Clinical Relevance of CRp in Untreated AML.

For many years response to induction therapy for AML was classified as CR or no CR. Recently, responses less than CR, e.g. CR with incomplete platelet recovery (CRp), have also been recognized. Attaining CRp suggests that a treatment is more “active” than if neither CR nor CRp had occurred (“resistant”). However, the question of whether CRp conveys clinical benefit has received relatively little attention; in particular, what is the effect of CRp on subsequent survival probability (“SSP”) relative to CR or resistant? The database we used to address this question consisted of 1051 consecutive pts with untreated AML (APL excepted) or high-risk MDS (> 10% blasts) considered for induction therapy at MDA from 2000 through 2004. 5% of the pts declined therapy, 45% achieved CR and 5% CRp, as usually defined, while 29% were resistant, i.e. they survived at least 1 month after beginning therapy, without ever achieving CR or CRp, or showed obvious reappearance of blasts before the end of this month; the remaining pts were called “early deaths” and were not further considered. CRp rates were higher among pts with abnormalities of chromosomes 5 and/or 7 (−5/−7; 15% CRp in 264 pts) than among other cytogenetic subsets (CRp rate 4–6%), with the following number of CRps for every 100 CRs: −5/−7 53.6, inv (16) or t(8;21) 5.5, normal karyotype 7.5, other cytogenetic abnormalities 15.4.The median number of days to CR was 31, CRp 44, and resistant 40, while the 75^th percentiles were 38, 60, and 59 respectively. Although many induction regimens were used, we, for simplicity, classified these as either “higher” or “lower” intensity, with the former (HI, 914 pts) corresponding to “chemotherapy” and the latter (LI) to “targeted therapy”, as commonly accepted. CR and CRp rates were 51% and 5% for HI and 5% and < 1% for LI. In general, pts continued to receive their initial induction regimen regardless of whether their reponse was considered CR or CRp. Because 75% of pts who eventually achieved CRp did so within 60 days of starting induction therapy, as did 90% of the CR pts, we categorized pts alive on day 60 according to whether they ultimately achieved CR, CRp, or neither (resistant). We then dated SSP from day 60:

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Sensitivity analyses dating SSP from day 30 or day 90, rather than day 60, produced similar results. We are: (1) doing a multivariate analysis examining the relative effects on SSP of response, cytogenetics (given the association of poor prognosis cytogenetics with CRp), and treatment after relapse, and (2) assessing whether the effects of CR vs CRp vary according to induction treatment. Our current results, however, constitute the first demonstration that CRp is of clinical relevance in untreated AML.