Allogeneic Transplantation for Minimal Residual Disease Negative Acute Lymphoblastic Leukemia According to 2016 Who Classification: A Single Center Retrospective Analysis
Authors: Cao Xingyu , Liu Deyan , Zhang Jianping , Wei Zhijie , Xiong Min , Lu Yue , Zhao Yanli , Zhou Jiarui , Sun Ruijuan , Liu Hongxing 
Published: October 2019

Abstract
The level of minimal residual disease (MRD) is one of the most important prognostic indicators for acute lymphoblastic leukemia (ALL). In this study, the data about 390 cases of ALL patients who obtained MRD negative after chemotherapy or CART therapy underwent allogenic hematopoietic stem cell transplantation (HSCT) in our center were retrospectively analyzed. The MRD was detected by flow cytometry or molecular methods such as fusion genes or gene mutations. 235 were males and 155 were females. Median age was 15 years old (range 2-64). According to 2016 WHO classification, the diagnosis were Pro-B-ALL(n=24), Common B-ALL(n=113), Pre-B-ALL(n=17), Hyperdiploid (n=8), BCR-ABL positive B-ALL(n=51), MLL rearranged B-ALL (n=19), TEL-AML positive B-ALL (n=13), E2A-PBX B-ALL (n=16), BCR-ABL1-like B-All (n=4), Pro-T-ALL(n=8), Pre-T-AL(n=21), Cortical T-ALL(n=17), Medullary T-ALL (n=6) and ETP T-ALL(n=1). Other 5 patients have complex karyotypes and 67 patients cannot be grouped because of absence complete information about immunophenotypes or genetic profiles. Total number of B-ALL was 295 (54 of which received CART therapy before transplant.) and T-ALL was 92. Another one was T-B mixed lineage and remaining two's lineages was unknown. 14% of the patients had sibling identical donors (n=54), 66% of the patients had haplo-identical relative donors (n=258) and others are unrelated donor (n=77) or cord blood (n=1) transplantation. Disease status before transplant are CR1 (n=228), CR2(n=134) and ≥CR3(n=28). MNC dose was 8.30(2.50-22.60)×108/kg, CD34+cells dose was 4.51(0.89-19.61) ×106/kg and CD3+cells was 1.58(0.01-37.63) ×108/kg. Preparative regimens were based on TBI (n=352) or Bu (n=38). The median time to neutrophil and platelets engraftment was 14 and 12 days. Five-years OS and disease-free survival (DFS) for all patients were 71.7% and 71.1% . Univariate analysis showed difference of impact on overall survival about the patient' gender, age, T or B immunotype, WHO classification, whether or not receiving CART therapy before transplant, conditioning regimen based on TBI or Bu, years of transplant, and time from diagnosis to transplant (≤1year, >1year, ≤2year, >2year, ≤3year, >3year) was not statistically significant. 5-ys OS for CR1, CR2, >CR2 were 77.4%, 60.9%, 67.8% (p=0.0018). Five-years OS for sibling-identical , unrelated donor and haplo-identical transplant were 74.8%, 68.8% and 79.6% (p=0.026). The incidence of gradeⅠ-Ⅱ aGVHD and grade Ⅲ-ⅣaGVHD within 100 days were 1.5% and 2.1%. Limited cGVHD was 10.3% and extensive cGVHD was 9.2%. 5 years cumulative relapse rate was 12.2%. In summary, when MRD were negative before transplantation, the result of allo-HSCT for ALL is good. The factors affecting the survival rate are disease status and interval between diagnosis and transplant time rather than gender, age, WHO classification, immunotype, whether or not receiving CART therapy and conditioning regimen.

Disclosures
No relevant conflicts of interest to declare.