1.
Pulmonary hypertension is associated with increased nonrelapse mortality after allogeneic hematopoietic cell transplantation for myelofibrosis
Gupta, R., Jamal, F., Yang, D., Chendri, C., Aldoss, I., Malki, M. A., Mei, M., Salhotra, A., Dobrin, S., Tran, M., et al
Bone marrow transplantation. 2019
Abstract
Allogeneic hematopoietic cell transplantation (alloHCT) is the only curative therapy for primary myelofibrosis (MF) as well as myelofibrosis secondary to other myeloproliferative neoplasms (MPN). Pulmonary hypertension (PH) is a known complication of MF and may occur in up to 50% of such patients. PH (defined as a mean pulmonary artery pressure ≥25 mmHg at rest) can eventually lead to right heart failure and may be associated with complications after alloHCT. We examined the association of PH with alloHCT outcome in patients with MF associated with MPN. Pre- and post-HCT echocardiograms were reviewed to estimate the peak pulmonary artery systolic pressure (PASP). Median PASP was 37.0 mmHg (range: 16.0-57.9) prior to HCT with 37 of 65 patients (57%) studied. With median follow-up of 35.0 months (range: 3.3-119.4) PH 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). The majority of the deaths (8 of 14) in patients with PH occurred within 100 days after HCT. In patients with an available post-HCT echocardiogram (n = 33), the median PASP was 30 mmHg (range: 5.0-56.2); eight patients (24%) had persistent PH. Compared with pre-HCT values, PASP was significantly reduced after HCT (p < 0.001). We conclude that PH is associated with inferior survival due to the increased NRM in patients with MF undergoing alloHCT. PH appears at least partially reversible after successful alloHCT. PH 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.
2.
MIPSS70+ v2.0 predicts long-term survival in myelofibrosis after allogeneic HCT with the Flu/Mel conditioning regimen
Ali, H., Aldoss, I., Yang, D., Mokhtari, S., Khaled, S., Aribi, A., Afkhami, M., Al Malki, M. M., Cao, T., Mei, M., et al
Blood advances. 2019;3(1):83-95
-
-
-
Free full text
-
-
Editor's Choice
Abstract
Although allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment for myelofibrosis (MF), data are limited on how molecular markers predict transplantation outcomes. We retrospectively evaluated transplantation outcomes of 110 consecutive MF patients who underwent allo-HCT with a fludarabine/melphalan (Flu/Mel) conditioning regimen at our center and assessed the impact of molecular markers on outcomes based on a 72-gene next-generation sequencing panel and Mutation-Enhanced International Prognostic Scoring System 70+ v2.0 (MIPSS70+ v2.0). With a median follow-up of 63.7 months, the 5-year overall survival (OS) rate was 65% and the nonrelapse mortality (NRM) rate was 17%. In mutational analysis, JAK2 V617F and ASXL1 mutations were the most common. By univariable analysis, higher Dynamic International Prognostic Scoring System scores, unrelated donor type, and very-high-risk cytogenetics were significantly associated with lower OS. Only CBL mutations were significantly associated with lower OS (hazard ratio [HR], 2.64; P = .032) and increased NRM (HR, 3.68; P = .004) after allo-HCT, but CALR, ASXL1, and IDH mutations did not have an impact on transplantation outcomes. Patient classification per MIPSS70 showed worse OS for high-risk (HR, 0.49; P = .039) compared with intermediate-risk patients. Classification per MIPSS70+ v2.0 demonstrated better OS when intermediate-risk patients were compared with high-risk patients (HR, 0.291) and much lower OS when very-high-risk patients were compared with high-risk patients (HR, 5.05; P ≤ .001). In summary, we present one of the largest single-center experiences of Flu/Mel-based allo-HCT, demonstrating that revised cytogenetic changes and MIPSS70+ v2.0 score predict transplantation outcomes, and thus can better inform physicians and patients in making decisions about allo-HCT.
PICO Summary
Population
110 consecutive MF patients who underwent allo-HCT with a fludarabine/melphalan (Flu/Mel) conditioning regimen
Intervention
Retrospective cohort study assessing the impact of molecular markers on outcomes based on a 72-gene next-generation sequencing panel and Mutation-Enhanced International Prognostic Scoring System
Comparison
none
Outcome
In the entire cohort, 5-year overall survival (OS) rate was 65% and the nonrelapse mortality (NRM) rate was 17%. Higher Dynamic International Prognostic Scoring System scores, unrelated donor type, and very-high-risk cytogenetics were significantly associated with lower OS. Only CBL mutations were significantly associated with lower OS. Patient classification per MIPSS70 showed worse OS for high-risk compared with intermediate-risk patients. Classification per MIPSS70+ v2.0 demonstrated better OS when intermediate-risk patients were compared with high-risk patients and much lower OS when very-high-risk patients were compared with high-risk patients.