Impact of MRD and TKI on allogeneic hematopoietic cell transplantation for Ph+ALL: a study from the adult ALL WG of the JSHCT

Abstract

To assess the impact of minimal residual disease (MRD) and tyrosine kinase inhibitor (TKI) administration on allogeneic hematopoietic cell transplantation (allo-HCT) for Ph-positive ALL (Ph+ALL), we retrospectively analyzed data from a registry database for 432 adult Ph+ALL patients in first CR (CR1) who received pre-transplant TKI administration. Negative MRD (MRD(− )) at allo-HCT was achieved in 277 patients. OS in patients transplanted in MRD( − ) was significantly better than that in patients transplanted in MRD(+) (MRD( − ): 67% vs MRD(+): 55% at 4 years; P = 0.001). MRD( − ) at allo-HCT was a significant risk factor for survival along with age at allo-HCT in multivariate analyses. Incidence of relapse in patients transplanted in MRD( − ) was significantly lower than that in patients transplanted in MRD(+) (MRD( − ): 19% vs MRD(+): 29% at 4 years; P = 0.006). In multivariate analyses, MRD(+) at allo-HCT was a significant risk factor for relapse. A post-transplant TKI was administered to 103 patients. In subanalyses regarding the effect of post-transplant TKI administration, post-transplant TKI administration was a significant risk factor for relapse in multivariate analyses (P o0.0001). MRD status at allo-HCT is one of the most important predictive factors for Ph +ALL patients transplanted in CR1.

The Persistence of Minimal Residual Disease in Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia: We Know It's Bad, Now What?

“…More recently, several retrospective studies have shown that MRD positivity measured prior to allogeneic hsct is also predictive relapse in adults with Ph+ ALL [3][4][5]. However, given that these have all been retrospective studies, patient populations, treatment strategies (including those with and without [6].…”

Tyrosine kinase inhibitor prophylaxis after transplant for Philadelphia chromosome‐positive acute lymphoblastic leukemia

“…13,14 Development of the ability to detect minimal residual disease (MRD) far below the level of 5% blast cells has changed the landscape of risk stratification over the last decade. 11,[15][16][17] Several studies have shown that chemotherapy combined with TKI, which gives a higher complete remission (CR) rate and further MRD reduction, enables allogenic HSCT in a larger proportion of patients. 18 Despite the evident benefit of giving TKI before allogenic HSCT, available data regarding the post-transplant use of TKI are limited.…”

Additional Cytogenetic Abnormalities with Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia on Allogeneic Stem Cell Transplantation in the Tyrosine Kinase Inhibitor Era

“…Although several studies have demonstrated the prognostic significance of additional cytogenetic abnormalities (ACAs) in Ph+ ALL [3,22], limited data are available in patients who have received TKI, which might alter the impact of ACAs. In addition, more attention has been paid to the fact that minimal residual disease (MRD), which reflects a deeper molecular response, has been shown to have significant predictive value for relapse over the last decade [15,[24][25][26][27][28]. Therefore, we evaluated the impact of ACAs in patients with Ph+ ALL who received allogenic HSCT in the TKI era, while considering various underlying factors including MRD status.…”