Rizwan Romee, MD
Physician, Dana-Farber
Associate Professor of Medicine, Harvard Medical School
For many patients with hematologic malignancies like Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS), or Myeloproliferative Neoplasms (MPN), the only curative option is stem cell transplant (SCT). However, for patients with residual disease after chemotherapy but before transplantation, more than 60 percent of them will relapse and do extremely poorly, according to Rizwan Romee, MD, Director, Haploidentical Donor Transplantation Program at Dana-Farber and Associate Professor of Medicine, Harvard Medical School. “And on top of that, if people have TP53 gene mutations, the most commonly mutated cancer gene, relapse is almost a certainty.”
Mopping Up Residual Disease
A new clinical trial1led by Romee, supported by the Leukemia & Lymphoma Society (LLS) and the Dana-Farber Accelerator, seeks to change this grim prognosis by leveraging the unique properties of natural killer (NK) immune cells. Romee and his team have discovered that these cells can be trained to enter a “memory-like” state, enhancing their anti-leukemia properties. “We hypothesized that if we give these memory-like NK cells from the same donor who provides the stem cell graft, those patients may have a better chance of curing their disease,” he explains. “These NK cells can clear or mop away the residual leukemia cells, significantly increasing the odds of success with the transplant.”
All manufacturing of the NK cells occurs at the Connell and O’Reilly Families Cell Manipulation Core Facility at Dana-Farber, with advanced immune monitoring methods employed to track the cells’ interactions within the body. “We hope to learn not only how to help patients but also to gain scientific insights into cell interactions and persistence.”
These NK cells can clear or mop away the residual leukemia cells, significantly increasing the odds of success with the transplant.
Rizwan Romee
The potential benefits of this trial for patients are immense. For those leukemia patients at high risk for post-allogeneic SCT relapse, the odds of relapse are dauntingly high, with traditional transplants offering less than a 20% chance of cure.
Romee’s approach could dramatically alter this landscape. “We are hoping to make a significant impact on the prognosis of these patients,” he asserts. “It’s a huge unmet need, and we believe our trial can address it.”
Understanding The Relapse Process
The trial was recently activated and is now enrolling patients, with funding from LLS covering the costs of the cells and the trial itself. A Dana-Farber Accelerator Award supports the deep dive into the biology and interaction of the cells, a critical component
of the research. “Without this type of collaboration and funding, which is a great example of how clinical and bench research inform each other, no discovery would happen,” Romee emphasizes. “These are highly complex, manipulative cells, and we need to know what they are doing in the body. Are they safe? Where are they going? How long are they persisting? These are critical questions.”
The trial’s success could pave the way for the next generation of therapies, offering hope to patients who currently face limited options. “We want to maximize how much we learn,” Romee says. “This is not standard treatment. It’s about understanding the immune escape mechanisms and why some patients still relapse. This trial is a critical piece of the puzzle.”
Team Members: Rizwan Romee, MD, Roman Shapiro, MD
Team Members
Roman Shapiro, MD
Instructor in Medicine, Harvard Medical School, Dana-Farber
