Table 4. Oral Complications of Hematopoietic Stem Cell Transplantation continued...
Oral mucositis usually begins 7 to 10 days after initiation of cytotoxic therapy and remains present for approximately 2 weeks after cessation of that therapy. Viral, fungal, and bacterial infections may arise, with incidence dependent on the use of prophylactic regimens, oral status prior to chemotherapy, and duration/severity of neutropenia. Frequency of infection declines upon resolution of mucositis and regeneration of neutrophils. This phenomenon appears to be more a temporal relation than a causative one, based on the predominant evidence. Despite the initial marrow recovery, however, the patient may remain at risk for infection, depending on status of overall immune reconstitution.
Salivary gland hypofunction/xerostomia secondary to anticholinergic drugs and taste dysfunction is initially detected in this phase; the toxicity typically resolves within 2 to 3 months.
In allogeneic transplant patients, while uncommon, hyperacute graft-versus-host disease (GVHD) can occur and can result in significant oral mucosal inflammation and breakdown that can complicate the oral course for patients. Clinical presentation will often not be sufficiently distinct to diagnosis this lesion. The clinical assessment is typically based on the patient experiencing more-severe-than-expected mucositis that will often not heal within the time line for mucosal recovery associated with oral mucositis caused by chemotherapy.
Phase III: Hematopoietic Recovery
Frequency and severity of acute oral complications typically begin to decrease approximately 3 to 4 weeks after cessation of chemotherapy. Healing of ulcerative oral mucositis in the setting of marrow regeneration contributes to this dynamic. Although immune reconstitution is developing, oral mucosal immune defenses may not be optimal. Generally stated, immune reconstitution will take between 6 and 9 months for autologous transplant patients and between 9 and 12 months for allogeneic transplant patients not developing chronic GVHD. Thus, the patient remains at risk for selected infection, including candidal and herpes simplex virus infections.
Mucosal bacterial infections during this phase occur less frequently unless engraftment is delayed or the patient has acute GVHD or is receiving GVHD therapy. Most centers will use systemic infection prophylaxis throughout this period (and, in many instances, longer) to reduce the risk of infections in general, a practice that positively influences the rate and severity of both systemic and local oral infections.
The hematopoietic stem cell transplant patient represents a unique cohort at this point. For example, risk for acute oral GVHD typically emerges during this time in allogeneic graft recipients.
Phase IV: Immune Reconstitution/Recovery from Systemic Toxicity
Oral lesions are principally related to chronic conditioning regimen–associated (chemotherapy with or without radiation therapy) toxicity and, in the allogeneic patient, GVHD. Late viral infections and xerostomia predominate. Mucosal bacterial infections are infrequent unless the patient remains neutropenic or has severe chronic GVHD.
Risk exists for graft failure, cancer relapse, and second malignancies. The hematopoietic stem cell transplant patient may develop oral manifestations of chronic GVHD during this period.