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NATURAL HISTORY OF SECONDARY MULTILINEAGE PROLIFERATION WITH MONOSOMY 7 FOLLOWING TREATMENT OF RELAPSED ACUTE LYMPHOBLASTIC LEUKEMIA
Author(s):
Joanna Bulsa
,
Joanna Bulsa
Affiliations:
Department of Pediatric Hematology and Oncology, Zabrze,Medical University of Silesia, Katowice, POLAND,Zabrze,Poland
Aneta Pobudejska-Pieniążek
,
Aneta Pobudejska-Pieniążek
Affiliations:
Department of Pediatric Hematology and Oncology, Zabrze,Medical University of Silesia, Katowice, POLAND,Zabrze,Poland
Łukasz Sędek
,
Łukasz Sędek
Affiliations:
Department of Microbiology and Immunology,Medical University of Silesia, Katowice,Zabrze,Poland
Antonio Lopez
,
Antonio Lopez
Affiliations:
Cancer Research Centre (IBMCC, USAL-CSIC), Institute for Biomedical Research of Salamanca (IBSAL); Department of Medicine and Cytometry Service (NUCLEUS Research Support Platform),University of Salamanca (USAL),Salamanca,Spain
Maria Jara-Acevedo
,
Maria Jara-Acevedo
Affiliations:
Cancer Research Centre (IBMCC, USAL-CSIC), Institute for Biomedical Research of Salamanca (IBSAL); Department of Medicine and Cytometry Service (NUCLEUS Research Support Platform),University of Salamanca (USAL),Salamanca,Spain
Agata Kowalska-Pawlak
,
Agata Kowalska-Pawlak
Affiliations:
Genetic Laboratory,1st Independent Public Clinical Hospital of the Medical University of Silesia, Zabrze, POLAND,Zabrze,Poland
Alicja Sonsala
,
Alicja Sonsala
Affiliations:
Department of Pediatric Hematology and Oncology, Zabrze,Medical University of Silesia, Katowice, POLAND,Zabrze,Poland
Alberto Orfao
,
Alberto Orfao
Affiliations:
Cancer Research Centre (IBMCC, USAL-CSIC), Institute for Biomedical Research of Salamanca (IBSAL); Department of Medicine and Cytometry Service (NUCLEUS Research Support Platform),University of Salamanca (USAL),Salamanca,Spain
Tomasz Szczepański
Tomasz Szczepański
Affiliations:
Department of Pediatric Hematology and Oncology, Zabrze,Medical University of Silesia, Katowice, POLAND,Zabrze,Poland
(Abstract release date: 05/18/17) EHA Library. Bulsa J. 05/18/17; 182338; PB1624
Joanna Bulsa
Joanna Bulsa
Contributions
PDF Abstract
Abstract

Abstract: PB1624

Type: Publication Only

Background

Approximately 90% of children with acute lymphoblastic leukemia (ALL) are cured with current treatment protocols. However, 15-20% of the patients still experience disease relapse. Moreover, a small subset of patients develop secondary therapy-related leukemia or myelodysplasia.

Aims

We present a case of a 11-year-old boy with the history of relapsed ALL followed by aberrant proliferation of several different subsets of precursor cells in bone marrow (BM), which was associated with progressive ineffective hematopoiesis.

Methods

A boy diagnosed with standard risk B-cell Precursor (BCP) ALL in 10-2009 was treated until 12-2011 with frontline chemotherapy according to ALL-IC BFM 2002 protocol. In 12-2012, one year after treatment completion he developed late combined ALL relapse (BM and testis). Unilateral orchidectomy was performed, while the biopsy of the second testis showed no leukemic infiltration. He received 2nd line chemotherapy according to IntReALL 2010 and local radiotherapy for the testicular area. Despite the borderline minimal residual disease (MRD) at the end of induction treatment, the SCT procedure wasn’t executed due to the lack of suitable matched donor. In June 2014, during maintenance treatment, the patient showed persistent pancytopenia.

Results
BM aspirate morphology showed 5% of blasts. However, detailed 8-color flow cytometry according to the EuroFlow protocols revealed no cells with BCP-ALL-specific immunophenotype, but several subsets of BCP with abnormal maturation (total 3.5%) and plasmacytoid dendritic cell precursors (2.1%). After cessation of maintenance therapy in 02-2016, continuous progression of infiltration was observed. Subsequent BM aspirates revealed increasing proliferation of five different cell populations which show rare, aberrant immunophenotypes. Three of them represented immature BCP: B1 (CD34+/CD19-/CD10+dim/CD20-/nTDT+dim/CD22+dim/CD38++/CD117+/CD123/HLA-DR+/++/SSCintermediate), B2 (CD34+/CD19+/CD10+heterogeneous/CD20-/nTDT+/++/ CD22+/CD38++/CD117-/CD123-/HLA-DR+/++/SSClow), and B3 (CD34-/CD19dim/CD10dim/CD20-). The fourth population corresponded to non-lymphoid/non-dendritic cell precursors (CD34+/CD19-/CD10-/CD20-/nTDT-/CD22-/CD38++/CD117-/CD123-/HLA-DR++/SSChigh) and the fifth population showed the features of plasmacytoid dendritic cell precursors with aberrant CD10 expression (CD34+dim/CD19-/CD10+/CD20-/nTDT-/CD22+/CD38+dim/CD117-/CD123++/HLA-DR+/SSC intermediate). Analysis of clonality via PCR assessment of IGH gene rearrangements revealed polyclonal pattern in all BCP subsets. Cytogenetic analysis showed an altered 45,XY,del(4)(q31?),-7,der(9) [20] karyotype, while interphase FISH showed monosomy 7 in >80% of all BM cells. Retrospective FISH analysis at 1st relapse showed normal chromosome 7 in all cells. CytoScan® 750K array (Affymetrix®) analysis in 10 sorted cell populations showed a complex karyotype highlighting monosomy of chromosome 7 and loss of chromosome 4q (del4q21.1-q25; 40Mb) associated with gain of chromosome 14 (14q32.33; 200Kb). In addition, several gains of minor chromosomal regions were detected in CD34+/CD19-/CD10- and CD34+/CD10+/CD19- cells. Due to progressive increase of all subsets of abnormal precursor cells (27,5% in total) and hepatosplenomegaly, further treatment direction was set at haploidentical stem cell transplantation.

