Short chemotherapy regimen can control immune disease after some bone marrow transplants

A very short course of the chemotherapy drug cyclophosphamide can not only prevent a life-threatening immune response in some bone marrow transplant recipients, but also can eliminate such patients' need for the usual 6 months of immune suppression medicines commonly prescribed to prevent severe forms of this immune response, according to a new study. Patients receive cyclophosphamide for 2 days after their bone marrow transplant, in addition to two other chemotherapy drugs given before the transplant.

Scientists at Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland, first used cyclophosphamide to prevent severe graft-versus-host disease (GVHD) after bone marrow transplant involving haploidentical or half-matched transplants, a treatment first used in 2000 at the Cancer Center to treat leukemias and other blood cancers. The scientists began to use posttransplant cyclophosphamide in clinical trials of fully matched bone marrow transplants in 2004.

Now, the new multicenter study confirms that posttransplant cyclophosphamide is safe and effective for people who have received fully matched bone marrow transplants. The regimen is described in the Journal of Clinical Oncology (2014; doi:10.1200/JCO.2013.54.0625).

The shortened regimen begins with intravenous busulfan and fludarabine, two chemotherapeutic drugs that wipe out a patient's immune system and prepare his or her body to receive donated marrow. After the transplant, patients receive 2 days of cyclophosphamide to prevent GVHD and rejection of the new bone marrow. Conventionally, most transplant patients receive 6 months of immunosuppressive treatment for that purpose.

The bookended pre- and posttransplant treatments, which have been tested separately in other studies, already had promising track records in controlling cancer and preventing severe GVHD. Those successes led researchers from three hospitals, including Johns Hopkins, to combine the two therapies, said study leader Leo Luznik, MD, of Johns Hopkins.

The new study enrolled 92 patients with high-risk blood cancers. Forty-five of the 92 patients received matched transplants from relatives, while 47 received matched transplants from unrelated donors.

After their transplants, 51% of the patients experienced grades II to IV acute GVHD, the milder form, and 15% percent of the patients experienced the severe forms of acute GVHD (grades III to IV). Only 14% of the patients developed chronic GVHD. A leading cause of post bone marrow transplant deaths, chronic GVHD affects approximately one-half of patients who receive conventional treatments.

Two years after their transplants, 67% of patients were living, and 62% of all patients were cancer-free.

Luznik says he was encouraged by the low rate of chronic GVHD seen with the regimen, noting that the percentages of acute GVHD cases are similar to those seen with the standard 6-month regimen of immunosuppressive drugs. Reducing the posttransplantation treatment to 2 days with cyclophosphamide, he explains, also allows for the earlier integration of other treatments.

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