Molecular Studies in Early Detection of Minimal Residual Disease (MRD) of B Lymphoblastic Leukemia (B-ALL) Status Post Allogeneic Hematopoietic Stem Cell Transplant (Allo-Hsct) Correlated with Risk of Relapse
Panagiotis Pantazopoulos, Ling Zhang, Kaaron Benson, Dahui Qin, Lynn Moscinski, Pedro Horna. University of South Florida, Tampa, FL; Moffitt Cancer Center, Tampa, FL
Background: Detection of MRD in B-ALL remains a diagnostic challenge. Immunophenotypic and molecular testing is critical in the evaluation of post-transplant bone marrow biopsies to assess for early recurrent disease. RT-PCR for BCR-ABL1 fusion transcript is a sensitive way to detect Philadelphia chromosome positive B-ALL (ph+ ALL), while B-cell gene rearrangement (B-GR) testing is an alternative method used in the detection of B-ALL lacking disease specific cytogenetic or molecular markers. This study aims to evaluate the molecular diagnostic strategies in B-ALL post HSCT and determine its significance for MRD assessment and risk of relapse.
Design: Sixty one bone marrow biopsies from 30 patients diagnosed with B-ALL, post allo-HSCT, were included in the study and followed for relapse of disease. The laboratory evaluation included flow cytometry, B-GR studies, morphologic, chromosomal and engraftment analyses, FISH and RT-PCR for BCR-ABL1, where applicable.
Results: All 61 bone marrow biopsies were obtained post allo-HSCT with a median follow up of 29 months. 14 of 30 patients (47%) had ph+ ALL at diagnosis. Of these patients, 6 (43%) had relapsed at 3 to 36 months post-transplant by positive molecular testing. The molecular tests with the most prognostic/diagnostic lead time was p210/p190 RT-PCR (4 of 14 patients), followed by qRT-PCR (1 of 14 patients) with 9.6 and 8.3 months respectively. Of note, 5 of the 6 patients diagnosed with molecular MRD progressed to morphologic relapse with a lead time median of 0.23 months. FISH (BCR-ABL-1) and B-GR studies (igh and igl) were negative in all 14 patients, before diagnosis of morphologic relapse for ph+ B-ALL. B-GR studies showed a clonal population in 4 of 7 studies from 3 patients with a history of BCR-ABL1-negative B-ALL. Two of these patients progressed to morphologic relapse 0.9 and 1.8 months later. The remaining patient had no evidence of morphologic relapse after 22 months. A correlation between time-matched, molecular relapse and post-transplant engraftment analysis of CD3 and CD33 sorted donor cells, showed no significant loss of donor cells.
Conclusions: RT PCR for BCR-ABL transcripts is one of the most reliable indicators of imminent relapse in patients with t(9;22) B-ALL. Positive B-GR and FISH studies may be indicative of imminent relapse, when interpreted in conjunction with flow cytometry to assess for adequate levels of B lymphoid cells for analysis.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 228, Monday Morning