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Newswise Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. It is the most common acute leukemia affecting adults, and its incidence increases with age. Although AML is a relatively rare disease, accounting for approximately 1.2 percent of cancer deaths in the United States, its incidence is expected to increase as the population ages.

AML has several subtypes, but treatment and prognosis are similar for all subtypes except M3 (acute promyelocytic leukemia), which is treated differently and has a much better prognosis. AML is treated initially with combination chemotherapy aimed at inducing a remission; patients may go on to receive additional chemotherapy or hematopoietic stem cell transplant (HSCT). The latter can be either a bone marrow transplant (BMT) or transplant of blood stem cells isolated from peripheral blood (PBSC). In either case, it involves transplanting cells capable of restoring normal bone marrow function into a patient. Even though peripheral blood stem cells are used nowadays more often than bone marrow stem cells, all HSCT treatments are commonly referred to as bone marrow transplants and many academic institutions and associations still retain the term bone marrow transplant in their names.

An increasing number of patients in need of HSCT are over age 55, but many in this group are ruled ineligible. This is because the high-dose chemotherapy or chemotherapy combined with high doses of radiation used to prepare patients for HSCTstandard therapy for younger patientsare often deemed too harsh even for healthy looking older people. Indeed, in certain indications, more than one-third of patients over 50 treated with standard transplant regimens die as a direct consequence of treatment while almost half still have the leukemia recur.

Since more than half of AML patients are over 65 years old, new tactics are needed. For example, what if a patients existing bone marrow could be prepared prior to the transplant in the process called myeloconditioning in a way that eliminated the need for high-dose chemotherapy? This promising approach is being pursued by Actinium Pharmaceuticals, Inc., a New York City-based biotech company, under the guidance of its Chief Medical Officer, Dragan Cicic, M.D.

The companys approach to cancer treatment is based on combining the cancer-targeting precision of monoclonal antibodies (mAb) with the power of radioisotopes. To this end, it has developed two compounds currently in clinical trials, Iomab-B and Actimab-B.

Actiniums lead compound, Iomab-B, has been successfully harnessed as a myeloconditioning agent in Phase 1/2 trials involving more than 250 patients including cases of incurable blood cancers such as AML resistant to all available therapies. It has demonstrated the ability to prepare such patients for bone marrow transplants when no other treatment was indicated.

Iomab-B is a radioimmunoconjugate consisting of BC8, a novel murine monoclonal antibody, and iodine 131 radioisotope. BC8 was developed at the Fred Hutchinson Cancer Research Center to target CD45, a pan-leukocytic antigen widely expressed on white blood cells but not on other tissues. This antigen makes BC8 potentially useful in targeting white blood cells in preparation for HSCT in a number of blood cancer indications, including AML, chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, Hodgkin disease, Non-Hodgkin lymphomas and multiple myeloma. When labeled with radioactive isotopes, BC8 carries radioactivity directly to the site of cancerous growth and bone marrow while avoiding effects of radiation on most healthy tissues.

With any cancer treatment, success is usually increased when treatment initiates soon after diagnosis. This is especially true when projected survival is only a few months. Waiting for half that time to initiate a therapy can have a serious impact. Very significantly, treatment with Iomab-B prepares a patient for bone marrow transplant in only 10 days, compared to approximately six weeks required with traditional carea potentially vital difference in the face of a fast-evolving cancer.

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Making Bone Marrow Transplants More Accessible for AML Patients with New Therapy