Researchers say NSAIDs can boost stem cells for transplants for cancer patients
The compounds, known as NSAIDs and which include aspirin, ibuprofen and other painkillers, increased the number of stem and progenitor cells harvested from the blood in animal testing and a small human study, according to work published online Wednesday in the journal Nature by a research team led by Indiana University School of Medicine scientists.
Stem cells and their immediate descendants, progenitor cells, are responsible for nearly all of the billions of blood and immune system cells produced in the body each day. Those key ancestor cells spend most of their lives in the bone marrow, where they are destroyed when physicians use high-dose chemotherapy to treat diseases such as multiple myeloma and non-Hodgkin’s lymphoma. So before the bone marrow transplant begins, physicians collect stem and progenitor cells from the blood and then transplant them back to the patient following intensive chemotherapy, restoring the patient’s ability to produce blood and immune system cells.
To increase the numbers of stem and progenitor cells collected, physicians treat patients with proteins called growth factors, which mobilize some stem and progenitor cells to leave the bone marrow and enter the circulating blood. However, up to 40 percent of patients fail to mobilize enough cells to get an optimum dose, potentially reducing transplant effectiveness. The drug Plerixafor is approved to help increase the cell mobilization; however its use can add about $25,000 per patient.
"Researchers have been looking for new, more effective mobilizing agents, and NSAIDS could be those agents, and at a very low cost," said Louis M. Pelus, Ph.D., professor of microbiology and immunology at the IU School of Medicine and principal investigator for the study.
In animal studies, using an NSAID alone increased stem and progenitor cell counts in the circulating blood by four to six times, though the numbers of cells remained small. However, in combination with growth factors, the mobilization of cells was significantly greater than when the growth factors were used alone.
The mobilization effects of the NSAIDs were attributable to their role in blocking the production of Prostaglandin E, the same role that produces NSAIDs' benefits in reducing pain and inflammation.
"We showed that NSAIDS moved these cells out of the bone marrow on their own, and with a greater-than-additive, even synergistic effect, when used in combination with the growth factor that is normally used clinically to mobilize cells," said Dr. Pelus, an investigator with the Indiana University Melvin and Bren Simon Cancer Center.
Moreover, in the animal studies transplanted cells mobilized with NSAID assistance were more effective in repopulating the recipients' bone marrow than were those mobilized with growth factors alone.
In tests on seven healthy human volunteers, NSAIDS alone increased cell mobilization, but no tests using both growth factors and NSAIDS were conducted with the human volunteers.
However, researchers have prepared grant proposals to conduct human clinical trials of the effectiveness of adding NSAIDs to the standard transplant protocols, Dr. Pelus said. The trials would likely use meloxicam, which is less likely to cause gastrointestinal discomfort and bleeding than other NSAIDs, he said.
In addition to Dr. Pelus, investigators contributing to the research were first author Jonathan Hoggatt of the IU School of Medicine and Harvard Medical School; Amber F. Hoggatt of the IU School of Medicine and the University of Illinois at Chicago; Khalid S. Mohammad, Pratibha Singh, Brahmananda R. Chitteti, Jennifer M. Speth, Peirong Hu, Bradley A. Poteat, Kayla N. Stilger, Sherif S. Farag, Magdalena Czader, Carlos H. Serezani, Theresa A. Guise and Edward F. Srour of the IU School of Medicine; Francesca Ferraro, Lev Silberstein, Frankie K. Wong and David T. Scadden of Harvard Medical School; and Ginger L. Milne and Richard M. Breyer of Vanderbilt University.
The research was supported by National Institutes of Health grants HL096305, CA143057, CA069 158, HL1 00402, DK37097, DK07519, HL07910 and HL087735, National Cancer Institute grant P30 CA082709 and a Center of Excellence in Hematology grant P0l DK090948.