City of Hope physicians and scientists have their hands in every aspect of hematologic cancers, from their biological mechanisms to their community impact.
And in case anyone was wondering about it, the recent American Society of Hematology conference confirmed the breadth of their work.
Among the many findings they presented at the December meeting:
- They showed that patients’ own blood stem cells can be genetically re-engineered to be HIV resistant and may lead to a future drugfree treatment for HIV.
- They discussed a medication from an up-andcoming class of drugs that offers potential benefits for relapsed lymphoma patients.
- Another study reviewed health-related disparities among Latino bone marrow transplant survivors, providing important insight into the role of cultural differences and language barriers in this understudied population.
 Amrita Krishnan (Photo by Walter Urie) |
Anti-HIV gene therapy
Amrita Krishnan, M.D., director of the Multiple Myeloma Program in the Department of Hematology & Hematopoietic Cell Transplantation (HCT), presented data on a gene therapy treatment for HIV-positive patients with AIDS-related lymphoma that could potentially treat both the cancer and the HIV infection.
Four patients in the study underwent autologous hematopoietic stem cell transplantation in which their own blood stem cells were harvested and genetically re-engineered with three anti-HIV genes that encode small RNAs (ribonucleic acid, a form of genetic information) that block HIV from infecting new cells.
Autologous HCT is a standard treatment for high-risk lymphomas and uses high doses of chemotherapy to wipe out cancerous and healthy cells in the bone marrow before patients’ stem cells are reintroduced. For people who are HIV-positive and have related lymphomas, transplantation may send lymphoma into remission, but the underlying HIV infection remains.
City of Hope researchers John J. Rossi, Ph.D., Lidow Family Research Chair and chair of the Department of Molecular Biology, and John A. Zaia, M.D., Aaron D. and Edith Miller Chair in Gene Therapy and chair of the Department of Virology, came up with a strategy to fight the virus as part of the transplant procedure. They are testing genetically engineered anti-HIV RNAs developed by Rossi.
Researchers incorporate these RNAs into patients’ harvested stem cells. After patients receive their transplant, their engineered stem cells spawn new, HIV-resistant blood cells. That aims to prevent HIV from infecting new cells and replicating.
Blood and bone marrow in patients who received the genetically altered, HIV-resistant stem cells show evidence that the cells successfully engrafted.
“If we can develop this approach in a way that could be applied to other AIDS patients,” said Krishnan, “then genetic therapy for HIV could become a reality.”
Drugs for relapsed lymphoma
 Mark H. Kirschbaum (Photo by Vanessa Preziose) |
Mark H. Kirschbaum, M.D., director of new drug development in the Department of Hematology & HCT, presented data on vorinostat, an oral drug that shows promise in treating patients whose lymphomas have relapsed after treatment.
The results were particularly exciting because the drug may be an option for patients with indolent non-Hodgkin’s lymphoma. This lymphoma generally is diagnosed at late stages, frequently relapses and is considered incurable. Vorinostat, which currently is approved only for cutaneous T-cell lymphoma, would significantly add to physicians’ arsenal against this form of lymphoma.
Patients in the phase II trial tolerated the drug well. Of 26 patients who took the drug, 10 patients achieved complete or partial remission.
The 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 that possibility of greater efficacy with less toxic side effects.”
Disparities in outcomes after transplantation
English-speaking Latino survivors of bone marrow transplantation are less likely than Latinos who primarily speak Spanish to report having severe or life-threatening health conditions in the years after transplant, according to Saro Armenian, D.O., M.P.H., assistant professor in the Department of Population Sciences.
These conditions may include congestive heart failure, renal failure or stroke.
The survey of nearly 1,500 survivors was the first to examine the chronic disease burden in Latino long-term HCT survivors.
 Saro Armenian (Photo by Liton Francisco) |
Armenian and colleagues found that Englishspeaking Latinos were less likely to report having life-threatening conditions, while those who used the Spanish version of a detailed 250-item questionnaire were more likely to report these problems compared to white transplant survivors. This difference persisted even after taking into account socioeconomic status, age and other important factors.
The research suggests that disparities in healthrelated knowledge among Latinos may be as much a function of language proficiency as it is about well-described barriers like education, socioeconomic status and health-care access.
“The study identifies the critical role of language in health-related knowledge for this growing population of survivors, and underscores the critical need for culturally adapted awareness of health-care needs and issues,” said Armenian.
The National Cancer Institute funded the collaborative study involving City of Hope and the University of Minnesota. Smita Bhatia, M.D., M.P.H., chair and professor of the Department of Population Sciences and director of the Center for Cancer Survivorship, was principal investigator.
“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 survival rates in this high-risk survivor population,” Armenian added.