S1626 INCOMPLETE COUNT RECOVERY IN PATIENTS WITH COMPLETE REMISSION PRIOR TO ALLOGENEIC HCT FOR AML IS ASSOCIATED WITH A HIGH NON‐RELAPSE MORTALITY WITHOUT AN INCREASED RELAPSE RISK
Authors: Innes A. , Wooley P. , Szydlo R. , Lozano S. , Fernando F. , Bansal D. , Palanicawandar R. , Milojkovic D. , May P. , Nadal‐Melsio E. , Yebra‐Fernandez E. , Olavarria E. , Apperley J. , Pavlu J. 
Published: June 2019

Background:

Allogeneic hematopoietic cell transplantation (HCT) offers the best prospect of cure for most patients with AML. However both the risk of relapse and non‐relapse mortality remain stubborn barriers to successful outcome for many. It is established that remission status prior to HCT is one of the strongest predictors of outcome, with those achieving complete remission (CR) prior to HCT achieving the most favorable results. However, frequently, these data are extrapolated to risk‐stratify all patients with less than 5% blasts, and do not discriminate between those in CR and those in CR with incomplete count recover (CRi).

Aims:

The aim of this retrospective study was to determine the effect of incomplete count recovery on transplant outcome in patients undergoing HCT for AML in complete remission

Methods:

All patients undergoing HCT for AML between January 2005 and December 2017 were included in this analysis. Disease status was classified immediately prior to HCT as complete remission (CR), complete remission with incomplete count recovery (CRi) or active disease (AD). The conventional definition of complete remission (<5% marrow blasts by morphology) was employed and incomplete count recovery was defined as platelet count <100 x 109/L and/or neutrophil count < 1 x 109/L. Measurable residual disease (MRD) was defined by detectable disease by a contemporaneously accepted standard methodology at the time of transplant. The primary outcome measure was overall survival, and secondary endpoint of non‐relapse mortality (NRM) and relapse were also assessed. These endpoints were also assessed in a sub‐group analysis of MRD negative patients.

Results:

155 patients underwent allogeneic HCT for AML at our institution during the study period. Disease status was defined as CR in 80 (52%), CRi in 55 (35%) and AD in 20 (13%). There were no significant demographic or transplant characteristics between the groups. The 5‐year probability of survival for CR patients was 51.3% (95%CI 40.2–65.4), compared to 24.4% (95%CI 14.1–42.4) for CRi and 12.7% (95%CI 3.6–45.2) for AD (p<0.001) (adjusted HR 1.92 (95% CI 1.20–3.06, p = 0.006) for CRi and 2.82 (95% CI 1.39–5.72, p < 0.001) for AD). 100 day NRM was 6.3%, 23.6% and 35.0% for CR, CRi and AD groups respectively (p < 0.001), with 5‐year with cumulative incidence of NRM of 26.8%, 46.8% and 48.1% (p < 0.001). The cumulative incidence of relapse at two years was higher for the AD group (36.9%), but did not differ significantly between the CR and CRi groups (19.3% vs 20.6%, p = 0.86). These finding persistent in MRD negative patients (n = 107), with 5 year OS 37.5% vs 56.7% (p = 0.006) and NRM of 46.4% vs 30.4% (p = 0.003) for CR and CRi groups respectively, with no difference in the probability of relapse.

Summary/Conclusion:

Our data shows that patients undergoing HCT in CRi have a poorer survival and higher NRM without increased relapse risk compared to those transplanted in CR. The persistently increased NRM in CRi patients without MRD supports the notion that the poorer survival may result from poor fitness for transplant and increased susceptibility to transplant related complications rather than an imminent relapse. With the advent of increasingly sensitive MRD technologies, these data may suggest that further pre‐transplant optimization to promote marrow recovery may be permissible in order to minimize NRM without risking increased relapses in CRi patients. The high NRM may also caution against pursuing MRD negativity at all cost, particularly if that risks incomplete count recovery.

image