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.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $102.00 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Razavi P, Rand KA, Cozen W, Chanan-Khan A, Usmani S, Ailawadhi S. Patterns of second primary malignancy risk in multiple myeloma patients before and after the introduction of novel therapeutics. Blood Cancer J. 2013;3:e121.
Jonsdottir G, Lund SH, Bjorkholm M, Turesson I, Hultcrantz M, Porwit A, et al. The impact of prior malignancies on second malignancies and survival in MM patients: a population-based study. Blood Adv. 2017;1:2392–8.
Barlogie B, Tricot G, Haessler J, van Rhee F, Cottler-Fox M, Anaissie E, et al. Cytogenetically defined myelodysplasia after melphalan-based autotransplantation for multiple myeloma linked to poor hematopoietic stem-cell mobilization: the Arkansas experience in more than 3000 patients treated since 1989. Blood. 2008;111:94–100.
Usmani SZ, Sexton R, Hoering A, Heuck CJ, Nair B, Waheed S, et al. Second malignancies in total therapy 2 and 3 for newly diagnosed multiple myeloma: influence of thalidomide and lenalidomide during maintenance. Blood. 2012;120:1597–1600.
Rollison DE, Komrokji R, Lee JH, Hampras S, Fulp W, Fisher K, et al. Subsequent primary malignancies among multiple myeloma patients treated with or without lenalidomide. Leuk Lymphoma. 2017;58:560–8.
Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366:1782–91.
McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366:1770–81.
Aldoss I, Dagis A, Palmer J, Forman S, Pullarkat V. Therapy-related ALL: cytogenetic features and hematopoietic cell transplantation outcome. Bone Marrow Transplant. 2015;50:746–8.
Tang G, Zuo Z, Thomas DA, Lin P, Liu D, Hu Y, et al. Precursor B-acute lymphoblastic leukemia occurring in patients with a history of prior malignancies: is it therapy-related? Haematologica. 2012;97:919–25.
Kishimoto W, Shirase T, Chihara D, Maeda T, Arimoto-Miyamoto K, Takeoka T, et al. Double-hit lymphoma with a feature of follicular lymphoma concurrent with clonally related B lymphoblastic leukemia: a preference of transformation for the bone marrow. J Clin Exp Hematop. 2012;52:113–9.
Chakhachiro Z, Yin CC, Abruzzo LV, Aladily TN, Barron LL, Banks HE, et al. B-lymphoblastic leukemia in patients with chronic lymphocytic leukemia: a report of four cases. Am J Clin Pathol. 2015;144:333–40.
Dilworth D, Liu L, Stewart AK, Berenson JR, Lassam N, Hogg D. Germline CDKN2A mutation implicated in predisposition to multiple myeloma. Blood. 2000;95:1869–71.
Manier S, Park J, Capelletti M, Bustoros M, Freeman S, Ha G, et al. Whole-exome sequencing of cell-free DNA and circulating tumor cells in multiple myeloma. Nat. Commun. 2018; In press. Volume 9: p. 1691.
Venkatraman ES, Olshen AB. A faster circular binary segmentation algorithm for the analysis of array CGH data. Bioinformatics. 2007;23:657–63.
DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet. 2011;43:491–8.
McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20:1297–303.
Landgren O, Thomas A, Mailankody S. Myeloma and second primary cancers. N Engl J Med. 2011;365:2241–2.
Smith SM, Le Beau MM, Huo D, Karrison T, Sobecks RM, Anastasi J, et al. Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series. Blood. 2003;102:43–52.
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.
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.