Complete remission with incomplete count recovery (CRi) prior to allogeneic HCT for acute myeloid leukaemia is associated with a high non-relapse mortality

Abstract

Consolidation of chemotherapy with allogeneic haematopoietic cell transplantation (HCT) improves outcome in a large proportion of patients with acute myeloid leukaemia (AML) by reducing relapse risk and improving survival [1]. Disease response is a powerful predictor of outcome, and is incorporated into standard risk stratification models such as the EBMT score [2]. However, it is becoming increasingly clear that the group of patients categorised as complete remission (CR) encompasses a heterogenous population. The European LeukemiaNET (ELN)-2017 response criteria recognise this, and permits further subclassification of CR patients into CRMDRfor those with undetectable measurable residual disease (MRD), as well as CRi for those in remission but with incomplete haematologic recovery [3]. The impact of MRD in AML is established [4, 5] and its impact on HCT outcome has recently been shown [6, 7], however, the impact of incomplete count recovery is less clear, and unknown in the setting of HCT. We therefore compared the outcomes of patients undergoing HCT for AML in CR to those in CRi and active disease (AD). This single centre retrospective observational study included all patients undergoing HCT for AML at our institution from January 2005 until December 2017. All patients gave informed consent for data collection and use for research in line with the declaration of Helsinki. All patients met the WHO criteria for AML [8] and had received induction chemotherapy, either in line with the UK-NCRI AML study protocols or by physician choice of institutionally approved regimens (most commonly 2 cycles of daunorubicin and cytarabine-based regimens with or without consolidation with high dose cytarabine based regimens). Timing of transplant, donor choice, and conditioning regimen were in line with UK-NCRI AML studies or at the discretion of the treating physician within the scope of institutionally approved protocols. Patients were grouped by disease status immediately prior to transplantation. CR was defined as less than 5% blasts on bone marrow (BM) examination with peripheral platelet count ≥100 × 10/L and neutrophils ≥1 × 10/L. CRi was defined as less than 5% blasts on BM examination with peripheral platelets <100 × 10/L and/or neutrophils <1 × 10. Any other disease status was categorised as AD. MRD positivity was defined as detectable disease by a contemporaneously accepted standard methodology at the time of transplant (e.g. PCR, immunophenotyping or fluorescence in situ hybridisation for known disease markers), with all other patients deemed MRD negative. Transplant risk was determined using the standard EBMT risk score [2] and grouped into low-(EBMT score 0–3) or high-(EBMT score 4–7) risk groups. The ELN-2017 guideline definitions of cytogenetic risk categories were used [3] The primary endpoint was survival, with non-relapse mortality (NRM) and relapse risk being secondary endpoints. Probabilities of survival were calculated using the * Jiří Pavlů [email protected]