Conference Abstracts - 2025 Summit on Hematologic Cancers
Vol. 5, Issue Supplement 1, 2025 · S1-2
A Case Series of Clonally Distinct Treatment-related B-cell Acute Lymphoblastic Leukemia After Prior B-cell Malignancy
Mehndi Dandwani, MD,Prajwal Dhakal, MD,Grerk Sutamtewagul, MD,Christopher Strouse, MD,Kittika Poonsombudlert, MD
Submission received: 2025-07-03 / Accepted: 2025-07-28 / Published: 2025-09-17
Abstract
Context
The pathogenesis of treatment-related B-cell acute lymphoblastic leukemia (tB-ALL) is not well understood, especially when it develops in patients with prior B-cell malignancies.
Objective
This study investigates the clonal relationship between B-cell malignancies and subsequent tB-ALL in 4 patients. Despite sharing a B-cell origin, the diseases were found to be clonally distinct. The clonoSEQ assay, using next-generation sequencing (NGS) to analyze VDJ rearrangements in immunoglobulin gene sequences, confirmed the clonal independence of tB-ALL from the initial B-cell malignancies in all 4 cases.
Design
Patient #1: Mr. H, 45, initially achieved remission from T-cell histiocyte-rich DLBCL with R-CHOP. 9 months later, he developed Ph-negative (Ph-) B-ALL. ClonoSEQ® assay identified 2 unique clones from DLBCL and 7 unique clones from B-ALL. He achieved complete remission (CR) with inotuzumab ozogamicin (IO) + mini-HCVD (cyclophosphamide, vincristine, and dexamethasone) and blinatumomab (blin).
Patient #2: Mr. M, 59, in remission from IgA lambda MM, developed Ph- B-ALL with CDKN2A loss on maintenance lenalidomide. ClonoSEQ® confirmed 4 unique clones from MM and 2 unique clones from B-ALL. He achieved MRD-negative remission with IO while continuing consolidation therapy (CT) with blin in sustained CR.
Patient #3: Mrs. Y, 67, achieved remission from plasmacytoma but later developed Ph- IKZF1 deleted B-ALL after 70 months of maintenance lenalidomide. The ClonoSEQ® identified 2 unique clones from MM and 2 unique clones from B-ALL. She achieved MRD negativity with IO+ miniHCVD followed by blin, and remains in CR during CT with blin.
Patient #4: Mrs. O, 74, developed Ph- B-ALL after 26 months of lenalidomide maintenance for MM. ClonoSEQ® identified 3 unique clones from MM and 2 unique clones from B-ALL. She is undergoing induction therapy with IO+ mini-HCVD.
Results
Factors contributing to tB-ALL include old age, genetic predispositions, lenalidomide maintenance, and cytogenetic anomalies. Advances in targeted therapies, like blin, IO, and CAR T-cell therapies, have improved responses and tolerance, even in older patients, as shown in the case series.
Conclusion
tB-ALL and prior B-cell malignancies share a B-cell origin but can be clonally distinct. Advanced NGS technologies, such as clonoSEQ®, are essential for understanding tB-ALL pathophysiology and developing personalized treatments.