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Risk of myeloid neoplasms after solid organ transplantation.

Morton LM, Gibson TM, Clarke CA, Lynch CF, Anderson LA, Pfeiffer R, Landgren O, Weisenburger DD, Engels EA - Leukemia (2014)

Bottom Line: However, little is known about risks for hematologic malignancies of myeloid origin.Solid organ transplant recipients had a significantly elevated risk for myeloid neoplasms, with standardized incidence ratios (SIRs) of 4.6 (95% confidence interval 3.8-5.6; N=101) for myelodysplastic syndromes (MDS), 2.7 (2.2-3.2; N=125) for acute myeloid leukemia (AML), 2.3 (1.6-3.2; N=36) for chronic myeloid leukemia and 7.2 (5.4-9.3; N=57) for polycythemia vera.Azathioprine for initial maintenance immunosuppression increased risk for MDS (P=0.0002) and AML (2-5 years after transplantation, P=0.0163).

View Article: PubMed Central - PubMed

Affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD, USA.

ABSTRACT
Solid organ transplant recipients have elevated cancer risks, owing in part to pharmacologic immunosuppression. However, little is known about risks for hematologic malignancies of myeloid origin. We linked the US Scientific Registry of Transplant Recipients with 15 population-based cancer registries to ascertain cancer occurrence among 207 859 solid organ transplants (1987-2009). Solid organ transplant recipients had a significantly elevated risk for myeloid neoplasms, with standardized incidence ratios (SIRs) of 4.6 (95% confidence interval 3.8-5.6; N=101) for myelodysplastic syndromes (MDS), 2.7 (2.2-3.2; N=125) for acute myeloid leukemia (AML), 2.3 (1.6-3.2; N=36) for chronic myeloid leukemia and 7.2 (5.4-9.3; N=57) for polycythemia vera. SIRs were highest among younger individuals and varied by time since transplantation and organ type (Poisson regression P<0.05 for all comparisons). Azathioprine for initial maintenance immunosuppression increased risk for MDS (P=0.0002) and AML (2-5 years after transplantation, P=0.0163). Overall survival following AML/MDS among transplant recipients was inferior to that of similar patients reported to US cancer registries (log-rank P<0.0001). Our novel finding of increased risks for specific myeloid neoplasms after solid organ transplantation supports a role for immune dysfunction in myeloid neoplasm etiology. The increased risks and inferior survival should heighten clinician awareness of myeloid neoplasms during follow-up of transplant recipients.

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Standardized incidence ratios* for specific myeloid neoplasms by time since transplantation among 207 859 solid organ transplants in the United States, 1987–2009Abbreviations: confidence interval (CI), standardized incidence ratio (SIR). SIRs are presented for <1, 1–1.9, 2–2.9, 3–3.9, 4–4.9, 5–6.9, 7–8.9, and 9+ years, with estimates centered over these intervals.* SIRs are not presented when <3 cases were observed due to imprecise estimates.
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Figure 2: Standardized incidence ratios* for specific myeloid neoplasms by time since transplantation among 207 859 solid organ transplants in the United States, 1987–2009Abbreviations: confidence interval (CI), standardized incidence ratio (SIR). SIRs are presented for <1, 1–1.9, 2–2.9, 3–3.9, 4–4.9, 5–6.9, 7–8.9, and 9+ years, with estimates centered over these intervals.* SIRs are not presented when <3 cases were observed due to imprecise estimates.

Mentions: For AML and polycythemia vera, SIRs also varied significantly by time since transplantation (Figure 2). Risks for AML were increased 2.0-fold during the first year following transplantation and peaked at 4.6-fold during 1–1.9 years following transplantation, with declining risk thereafter (Phomogeneity=0.0456). In contrast, polycythemia vera risk was increased 22.0-fold during the first year following transplantation, with SIRs dropping precipitously thereafter, yet remaining significantly increased 2.9–6.7-fold (Phomogeneity=0.0003). For MDS, risks appeared to decline consistently during the first five years following transplantation and increase again thereafter, although these changes were not statistically significant (Phomogeneity=0.5170). For CML, risk did not vary by time since transplantation (Phomogeneity=0.8049).


