+: <20%, ++:20‐50%; +++: >50%, CNI, calcineurin inhibitor
The usual suspects for late‐onset bacterial infections include staphylococcus species, pseudomonas species, and the encapsulated bacteria [16–18]. The risk of pneumococcal infection is greatest among patients with IgG deficiencies and with severe cGVHD [19], thereby re‐enforcing the need for prophylactic antibiotics (e.g., oral penicillin therapy) and pneumococcal vaccinations. Recently, Clostridium difficile (C. diff) colitis has been found to have a significantly increased incidence in HCT recipients [20], which occurred more frequently in early HCT periods. Interestingly, GI GVHD was found to be strongly associated with an increased risk for recurrent C. diff colitis (OR 4.23, P = 0.02).
HCT recipients residing in certain developing countries may be more susceptible to endemic conditions (e.g., tuberculosis, Chagas disease, and schistosomiasis) which may manifest as late effects post‐allogeneic‐HCT. These endemic infections can have a detrimental effect on QOL of HCT recipients who are already prone to organ dysfunction due to organ involvement; for example, ocular GVHD patients living in areas where Chlamydia trachomatis is endemic are at significantly higher risk of blindness compared with the trachoma‐free geographic locations.
Post‐HCT hypoglobulinemias can be related to cGVHD and are found most commonly in the cases of chronic lymphocytic leukemia. Routine use of antibiotics in asymptomatic hypoglobulinemic patients without evidence of recurrent infections is not indicated.
Cutaneous complications
Among the late effects, cutaneous cGVHD (skin and oral mucosal) is the most common organ/system involved by GVHD [21]. It expresses itself in a variety of manifestations from chronic eczematous form [22], to lichen planus‐like lesions [23]. The affected skin can become progressively indurated and fixed to the underlying fascia, resulting in prominent morphea and scleroderma, which can lead to joint contractures [24] and a significant compromise in QOL of HCT patients.
Though skin cGVHD is one of the leading causes of morbidity in HCT recipients, a thorough evaluation for other causes of cutaneous complications pertinent to allogeneic‐HCTs is warranted in symptomatic patients. Invasive mold infections can affect the skin of HCT recipients. Photosensitive rash may represent GVHD or may occur as an adverse effect of certain medications commonly utilized in HCT recipients for treatment or prevention of infections particularly with voriconazole [25]. In some patients, pre‐HCT chemotherapy with busulfan, cyclophosphamide, or hydroxyurea may lead to permanent darkening and/or thickening of the skin, which may masquerade as initial stages of cGVHD. Skin cancers are the most common solid malignancies occurring post‐HCT. Routine surveillance with dermatologic exams at annual intervals is recommended [1,26].
Oral/dental complications
The oral mucosal involvement with GVHD frequently leads to extreme xerostomia, often resulting in pain secondary to aphthous‐like ulcers [27]. Erythema within lichenoid plaques of the buccal mucosa is diagnostic of cGVHD; however, a biopsy is frequently required to exclude the presence of co‐infections or oral cancers. Oral cGVHD along with skin cGVHD can result in difficulty opening the mouth (similar to the manifestations of oral scleroderma), which can lead to many complications, including malnutrition and poor dental health. Complete loss of taste can also happen in oral cGVHD, which may further decrease QoL significantly. Prompt recognition of early oral cGVHD and referral to oral surgery for localized treatments (along with systemic therapy) may help in preventing the above‐mentioned complications.
Late dental complications may arise as a result of TBI, chemotherapy, oral cGVHD, DM, or corticosteroid therapy [28]. Common effects include dental caries, endodontic disease, and periodontal disease. General principles of dental care of cancer patients should be adopted [44]. Detailed management options are given in Chapter 17.