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‘Haplo’ Transplant Valid Option for Patients without Conventional Donors

Carlson, Robert H.

doi: 10.1097/


SAN DIEGO—Patients with high-risk hematological malignancies who lack conventional donors can still achieve excellent relapse-free survival with haplo-identical transplantation using T-cell replete peripheral blood stem cells (PBSCs) and myeloablative conditioning, according to a study presented here at the American Society of Hematology Annual Meeting (Abstract 889). The post-transplant regimen included cyclophosphamide.

Engraftment was achieved by all 20 patients in the study regardless of risk profile, reported first author Connie A. Sizemore, PharmD, Lead PharmD in the Bone Marrow Transplant Program of Northside Hospital in Atlanta.

In a news conference at the meeting about promising transplant-related research, the study's senior author, Scott R. Solomon, MD, Medical Director of the Stem Cell Processing Laboratory and the Matched Unrelated Donor Program at the hospital, said, “What we show is that the outcomes for patients using haplo-identical donors are equivalent to those with fully matched, unrelated donors from the registry.”

The clinical trial enrolled 20 patients with high-risk leukemia or Hodgkin or non-Hodgkin lymphoma who underwent haplo-identical hematopoietic cell transplantation between January 2009 and March 2011. Patients were eligible if they were 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 (45%) had standard-risk disease. The majority of patients were in remission but had poor-risk features such as high-risk cytogenetics, high-grade myelodysplastic syndrome, and resistance to tyrosine kinase inhibitors.

Initial conditioning consisted of fludarabine at 30 mg/m2 at seven days and two days before unmanipulated PBSC infusion; IV busulfan at 130 mg/m2 at seven and four days prior to transplant; and cyclophosphamide at 14.5 mg/kg on days 3 and 2 before transplant.

Sizemore reported that in response to increased rates of mucositis, fludarabine and busulfan doses were decreased by 30% and 15%, respectively, in subsequent patients. Post-grafting immunosuppression consisted of cyclophosphamide at 50 mg/kg/day on days 3 and 4, mycophenolate mofetil, and tacrolimus.

After the administration of the myeloablative preparative regimen, patients underwent transplantation with PBSCs, followed by an immunosuppressive regimen of cyclosporine at 50 mg/kg/day on days 3 and 4 post-transplant along with other supportive therapies.



Donor engraftment occurred in all 20 patients, with a median time to neutrophil and platelet recovery of 16 and 27 days, respectively. All evaluable patients achieved complete donor T cell and myeloid chimerism by day 30 or later.

After a median follow-up of 14 months, the investigators reported an estimated one-year overall survival rate of 74% and a disease-free survival rate of 51% for all patients; for standard-risk patients, the one-year overall survival rate was 100 percent and the disease-free survival rate was 76 percent. The non-relapse mortality rate at 100 days and 12 months was 10 percent for all 20 patients, 18 percent for the 11 high-risk patients, and zero percent for standard-risk patients. The cumulative incidence of chronic graft-versus-host disease (GVHD) at one year was 42 percent.

The cumulative incidence of grades II-IV and grades III-IV acute GVHD was 30% and 20%, respectively. The cumulative incidence of chronic GVHD at one year was 42%.

With a median follow-up of 14 months, the estimated one-year overall and disease-free survival rate was 74% and 51%, respectively, for all patients; 100% and 76%, respectively, for standard-risk patients; and 55% and 33% for high-risk patients.

In an interview, Solomon said it is clear that graft-versus-tumor is preserved in these patients, because these patients are not relapsing at higher rates than one would expect with a matched donor—”And their GVHD rates are very, very acceptable, given the fact that these are completely mismatched donor recipient patients.”

He said he believes that these findings will change the way transplants are done in the future, “because, let's face it, pretty much everybody has a haplo-identical donor, a parent, a child, a sibling.”

“For patients without a matched donor, for patients who can't find a donor in a quick enough time because it's taking too long for a registry search, you can get them to a haplo-identical transplant very quickly and provide them with outcomes that are indistinguishable from what you would see from an unrelated donor.”

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Use of PBSCs, Myeloablative Conditioning Unusual

In a news conference at the meeting that focused on promising transplantation research, the moderator, Stephanie J. Lee, MD, a transplant specialist at Fred Hutchinson Cancer and Professor of Medicine at the University of Washington School of Medicine, noted that this approach is one of many new ones being tested.

What makes this one unusual, though, is that it uses peripheral blood, whereas most haplo-identical transplants in the US have used bone marrow, Lee said by e-mail, elaborating on the point a few weeks after the meeting. The approach also uses myeloablative conditioning, whereas most haplo-identical transplants in the US have used less intense regimens.

She said that because of the small numbers of patients in the study, it is not possible to determine yet whether these two changes actually succeed in improving outcomes by decreasing toxicity and relapse.

The technique “is not ready for prime time, [because] it is not readily available at most centers and most patients would be treated on a clinical trial, but the outcomes reported are in line with what we see using more traditional transplant approaches.”

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Also Consider Cord Blood

Lee said this haplo-identical transplantation technique could be useful in patients who are at higher risk of relapse but are also healthy enough to tolerate the higher dose conditioning, as well as in patients who need a transplant quickly or don't have a readily available HLA-identical sibling or unrelated donor.

These patients could also consider cord blood, she said, noting that there will be a randomized trial between haplo transplant and cord blood soon, sponsored by the Blood and Marrow Transplantation Clinical Trials Network, which will hopefully expand data on the pros and cons of haplo-identical versus cord blood.

© 2012 Lippincott Williams & Wilkins, Inc.
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