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

Jonsdottir, Gudbjorg ; Björkholm, Magnus ; Turesson, Ingemar LU ; Hultcrantz, Malin ; Diamond, Benjamin ; Porwit, Anna LU ; Landgren, Ola and Kristinsson, Sigurdur Y. (2021) In European Journal of Haematology 107(2). p.275-282
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... (More)

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.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
acute myeloid leukemia/myelodysplastic syndromes, alkylating therapy, melphalan, multiple myeloma, second malignancies
in
European Journal of Haematology
volume
107
issue
2
pages
275 - 282
publisher
Wiley-Blackwell
external identifiers
  • scopus:85106755597
  • pmid:33966293
ISSN
0902-4441
DOI
10.1111/ejh.13650
language
English
LU publication?
yes
id
3416cba3-38ba-4c5a-b7c6-71b7f5206977
date added to LUP
2021-06-24 10:17:22
date last changed
2024-12-15 08:41:23
@article{3416cba3-38ba-4c5a-b7c6-71b7f5206977,
  abstract     = {{<p>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 &lt;.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.</p>}},
  author       = {{Jonsdottir, Gudbjorg and Björkholm, Magnus and Turesson, Ingemar and Hultcrantz, Malin and Diamond, Benjamin and Porwit, Anna and Landgren, Ola and Kristinsson, Sigurdur Y.}},
  issn         = {{0902-4441}},
  keywords     = {{acute myeloid leukemia/myelodysplastic syndromes; alkylating therapy; melphalan; multiple myeloma; second malignancies}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{275--282}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{European Journal of Haematology}},
  title        = {{Cumulative exposure to melphalan chemotherapy and subsequent risk of developing acute myeloid leukemia and myelodysplastic syndromes in patients with multiple myeloma}},
  url          = {{http://dx.doi.org/10.1111/ejh.13650}},
  doi          = {{10.1111/ejh.13650}},
  volume       = {{107}},
  year         = {{2021}},
}