Cumulative exposure to melphalan chemotherapy and subsequent risk of developing acute myeloid leukemia and myelodysplastic syndromes in patients with multiple myeloma

Gudbjorg Jonsdottir, Magnus Björkholm, Ingemar Turesson, Malin Hultcrantz, Benjamin Diamond, Anna Porwit, Ola Landgren, Sigurdur Y. Kristinsson

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Objectives: The aim of this study was to determine risk factors for development of acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) in patients with multiple myeloma (MM). Methods: We identified all patients diagnosed with MM in Sweden from January 1st, 1958 to December 31, 2011. A total of 26 627 patients were diagnosed with MM with during the study period. Of these, 124 patients (0.5%) developed subsequent AML/MDS. For each patient with MM and a subsequent AML/MDS diagnosis, we randomly selected a matched (age, sex, and date of MM diagnosis) MM patient without a subsequent second malignancy diagnosis. Results: The cumulative melphalan exposure was significantly higher (OR = 2.8, 95% CI 1.7-5.2; P <.001) among cases (median 988 mg; IQR 644-1640) compared with controls (median 578 mg; IQR 360-967). Median time to AML/MDS development was 3.8 years (IQR 2.8-5.8). Risk of AML/MDS was not statistically altered by M protein isotype, anemia, renal failure, hypercalcemia, lytic bone lesions, or radiation therapy. Conclusion: In this nationwide population-based study, we show that increased cumulative doses of alkylating therapy with melphalan increases the subsequent risk of developing AML/MDS in patients with MM. Given improved survival in MM patients over the last decade future studies will be important to better define long-term risks.

Original languageEnglish (US)
Pages (from-to)275-282
Number of pages8
JournalEuropean Journal of Haematology
Volume107
Issue number2
DOIs
StatePublished - Aug 2021

Keywords

  • acute myeloid leukemia/myelodysplastic syndromes
  • alkylating therapy
  • melphalan
  • multiple myeloma
  • second malignancies

ASJC Scopus subject areas

  • Hematology

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