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Role of Stem Cell Transplants in Richter’s Transformation

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

Medically Reviewed by Dr. Brian Koffman

Richter’s transformation is a rare and very aggressive complication of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), where the disease turns into a much more aggressive lymphoma, usually diffuse large B cell lymphoma (DLBCL). Haemopoietic (blood forming) stem cell transplants (HSCT) are one of the only successful therapies for Richter’s transformation, but they are rarely used. In this interview, Dr. Brian Koffman spoke with Dr. Adam Kittai, an associate professor of medicine at Mount Sinai. They discussed the role of haemopoietic stem cell transplants in treating Richter’s transformation.

What is a stem cell transplant?

“Blood stem cells are found in the bone marrow and can produce any type of blood cell the body needs. They are constantly dividing and making new blood cells, so any condition that impairs their ability to create new blood cells can cause serious health problems. A stem cell transplant (sometimes referred to as a bone marrow transplant) is a type of procedure used to treat conditions where the bone marrow is damaged or cancerous and can no longer produce healthy stem cells.”

As part of a stem cell transplant, healthy stem cells are collected from the patient or from a donor. In the past, all patients then received high-dose chemoimmunotherapy (CIT) or radiation therapy to prepare the body by wiping the marrow clean of cancer or other diseases to receive the new stem cells. After this conditioning, new stem cells are infused into the patient, “rescuing” the patient from the high-dose CIT. Today, in nearly all CLL patients, reduced intensity CIT is used where the new cells hopefully “engraft” and take over the marrow, and the benefit is realized not so much from the CIT but rather when the new immune system recognizes any persistent CLL cells as foreign and tries to destroy them. There are two types of transplants: autologous stem cell transplants and allogeneic stem cell transplants.”

What is an autologous stem cell transplant?

“Autologous stem cell transplants are where patients undergo high-dose chemoimmunotherapy and then rescue themselves with their own stem cells. This type of transplant can be used to treat DLBCL and other aggressive lymphomas. However, autologous stem cell transplants don’t work well for patients with Richter’s transformation, because these patients don’t respond well to chemoimmunotherapy which is necessary for the transplant to work.

Autologous stem cell transplants also aren’t used in treating CLL for a few reasons. First, patients with CLL who progress far enough to need a transplant tend to be refractory to chemoimmunotherapy. Second, the high load of CLL cells in the bone marrow makes it difficult for patients to rescue themselves because there is a high chance that CLL cells will be collected with the stem cells. And finally, probably because of the first two points, the outcomes proved disappointing in past clinical trials of autologous stem cell transplants.”

What is an allogeneic stem cell transplant?

“Allogeneic stem cell transplants are where patients get a whole new immune system from someone else. For this type of transplant, the patient must be matched with a donor whose tissue type closely matches theirs. This could be a relative or a well-matched unrelated donor. Allogeneic stem cell transplants can be used to treat Richter’s transformation and CLL / SLL.

Good disease control before the transplant is essential for the best chance of success with an allogeneic stem cell transplant. This is a major barrier for patients with Richter’s transformation because current therapies are not always good enough to achieve good disease control.”

What are some of the risks of getting a stem cell transplant?

“Allogeneic stem cell transplants have serious risks and side effects that must be considered carefully. There is a chance that the new donor stem cells will attack the cells of the patient’s body and cause serious damage. This is called graft versus host disease. Doctors try to minimize this risk by closely matching the patient and the donor and also by using drugs to suppress the immune system. There is also a risk of death from the procedure itself or complications or infections. Allogeneic stem cell transplants are also really tough on older patients, so sometimes a patient’s age and other health conditions can prevent them from getting a transplant.”

Any final thoughts?

“Patients with Richter’s transformation who are able to achieve good disease control should consider an allogeneic stem cell transplant. It can be curative for some and offer long-term disease control for others. It is always a good idea to get a second opinion from a doctor who sees a lot of patients with Richter’s transformation at a site that can perform allogeneic stem cell transplants or CAR-T therapy.

Watch the interview with Dr. Adam Kittai:

Role of Stem Cell Transplants in Richter’s Transformation – Dr. Adam Kittai

Take care of yourself first.

Ann Liu, PhD