8]. The true influence 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 the content and writing of the paper. REFERENCES [1] Van der Linden MH, Valsecchi MG, Lorenzo PD, et al. Outcome of congenital acute lymphoblastic leukemia treated on the Interfant-99 protocol. Blood. 2009;114:3764–3768. C Informa Healthcare USA, Inc. Copyright
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Bath on 10/04/14 For personal use only.
E. Hatzipantelis et al.
[2] Wu X, Sulavik D, Roulston D, Lim MS. Spontaneous remission of congenital acute myeloid leukemia with 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 Su´arez MP, L´opez Brito J, Santana Reyes C, et al. Congenital acute lymphoblastic leukemia: a twocase 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 11q23 translocation. Leukemia Res. 2008;32:1523–1529. [7] Kowarz E, Burmeister T, Lo Nigro L, et al. Complex MLL rearrangements in t(4;11) leukemia patients with absent AF4.MLL fusion allele. Leukemia. 2007;21:1232–1238. [8] Coenen EA, Raimondi SC, Harbott J, et al. Prognostic significance of additional cytogenetic aberrations in 733 de novo pediatric 11q23/MLL-rearranged AML patients: results of an international study. Blood. 2011;117:7102–7111.
Pediatric Hematology and Oncology
