Newswise Doctors at Washington University School of Medicine in St. Louis have shown that a new drug makes chemotherapy more effective in treating acute myeloid leukemia, a cancer of the white blood cells. Instead of attacking these cells directly, the drug helps drive them out of the bone marrow and into the bloodstream, where they are more vulnerable to chemotherapy.

Were usually very good at clearing these leukemia cells from the blood, says Geoffrey L. Uy, MD, assistant professor of medicine and co-first author on the study published in the journal Blood. But its much harder to clear these cancerous cells from the bone marrow.

This combined phase 1 and 2 clinical trial included 52 patients with acute myeloid leukemia (AML) who had relapsed or whose AML was resistant to the standard chemotherapy regimen. In the phase 2 portion with 46 patients, all received the investigational drug, and 46 percent achieved complete remission, meaning no evidence of cancer could be found in the blood or bone marrow after treatment.

In general, we see complete remission rates between 20 and 30 percent, says Uy, who treats patients at the Alivn J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital. But a lot depends on individual patient characteristics.

Indeed, recent genetic studies have shown that mutations leading to AML may differ greatly among patients. But regardless of individual mutations, all of these leukemia cells rely in some way on the protective effects of the bone marrow, according to senior author John F. DiPersio, MD, PhD, the Virginia E. and Sam J. Golman Professor of Medicine.

With DNA sequencing identifying so many mutations that are unique to one patient, it may be very hard to find therapies that work directly on the cancer, says DiPersio, who also treats patients at the Siteman Cancer Center. Instead, we are targeting a common pathway that all leukemic cells are addicted to in this case, the relatively normal environment of the bone marrow.

DiPersio calls the results of this study encouraging and worthy of additional exploration.

If these results are repeated in a larger study, it would be transformative, he says. It would change the standard way we treat these patients we would use this approach with everybody. In addition, the approach of targeting the tumor microenvironment could also be exploited for the treatment of other hematologic and solid tumor malignancies.

Bone marrow protects leukemia cells by inhibiting the cell-suicide response that might otherwise lead AML cells to self-destruct. Although leukemia cells in the bone marrow do not rapidly divide, their stability makes them very resistant to treatment. And while chemotherapy can clear the bloodstream of leukemia for a period of time, these protected cells in the bone marrow may cause the cancer to return.

The drug used in this study, called plerixafor, blocks the leukemia cells from attaching to the bone marrow. Released from their protective environment into the bloodstream, the cells lose the bone marrows survival signals and begin to divide. Rapidly dividing cells are more sensitive to chemotherapy.

Original post:
Drug Makes Leukemia More Vulnerable to Chemo

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