Photo Credit: Tiratus Phaesuwan

Updated guidelines on allogeneic hematopoietic stem cell transplantation for myelofibrosis examine spleen-related complications, iron overload, and more.

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is currently the only known cure for myelofibrosis (MF). Although the potential for a curative outcome makes this procedure highly valuable, the risk for life-threatening complications has made practitioners approach this course of treatment with caution.

The 2015 guidelines on the Indication and Management of Allogeneic Hematopoietic Stem-cell Transplantation in MF were updated by the European Society for Blood and Marrow Transplantation and European LeukemiaNet International Working Group using a consensus-building methodology. Recommendations included screening patients for eligibility to undergo allo-HCT with limited risk. Post-transplantation monitoring was also a vital part of achieving a positive outcome.

Although the updated guidelines provide insights on scoring patients for transplant eligibility and managing patients with MF to reach eligibility for transplant, there are still unanswered questions regarding the complexity of the disease and treatment complications.

To address these issues, Nicola Polverelli, MD, PhD, and colleagues constructed a narrative review of the updated guidelines and current available subject knowledge to provide an in-depth and contextualized overview of some gray areas regarding MF management, treatment, and complications. Bone Marrow Transplantation published the findings of the review.

Splenomegaly & Complications

Many patients with MF experience an enlarged spleen of greater than 15 cm. Known as splenomegaly, this condition is associated with poor outcomes after transplant in addition to complications such as splanchnic vein thrombosis (SVT) and portal hypertension (poHT). Reducing the spleen size in patients affected is a priority and may call for non-pharmacological approaches such as pre-allo-HCT splenectomy or spleen irradiation. Moving forward with a transplant once splenomegaly has been managed is recommended by the guidelines.

The presence of SVT complicates the management of myelofibrosis in that long-term anticoagulation therapy needs to be established, in addition to an increased need for platelet transfusions. Likewise, poHT should be identified as soon as possible in patients with MF because it can also produce severe complications after allo-HCT. This does not mean the detection of poHT removes transplantation as a treatment option but that the patient would need multidisciplinary management to limit risk.

Pulmonary hypertension (puHT) is another uncommon but significant complication of MF. Complications can include left heart failure, myeloid metaplasia in the lung, persistent thromboembolic pulmonary hypertension, and a cytokine-mediated pro-angiogenic status. Studies have shown that puHT is a risk factor for poor post allo-HCT survival. Therefore, performing baseline transthoracic echocardiography and bloodwork for N-terminal pro-B-type natriuretic peptide levels during the screening process for eligibility for allo-HCT is strongly recommended in patients with MF. A chest contrast-enhanced computed tomography scan may help assess puHT and identify pulmonary myeloid metaplasia. As with SVT and poHT, a multidisciplinary approach to care in patients with MF and puHT should be integral to pre-transplant medical optimization measures.

Patients With Cytopenia

The diagnosis, management, and treatment of cytopenia in patients with MF is a challenge, especially when the patient is being considered for allo-HCT. Anemia, which presents in over 40% of newly diagnosed MF cases, is considered one of the most important adverse prognostic factors and is vital in screening for transplant eligibility. This, in addition to thrombocytopenia and/or ameliorate transfusion dependency, needs to be carefully managed to proceed with transplant. Pharmacological interventions and combination protocols are available, but more data are needed to confirm their viability.

Iron overload is another issue associated with MF and, if not properly addressed, can lead to both short and long-term complications post-allo-HCT, including increased susceptibility to infection, liver dysfunction, and sinusoidal obstructive syndrome. If persistent hepatic iron overload continues unchecked, there is a danger of organ toxicity and endocrinopathies. The guidance is that patients with pronounced iron loading, hyperferritinemia (ferritin >1,000 ng/mL), or red blood cell transfusion requirements greater than ten units, also being considered for allo-HCT, need early intervention with iron chelation strategies.

Additional Considerations & Practical Use

Additional comorbidities (eg, obesity) and patient characteristics (eg, frailty) must be considered when developing and executing a treatment plan for patients with MF. Each variation adds its own risk and requires adjustments to the treatment protocol.

Extreme heterogeneity among patients with MF “makes standard recommendations unsuitable for evaluating transplant eligibility in many patients,” Dr. Polverelli and colleagues wrote, noting an individualized strategy is necessary.