Prognostic Impact of Adverse Karyotype and Treatment in Patients with Myelodysplastic Syndrome and Acute Myeloid Leukemia

INTRODUCTION

Karyotype is a key prognostic factor in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Adverse karyotype (AK) significantly influences on response to treatment, prognosis and survival in older MDS and AML patients(pts)^1,2.

AIMS

Evaluate the frequency of adverse karyotype over the total number of patients (pts) diagnosed with MDS and AML in our institution, demographic features, treatment received and overall survival (OS) estimates. Second, to analyze prognostic factors associated to OS in this cohort of pts.

PATIENTS AND METHODS

A retrospective and observational analysis was performed including all consecutive cases of MDS and AML with adverse karyotype. Period of analysis was from 2008-2015 for AML and from 1990-2015 for MDS pts. Adverse karyotype was defined as categories Intermediate-II and adverse from European LeukemiaNet recommendations in AML³, whereas IPSS⁴ was used for MDS pts. Complex and monosomal karyotype (CK/MK) were defined by the presence of ≥3karyotypic abnormalities in the absence of recurrent cytogenetic alterations based on the WHO classification, and the presence of ≥2 distinct autosomal monosomies or a single autosomal monosomy associated with at least 1 structural abnormality; respectively. Patients were stratified based on type of treatment received: active [intensive chemotherapy(IC)/azacitidine (AZA) followed or not by allogeneic transplant) vs supportive care (SC; including pts not candidates to active treatment due to comorbidity, poor ECOG status or advanced age >70).

RESULTS

A total of 98 pts were identified (N=49 cases of MDS and AML each). Median age at diagnosis was 65 years (range: 14-89). Demographic and baseline characteristics are described in table 1. The frequency of AK from the global cohort of MDS and AML from our institution was 20% and 19% respectively. Ten out of 49 (21%) pts with AML displayed recurrent cytogenetic alteration according to WHO classification [t(9;11) and other alterations in MLL, t(6;9), inv(3) or t(3;3)] and 28/49 (57%) and 18/49 (38%) had a CK or MK, respectively. In the MDS cohort, 25/49 pts (51%) had a chromosome 7 abnormality and 30/49 (61%) presented with a MK. Globally (AML and MDS), almost half of pts (49.8%) had a MK. Most pts <65y received active treatment (as previously stated) as compared to pts >65y (69% vs 37%; p<0.001). After 49 months median follow-up (range: 1-100), 22% pts (22/98) are alive with a median OS of 9 months for the global series (95% CI, 5.6-12.3). Median OS for pts treated with intensive chemotherapy, azacitidine or SC was 11 (CI 95%; 3.2-20.7), 14 (IC 95%; 10-17) and 5 months (IC 95%; 2-7); respectively (p=0.001). No difference in OS was observed between AML or MDS cases. Age >65y, KC, MK and treatment received (SC) had a negative impact on OS (p<0.05 all cases). In multivariate analysis, only the presence of MK [HR: 1.7, 95% IC (1.06-2.7); p=0.02] and receiving active treatment [HR: 0.49, 95% IC (0.3-0.8), p=0.006] remained statistical significant for OS.

DISCUSSION

Adverse, and particularly MK predict poor survival in AML/MDS. Both IC and AZA offer significant survival advantage over SC.

References

1. Grimwade D, et al. Blood . 1998;92(7):2322-33

2. Dombret H, et al. Blood. 2015. 16;123(3):291-9

3. Döhner H, et al. Blood. 2010 Jan 21;115(3):453-74

4. Greenberg P, et al. Blood. 1997; 89:2079-88