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Novel Therapies Likely to Change Role of Stem Cell Transplants in Blood Cancers

Andrew D. Smith
Published: Friday, Jan 15, 2016
Kenneth C. Anderson, MD

Kenneth C. Anderson, MD

Stem cell transplantation was rightly hailed as a breakthrough treatment for people with many blood-based cancers when pioneering hematologists began using them regularly in the 1970s. Their popularity grew slowly but steadily throughout the 1980s and then took off in the 1990s as multiple studies demonstrated their efficacy and new techniques made them safer. Total annual US transplantation figures grew from less than 2000 in 1990 to more than 19,000 in 2013, according to the Center for International Blood & Marrow Transplant Research (CIBMTR).1

The technique has undoubtedly saved or extended hundreds of thousands of lives, but even with steady improvements to the underlying technique, it is still dangerous. Treatment-related mortality may still approach 1%. Stem cell transplants are also expensive and agonizing. Total costs when patients receive their own stem cells can reach $100,000.2 Total costs when patients receive stem cells from others can reach $200,000.2

In both cases, the treatment and recovery rank among the more grueling of all cancer protocols. Many experts believe that new targeted therapies and new immunotherapies will eventually eliminate the need for most stem cell transplants.

They predict that such treatments will offer patients far easier ways to achieve better outcomes. So far, there are only a few instances where new treatment protocols have begun replacing transplants, but there are dozens of trials at various stages of completion that could significantly reduce the use of transplants for some cancers over the next few years.

At the same time, however, transplant techniques are improving. Mortality and morbidity both appear to be declining with the emergence of better antibiotics and growth factors, so hematologists are beginning to consider transplants for patients who were once considered too old or too sickly to endure anything as harsh as a stem cell transplant.

Mixed Picture in Leukemias

“We have seen the numbers of patients transplanted for certin diseases move in both directions,” Martin S. Tallman, MD, chief of the Leukemia Service at Memorial Sloan Kettering Cancer Center (MSK), said in an interview. “Targeted therapies have greatly reduced our use of stem cell transplants in patients with chronic myeloid leukemia [CML] and begun to reduce them in patients with chronic lymphocytic leukemia [CLL]. On the other hand, patients historically felt to be too old to meet traditional transplantation guidelines may now undergo reduced-intensity transplantation.”

According to Tallman, the decline in transplants for patients with CML at MSK stems almost entirely from the introduction of tyrosine-kinase inhibitors (TKIs) such as imatinib (Gleevec).

A Snapshot of Stem Cell Transplants in United States

Hematopoietic cell transplant activity for 2013 as reported to the Center for International Blood and Marrow Transplant Research (CIBMTR).

ALL indicates acute lymphoblastic leukemia; AML, acute myeloid leukemia; CML, chronic myeloid leukemia; HL, Hodgkin lymphoma; MDS, myelodysplastic syndromes; MPN, myeloproliferative neoplasms; NHL, non-Hodgkin lymphoma.

REFERNECES

1. Center for International Blood and Marrow Transplant. Transplant Activity Report. US Department of Health and Human Services website http://goo.gl/lPydMP. Reported September 16, 2013. Updated May 18, 2015. Accessed January 4, 2016.
2. Pasquini MC, Zhu X. Current uses and outcomes of hematopoietic stem cell transplantation: 2014 CIBMTR Summary Slides. http://www.cibmtr.org. Accessed January 4, 2016.

Imatinib was first approved in 2001 for patients who relapsed after stem cell transplants, but it is now used for the treatment of newly diagnosed patients, as are several other TKIs. Stem cell transplants are now conducted after patients fail on TKIs, when they are performed at all.

A different class of novel medications has brought about a similar decline in the number of stem cell transplants that Tallman’s department performs on patients with CLL. The B-cell signaling pathway inhibitors ibrutinib (Imbruvica) and idelalisib (Zydelig), which are currently used as second-line treatments for the disease, can produce better outcomes and far less toxicity than protocols involving stem cell transplants.


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