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By Nilanjan Ghosh, MD, PhD

To treat patients with non-Hodgkin lymphoma (NHL), doctors sometimes use hematopoietic stem cell transplant. The process typically involves a conditioning regimen of chemotherapy with or without radiation. A central question in recent years has been, what is the role of the intensity of conditioning regimen on outcomes? A more intensive regimen may be associated with reduced risk of relapse – but if it’s also associated with greater toxicity to the patient, is it really the best option?

Based on the results of a large study conducted by me and colleagues at the Center for International Bone Marrow Transplantation Research (CIBMTR), which were recently published in JAMA Oncology, the short answer may be “no.”

Head-to-head comparisons of treatment intensities

We looked over data from the Center for International Blood and Marrow Transplant Research on 1,823 adults with NHL who underwent allogeneic stem cell transplant (that is, transplant in which stem cells come from donors). The participants were given one of four therapies known as reduced-intensity conditioning and non-myoablative conditioning (RIC-NMAC) regimens: fludarabine-intravenous busulfan (Flu-Bu), fludarabine-melphalan (Flu-Mel140), fludarabine-cyclophosphamide (Flu-Cy) or Flu-Cy with 2 Gy total body irradiation (Flu-Cy-2GyTBI).

Flu-Mel140 is a higher-intensity regimen, whereas the other three are all on the lower end of the spectrum.

We were interested in a few outcomes in particular: overall survival, nonrelapse mortality over four years, and incidence of acute and chronic graft-vs-host disease (GVHD). We found some important differences for Flu-Mel140:

  • Overall survival for the Flu-Mel140 group was 49%, compared to 58% for Flu-Bu, 63% for Flu-Cy, and 67% for Flu-Cy-2GyTBI.
  • Nonrelapse mortality incidence for patients in the Flu-Mel140 group was 26% (for Flu-Bu, Flu-Cy, and Flu-Cy-2GyTBI, it was 16%, 17%, and 17%, respectively).
  • The Flu-Mel140 cohort also had a higher risk of chronic GVHD compared with the Flu-Cy cohort.

Choosing the right treatment

Even after adjustment for potential confounding variables, our results suggest that the more intense Flu-Mel140 regimen may be linked with greater risk of higher nonrelapse mortality and lower overall survival, relative to the other three regimens.

To our knowledge, this is the largest study to directly compare conditioning regimens against one another. Smaller studies had looked into the question, but no firm consensus had been reached. We suggest that the current results may be practice-changing for hematologists and oncologists who routinely use RIC-NMAC to treat patients with NHL.

The caveat, of course, is that the results are only applicable to NHL, not necessarily to other forms of cancer.

Where research meets practice

Clinicians at Levine Cancer Institute (LCI) have not used Flu-Mel140 for NHL patients undergoing allogenic transplant; the current study suggests that this was a prudent move.

Levine Cancer Institute has a long history of clinical research along with tailored cancer care. It is the Charlotte region’s only comprehensive transplant and cellular therapy center, and offers specialized therapies such as hematopoietic stem cell transplant and chimeric antigen receptor T cell (CAR T) therapy. Researchers at LCI continue to partner with teams around the world, as we did in this analysis, to study fundamental questions of cancer and its care. As always, the hope is to arrive at answers that can improve treatment practices – and outcomes – for patients and their families.

Faculty at Atrium Health, Levine Cancer Institute have led several national CIBMTR studies to answer important questions in hematopoietic stem cell transplantation.

For more information on LCI’s Transplant and Cellular Therapy Program or to refer a patient, please call 980-442-2900 or email LCIReferralCoordination@AtriumHealth.org.

Read the paper and accompanying editorial in JAMA Oncology.

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