Patients with acute myeloid leukemia (AML) may have a promising new treatment option. Research shows that stem cell transplant from a “half matched” related donor plus chemotherapy results in similar survival as a transplant from an unrelated matched donor. Further more, transplant from a half matched donor lowers the risk of graft-versus-host disease (GVHD). These findings were reported in the journal Blood.
Acute myeloid leukemia is a cancer of the bone marrow (spongy portion found in the middle of bones) and blood characterized by the rapid, uncontrolled growth of immature white blood cells known as myelocytes. The disease is more common in adults than in children; the average age at diagnosis is over 65. Treatment of elderly patients with AML remains unsatisfactory, and most elderly patients die within a months of diagnosis.
Acute myeloid leukemia can be treated with a procedure called an allogeneic stem cell transplant. When leukemia damages your bone marrow, it can no longer make normal blood cells. Treatment with a stem cell transplant delivers healthy stem cells into your body to help your bone marrow work right. When the stem cells come from another person (a donor), the procedure is called an allogeneic stem cell transplant.
Although doctors try to make sure the donor’s immune system closely matches the patient’s, sometimes the donor cells recognize the recipient’s cells as foreign and attack them. This is called graft-versus-host disease and can be a very serious condition.
An alternative procedure called haploidentical stem cell transplant is designed to provide the benefits of stem cell transplant with a lower risk of GVHD. In a haploidentical transplant, doctors transplant cells that aren’t an identical match. These “half matched” cells can come from family members. Parents and children are always a half match for each other, and siblings have a 50% chance of being a half match for each other. In addition to lowering risk of GVHD compared with allogeneic transplant, haploidentical transplant also helps doctors find potential donors more quickly.
To compare outcomes between haploidentical and allogeneic transplants, researchers studied both techniques in patients with AML. They reviewed information from the Center for International Blood and Marrow Transplant Research that included 192 patients who underwent haploidentical transplant and 1,982 patients who underwent allogeneic transplant from a closely matched unrelated donor.
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The patients who received a haploidentical transplant received the chemotherapy drug cyclophosphamide as well as additional treatment to prevent GVHD. Those who received an allogeneic transplant also received treatment to prevent GVHD. Some patients in each group received treatment to severely or completely deplete bone marrow cells (myeloablation), while others received a less aggressive treatment (reduced intensity conditioning regimen).
After 30 days the patients in the haploidentical group who received myeloablative treatment had a slightly lower rate of neutrophil (a type of white blood cell) recovery compared with those in the allogeneic group (90% versus 97%, respectively). Likewise, patients in the haploidentical group with underwent reduced intensity conditioning transplants had lower neutrophil recovery than those in the allogeneic group (93% versus 96%, respectively).
Patients who received haploidentical transplants had lower incidence of GVHD compared with the allogeneic treatment group with both myelablation and reduced intensity conditioning regimens. At three months fewer haploidentical patients experienced acute GVHD after myeloablation (16% versus 33%), and at three years fewer haploidentical patients experienced chronic GVHD. Similarly, after reduced intensity conditioning transplants, 19% of haploidentical patients experienced acute GVHD versus 28% of allogeneic patients, and 34% of haploidentical patients experienced chronic GVHD compared with 52% of allogeneic patients.
Survival outcomes between haploidentical and allogeneic transplants were mixed but fairly similar. On the one hand, patients in the haploidentical group who received myeloablative treatment had a slightly lower probability of three-year survival compared with allogeneic patients (45% versus 50%, respectively). On the other hand, however, patients in the haploidentical group on reduced intensity conditioning transplants had a slightly higher probable three-year survival at 46% versus 44%.
Because the haploidentical patients also received cyclophosphamide, these findings suggest that patients with AML who undergo haploidentical transplant followed by cyclophosphamide have a similar survival as patients who get a transplant from a matched unrelated donor. This research may help patients for whom finding a matched unrelated donor is difficult as well as provide an option for stem cell transplant with lower risk of GVHD.
Reference: Ciurea SO, Zhang MJ, Bacigalupo AA, et al. Haploidentical transplant with post-transplant cyclophosphamide versus matched unrelated donor transplant for acute myeloid leukemia. Blood [early online publication]. June 30, 2015.
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