opsonization, and hyposplenism in certain cases. The risks of acute infections are heightened by mucocutaneous damage, which occurs due to skin, oral, and gastrointestinal (GI) cGVHD, and due to iatrogenic reasons (e.g., intravenous [IV] catheters for extracorporeal photophoresis). Extra care should be taken to examine the catheter sites, and for surveillance of skin or oral mucosal tears due to cGVHD.
Among the late viral infections, Epstein–Barr virus is exceedingly common, but infrequently causes any permanent late sequelae (except posttransplant lymphoproliferative disorder, as discussed later) Varicella zoster virus (VZV) and cytomegalovirus (CMV) are the most common organisms causing complications. The VZV‐mediated infections typically occur during the first 6–12 months post‐HCT (approximately 80% of cases) [12]; the disseminated disease is much more common in allogeneic‐HCTs than in autologous HCTs (45% versus 25%) and the lesions are likely to last longer and heal more slowly than in normal adults [13], necessitating the need for prophylactic therapy with anti‐VZV drugs for a long period even in the absence of cGVHD. Herpes simplex encephalitis, JC/BK infections, hepatitis B and C virus infections and reactivations, and HIV infection are rare late effects and do not necessarily need long‐term surveillance.
Human herpesvirus 6 (HHV‐6) infections occurring after HCT deserve special attention as significant late morbidity and mortality can be associated with this infection [15]. HHV‐6 infection can lead to memory loss, insomnia, confusion, hyperintense signals of the hippocampi on brain magnetic resonance imaging, and temporal lobe seizure activity on electroencephalography [14]. Since similar symptoms may occur in acute meningitis and some cases of calcineurin inhibitor (CNI)‐associated encephalopathy, a high level of suspicion for HHV‐6 encephalitis is required to send the appropriate diagnostic tests for this condition.
Late‐onset fungal infections include candida species, invasive aspergillosis, Fusarium species, and the Zygomycetes. They are more common within a few months of allogeneic‐HCTs and do not require surveillance besides a heightened awareness and prompt diagnostic testing in symptomatic patients for urgent treatment, particularly in high‐risk patients such as cGVHD patients on high‐dose corticosteroids.
Table 6.1 Non‐relapse late and very late effects after allogeneic HCT
| Late effect | Incidence | Risk factor | Surveillance/screening | Preventable | Treatable |
|---|---|---|---|---|---|
| 1. Acute and chronic infections | ++ | Prolonged immunosuppression, steroids | CT, PCR, serum test | Yes | Yes |
| 2. Cutaneous complications | +++ | GVHD | Dermatology exam yearly | No | Yes |
| 3. Oral/dental complications | ++ | GVHD | Oral exam yearly | No | Yes |
| 4. Hepatic complications | + | HBV, HCV, complementary and alternative medicine, iron overload | T.bil, ALT, US, HBV/HCV viral load, ferritin, T2* MRI, FerriScan, SQUID | No/Yes | Yes/No |
| 5. GI complications | + | GVHD, steroids, mychophenolate mofetil | Endoscopy | No | Yes |
| 6. Genital complications | + | GVHD | Genital exam yearly | No | Yes |
| 7. Renal complications | + | Nephrotoxic medications including CNI | Urine test, serum creatinine | No | Yes/No |
| 8. Ocular complications | ++ | GVHD, radiation, steroids | Eye exam yearly and when symptomatic [76] | No/Yes | Yes/No |
| 9. Endocrine complications | ++ | Radiation, steroids, CNI | Thyroid‐stimulating hormone, thyroxine levels, glucose level, HbA1c, glycoalbumin (see reference [77]) | No/Yes | Yes |
| 10. Hypogonadism, fertility loss, pregnancy, and lactation issues | +++ | Radiation, busulfan | FSH, LH, estrogen, testosterone levels, sperm test | No/Yes | Yes/No |
| 11. Musculoskeletal and bone complications | ++ | Steroids, GVHD | Dual‐energy X‐ray absorptiometry, MRI | Yes | Yes |
| 12. Pulmonary complications and obliterating bronchiolitis | + | Smoking, radiation, busulfan | Pulmonary function test, high‐resolution chest CT | No | Yes |
| 13. Neurologic complications | ++ | MRI, neurologic test (see reference [78]) | No | Yes/No | |
| 14. psychological and social complications | ++ | psychological test, MRI | No | Yes | |
| 15. Sexual dysfunction | +++ | GVHD | No | Yes | |
| 16. Subsequent hematologic malignancies | + | Patient age, radiation | Blood cell count | No | Yes |
| 17. Cardiovascular complications | + | Thoracic radiation, anthracyclines, cardiovascular risk factors, steroids, genetic polymorphisms | Blood pressure, chest X‐ray, lipid panel, electrocardiogram, echocardiogram, brain natriuretic peptide level | Yes |
Yes
|
