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JCO Exclusive: Sibling Transplants Versus Unrelated Donor in Young Patients with ALL

Mar 09, 2015

By Shira Klapper, Senior Writer/Editor

For children and adolescents being treated for acute lymphoblastic leukemia (ALL), those who receive a stem-cell transplant from an unrelated donor have the same overall survival (OS) as those who receive the transplant from a sibling. That’s according to a new Journal of Clinical Oncology (JCO) study, “Stem Cell Transplantation in Children with Acute Lymphoblastic Leukemia: A Prospective International Multicenter Trial Comparing Sibling Donors with Matched Unrelated Donors,” which looked at 411 young patients with ALL.

Among the 411 patients, 105 received transplants from siblings and 306 received transplants from unrelated donors with whom they shared a 9/10 or 10/10 Human leukocyte antigen (HLA) match; HLA is a protein on the surface of cells which indicates whether a transplant will be accepted. The source of the stem cells was either bone marrow or peripheral stem cells. All patients were conditioned beforehand with total body irradiation and etoposide.

According to first author, Christina Peters, MD, the study, published online, ahead of print, March 9, 2015, is the first prospective study to compare the two types of allogenic transplants—sibling versus nonrelated donor—among this ALL population. One of the study’s strong points is that all patients received the Berlin-Frankfurt-Munster chemotherapy regimen, allowing for a more robust comparison between groups. The study was carried out in Germany, Austria, and Switzerland, and based on its success, is now being carried out in several European countries.

Good news for high-risk patients who do not match with siblings

The children and adolescents in the study all had high-risk ALL and were in a first or later remission. While the majority of children with ALL are cured with chemotherapy, “high risk” patients are not; for these patients, allogeneic hematopoietic stem cell transplantation (HSCT) is the standard of care and involves transplanting stem cells from a sibling or unrelated person into the patient. The goal is to replace the patient’s blood cells with healthy, noncancerous ones and to provide a so called “graft-versus-leukemia effect,” in which donor T cells target malignant residual host T cells.

But until this current JCO study, all prospective studies showed a greater mortality rate among these high-risk patients after transplants from nonrelated donors, compared with siblings. “When we initiated our trial in the year 2002, transplant from an unrelated donor was still associated with nonrelapse mortality between 20% and 30%, compared with the safer transplantation from sibling donors, in which mortality was around 10%,” said Dr. Peters. “So, our primary goal was to improve the outcome for those children who did not have sibling donors, a group that constitutes 20% to 25% of children who receive allogenic HSCT.”

According to Dr. Peters, several factors likely contributed to the high overall survival (OS) among patients in this study who received transplants from unrelated donors. First, all patients in this groups had a 9/10 or 10/10 match in HLA. Second, patients received an intensive immunosuppression including ATG plus contemporary supportive care, and third, all transplants were carried out in highly experienced centers.

Overall survival is the same, but some differences exist

Similar to OS, there were no differences between the two groups in terms of event-free survival, defined as the absence of relapse, secondary malignancy, or death from any cause. There were also no significant differences between the two transplant groups in terms of the rate of graft-versus-host disease.

However, differences between groups were present: patients who received transplants from unrelated donors experienced engrafment, the biological process in which new blood-forming cells start to grow, five to 10 days later than those who received sibling transplants. In addition, those in the unrelated donor group had a significantly higher rate of severe infections, tending towards pulmonary complications. No differences in outcomes were found between those with 9/10 and 10/10 HLA matches. Furthermore, the low rates of severe, chronic GVHD—which can be a devastating disease for children—did not translate into a higher incidence of relapse.

For Dr. Peters, these are exciting outcomes. “This data shows that we can now make allogenic stem cell transplantation possible for the majority of high-risk patients who do not have sibling donors.” 


Christina Peters, MD, is a Professor of Pediatrics in the Department of Stem Cell Transplantation at St. Anna Children’s Hospital, in Vienna, Austria.


 

 


Abstract of the original JCO article. 

 


PDF of the original JCO article.
 

Peters C, Schrappe M, von Stackelberg A. Stem cell transplantation in children with acute lymphoblastic leukemia: a prospective international multicenter trial comparing sibling donors with matched unrelated donors. J Clin Oncol. Epub 2015 March 9.


The Exclusive Coverage series on ASCO.org highlights selected research from JCO and JOP with additional perspective provided by the lead or corresponding author.

@ 2014 American Society of Clinical Oncology

 

 

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