Pre-Transplant Chromosome Genomic Array Testing Improves Prognosis for Myelofibrosis Patients Undergoing Transplantation.

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Despite its known superior diagnostic yield for chromosomal anomalies compared to karyotype and FISH studies, Chromosome Genomic Array Testing (CGAT) is not used as a routine clinical test for myelofibrosis. Meanwhile, although many prognostic systems exist that risk stratify patients at diagnosis, limited tools are available to prognosticate transplant outcome. The current study aimed at testing if CGAT results obtained before transplantation improves prognosis of post-transplant outcome in myelofibrosis patients compared with current risk categorization systems namely DIPSS plus. We studied myelofibrosis patients who underwent hematopoietic cell transplantation between 2000 and 2017 at our center (n=44). We assessed the prognostic significance of CGAT, DIPSS plus, and the total count of gene mutations, for post-transplant clinical outcomes including relapse-free survival (RFS), overall survival (OS), and graft-versus-host-disease (GVHD). Abnormal CGAT results were seen in 24 patients (55%), including 18 with copy-neutral loss of heterozygosity (cnLOH, 41%). With a median follow-up of 91 (range 2-258) months starting from the CGAT sample date, RFS was 59%, and OS was 68%. The outcome analysis showed significant prognostic implication from CGAT (normal vs abnormal), specifically for patients with intermediate-risk by DIPSS-plus scores and those with 0∼2 mutations. CGAT alone significantly stratified the patients' RFS outcome (P=0.03). The addition of CGAT to DIPSS-plus improved the significance from a P value of 0.08 to 0.003, while the addition of CGAT to mutation count improved the P value from 0.02 to 0.01. The best stratification system for RFS was achieved when CGAT, DIPSS-plus, and mutation count were all considered (P = 1e-08). The current study also confirmed individual anomalies that are prognostically significant, including U2AF1 mutation (n=5, P=0.03) and 1q gain (n=3, P=0.01), which were associated with worse RFS. ASXL1 mutations (n=14) appeared to associate with a later onset of chronic GVHD (P=0.03). Pre-transplant CGAT analysis augments the existing risk stratification tools and may be considered as routine clinical testing for myelofibrosis.