Loss of the Y Chromosome Predicts Lower Complete Cytogenetic Remission Rate in Patients (pts) with Chronic Myeloid Leukemia (CML)
Authors: Abdelfatah Mohamed , Al-Alwan Adel , Kanaan Zeyad , Litzow Mark R , Wolanskyj Alexandra , Begna Kebede , Hogan William , Van Dyke Daniel L. , Al-Kali Aref 
Published: October 2019

Abstract
Abstract 4804

Background:
Chronic myeloid leukemia (CML) is one of the classic myeloproliferative neoplasms characterized by a reciprocal translocation of BCR and ABL t(9;22)(q34;q11). Tyrosine kinase inhibitors (TKI) have revolutionized the management of CML in inducing rapid and prolonged responses. However; clonal evolution (CE) is considered a poor prognostic factor and a criterion for accelerated phase (AP) CML by the World Health Organization (WHO). Deletion of chromosome Y (−Y) is frequently considered an age-related abnormality and the exact prognostic value has not yet been determined.

Aim:
To determine if –Y carries an impact on the clinical outcome of male pts with CML.

Methods:
All male patients diagnosed with chronic phase CML in our institution between 1993 and 2011 were screened for -Y. Data were collected in a retrospective manner and compared (using t-test) to male patients with sole BCR-ABL translocation after excluding patients with advanced stages (accelerated phase, blast phase). Demographics, laboratory tests, cytogenetic analysis, molecular testing and survival data were abstracted. Kaplan-Meier estimates of overall survival were used via JMP software v9.0. Institutional Review Board (IRB) approval was obtained for this study in accordance with the Helsinki Declaration.

Results:
20 of 162 (12%) males with CML were found to have –Y abnormality (group 1). CML male patients with sole Philadelphia chromosome abnormality were the control cohort (group 2). In group1; the median age was 57 years, BMI 27.7, hemoglobin 12.2 g/dL, white blood cell count (WBC) 32.8 x109/L, platelet 270 x109/L, and peripheral blood blasts 1%. Sokal risk was low in 30%, intermediate in 65% and high in 5% of pts. Nine pts (45%) were treated with interferon (IFN) prior to TKI. In group 2; the median age was 54 years, hemoglobin 12 g/dL, WBC 57 x109/L, and platelet 282 x109/L. Sokal risk was low in 37%, intermediate in 47%, and high in 16%. 46 of 142 patients (32%) had received previous interferon therapy. All patients in both groups had chronic phase CML at the time of diagnosis, with a median bone marrow cellularity of 95%. In group 1, 14 of 20 pts (70%) received imatinib, all of whom achieved a complete hematological response (CHR), 7 of 14 pts (50%) had partial cytogenetic response, 2 of 14 pts (14%) achieved a complete cytogenic response (CCyR);1 (7%) pt achieved CCyR within 12 months and an additional 1 (7%) by 18 months). Two pts of 12 (16%) achieved at least a major molecular response (MMR); one of whom (8%) achieved a complete molecular response (CMR). In comparison, 107of 142 pts (75%) in group 2 received imatinib, all of whom achieved CHR. Twenty-one pts (20%) achieved partial cytogenetic remission. CCyR was more frequently achieved than group 1 (48/107 pts (45%), p 0.026); 24 pts (22%) achieved CCyR within 12 months of therapy and an additional 10 pts by 18-months. MMR and/or CMR was higher in group 2 compared to group 1 (34 /101 (34%), p 0.18); 16 (16%) of which were CMR. In group 1; 6 (30%) pts had disease progression; 4 of 20 pts (20%) progressed to blast phase (BP) and 2 pts (10%) progressed to AP, compared to 32 (22%) pts in group 2 (p 0.17); 22 (15%) of whom progressed to BP and 10 (7%) patients progressed to AP. Median overall survival was 110 months in group 1 compared to 155 months in group 2 (log rank p=0.48). On multivariate analysis, CCyR was an independent factor for a better OS (p 0.03), but not –Y (p 0.7).

Conclusion:
Loss of the Y chromosome in chronic myelogenous leukemia is an infrequent phenomenon (12%). Although patients with –Y had a statistically significant less chance to achieve CCyR, loss of the Y chromosome did not affect the progression rate or overall survival. Larger scale studies are needed to confirm our observations

Disclosures:
No relevant conflicts of interest to declare.