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

Leukemia. 2019 Jan;33(1):266-270. doi: 10.1038/s41375-018-0213-y. Epub 2018 Jul 19.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Chromosome Aberrations*
  • Clone Cells / pathology*
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Immunologic Factors / adverse effects*
  • Male
  • Middle Aged
  • Multiple Myeloma / pathology
  • Multiple Myeloma / therapy*
  • Neoplasms, Second Primary / etiology*
  • Neoplasms, Second Primary / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / etiology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Prognosis
  • Transplantation, Homologous


  • Immunologic Factors