Hematopoietic stem cell transplantation for pediatric mature B-cell acute lymphoblastic leukemia with non-L3 morphology and MLL-AF9 gene fusion: three case reports and review of the literature
- 292 Downloads
Abstract
Mature B-cell acute lymphoblastic leukemia (B-ALL) is typically associated with French-American-British (FAB)-L3 morphology and MYC gene rearrangement. However, rare cases of mature B-ALL with non-L3 morphology and MLL-AF9 fusion have been reported, and such cases are characterized by a rapid and aggressive clinical course. We here report three such cases of pediatric mature B-ALL in female patients respectively aged 15 months, 4 years, and 4 months. Bone marrow smears at diagnosis showed FAB-L1 morphology in all patients. Immunophenotypically, they were positive for cluster of differentiation (CD)10, CD19, CD20 (or CD22), Human Leukocyte Antigen-DR, and surface immunoglobulin λ. No evidence of MYC rearrangement was detected in any of the cases by fluorescent in situ hybridization (FISH) analysis. However, MLL rearrangement was detected by FISH, and MLL-AF9 fusion was confirmed by reverse transcriptase-polymerase chain reaction. All patients achieved complete remission after conventional chemotherapy and subsequently underwent hematopoietic stem cell transplantation as high-risk ALL; patient 3 for infantile ALL with MLL rearrangement and the others for ALL with MLL rearrangement and hyperleukocytosis (white blood cell count at diagnosis >50 × 109/L). At the latest follow-up for each case (12–98 months post-transplantation), complete remission was maintained. Moreover, we discuss the clinical, genetic, and immunophenotypic features of this rare disease.
Keywords
MLL-AF9 Non-L3 morphology Stem cell transplantation Mature B-ALLNotes
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interests.
References
- 1.Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia. 1995;9:1783–6.PubMedGoogle Scholar
- 2.Rubnitz JE, Behm FG, Downing JR. 11q23 rearrangements in acute leukemia. Leukemia. 1996;10:74–82.PubMedGoogle Scholar
- 3.Brunning RD, Borowitz M, Matutes E, Head D, Flandrin G, Swerdlow SH, et al. Precursor B lymphoblastic leukaemia/lymphoblastic lymphoma. Pathology and Genetics of Tumors of Hematopoietic an Lymphoid tissues. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. World Health Organization Classification of Tumours. Lyon: IARC Press; 2001. p. 111–4.Google Scholar
- 4.Frater JL, Batanianet JR, O’Connor DM, Grosso LE. Lymphoblastic leukemia with mature B-cell phenotype in infancy. J Pediatr Hematol Oncol. 2004;26:672–7.CrossRefPubMedGoogle Scholar
- 5.Lee GR, Foerster J, Lukens J, Paraskevas I, Greer JP, Rodgers GM, editors. Wintrobe’s Clinical Hematology. 10th ed. Baltimore: Williams & Wilkins; 1999. p. 2246.Google Scholar
- 6.Tsao L, Draoua HY, Osunkwo I, Nandula SV, Murty VV, Mansukhani M, et al. Mature B-cell acute lymphoblastic leukaemia with t(9;11) translocation: a distinct subset of B-cell acute lymphoblastic leukemia. Mod Pathol. 2004;17:832–9.CrossRefPubMedGoogle Scholar
- 7.Meyer C, Schneider B, Jakob S, Strehl S, Attarbaschi A, Schnittger S, et al. The MLL recombinome of acute leukemias. Leukemia. 2006;20:777–84.CrossRefPubMedGoogle Scholar
- 8.Yokoyama A. Molecular mechanisms of MLL-associated leukemia. Int J Hematol. 2015;101:352–61.CrossRefPubMedGoogle Scholar
- 9.Blin N, Mëchinaud F, Talmant P, Garand R, Boutard P, Dastugue N, et al. Mature B-cell lymphoblastic leukemia with MLL rearrangement: an uncommon and distinct subset of childhood acute leukemia. Leukemia. 2008;22:1056–9.CrossRefPubMedGoogle Scholar
- 10.Lorenzana AN, et al. Immunoglobulin gene rearrangements in acute lymphoblastic leukemia with the 9;11 translocation. Genes Chromosom Cancer. 1991;3:74–7.CrossRefPubMedGoogle Scholar
- 11.Woessmann W, Seidemann K, Mann G, Zimmermann M, Burkhardt B, Oschlies I, et al. The impact of the methotrexate administration schedule and dose in the treatment of children and adolescents with B-cell neoplasms: a report of the BFM group study NHL-BFM95. Blood. 2005;105:948–58.CrossRefPubMedGoogle Scholar
- 12.Koh K, Tomizawa D, Moriya Saito A, Watanabe T, Miyamura T, Hirayama M, et al. Early use of allogeneic hematopoietic stem cell transplantation for infants with MLL gene-rearrangement-positive acute lymphoblastic leukemia. Leukemia. 2015;29:290–6.CrossRefPubMedGoogle Scholar
- 13.Iwamoto S, Deguchi T, Ohta H, Kiyokawa N, Tsurusawa M, Yamada T, et al. Flow cytometric analysis of de novo acute lymphoblastic leukemia in childhood: report from the Japanese Pediatric Leukemia/Lymphoma Study Group. Int J Hematol. 2011;94:185–92.CrossRefPubMedGoogle Scholar
- 14.Attarbaschi A, Mann G, König M, Steiner M, Strehl S, Schreiberhuber A, et al. Mixed lineage leukemia-rearranged childhood pro-B and CD10-negative pre-B acute lymphoblastic leukemia constitute a distinct clinical entity. Clin Cancer Res. 2006;12:2988–94.CrossRefPubMedGoogle Scholar
- 15.Jansen MW, Corral L, van der Velden VH, Panzer-Grümayer R, Schrappe M, Schrauder A, et al. Immunobiological diversity in infant acute lymphoblastic leukemia is related to the occurrence and type of MLL gene rearrangement. Leukemia. 2007;21:633–41.PubMedGoogle Scholar
- 16.Pui CH, Gaynon PS, Boyett JM, Chessells JM, Baruchel A, Kamps W, et al. Outcome of treatment in childhood acute lymphoblastic leukemia with rearrangements of the 11q23 chromosomal region. Lancet. 2002;359:1909–15.CrossRefPubMedGoogle Scholar
- 17.Oliansky DM, Camitta B, Gaynon P, Nieder ML, Parsons SK, Pulsipher MA, et al. Role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of pediatric acute lymphoblastic leukemia: update of the 2005 evidence-based review. Biol Blood Marrow Transplant. 2012;18:505–22.CrossRefPubMedGoogle Scholar