Researchers have found that a new preparatory regimen prior to haploidentical hematopoietic stem cell transplantation (HCT) may improve outcomes in patients with high-risk blood cancers who lack a matched donor.

Patients with blood cancers are often treated with HCT, the transplantation of blood-forming bone marrow stem cells, including peripheral blood stem cells (PBSCs), stem cells originally found in the bone marrow that have been moved, or mobilized, into the blood stream.

According to experts, the gold standard for HCT is to have a transplant from a matched donor, but for some patients a matched donor is not available. A haploidentical (partial match) HCT is the next best treatment option, but it comes with higher risk of relapse and non-relapse mortality.

For those patients without a matched donor, past approaches including ex vivoT-cell depletion and myeloablative preparative regimens (intense chemotherapy and/or radiation to help prevent the immune system from attacking transplanted cells) have been associated with high rates of graft rejection, infection, and severe GVHD.

Some progress has been demonstrated recently by using a less aggressive, non-myeloablative preparative regimen, followed by an infusion of unmanipulated bone marrow and the post-transplant use of a common chemotherapy drug, cyclophosphamide (Cy), but relapse is relatively common, especially in those with high-risk myeloid malignancies.

This study sought to determine whether it is possible to decrease the probability of relapse in these high-risk patients by using a myeloablative preparative regimen with PBSCs, instead of bone marrow, as the graft source.

Between January 2009 and March 2011, the investigators initiated a clinical trial enrolling 20 patients with high-risk blood cancers, including leukemia and both Hodgkin and non-Hodgkin lymphoma, undergoing haploidentical HCT.

Participants were eligible for the trial if they were perceived to be at a high risk of relapse using a less aggressive preparative regimen following transplantation. Eleven patients (55%) had relapsed or refractory disease, while the remaining nine patients (45%) had standard-risk disease, the majority being leukemia patients in remission but associated with poor-risk features.

After the administration of the myeloablative preparative regimen, patients underwent transplantation with PBSCs, followed by an immunosuppressive regimen of Cy (50mg/kg/day) on days three and four post transplant along with other supportive therapies.

After an average follow-up of 14 months, investigators reported an estimated one-year overall survival rate of 74 percent and a disease-free survival (DFS) rate of 51 percent for all patients; for standard risk patients, one year overall survival was 100 percent and DFS was 76 percent. Non-relapse mortality at 100 days and 12 months was 10 percent for all patients and zero for standard risk patients. The cumulative incidence of chronic GVHD at one year was 42 percent.

Non-infectious fever developed in 90 percent of patients within a median of 2.5 days of transplant and was resolved by day six following post-transplant administration of Cy. Viral cystitis (viral infection of the bladder) occurred in 75 percent of patients and was severe in 35 percent of patients. Other severe infections were not seen at increased frequency compared to conventional donor myeloablative transplants conducted at the transplant center.

“The results of our study demonstrate that haploidentical HCT using this unique pre- and post-transplant conditioning regimen is associated with improved rates of engraftment, GVHD, non-relapse mortality, and disease-free survival, making it a potentially important option to help improve outcomes in patients with high-risk malignancies who may not have a matched donor,” said senior author Scott R. Solomon, MD, Medical Director of the Stem Cell Processing Laboratory and the Matched Unrelated Donor Program at Northside Hospital in Atlanta. 

“With the exception of viral cystitis, post-transplant toxicity was manageable and similar to what might be expected with any myeloablative transplant regimen in high-risk patients.

Future studies aim to reduce the incidence of viral cystitis, which, although not life-threatening, can be a significant problem for patients.”