SECONDARY B-LYMPHOBLASTIC TRANSFORMATION IN A PATIENT WITH MULTIPLE MYELOMA FOLLOWING AUTOLOGOUS TRANSPLANTATION AND LENALIDOMIDE MAINTENANCE: A CASE REPORT
- 1Hospital Santa Izabel, Oncoclínicas, Salvador, BA, Brazil
Abstract
Background: Second neoplasms arising from the very therapies used to treat an initial hematologic malignancy remain a major clinical challenge. Despite substantial advances in understanding disease biology, unexpected trajectories still occur. We report a patient with multiple myeloma who, approximately seven years after diagnosis, developed B-cell acute lymphoblastic leukemia (B-ALL). Case report: A 58-year-old woman was diagnosed with multiple myeloma in 2018 and treated with bortezomib, cyclophosphamide, and dexamethasone (VCD) plus denosumab, achieving complete response before autologous stem cell transplantation in 2019. She remained on lenalidomide maintenance, with seven-day interruptions for leukopenia, and sustained a durable response, with negative serum/urine immunofixation and 3% bone marrow plasma cells. In 2025, she developed progressive cytopenias (neutrophils 400–700/mm³; platelets 90,000–130,000/mm³). Marrow reassessment in October 2025 showed hypocellularity with dysplastic erythroid and megakaryocytic lineages and 12.6% aberrant B lymphoblasts by flow cytometry, without monoclonal plasma cells; biopsy confirmed 20–30% CD34-positive cells. Karyotype was normal, and KMT2A rearrangement and BCR-ABL p190 were negative. She is currently receiving Hyper-CVAD, with negative measurable residual disease (MRD). Discussion: Therapy-related myeloid neoplasms classically progress to acute myeloid leukemia, and transition from multiple myeloma to myelodysplasia has previously been linked to myelosuppressive regimens such as lenalidomide combined with melphalan (1). This case instead describes lymphoid transformation, raising the question of an immunomodulatory drug (IMiD)-driven process versus an independent, treatment-unrelated neoplasm. The absence of KMT2A rearrangement or other high-risk cytogenetic abnormalities mirrors prior reports of IMiD-associated secondary ALL (2), which, unlike classic therapy-related leukemia after genotoxic chemotherapy, lacks a recurrent molecular signature, supporting a mechanism driven by lenalidomide's immunomodulatory effects on B-lymphoid progenitors rather than direct mutagenesis. Conclusion: This case illustrates secondary B-ALL in a myeloma patient on prolonged lenalidomide maintenance, with a latency of approximately seven years, at the upper end of previously reported ranges (2). It reinforces that persistent, unexplained cytopenias during IMiD maintenance warrant bone marrow evaluation, even years into an otherwise stable course (3), and highlights the value of broader molecular profiling, such as next-generation sequencing, in clarifying the mutational basis of this rare transformation.
Related
- A Case of Acute Lymphoblastic Leukemia Developing After a Diagnosis of Myelodysplastic Syndrome Following Lenalidomide Therapy for Multiple Myeloma
- Lenalidomide-associated B-cell acute lymphoblastic leukemia in a multiple myeloma patient: a case report
- Lenalidomide maintenance after initial immunochemotherapy in chronic lymphocytic leukaemia—Final analysis of the international phase III CLL6 RESIDUUM study of the ALLG and FILO groups
- Autologous bone marrow transplantation in a case of acute adult leukemia
- Structural and Vascular Findings in Autologous Retinal Transplantation for Macular Hole
BibTeX
@article{portugal2026secondary,
title = {{SECONDARY B-LYMPHOBLASTIC TRANSFORMATION IN A PATIENT WITH MULTIPLE MYELOMA FOLLOWING AUTOLOGOUS TRANSPLANTATION AND LENALIDOMIDE MAINTENANCE: A CASE REPORT}},
author = {Beatriz Moura PORTUGAL and Maura Alice Santos ROMEO and Valney Oliveira Santos JUNIOR and Lorhane Nunes dos ANJOS and Giulia Beatriz Correia MATOS and Luiz Henrique dos Santos DE ASSIS},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.107690},
url = {https://doi.org/10.1016/j.htct.2026.107690},
note = {CC BY},
}
RIS
TY - JOUR
TI - SECONDARY B-LYMPHOBLASTIC TRANSFORMATION IN A PATIENT WITH MULTIPLE MYELOMA FOLLOWING AUTOLOGOUS TRANSPLANTATION AND LENALIDOMIDE MAINTENANCE: A CASE REPORT
AU - Beatriz Moura PORTUGAL
AU - Maura Alice Santos ROMEO
AU - Valney Oliveira Santos JUNIOR
AU - Lorhane Nunes dos ANJOS
AU - Giulia Beatriz Correia MATOS
AU - Luiz Henrique dos Santos DE ASSIS
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.107690
UR - https://doi.org/10.1016/j.htct.2026.107690
AB - Background: Second neoplasms arising from the very therapies used to treat an initial hematologic malignancy remain a major clinical challenge. Despite substantial advances in understanding disease biology, unexpected trajectories still occur. We report a patient with multiple myeloma who, approximately seven years after diagnosis, developed B-cell acute lymphoblastic leukemia (B-ALL). Case report: A 58-year-old woman was diagnosed with multiple myeloma in 2018 and treated with bortezomib, cyclophosphamide, and dexamethasone (VCD) plus denosumab, achieving complete response before autologous stem cell transplantation in 2019. She remained on lenalidomide maintenance, with seven-day interruptions for leukopenia, and sustained a durable response, with negative serum/urine immunofixation and 3% bone marrow plasma cells. In 2025, she developed progressive cytopenias (neutrophils 400–700/mm³; platelets 90,000–130,000/mm³). Marrow reassessment in October 2025 showed hypocellularity with dysplastic erythroid and megakaryocytic lineages and 12.6% aberrant B lymphoblasts by flow cytometry, without monoclonal plasma cells; biopsy confirmed 20–30% CD34-positive cells. Karyotype was normal, and KMT2A rearrangement and BCR-ABL p190 were negative. She is currently receiving Hyper-CVAD, with negative measurable residual disease (MRD). Discussion: Therapy-related myeloid neoplasms classically progress to acute myeloid leukemia, and transition from multiple myeloma to myelodysplasia has previously been linked to myelosuppressive regimens such as lenalidomide combined with melphalan (1). This case instead describes lymphoid transformation, raising the question of an immunomodulatory drug (IMiD)-driven process versus an independent, treatment-unrelated neoplasm. The absence of KMT2A rearrangement or other high-risk cytogenetic abnormalities mirrors prior reports of IMiD-associated secondary ALL (2), which, unlike classic therapy-related leukemia after genotoxic chemotherapy, lacks a recurrent molecular signature, supporting a mechanism driven by lenalidomide's immunomodulatory effects on B-lymphoid progenitors rather than direct mutagenesis. Conclusion: This case illustrates secondary B-ALL in a myeloma patient on prolonged lenalidomide maintenance, with a latency of approximately seven years, at the upper end of previously reported ranges (2). It reinforces that persistent, unexplained cytopenias during IMiD maintenance warrant bone marrow evaluation, even years into an otherwise stable course (3), and highlights the value of broader molecular profiling, such as next-generation sequencing, in clarifying the mutational basis of this rare transformation.
SN - 2531-1379
SN - 2531-1387
ER -