Hematopoietic Stem Cell Transplantation and Primary Myelofibrosis

Review of Stem Cell Transplantation for Primary Myelofibrosis

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Doctor and Patient. Dan Dalton/Creative RF/Getty Images

Choosing the optimal treatment for primary myelofibrosis can be challenging. Often there is not one clear choice. There are several treatments for primary myelofibrosis, but only hematopoietic stem cell transplantation (also referred to as bone marrow transplant) is curative.

Why Doesn't Everyone Get a Transplant?

A cure sounds wonderful, so you may wonder why everyone with primary myelofibrosis doesn't receive a transplant.

It is all about the balance of risk and benefit.

Treatment in primary myelofibrosis is driven by risk category based on signs and symptoms you are experiencing. If you have no symptoms or have symptoms with low-risk disease, the mean survival after diagnosis is 15.4 years. In this case, the potential complications (acute or chronic graft versus host disease and death) associated with transplant outweigh the benefit of cure. Studies have shown that five-year survival in people with low risk or intermediate-1 risk disease was lower if they had undergone a hematopoietic stem cell transplant. However, in intermediate-2 and high-risk disease,five-year survival was improved in people who received a transplant compared to those who did not.

If you have intermediate-2 or high-risk primary myelofibrosis, hematopoietic stem cell transplant (HSCT) is the preferred treatment. Because older age increases the risk of transplant-related complications (predominantly secondary to graft versus host disease), HSCT has historically been reserved for people with primary myelofibrosis under the age 60.

Since the median age of people with primary myelofibrosis at diagnosis is 67, this significantly limits the number of people with primary myelofibrosis who are potential candidates for this therapy. Additionally, the preferred donor for HSCT is a matched sibling. A full sibling (same mother and father as the recipient) has a one in four chance of being a match, further limiting the number of people who can undergo this therapy.

Post-Transplant Prognosis

Currently, 40 to 60 percent of people with primary myelofibrosis who undergo transplant live for at least three to four years. There is some evidence to suggest that undergoing splenectomy (surgical removal of the spleen) prior to transplantation is associated with improved survival rates particularly in men, but the reason for this is not fully understood. Additionally, people who develop myelofibrosis after polycythemia vera or essential thrombocythemia appear to have a better survival rate after transplant than people with primary myelofibrosis.

Who Is Not Eligible?

Some people with high-risk disease are not candidates for HSCT. This is primarily determined by the likelihood of survival after HSCT.

Things like excessive large spleen (more than eight inches below rib cage) and more than 20 blood transfusions prior to transplant (particularly if you have both) have been associated with lower five-year survival after transplantation.  

What If You're Not Eligible?

So what is recommended if you have high-risk primary myelofibrosis but you are ineligible for HSCT or you don't have a donor?

If you have symptoms such as painful enlargement of spleen, fatigue, bone pain, night sweats, etc., ruxolitinib might be a reasonable therapy.

Ruxolitinib has been shown to reduce symptoms, reduce spleen size, and improve anemia in people with primary myelofibrosis. Another alternative to HSCT might be enrollment on a clinical trial. This would give you access to medications being studied as potential therapy for primary myelofibosis early.

It's not easy learning that you're not eligible for a cure, but remember to explore all of your options.

The Future of Transplants as Treatment

With improvements in the treatments around transplantation, such as the regimen used to prep bone marrow prior to transplantation and the medications used to prevent graft versus host disease, more transplants are being performed in people over the age of 60 and with alternative donors (relatives not perfectly matched or matched unrelated donors). Some centers will transplant people with myelofibrosis up to age 75.

Hopefully, with continued improvements, HSCT will be available to more people with myelofibrosis. Because primary myelofibrosis is a rare condition, it will take years before we have clear understanding of the role of alternative donors in HSCT for this disorder.  

Sources:

Ballen K. How to manage the transplant question in myelofibrosis.  Blood Cancer Journal. 2012;2:e59.

Tefferi A. Management of primary myelofibrosis. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on June 29, 2016.)

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