Tuesday, March 29, 2011

NCCN Issues 1st Clinical Guidelines for Post-Transplant Lymphoproliferative Disorder

NCCN Issues 1st Clinical Guidelines for Post-Transplant Lymphoproliferative Disorder


By Anna Azvolinsky, PhD
March 29, 2011

"PTLD generally manifests itself within the first year of a transplant. Cytomegalovirus and hepatitis C virus are covariants in the risk of PTLD development, according to Dr. Andrew D. Zelenetz, the Chair of the 29-member NCCN Guidelines Panel for Non-Hodgkin’s Lymphoma and chief of the Lymphoma Service at Memorial Sloan Kettering Cancer Center in New York."

The National Comprehensive Cancer Network presented the first treatment algorithm for post-transplant lymphoproliferative disorder (PTLD) at the 16th annual NCCN Conference on Clinical Practice Guidelines and Quality. The new guidelines, presented on March 11, 2011, contain diagnosis, follow-up, treatment options for PTLD and can be found on the NCCN website.

Post-transplant lymphoproliferative disorder defined

PTLD is a type of life-threatening lymphoma that results as a complication after either a hematopoietic stem cell or solid organ transplant. It is generally associated with the Epstein-Barr virus (EBV) infection of a B cell. T-cell lymphomas not associated with EBV and Hodgkins lymphoma have also been documented. There are two ways that PTLD occurs: either from an infection from the transplant donor who is a carrier or through reactivation of the virus within the recipient after the transplant. B-cell proliferative disorders not associated with EBV infection after a transplant have also been documented. The greatest risk factor for PTLD appears to be a mismatch in the EBV between the donor and the recipient. PTLD occurs most frequently in patients receiving a small bowel transplant (20% of patients at risk) followed by lung transplant patients (10% at risk).

PTLD generally manifests itself within the first year of a transplant. Cytomegalovirus and hepatitis C virus are covariants in the risk of PTLD development, according to Dr. Andrew D. Zelenetz, the Chair of the 29-member NCCN Guidelines Panel for Non-Hodgkin’s Lymphoma and chief of the Lymphoma Service at Memorial Sloan Kettering Cancer Center in New York.

The NCCN Guidelines Panel stated that PTLD has become a significant complication of both solid organ and allogeneic bone marrow transplants, stimulating the panel to address these important updates. The guidelines are updated through a rigorous review of evidence based-practices and scientific evidence by an expert and multidisciplinary panel from institutions that are NCCN members.

“Despite recent advances, it remains a major challenge to define indications for preemptive therapies for PTLD and to integrate novel therapeutic approaches with conventional therapies. The NCCN Guidelines now help to provide a solid framework to assist in diagnosis and treatment decisions,” said Dr. Zelenetz. He added that the current understanding of pathogenesis and the utilization of early detection strategies such as measurement of EBV-DNA load in peripheral blood samples have facilitated the identification of patients at high-risk for developing PTLD.

Diagnosis and treatment options

The NCCN Guidelines separate diagnostic tests into “essential” and “useful under certain circumstances” categories to guide clinicians. Determining the EBV status of the patient is in the "essential" category as it is particularly important for prognosis and treatment options.

Because PTLD represents more than one condition, it is very important to categorize the sub-type of PTLD in order to tailor the treatment accordingly. For example, if the PTLD is determined to be the classic Hodgkin’s lymphoma form, clinicians are referred to the existing Hodgkin’s treatment guidelines

The stage, EBV status of the PTLD patient, and whether a B or T cell lymphoma is involved determine the treatment options. Early lesions usually dictate reduction in immunosuppression, depending on the organ of transplant and risk of rejection of the transplanted organ. Immunosuppression reduction alone can result in a complete response in 25% to 50% of cases.

Antiviral prophylaxis such as Roche’s Cytovene is recommended if the PTLD is EBV-positive. If initial treatment fails to result in a complete response, an anti-CD20 antibody such as Genentech’s Rituxan is recommended, and results in response rates as high as 90% for early and polymorphic lesions, according to Dr. Zelenetz. Other treatment options are chemoimmunotherapy for more advanced disease or a combination of Rituxiban and cytotoxic drugs such as prednisone or doxorubicin. Radiotherapy may also be prescribed if a polymorphic lesion is localized. Participation in a clinical trial is also encouraged as an alternative for patients with persistent disease

http://www.cancernetwork.com/practice/content/article/10165/1832277

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