Potential Cure For Lymphoma In HIV Patients

Because of the immunodeficiency associated with HIV, HIV-positive Patients are more likely to develop lymphoma than HIV-negative individuals, and the treatment for their cancer is far less likely to be successful.

Sonali Smith, M.D., Assistant Professor of Medicine at the University of Chicago notes, "The treatment of malignant lymphomas in HIV-infected individuals remains challenging, due to both the high incidence of refractory disease and the high risk of treatment-related complications. The ability of high dose chemotherapy as demonstrated in this pilot study to effectively treat even refractory disease is highly encouraging and certainly warrants further study."

Researchers from the City of Hope Cancer Center studied 20 Patients (aged 11 to 68) who had HIV and lymphoma, either Hodgkin's or non-Hodgkin's. The selected Patients had undergone previous standard-dose frontline chemotherapy for their lymphoma, but the majority either failed to achieve a complete remission or had relapsed after an initial remission. The median length of study follow-up was approximately two and a half years, with a range of about six months to six years.

All study Patients were to undergo autologous stem cell rescue. In an autologous transplant, stem cells are removed from the patient and frozen for later use. The patient receives high-dose chemotherapy to kill any lymphoma in the body, and the autologous stem cells are then infused back into the patient to repopulate the bone marrow wiped out by the chemotherapy.

Before the transplant, Patients were given one of two conditioning regimens, either high dose chemotherapy alone or in combination with radiation therapy, to destroy the cancerous cells. Most (17 Patients versus three) received the chemotherapy-only option. Radiation therapy was selected for Patients younger than 55 who had poorer prognostic factors: either the cancer had spread to multiple lymph nodes or the patient had bulky disease (indicated by a cancerous mass greater than 5 – 10 cm).

Reversible abnormalities in liver function, a side effect of the intensive treatment, were experienced in a majority of the Patients. One patient, the oldest in the study, developed cardiomyopathy (a weakening of the heart) and kidney failure due to treatment toxicities and died a few weeks after the transplant. Opportunistic infections, such as herpes zoster and cytomegalovirus infection, also occurred in a few Patients after the transplant, but were managed with appropriate therapy.

Throughout the study, all Patients were to receive highly active antiretroviral therapy (HAART) to help reduce these opportunistic infections and improve immunodeficiency, however, only nine Patients were able to tolerate this treatment for the entire study due to side effects such as nausea and inflammation of the mouth lining. The majority of Patients, though, did resume the HAART therapy soon after discharge from the hospital.

Although two Patients died of relapsed lymphoma a few months after transplant, 17 of the 20 Patients (85 percent) are currently alive and in remission. In addition, the underlying HIV infection did not worsen as a result of the transplant and associated treatments.

"The results of this study are significant because, despite the use of effective antiviral drugs such as HAART, lymphoma is still a major cause of suffering and death in HIV-infected individuals. It's important to know that stem cell transplant is an available and highly successful treatment option for these Patients," said Amrita Krishnan, M.D., a staff physician at the City of Hope Cancer Center and lead author of the study.

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This work was supported in part by United States Public Health Service Grants CA30206, CA33572, AI38592, and MO1 RR-43 from the General Clinical Research Center branch of the National Center for Research Resources, National Institutes of Health. Amrita Krishnan, M.D., was the recipient of a Lymphoma Research Foundation of America Fellowship Award. Co-author Arturo Molina, M.D., was the recipient of an American Cancer Society Clinical Oncology Career Development Award.

The American Society of Hematology (http://www.hematology.org) is the world's largest professional society concerned with the causes and treatment of blood disorders. Its mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems, by promoting research, clinical care, education, training, and advocacy in hematology.

Blood, the official journal of the American Society of Hematology, is the most cited peer-reviewed publication in the field. Blood is issued to Society members and other subscribers twice per month, available in print and online at http://www.bloodjournal.org.