AML Relapse Mirrors Pulmonary Hypertension Worsening in Rare Case

A newly published case report highlights a rare and clinically significant connection between pulmonary hypertension (PH) and hematologic malignancies, particularly acute myelogenous leukemia (AML) evolving from myeloproliferative neoplasm (MPN). The findings, published in JACC: Case Reports, highlight not just the rare association between PH and MPN, but also how progression or relapse of hematologic disease can coincide with cardiopulmonary manifestations.¹

The report details the case of a 32-year-old woman with a history of JAK2 mutation-positive polycythemia vera, myelofibrosis with transformation to AML, and Behçet’s disease complicated with Budd-Chiari syndrome.

The rarity of PH in MPN/AML, coupled with variable mechanisms and response to therapy, makes standardized risk tools and protocols difficult to implement. | Image Credit: Dr_Microbe - stock.adobe.com

The patient initially presented with exertional dyspnea prior to a scheduled allogeneic hematopoietic stem cell transplantation (HSCT). Her physical exam revealed only a prominent pulmonary second heart sound, without peripheral edema or rales.

Echocardiography revealed markedly elevated right ventricular systolic pressure (80-85 mm Hg), right ventricular dilation, and systolic septal flattening. A ventilation/perfusion scan excluded chronic thromboembolic disease, and right heart catheterization confirmed precapillary PH with a mean pulmonary artery pressure of 65 mm Hg, pulmonary vascular resistance of 11.0 Wood units, and normal pulmonary capillary wedge pressure. The patient also showed clinically significant leukemia, with white blood cells 59% blasts. Her REVEAL Lite 2.0 score was 8, indicating intermediate one-year mortality risk.

The patient was started on macitentan and tadalafil, leading to a substantial reduction in right ventricular systolic pressure (36-40 mm Hg) and improvement in functional class.

After completing several courses of decitabine and ruxolitinib therapy, the patient underwent HSCT. Thirty days post-transplant, a repeat bone marrow biopsy confirmed disease remission. The patient remained on combination PH therapy.

However, approximately 330 days post-HSCT, she was readmitted with signs of right heart failure, requiring high-flow oxygen and diuretics. Imaging excluded pulmonary embolism, pneumonia, and graft-vs-host disease. Repeat catheterization revealed severe PH with a mean pulmonary artery pressure of 94 mm Hg and pulmonary vascular resistance of 15.0 Wood units. A concurrent bone marrow biopsy confirmed AML relapse, with measurable residual disease (~0.6% of total events) and immunophenotyping consistent with AML. The patient's REVEAL Lite 2.0 risk score had worsened to 9.

“Our case highlights the interplay between PH and hematologic malignancies,” the authors write, noting that PH progression may mirror disease activity in MPN and AML.

The patient was restarted on ruxolitinib and decitabine, along with transition from epoprostenol to subcutaneous treprostinil for PH. Although initially stabilized, she developed pneumonia 3 months later and died from respiratory failure.

Known mechanisms linking PH and MPN/AML, including chronic thromboembolic disease and group 5 PH, were ruled out, as well as drug-induced PH, as she had not been exposed to agents like tyrosine kinase inhibitors or proteasome inhibitors. The authors discuss several possible mechanisms linking PH and MPN/AML, including hyperviscosity from circulating myeloid progenitors leading to shear stress and vascular remodeling, and emerging research pointing to shared genetic mutations such as Tet-methylcytosine dioxygenase-2 (TET2), which is implicated in both adverse pulmonary vascular remodeling and leukemogenesis.^2,3 

Ruxolitinib, used here for AML and myelofibrosis, may have contributed to PH improvement in this patient, as previous reports have shown it can modulate cytokine levels and nitric oxide production in myelofibrosis-related PH.⁴ This dual effect may be critical for patients with overlapping hematologic and cardiovascular pathology.

PH in MPN patients remains rare and is classified as World Health Organization group 5 PH, which encompasses multifactorial or unclear mechanisms.⁵ In a population-based cohort studied by Montani et al, the most common precapillary PH types in MPN were chronic thromboembolic PH and group 5 PH.³ The authors stress that risk stratification tools validated for group 1 pulmonary arterial hypertension, such as REVEAL Lite 2.0, may not directly translate to patients with group 5 PH secondary to hematologic malignancy.

The rarity of PH in MPN/AML, coupled with variable mechanisms and response to therapy, makes standardized risk tools and protocols difficult to implement. Yet, as in this patient, the progression of one disease may herald the relapse or evolution of the other. “Prompt recognition of PH in those with MPNs is needed to facilitate appropriate interventions in a multidisciplinary manner,” researchers noted.

References

1. Kaous M, Ryoo Ali HJ, Ok CY, et al. Relapse of acute myelogenous leukemia with history of myeloproliferative neoplasm and exacerbation of pulmonary hypertension. JACC Case Rep. 2025;30(20):104136. doi:10.1016/j.jaccas.2025.104136
2. Montani D, Thoré P, Mignard X, et al. Clinical phenotype and outcomes of pulmonary hypertension associated with myeloproliferative neoplasms: A population-based study. Am J Respir Crit Care Med. 2023;208(5):600-612. doi:10.1164/rccm.202210-1941OC
3. Potus F, Pauciulo MW, Cook EK, et al. Novel mutations and decreased expression of the epigenetic regulator TET2 in pulmonary arterial hypertension. Circulation. 2020;141(24):1986-2000. doi:10.1161/CIRCULATIONAHA.119.044320
4. Tabarroki A, Lindner DJ, Visconte V, et al. Ruxolitinib leads to improvement of pulmonary hypertension in patients with myelofibrosis. Leukemia. 2014;28(7):1486-93. doi:10.1038/leu.2014.5
5. Leiva O, Ren S, Neuberg D, et al. Pulmonary hypertension is associated with poor cardiovascular and hematologic outcomes in patients with myeloproliferative neoplasms and cardiovascular disease. Int J Hematol. 2023;117(1):90-99. doi:10.1007/s12185-022-03454-1