DUARTE, Calif., December 9, 2008 — A patient’s own blood stem cells can be genetically re-engineered to be HIV resistant and may lead to a future drug-free treatment for HIV. A drug designed to block certain genes from functioning offers potential benefits for relapsed lymphoma patients. A study reviewing health disparities among Hispanic long-term cancer survivors reveals that health-care providers need to be more cognizant of cultural differences and language barriers. These are among the studies being presented by City of Hope researchers during the 50th annual American Society of Hematology (ASH) conference in San Francisco from Dec. 6 to 9.
Research Highlights include:
“First in Human Engraftment of Anti-HIV Lentiviral Vector Gene Modified CD34+Perpheral Progenitor Cells in the Treatment of AIDS Related Lymphoma (ARL)”
ASH Abstract #2348
City of Hope clinical researcher Amrita Krishnan, M.D., director, Multiple Myeloma Program, and associate director, medical education and training, Department of Hematology & Hematopoietic Cell Transplantation, will present data on a promising gene therapy treatment for HIV positive patients with AIDS-related lymphoma that could potentially treat both the cancer and the HIV infection. Five patients underwent autologous hematopoietic cell transplantation (HCT) in which their own blood stem cells were harvested and genetically re-engineered with three anti-HIV proteins that block HIV from infecting new cells. A standard treatment for high-risk lymphomas, autologous HCT, allows the delivery of high doses of chemotherapy that wipe out cells in the bone marrow. Although the lymphoma may be put into remission, the underlying HIV infection still remains for HIV-positive patients. Patients are kept on lifelong antiretroviral therapy, but resistance to these drugs often can occur. The genetically engineered anti-HIV proteins, which were developed by City of Hope’s John Rossi, Ph.D., Lidow Family Research Chair and chair and professor, Molecular Biology, offer the potential for the patients to produce HIV-resistant blood cells thereby preventing the HIV virus from infecting new cells and replicating. Five patients received high dose chemotherapy and four of them received the genetically altered stem cells. Post transplant, their blood and bone marrow have demonstrated the presence of these genes which suggest that the genetically altered HIV resistant stem cells successfully engrafted.
“These are very exciting results for our first-in-human trials,” said Krishnan. “We can graft cells into AIDS patients that have the potential to limit the HIV infection. If we can develop this approach in a way that could be applied to other AIDS patients, then genetic therapy for HIV could become a reality.”
A Phase ll Study of Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) in Relapsed or Refractory Indolent Non-Hodgkin’s Lymphoma. A California Cancer Consortium Study
ASH Abstract #1564
An estimated 66,120 adults in the U.S. will be diagnosed with non-Hodgkin’s lymphoma in 2008, according to the American Cancer Society. Indolent non-Hodgkin’s lymphoma tends to be diagnosed at late stages, and despite standard chemotherapy, patients often relapse. A study led by City of Hope’s Mark H. Kirschbaum, M.D., director of new drug discovery in the Division of Hematology & HCT, and associate member, Hematologic Malignancies Program, Comprehensive Cancer Center, reveals that Vorinostat, an oral anticancer agent that alters gene expression, shows promise in treating patients whose lymphomas have relapsed or refracted after prior treatment. Vorinostat, currently approved for only cutaneous T cell lymphoma, was well-tolerated in the patient population, with the most common side effects reported as dizziness, fatigue and diarrhea. Of the 26 patients with relapsed lymphoma, 10 patients achieved complete or partial remission. The phase II study was conducted in collaboration with the National Cancer Institute through the California Cancer Consortium.
“We have an epigenetic agent that is showing promising activity in diseases that progressed after chemotherapy,” said Kirschbaum. “Vorinostat has potential as a targeted therapy that offers the possibility of greater efficacy with less toxic side effects.”
“Differential Morbidity by Ethnicity in Long-term Survivors of Hematopoietic Cell Transplant: A Report From the Bone Marrow Transplant Survivors Study”
ASH Abstract #454
Hispanics are the largest ethnic minority in the U.S., comprising nearly 15 percent of the population. Compared to non-Hispanic whites, Hispanics are at a higher risk for adverse health-related outcomes due to socioeconomic, cultural and language barriers as well as barriers within the health-care system. According to the Center for International Blood and Marrow Transplant Research, Hispanics have the poorest survival rate of all ethnic groups following HCT. In the first study to describe the chronic disease burden in long-term Hispanic survivors of HCT, Saro Armenian, D.O., M.P.H., assistant professor, Department of Population Sciences at City of Hope, will present data that suggests Hispanics are less likely to report having many life-threatening conditions such as congestive heart failure, renal failure or stroke following their transplantation. English-speaking Hispanics were least likely to report having a medical condition while those who used the Spanish version of a detailed 250-item questionnaire were more likely to report these complications. The study suggests that disparities in health-related knowledge in Hispanics may be as much a function of language proficiency as it is about well-described barriers such as education, socioeconomic status and health-care access. These findings are from a collaborative effort between City of Hope and University of Minnesota, funded by the National Cancer Institute, evaluating health-related outcomes in nearly 1,500 long-term survivors of HCT. Outcomes of interest include medical late effects, medication use, socioeconomic indicators, insurance coverage, pregnancy history and health screening practices. (The study’s principal investigator was Smita Bhatia, M.D., M.P.H., chair and professor, population sciences, and director, Center for Cancer Survivorship at City of Hope.)
“This study identifies the critical role of language in health-related knowledge for this growing population of cancer survivors, and further underscores the critical need for culturally adapted awareness of health-care needs and issues among these survivors,” said Armenian. “Information obtained may be used to develop culturally competent intervention strategies to minimize disparities in health-care access and health-related knowledge, and potentially improve the long-term morbidity and mortality in this high-risk survivor population,” he added.
