Pediatric Hematology
Contributions
Type: Publication Only
Background
Lineage switch was reported in relapsed acute leukemia.
Aims
Leukemia-associated immunophenotypes in patients with acute lymphoblastic leukemia (ALL) at diagnosis and relapse were investigated.
Methods
The immunophenotype of leukemia cells from 28 relapsed patients at diagnosis and relapse was detected by four-color flow cytometry (FCM). Isolated testicular relapse was excluded. Antibodies used in the panel were CD2, CD3, cyCD3, CD5, CD7, CD13, CD14, CD15, CD33, CD10, CD19, CD20, CD22, cyCD79a, CD34, CD117, MPO, TdT, glicophorin A, CD41 and HLA-DR. The classification was according to the European group for the immunologic group. Cut-off for positive antigens was ≥ 20%.
Results
Mean age at the diagnosis was 7.57 + 4.32 years and 71.43% (n=20) of the patients were male. Median time from diagnosis to relapse was 25 months (6 -138 months). According to BFM criteria 11, 9 and 8 patients had very early, early and late relapse, respectively. Sites of relapse were isolated bone marrow in 19, bone marrow and testis in 5, bone marrow and central nervous system (CNS) in 3 and isolated CNS in 1 patient. At presentation precursor B-ALL, T-ALL, and mix lineage leukemia was detected in 21, 3 and 4 patients respectively.
Immunophenotypic switch occurred in 28.57% (n=8) of the relapsed patients (two patients from precursor B-ALL to T-ALL, three patients from precursor B-ALL to mix lineage leukemia, one patient from precursor B-ALL to AML-M5; and of the two patients with mix lineage leukemia one switched to precursor B-ALL and the other to T-ALL). There was no relation between immunophenotypic switch and site and time of relapse.
HLA-DR expression decreased at relapse (50.99 ± 32.01% at diagnosis, 38.67±27.4% at relapse, p=0.029). However, CD33 and TdT expression increased at relapse (CD33 from 34.02±32.26% to 58.05±31.28% and TdT from19.83±24.84% to 44.0934.86±%; p values were 0.006 and 0.031, respectively.
Summary
There are many hypotheses in lineage switch as physiological plasticity of the original clone or emerging of a new clone or expansion of secondary clone after eradication of the dominant clone by chemotherapy. In the present study, immunophenotypic switch was detected about one fourth of the patients at relapse. In addition, there were significant differences in the expression levels of HLA-DR, CD33 and TdT. Their clinical implications require further study.
Keyword(s): Acute lymphoblastic leukemia, Flow cytometry, Immunophenotype
Session topic: Publication Only
Type: Publication Only
Background
Lineage switch was reported in relapsed acute leukemia.
Aims
Leukemia-associated immunophenotypes in patients with acute lymphoblastic leukemia (ALL) at diagnosis and relapse were investigated.
Methods
The immunophenotype of leukemia cells from 28 relapsed patients at diagnosis and relapse was detected by four-color flow cytometry (FCM). Isolated testicular relapse was excluded. Antibodies used in the panel were CD2, CD3, cyCD3, CD5, CD7, CD13, CD14, CD15, CD33, CD10, CD19, CD20, CD22, cyCD79a, CD34, CD117, MPO, TdT, glicophorin A, CD41 and HLA-DR. The classification was according to the European group for the immunologic group. Cut-off for positive antigens was ≥ 20%.
Results
Mean age at the diagnosis was 7.57 + 4.32 years and 71.43% (n=20) of the patients were male. Median time from diagnosis to relapse was 25 months (6 -138 months). According to BFM criteria 11, 9 and 8 patients had very early, early and late relapse, respectively. Sites of relapse were isolated bone marrow in 19, bone marrow and testis in 5, bone marrow and central nervous system (CNS) in 3 and isolated CNS in 1 patient. At presentation precursor B-ALL, T-ALL, and mix lineage leukemia was detected in 21, 3 and 4 patients respectively.
Immunophenotypic switch occurred in 28.57% (n=8) of the relapsed patients (two patients from precursor B-ALL to T-ALL, three patients from precursor B-ALL to mix lineage leukemia, one patient from precursor B-ALL to AML-M5; and of the two patients with mix lineage leukemia one switched to precursor B-ALL and the other to T-ALL). There was no relation between immunophenotypic switch and site and time of relapse.
HLA-DR expression decreased at relapse (50.99 ± 32.01% at diagnosis, 38.67±27.4% at relapse, p=0.029). However, CD33 and TdT expression increased at relapse (CD33 from 34.02±32.26% to 58.05±31.28% and TdT from19.83±24.84% to 44.0934.86±%; p values were 0.006 and 0.031, respectively.
Summary
There are many hypotheses in lineage switch as physiological plasticity of the original clone or emerging of a new clone or expansion of secondary clone after eradication of the dominant clone by chemotherapy. In the present study, immunophenotypic switch was detected about one fourth of the patients at relapse. In addition, there were significant differences in the expression levels of HLA-DR, CD33 and TdT. Their clinical implications require further study.
Keyword(s): Acute lymphoblastic leukemia, Flow cytometry, Immunophenotype
Session topic: Publication Only