Risk of myeloid neoplasms after solid organ transplantation.

Morton LM, Gibson TM, Clarke CA, Lynch CF, Anderson LA, Pfeiffer R, Landgren O, Weisenburger DD, Engels EA - Leukemia (2014)

Standardized incidence ratios* for specific myeloid neoplasms by time since transplantation among 207 859 solid organ transplants in the United States, 1987–2009Abbreviations: confidence interval (CI), standardized incidence ratio (SIR). SIRs are presented for <1, 1–1.9, 2–2.9, 3–3.9, 4–4.9, 5–6.9, 7–8.9, and 9+ years, with estimates centered over these intervals.* SIRs are not presented when <3 cases were observed due to imprecise estimates.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4197126&req=5

Figure 2: Standardized incidence ratios* for specific myeloid neoplasms by time since transplantation among 207 859 solid organ transplants in the United States, 1987–2009Abbreviations: confidence interval (CI), standardized incidence ratio (SIR). SIRs are presented for <1, 1–1.9, 2–2.9, 3–3.9, 4–4.9, 5–6.9, 7–8.9, and 9+ years, with estimates centered over these intervals.* SIRs are not presented when <3 cases were observed due to imprecise estimates.
Mentions: For AML and polycythemia vera, SIRs also varied significantly by time since transplantation (Figure 2). Risks for AML were increased 2.0-fold during the first year following transplantation and peaked at 4.6-fold during 1–1.9 years following transplantation, with declining risk thereafter (Phomogeneity=0.0456). In contrast, polycythemia vera risk was increased 22.0-fold during the first year following transplantation, with SIRs dropping precipitously thereafter, yet remaining significantly increased 2.9–6.7-fold (Phomogeneity=0.0003). For MDS, risks appeared to decline consistently during the first five years following transplantation and increase again thereafter, although these changes were not statistically significant (Phomogeneity=0.5170). For CML, risk did not vary by time since transplantation (Phomogeneity=0.8049).

Bottom Line: However, little is known about risks for hematologic malignancies of myeloid origin.Solid organ transplant recipients had a significantly elevated risk for myeloid neoplasms, with standardized incidence ratios (SIRs) of 4.6 (95% confidence interval 3.8-5.6; N=101) for myelodysplastic syndromes (MDS), 2.7 (2.2-3.2; N=125) for acute myeloid leukemia (AML), 2.3 (1.6-3.2; N=36) for chronic myeloid leukemia and 7.2 (5.4-9.3; N=57) for polycythemia vera.Azathioprine for initial maintenance immunosuppression increased risk for MDS (P=0.0002) and AML (2-5 years after transplantation, P=0.0163).

View Article: PubMed Central - PubMed

Affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD, USA.

ABSTRACT
Solid organ transplant recipients have elevated cancer risks, owing in part to pharmacologic immunosuppression. However, little is known about risks for hematologic malignancies of myeloid origin. We linked the US Scientific Registry of Transplant Recipients with 15 population-based cancer registries to ascertain cancer occurrence among 207 859 solid organ transplants (1987-2009). Solid organ transplant recipients had a significantly elevated risk for myeloid neoplasms, with standardized incidence ratios (SIRs) of 4.6 (95% confidence interval 3.8-5.6; N=101) for myelodysplastic syndromes (MDS), 2.7 (2.2-3.2; N=125) for acute myeloid leukemia (AML), 2.3 (1.6-3.2; N=36) for chronic myeloid leukemia and 7.2 (5.4-9.3; N=57) for polycythemia vera. SIRs were highest among younger individuals and varied by time since transplantation and organ type (Poisson regression P<0.05 for all comparisons). Azathioprine for initial maintenance immunosuppression increased risk for MDS (P=0.0002) and AML (2-5 years after transplantation, P=0.0163). Overall survival following AML/MDS among transplant recipients was inferior to that of similar patients reported to US cancer registries (log-rank P<0.0001). Our novel finding of increased risks for specific myeloid neoplasms after solid organ transplantation supports a role for immune dysfunction in myeloid neoplasm etiology. The increased risks and inferior survival should heighten clinician awareness of myeloid neoplasms during follow-up of transplant recipients.

Show MeSH
Related in: MedlinePlus