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Acute lymphoblastic leukemia

Acute lymphoblastic leukemia as a clonally unrelated second primary malignancy after multiple myeloma


Multiple myeloma (MM) patients have an 11-fold increased risk of developing myeloid neoplasms compared to the general population; however, acute lymphoblastic leukemia (ALL) is rarely observed. Given that both MM and the majority of ALL are of B cell origin, this raises the question of whether ALL in patients with MM arises from the same clone. We report 13 cases of B-cell ALL following therapy for MM. The interval from MM diagnosis to ALL onset was 5.4 years (range 3.3–10). The median age at the time of ALL diagnosis was 60 years (range 43–67). MM therapy included immunomodulatory agents in all patients and autologous hematopoietic cell transplantation in 10 (77%) patients preceding ALL diagnosis. ALL genetics showed a normal karyotype, TP53 mutation/deletion, and monosomy 7 or 7q deletion in 5, 3, and 2 cases, respectively. Analysis of paired samples of MM and ALL using whole exome sequencing demonstrated that the malignancies arose from different clones. Thus, ALL as a second primary malignancy following MM is not clonally related but could potentially represent a therapy-related leukemia.

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The Biostatistics and Molecular Pathology Cores at City of Hope were supported by the National Institutes of Health under award number P30CA033572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author contributions

Designed studies: I.A., M.C., I.G., A.K., data collection: I.A., performed experiments: M.C., analysis: I.A., T.S., M.C., J.P., R.S.P., J.S., I.G., writing: I.A., J.S., A.K., review and editing: all authors.

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Conflict of interest

I.A. serves on the speakers’ bureau for Jazz Pharmaceuticals. A.K. is a consultant and serves on the speakers’ bureau for Janssen, Celgene, Takeda, and Onyx. The remaining authors declare that they have no conflict of interest.

Correspondence to Irene M. Ghobrial or Amrita Krishnan.

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