Pulmonary Arterial Hypertension (PAH) Is Associated with Increased Non-Relapse Mortality after Allogeneic Hematopoietic Cell Transplantation (allo HCT) for Myelofibrosis

Abstract

Background AlloHCT is the only curative therapy for primary and secondary myelofibrosis (MF). Pulmonary arterial hypertension (PAH) can be seen in 30% of patients with MF. PAH can eventually lead to right heart failure and may be associated with complications after alloHCT. The primary objective was to determine the association of PAH with alloHCT outcome in patients with MF. Secondary objectives included the effect of HCT on the underlying PAH as well as incidence of specific transplant-related complications in these patients. Methods All patients with MF who underwent alloHCT from 2008 to early 2018 at the City of Hope Medical Center with evaluable pre-HCT echocardiography were considered for this retrospective analysis. Pre and postHCT echocardiograms were reviewed to evaluate the pulmonary arterial systolic pressure (PASP). Descriptive statistics were used for baseline patient and transplant related characteristics stratified by PAH. Paired t-test was used to detect the change in the pulmonary vascular pressure after HCT. Kaplan-Meier and cumulative incidence curves were constructed for OS and NRM), respectively. Log-rank test and Gray's test were used whenever appropriate. Results 65 patients with MF that met the inclusion criteria were studied. Median age at HCT was 61 years with 36 (55%) males. 39 (60%) patients had intermediate 2 or high DIPPS score at the time of HCT. 37 (57%) had JAK2 positive MF. . Median PASP was 37.0 mmHg (range: 16.0-57.9) prior to HCT with 37 out of 65 patients (57%) meeting the diagnostic criteria for PAH. With median follow-up of 35.0 months (range: 3.3 – 119.4), PAH was significantly associated with inferior OS (58.9% vs. 88.8%, p=0.025), primarily due to increased NRM (21.6% vs. 7.1%, p= 0.007). 57% of deaths (8 of 14) in patients with PAH occurred within day 100 after HCT. In patients with available post-HCT echocardiogram (n=33) eight patients (24%) had persistent PAH with the median pulmonary artery pressure of 30mmHg. Compared with pre-HCT values pulmonary arterial pressure was significantly reduced after HCT (p Conclusion PAH is associated with inferior survival due to increased NRM in patients with MF undergoing alloHCT. About half of deaths in patients with PAH occurred within 100 days of HCT. PAH appears at least partially reversible after successful alloHCT. Based on our data, PAH should be considered a risk factor for early mortality after alloHCT and surveillance of pulmonary artery pressure in MF patients being considered for alloHCT may be useful.