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Lineage Switch in an Infant B-Lymphoblastic Leukemia With t(1;11)(p32;q23); KMT2A/EPS15, Following Blinatumomab
Jing Du1, Karen M Chisholm1,2, Karen Tsuchiya1,2
1Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington.
Insights
A rare infant B-acute lymphoblastic leukemia (B-ALL) switched to acute myeloid leukemia (AML) after blinatumomab treatment. Clonal analysis revealed reprogramming and differentiation, highlighting treatment complexities.
Area of Science:
- Hematology
- Pediatric Oncology
- Cancer Genomics
Background:
- A 6-month-old infant presented with refractory B-acute lymphoblastic leukemia (B-ALL) harboring the t(1;11)(p32;q23) translocation with KMT2A/EPS15 rearrangement.
- Traditional chemotherapy was ineffective, necessitating alternative treatment strategies.
Observation:
- Administration of blinatumomab, a bispecific antibody, induced a lineage switch from B-ALL to acute myeloid leukemia (AML).
- Subsequent myeloid-directed chemotherapy achieved AML clearance, but a minimal residual B-ALL population persisted.
- Bridging blinatumomab therapy led to combined B-ALL and AML remission, followed by allogeneic hematopoietic stem cell transplant.
Findings:
- Relapse with CD19+ B-ALL occurred one month post-transplant.
- Next-generation sequencing (NGS) using ClonoSEQ® identified shared and novel clones across diagnostic, switched AML, and relapsed samples.
- Persistent clones throughout the disease course suggest cellular reprogramming and differentiation.
Implications:
- This is the first reported case of lineage switch in infant B-ALL with t(1;11).
- It is also the first lineage switch case utilizing ClonoSEQ® to define clonality in B-ALL, switched AML, and relapsed disease.
- The findings underscore the complex clonal dynamics and potential for cellular reprogramming in pediatric leukemia under therapy.
Abstract:
We report a 6 month-old infant girl with t(1;11)(p32;q23), KMT2A/EPS15-rearranged B-acute lymphoblastic leukemia (B-ALL) that was refractory to traditional ALL-directed chemotherapy. Following administration of blinatumomab, she experienced lineage switch from B-ALL to acute myeloid leukemia (AML). Myeloid-directed chemotherapy resulted in clearance of AML by flow cytometry, though a residual CD19+ B-ALL population persisted (0.14%). Following bridging blinatumomab, the patient achieved B-ALL and AML remission, as measured by flow cytometry. The patient subsequently underwent allogeneic hematopoietic stem cell transplant. Unfortunately, she relapsed with CD19+ B-ALL one-month post-transplantation. Next generation sequencing study of IGH/IGL using ClonoSEQ® analysis detected 3 dominant sequences all present in her original B-ALL, lineage switched AML, and post-transplant relapsed B-ALL, though the latter showed an additional 4 sequences, three of which were present at low abundance in the original diagnostic sample. The presence of the same clones throughout her disease course suggests cellular reprogramming and differentiation following chemotherapy and immunotherapy. This is the first reported case of lineage switch of B-ALL with t(1;11) and also the first report of a lineage switch case that used ClonoSEQ® to define the clonality of the original B-ALL, lineage switched AML, and relapsed B-ALL.
