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Development of therapy‐related hematologic and solid tumors is an important late complication after AHSCT and is the second leading cause of death in survivors [8]. In a large study on patients surviving ≥2 years after AHSCT, one‐fourth of late deaths were caused by secondary malignancies, with the most common entity being therapy‐related myeloid neoplasms (t‐MN) including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) [8]. Literature on incidence and risk factors for development of t‐MN after AHSCT has been mostly described in the context of primary lymphoma diagnosis [30–32]. A single‐institution study of approximately 500 patients undergoing AHSCT for lymphoma demonstrated a 7% actuarial incidence of t‐MN at 10 years [31]. Risk factors for t‐MN include pretransplant exposure to radiation therapy, four or more chemotherapy regimens prior to transplant, and apheresis duration of more than 5 days to collect enough stem cells. Another Italian study on more than 1000 transplant survivors with HL, NHL, and T‐cell lymphoma showed the cumulative 5‐ and 10‐year incidence of t‐MN to be 3.09 and 4.52% respectively [30]. Risk‐factors for t‐MN in this study were male sex and the use of second harvest peripheral blood stem cells. Stem cell mobilization with etoposide in lymphoma AHSCT recipients confers a 12‐fold increase in risk of t‐MN with 11q23/21q22 abnormalities [32]. Furthermore, the latency between exposure to etoposide and development of t‐MN is lower (2–3 years) compared to that after exposure to alkylating agents (≈5 years). Pretransplant CHIP is a novel risk factor for subsequent t‐MNs and is present in 30% of lymphoma patients prior to AHSCT [33]. In a cohort of 401 NHL patients undergoing AHSCT between 2003 and 2010, the 10‐year cumulative incidence of t‐MN in patients with and without CHIP was 14.1% and 4.3% respectively [33]. The median time to diagnosis of t‐MN was around 4 years from AHSCT. Patients with more than one CHIP mutation had a 17% risk of t‐MN compared to 4% in those with one mutation. Presence of CHIP was an independent predictor of t‐MN on multivariable analysis, along with exposure to a nucleoside analogue and lifetime dose of cyclophosphamide exceeding 10 g/m². Furthermore, patients with CHIP had an inferior overall survival at 10‐years compared to those without (30% vs 61% respectively), attributable to increased death from t‐MN as well as cardiovascular disease [33].

Therapy‐related solid cancers account for approximately 10% of late deaths after AHSCT, with the most common fatal solid cancer being unspecified adenocarcinoma [8]. The 5 and 10‐year cumulative incidence of solid tumors after lymphoma AHSCT in the rituximab era is 2.54% and 6.79% respectively. Risk factors for development of solid tumors are advanced age, exposure to radiation posttransplant, and the addition of rituximab to high‐dose therapy [30]. Frequent solid cancers noted in this study were that of lung, gastrointestinal (GI) tract, skin, head and neck, breast, and urinary bladder. An Australian study on 7765 AHSCT survivors found an increased risk of melanoma (standardized incidence ratio [SIR: 2.6]), NHL (SIR: 3.3), and t‐MN (SIR: 20.6) compared to the general population at a median follow‐up of 2.5 years [34]. Notably male sex, age>45 years, and posttransplant relapse of primary malignancy predicted melanoma risk in this study.

Transplant survivors should be counseled regarding the risk of secondary malignancies and educated about the signs and symptoms. All patients should undergo yearly physical examination and laboratory testing as clinically indicated at least up until 10 years after transplant. United States Preventative Services Task Force (USPSTF) guidelines should be followed for screening for subsequent cancers, including mammography for breast cancer, low‐dose chest computed tomography (CT) for lung cancer in high‐risk patients, prostate‐specific antigen for prostate cancer, and colonoscopy for colorectal cancer [27]. In females with exposure to chest radiation, annual breast examination, annual mammograms, and MRI scans should be considered beginning eight years after radiation or age 25, whichever occurs last [18]. Similarly, in patients exposed to TBI, colonoscopy should be performed every 5 years beginning 10 years after radiation or from age 35 [18]. The risk of secondary malignancies can change dynamically after transplant depending on posttransplant therapies (e.g. lenalidomide maintenance in MM, which will be discussed in greater detail below). Hence, continued monitoring of these patients and communication between the transplant physician and the treating oncologist is crucial for optimal surveillance.