2 days of chemotherapy drug may control immune disease post-transplant
Wednesday, November 05, 2014
A short course of a chemotherapy drug may control life-threatening immune response, according to a new study, and even eliminate transplant patients' need for six months of immune suppression therapy. Patients receive a two-day course of cyclophosphamide after bone marrow transplant surgery in addition to receiving two other chemotherapy drugs before surgery.
Researchers from Johns Hopkins Kimmel Cancer Center first used cyclophosphamide to prevent graft-versus-host-disease (GVHD) in haploidentical patients with an approach initially used back in 2000 to treat leukemia and other blood cancers. In 2004, the scientists began clinical trials testing post-transplant cyclophosphamide in fully-matched bone marrow transplants.
Cyclophosphamide is commonly used, either alone or in combination with other medications, to treat a wide variety of cancers including:
- Hodgkin's lymphoma
- Non-Hodgkin's lymphoma
- Cutaneous T-cell lymphoma (CTCL)
- Multiple myeloma
- Chronic lymphocytic leukemia
- Chronic myelogenous leukemia (CML)
- Acute myeloid leukemia (AML, ANLL)
- Acute lymphoblastic leukemia (ALL)
- Ovarian cancer
- Breast cancer
Physicians also prescribe cyclophosphamide to treat nephrotic syndrome in pediatric cases where the kidney disease does not improve, worsens or returns, and in pediatric cases where the patient experiences intolerable side effects from other medications. Cyclophoshamide is sometimes used as treatment for small cell lung cancer (SCLC), rhabdomyosarcoma and pediatric Ewing's sarcoma.
Cyclophosphamide is an alkylating agent that treats nephrotic syndrome by suppressing the immune system. When used as a treatment for cancer, it works by slowing or stopping cancer cell growth.
The Johns Hopkins researchers described their latest results online in the Journal of Clinical Oncology. The scientists enrolled 92 individuals with high-risk blood cancers. Of those, 45 received matched transplants from relatives, and 47 received matched transplants from unrelated donors. Researchers administered GVHD prophylaxis solely with PTCy at 50 mg/kg/day on post-transplantation days +3 and +4.
After receiving their transplants, just over half of all patients (51 percent) experienced the milder form of acute GVHD (grades II to IV) while 15 percent experienced the more severe grades III and IV of acute GVHD.
Most notably, only 14 percent of patients in the study developed chronic GVHD, which affects about half of all patients who undergo conventional treatment and is a leading cause of death after bone marrow transplants. The study results show that donor relatedness did not affect nonrelapse mortality, disease-free survival or overall survival rates.
The researchers followed up with participants and found that, two years after their transplants, 67 percent of patients in the study were alive and 62 percent of all participants were cancer-free. Patients in complete remission who did not show signs of minimal residual disease had markedly better disease-free and overall survival — at 80 percent each — than did those in remission who did show signs of residual disease.
Leo Luznik, M.D., the lead author of the study and associate professor of oncology at the Johns Hopkins University School of Medicine, said he was encouraged by the low rates of chronic GVHD seen in this study, noting the results of two days on cyclophosphamide are similar to those seen with conventional six-month immunosuppressive drug regimens. Reducing the length of post-transplantation therapies also allows for earlier implementation of other treatments, particularly immunotherapies to eradicate any remaining cancer cells.
The next step is to perform a phase III randomized clinical trial, directly comparing results in patients receiving a two-day course of cyclophosphamide treatment with those receiving the more traditional six-month immunosuppressive therapy or who had engaged in an experimental approach to prevent GVHD.
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