Long Term Follow-Up Post Allogeneic HSCT
Secondary Malignancy

Updated: October 2010

The incidence of secondary malignancy is increased 2-3 fold post transplant compared to gender, age and region matched population. The cumulative risk is 2.5% at 10 years and 8.8% at 20 years. The transplant related risk factors include radiotherapy, length and severity of immunosuppression and CGVHD. The risk increases with time after transplant especially for radiation induced malignancies.

The incidence of PTLDs is 1% at 10 years with the majority being EBV related and occurring within 6 months post transplant. The risk is increased with greater recipient-donor HLA disparity, T-depletion and GVHD.

The risk factors for Squamous cell carcinoma (SCC) include male sex, CGVHD and immunosupression. There is a 5 fold increase in SCC in patients with CGVHD at 1-4 years post-transplant with the risk remaining high for several years. The risk of cutaneous malignancy risk is increased by exposure to radiotherapy and photosensitive effects of medication.

Non-SCC (breast, thyroid, brain, bone, CNS, connective tissue, melanoma) risk is linked to radiotherapy, age at which radiotherapy was received and risk increases with increasing time from transplant. Patients who have been irradiated have a 10 fold higher risk compared to non-irradiated patients for up to 30 years post transplant. There is a 6 fold increase in breast malignancy in patients receiving local radiotherapy/TBI prior to transplant. The risk particularly increased after 10 years post-transplant. The risk is significantly increased when the radiotherapy was received prior to 18 years of age. The relative risk of developing thyroid malignancy is 6 times for patients post transplant. The risk increase with younger age, radiation exposure, female sex and CGVHD. The risk factors for developing CNS malignancy (RR almost 6) is younger age at transplant, radiotherapy and receipt of anthracyclines and alkylators. Risk for developing Melanomas (RR3.5) is radiation exposure, T-cell depletion and short (<1 year) latency period. High index of suspicion needs to be maintained for the diagnosis of all of the above as routine screening is not available for most.

Recommendations:

• Patients should be reminded to perform regular self breast and skin examinations.
• Patients should be advised to stop smoking.
• Patients should be advised to avoid excessive UV exposure and use sun-screen regularly.
• Mammography should commence at 40 years (for patients without a family history or who have not received mantle radiotherapy). In patients with Hodgkins Lymphoma or who have received local radiotherapy it should commence at 10 years post therapy or at 40 years whichever is earlier.
• Pap smears should be done every 1-2 years as per protocol.
• Yearly dental exam for oral malignancy should be done.
• Yearly gynaecological exam is recommended.
• Colorectal cancer screening in the form of yearly stool FOB should begin at 50 years as per BCCA protocol.
• Digital rectal examination (DRE) either routinely or in men with urinary symptoms should be considered in patients between 50-70 years. If DRE is abnormal perform PSA and refer to urologist if PSA >4.

The information contained in these guidelines is a statement of consensus of Leukemia/BMT Program of BC professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these documents is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. Use of these guidelines and documents is at your own risk and is subject to the Leukemia/BMT Program of BC’s terms of use available at Terms of Use.