Conclusion
We present an abnormal secondary proliferation, with increased numbers of aberrant BCP, myeloid and plasmacytoid dendritic cell precursors resulting from stem cell defect hallmarked by monosomy 7.

Session topic: 1. Acute lymphoblastic leukemia - Biology

Keyword(s): Relapsed acute lymphoblastic leukemia, Proliferation, Myelodysplasia, ALL

Abstract: PB1624

Type: Publication Only

Background

Approximately 90% of children with acute lymphoblastic leukemia (ALL) are cured with current treatment protocols. However, 15-20% of the patients still experience disease relapse. Moreover, a small subset of patients develop secondary therapy-related leukemia or myelodysplasia.

Aims

We present a case of a 11-year-old boy with the history of relapsed ALL followed by aberrant proliferation of several different subsets of precursor cells in bone marrow (BM), which was associated with progressive ineffective hematopoiesis.

Methods

A boy diagnosed with standard risk B-cell Precursor (BCP) ALL in 10-2009 was treated until 12-2011 with frontline chemotherapy according to ALL-IC BFM 2002 protocol. In 12-2012, one year after treatment completion he developed late combined ALL relapse (BM and testis). Unilateral orchidectomy was performed, while the biopsy of the second testis showed no leukemic infiltration. He received 2nd line chemotherapy according to IntReALL 2010 and local radiotherapy for the testicular area. Despite the borderline minimal residual disease (MRD) at the end of induction treatment, the SCT procedure wasn’t executed due to the lack of suitable matched donor. In June 2014, during maintenance treatment, the patient showed persistent pancytopenia.

Results
BM aspirate morphology showed 5% of blasts. However, detailed 8-color flow cytometry according to the EuroFlow protocols revealed no cells with BCP-ALL-specific immunophenotype, but several subsets of BCP with abnormal maturation (total 3.5%) and plasmacytoid dendritic cell precursors (2.1%). After cessation of maintenance therapy in 02-2016, continuous progression of infiltration was observed. Subsequent BM aspirates revealed increasing proliferation of five different cell populations which show rare, aberrant immunophenotypes. Three of them represented immature BCP: B1 (CD34+/CD19-/CD10+dim/CD20-/nTDT+dim/CD22+dim/CD38++/CD117+/CD123/HLA-DR+/++/SSCintermediate), B2 (CD34+/CD19+/CD10+heterogeneous/CD20-/nTDT+/++/ CD22+/CD38++/CD117-/CD123-/HLA-DR+/++/SSClow), and B3 (CD34-/CD19dim/CD10dim/CD20-). The fourth population corresponded to non-lymphoid/non-dendritic cell precursors (CD34+/CD19-/CD10-/CD20-/nTDT-/CD22-/CD38++/CD117-/CD123-/HLA-DR++/SSChigh) and the fifth population showed the features of plasmacytoid dendritic cell precursors with aberrant CD10 expression (CD34+dim/CD19-/CD10+/CD20-/nTDT-/CD22+/CD38+dim/CD117-/CD123++/HLA-DR+/SSC intermediate). Analysis of clonality via PCR assessment of IGH gene rearrangements revealed polyclonal pattern in all BCP subsets. Cytogenetic analysis showed an altered 45,XY,del(4)(q31?),-7,der(9) [20] karyotype, while interphase FISH showed monosomy 7 in >80% of all BM cells. Retrospective FISH analysis at 1st relapse showed normal chromosome 7 in all cells. CytoScan® 750K array (Affymetrix®) analysis in 10 sorted cell populations showed a complex karyotype highlighting monosomy of chromosome 7 and loss of chromosome 4q (del4q21.1-q25; 40Mb) associated with gain of chromosome 14 (14q32.33; 200Kb). In addition, several gains of minor chromosomal regions were detected in CD34+/CD19-/CD10- and CD34+/CD10+/CD19- cells. Due to progressive increase of all subsets of abnormal precursor cells (27,5% in total) and hepatosplenomegaly, further treatment direction was set at haploidentical stem cell transplantation.

Conclusion
We present an abnormal secondary proliferation, with increased numbers of aberrant BCP, myeloid and plasmacytoid dendritic cell precursors resulting from stem cell defect hallmarked by monosomy 7.

Session topic: 1. Acute lymphoblastic leukemia - Biology

Keyword(s): Relapsed acute lymphoblastic leukemia, Proliferation, Myelodysplasia, ALL

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