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Myelofibrosis-associated extramedullary hematopoiesis: Insights into hepatic, pulmonary, and thrombotic complications
Idoroenyi Amanam1, Salman Otoukesh1, Vinod Pullarkat1
1Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, United States of America.
Background:
Primary myelofibrosis (PMF), the most aggressive of the Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), is characterized by progressive marrow fibrosis, ineffective hematopoiesis, and a pro-inflammatory milieu. These pathobiologic features drive extramedullary hematopoiesis (EMH) and confer heightened risks for hepatic, pulmonary, and thrombotic complications, particularly in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT).
Objective:
Drawing on our institutional transplant experience in PMF, we review the pathophysiology, clinical manifestations, and management of EMH-related complications to optimize outcomes in this complex patient population.
Methods:
We synthesized current literature on EMH in MPNs and integrated contemporary data on hepatic portal hypertension, pulmonary hypertension, splanchnic vein thrombosis, and transplant-related complications. Key insights from recent European Society for Blood and Marrow Transplantation (EBMT) registry data are highlighted.
Results:
Portal hypertension affects 3-18 % of patients with myeloproliferative neoplasms (MPNs), driven by intrahepatic sinusoidal infiltration, splenic hyperdynamic circulation, and splanchnic thrombosis. Splanchnic vein thrombosis often precedes overt MPN diagnosis, with JAK2V617F detected in a substantial proportion of affected patients. Pulmonary complications-including extramedullary hematopoiesis (EMH), pulmonary hypertension, and peri-engraftment respiratory failure-contribute meaningfully to non-relapse mortality in the transplant setting. Ruxolitinib, reduced-intensity conditioning, and spleen-directed strategies have improved engraftment kinetics and mitigated graft-related complications in myelofibrosis patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT). Institutional observations are incorporated throughout to contextualize hepatic, pulmonary, and vascular manifestations of EMH in contemporary practice.
Conclusion:
These institutional observations complement published data and emphasize that EMH-related hepatic, pulmonary, and vascular complications are biologically active yet potentially reversible when clonal disease control is achieved. EMH-associated complications in PMF require a multidisciplinary management approach tailored to disease biology and transplant considerations. Advances in cytokine modulation, conditioning strategies, and emerging antifibrotic agents hold promise for improving patient outcomes.
Insights
Extramedullary hematopoiesis (EMH) complications in primary myelofibrosis (PMF) patients undergoing stem cell transplant are significant but potentially reversible. A multidisciplinary approach and advances in treatment offer improved outcomes.
Area of Science:
- Hematology
- Oncology
- Transplantation Medicine
Background:
- Primary myelofibrosis (PMF) is an aggressive Philadelphia chromosome-negative myeloproliferative neoplasm.
- PMF is characterized by marrow fibrosis, ineffective hematopoiesis, and inflammation, leading to extramedullary hematopoiesis (EMH).
- EMH increases risks for hepatic, pulmonary, and thrombotic complications, especially in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT).
Purpose of the Study:
- To review the pathophysiology, clinical manifestations, and management of EMH-related complications in PMF.
- To optimize outcomes for PMF patients undergoing allo-HCT by integrating institutional experience and current literature.
- To provide insights into managing hepatic, pulmonary, and vascular complications associated with EMH.
Main Methods:
- Synthesized current literature on EMH in myeloproliferative neoplasms (MPNs).
- Integrated contemporary data on hepatic portal hypertension, pulmonary hypertension, and splanchnic vein thrombosis.
- Highlighted key insights from European Society of Blood and Marrow Transplantation (EBMT) registry data and institutional observations.
Main Results:
- Portal hypertension affects 3-18% of MPN patients, driven by sinusoidal infiltration, splenic hyperdynamic circulation, and thrombosis.
- Splanchnic vein thrombosis can precede MPN diagnosis; JAK2V617F is often detected.
- Pulmonary complications, including EMH and pulmonary hypertension, significantly contribute to non-relapse mortality post-transplant.
- Ruxolitinib, reduced-intensity conditioning, and spleen-directed strategies have improved outcomes in PMF patients undergoing allo-HCT.
Conclusions:
- EMH-related complications are biologically active but potentially reversible with disease control.
- A multidisciplinary approach tailored to disease biology and transplant considerations is crucial for managing EMH in PMF.
- Advances in cytokine modulation, conditioning, and antifibrotic agents show promise for improving patient outcomes.
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