Minimal Residual Disease Detected Prior to Transplantation Is Associated with Adverse Outcome in Pediatric Acute Lymphoblastic Leukemia.

Background: Acute lymphoblastic leukemia (ALL) is the most common form of malignancy in children. Advances in treatments have made ALL the disease highly curable; however for those patients who relapse, hematopoeitic stem cell transplantation (HSCT) offers a reasonable chance of cure. Minimal residual disease (MRD) detection by Multiparametric Flow Cytometery (MPF) is being used for risk adapted treatment decisions in many ALL trials. We present a series of 31 pediatric ALL patients who had morphologic and MPF evaluation of disease burden prior to ablative HSCT.

Methods: Thirty one patients were treated at Children’s Hospital and Regional Medical Center, Seattle, WA for relapsed or very high risk ALL, were in complete morphologic remission, and received an ablative HSCT from May 2006-May 2008. Twelve patients were in second or third complete remission (CR) and 19 were in first CR. Eleven patients received a matched related donor, 20 patients received a unrelated donor graft. All patients underwent marrow evaluation including morphology and MPF within four weeks of their transplant date. The MPF was done by 7 or 9 color flow cytometry using the following reagents for B lineage: CD10, CD19, CD20, CD34, CD38, CD58 and CD45 and for T lineage: CD2, CD3, CD4, CD5, CD7, CD8, CD34, CD56, and CD45. Transplant regimens were total body irradiation-based (1320 cGy) with either cyclophosphamide (n=24) or fludarabine (n=6). MRD+ was any detectable leukemia >0.01% of cells. All patients were in morphologic remission (< 5% blasts) at time of transplant. Events were defined as relapse or deaths.

Results: 21 patients were MRD-, 10 were MRD+. The 2 year event free survival (EFS) for the entire group was 56% (+/−22%). The EFS at 20 months for those patients in CR1 and CR2/3 were 62% (+/−32%) and 40% (+/−32%), respectively. EFS, relapse risk and non relapse mortality was analyzed with respect to MRD status:

Discussion: We present a single institution series of patients treated for high risk or relapsed ALL who underwent disease evaluation prior to HSCT with MPF. With the small number of patients evaluated, it appears that any amount of disease detected by MPF was an adverse risk factor for recurrence. Those patients who were MRD+ experienced a higher risk of death from relapse, however, experienced no difference in non-relapse mortality. Resistant disease as detected by MRD analysis at time of transplant is a marker for poor outcome.