HOLLYWOOD, FL—After 16 years of creating guidelines for treatment of many different types of cancer, the National Comprehensive Cancer Network has now issued its first treatment algorithm for post-transplant lymphoproliferative disorder (PTLD).
The new guideline was presented here at the NCCN‘s 16th Conference on Clinical Practice Guidelines and Quality.
Post-transplant lymphoproliferative disorder is actually more than one condition, and that is quite important,” said Andrew D. Zelenetz, MD, PhD, Chair of the 29-member NCCN Guidelines Panel for Non-Hodgkin‘s Lymphoma.
Dr. Zelenetz, Chief of the Lymphoma Service at Memorial Sloan-Kettering Cancer Center, one of the 21-member institutions of the NCCN, explained that some early manifestations of the disease may resemble infectious mononucleosis; other presentations might be described as B-Cell or T-Cell lymphomas, and others can be similar when observed as classical Hodgkin‘s lymphoma.
The tumors often are associated with Epstein-Barr virus—most of the early lesions are associated with the virus; and that drops off to about 50% of the later lesions, Dr. Zelenetz noted.
Hepatitis C virus and cytomegalovirus are covariants in the risk of developing PTLD, he added.
The disorder occurs most frequently among patients who receive a small bowel transplant—about 20% of these patients are at risk of developing the disorder.
Lung transplant patients have a risk up to about 10%, heart and heart-lung transplant patients have up to a 6% risk. Kidney and liver patients have about a 1% to 3% risk, Dr. Zelenetz said.
The greatest risk factor, however, is a mismatch in EBV status. If the recipient is EBV seronegative, the risk of developing PTLD is increased 24-fold if the organ donor is infected with the virus.
Most of the PTLD lesions present within the first year following organ transplant, he said.
“Post-transplant lymphoproliferative disorder has emerged as a significant complication of solid organ and allogeneic bone marrow transplantation, which the panel felt was important to address in the updated Non-Hodgkin‘s Lymphoma Guidelines,” said Dr. Zelenetz.
Although the patient work-up is similar to other guidelines in lymphomas, he said that determining the EBV status of the patient is important because of the role that the virus can have in prognosis and in treatment options.
For early lesions, if possible, the guidelines suggest a reduction in the immunosuppressive regimen—although Dr. Zelenetz said that in heart transplant recipients a reduction “makes them nervous.”
“Obviously if we do remove the immunosuppression, we run the risk of loss of the transplanted organ.”
For patients who test positive for EBV, the use of the antiviral agent gancyclovir is suggested.
If there are complete responses to the reduced level of immunosuppression—which can occur in about 25% to 50% of cases—the guidelines suggest continuing the modified regimen and monitoring of EBV levels.
Dr. Zelenetz said that follow-up observation is appropriate for patients who achieve a complete response with a reduction in immunotherapy.
In cases where the initial treatment fails to achieve a complete response to PTLD the guidelines recommend treatment with rituximab.
“Response rates with rituximab in early lesions and in polymorphic lesions are as high as 90%,” Dr. Zelenetz said.
For more advanced histology, the treatment options are similar. For systemic polymorphic PTLD lesions, reduced immunotherapy is suggested if possible, gancyclovir is recommended if the patient exhibits virus, and chemo-immunotherapy with rituximab and other cytotoxic drugs in combination, including cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP).
For patients who may be frail or may have received a heart transplant, a chemotherapy regimen without anthracyclines can also produce acceptable responses, Dr. Zelenetz said.
Pertaining to diagnosis and workup of PTLD, the NCCN Guidelines provide recommendations for tests differentiated as either “essential” or “useful under certain circumstances” to help guide clinicians.
If the polymorphic lesion is localized, Dr. Zelenetz‘ committee recommended radiotherapy, surgery or single-agent rituximab. If disease persists, the guidelines recommend chemo-immunotherapy, participation in a clinical trial, or Epstein-Barr specific cytotoxic T-cell immunity therapy.
In cases where the pathologist determines that the PTLD lesion is monomorphic, the initial therapy is a reduction in immunosuppression, chemo-immunotherapy, or single-agent rituximab. If there is persistent disease, the guidelines suggest use of a treatment modality not used in first-line therapy.
As in all NCCN guidelines, participation in a clinical trial is an accepted and encouraged alternative for patients with persistent disease.
Dr. Zelenetz said the guidelines for the classic Hodgkin‘s lymphoma form of PTLD refer doctors to the existing Hodgkin‘s lymphoma guidelines.
“Stem cell transplant is usually reserved for relapse or refractory situations as we would manage other aggressive lymphomas,” he said