Minimal data are available on outcomes of second allogeneic hematopoietic stem cell transplantation from unrelated donors after a first transplant in patients with hematologic relapse of acute leukemia. In a study reported in Journal of Clinical Oncology, Maximilian Christopeit, MD, of University Hospital Halle, Germany, and colleagues in the German Registry for Stem-Cell Transplantation and the Cooperative German Transplant Group evaluated the role of second allogeneic stem cell transplant for relapsed acute leukemia after related or unrelated first transplant and analyzed the effect of donor change on second transplant outcome in both settings.1 They found that the second stem cell transplant produced 2-year overall survival of 25% among all patients and that donor change had neither a beneficial nor detrimental effect on overall survival.
The study involved 179 consecutive patients receiving a second allogeneic stem cell transplant for acute leukemia relapse after a first allogeneic transplant in Germany between 1998 and 2009. Median age at second transplant was 39 years (range, 16–68 years). Patients had acute myeloid leukemia (n = 132), acute lymphoblastic leukemia (n = 46), or unclassified leukemia (n = 1).
Donors at first transplant consisted of 75 matched related donors and 104 unrelated donors. At second transplant, 133 patients (74%) had unrelated donors. After related first transplant, a second transplant was performed from the same matched related donor in 51% of patients, a different matched related donor in 11%, and an unrelated donor in 39%. After unrelated first transplant, 42% received a second transplant from the same unrelated donor and 58% from a different unrelated donor.
Patient demographic and clinical characteristics were well balanced among patients receiving a first transplant from a matched related donor vs an unrelated donor, except that patients with unrelated first transplant received less total-body irradiation (P = .013), more in vivo T-cell depletion (P < .001), and more peripheral blood stem cell grafts (P = .007). At second transplant, patients with a related first transplant had more cyclosporine-based immunosuppression (P = .037) and less in vivo T-cell depletion (P = .02).
Overall, 78% of patients received chemotherapy and 21% received donor lymphocyte infusions for initial disease control after relapse. Twenty-six percent of patients received second transplant in complete remission.
Outcomes of Second Transplant
Independent of donor, 74% of patients achieved complete remission after second transplant, with half of these patients experiencing another relapse. Overall survival and leukemia-free survival rates after second transplant were 31% and 26% at 1 year and 25% and 21% at 2 years. Two-year overall survival was 39% after related second transplant and 19% after unrelated second transplant.
Long-term survivors were observed even after two unrelated second transplants. Longer remissions after second transplant than after first transplant were observed in 26% of patients. No significant differences in overall or leukemia-free survival were observed between patients with acute lymphoblastic leukemia and those with acute myeloid leukemia.
Overall survival from second transplant was greater in patients with related vs unrelated first transplant (2-year overall survival 37% vs 16%, hazard ratio [HR] = 1.53, P = .016). Independent of donor at first transplant, overall survival was longer after related vs unrelated second transplant (2-year overall survival 39.5% vs 19%, HR = 1.56, P = .03).
On univariate analysis, donor change (identical vs alternative door) slightly but nonsignificantly improved overall survival from second transplant (HR = 0.76, P = .114). There was no significant effect of donor change on overall survival on multivariate analysis (HR = 0.984, P = .933).
Outcomes by Related/Unrelated First Transplant
Among patients receiving first transplant from a matched related donor, 2-year overall survival and leukemia-free survival rates after second transplant were 37% and 31%, respectively. Donor change was not associated with better outcome (HR = 0.80, P = .449), although among patients receiving second transplant from a different matched related donor (n = 8), estimated 2-year overall survival was 88% (HR = 4.17, P = .048).
No difference was found between overall survival after second transplant from the same matched related donor and overall survival after second transplant from a new unrelated donor (2-year overall survival 34% vs 28%, HR = 1.02, P = .891). On multivariate analysis, donor change was not associated with overall survival (HR = 0.81, P = .512).
Among patients receiving first transplant from an unrelated donor, 2-year overall and leukemia-free survival rates after second transplant were 16% and 13%, respectively. On univariate analysis, change of donor at second transplant was associated with superior overall survival (estimated 2-year overall survival 11% for identical unrelated donors vs 20% for different unrelated donors, HR = 0.63, P = .037). This advantage was limited to patients without acute graft-vs-host disease greater than grade 2 and chronic graft-vs-host disease. On multivariate analysis, however, change to another unrelated donor was not significantly associated with overall survival (HR = 1.34, P = .245).
Multivariate analysis for overall survival from second transplant confirmed the significant effect of established risk factors, including remission duration after first transplant (HR = 2.37, P < .001) and stage at second transplant (HR = 0.53, P = .006).
The investigators concluded: “After relapse from allogeneic [first hematopoietic stem cell transplantation, a second transplant] can induce 2-year overall survival in approximately 25% of patients. Unrelated [second transplant] is feasible after related and unrelated [first transplant]. Donor change for [second transplant] is a valid option. However, a clear advantage in terms of overall survival could not be demonstrated.” ■
Disclosure: For full disclosures of the study authors, visit jco.ascopubs.org.
1. Christopeit M, Kuss O, Finke J, et al: Second allograft for hematologic relapse of acute leukemia after first allogeneic stem-cell transplantation from related and unrelated donors: the role of donor change. J Clin Oncol. August 5, 2013 (early release online).
Disease recurrence is a devastating event after allogeneic hematopoietic stem cell transplantation as treatment for acute myeloid leukemia (AML). Median time to relapse is approximately 4 months and the majority of relapses occur within 2 years after transplant. The prognosis is usually poor....