Richter transformation (Richter syndrome)

CLL and SLL are usually slow-growing cancers of B cells, a kind of white blood cell that makes antibodies. In a small share of people, the disease suddenly changes into a much faster-growing lymphoma. Doctors call this Richter transformation. You may also see the older name Richter syndrome; the World Health Organization now prefers “transformation.”

Most often the new lymphoma is diffuse large B-cell lymphoma (DLBCL), a lymphoma made of large, fast-dividing B cells. Less often it looks like Hodgkin lymphoma instead. The two forms are treated differently, so the exact type found in the biopsy matters.

Doctors also check whether the new lymphoma grew from the same cells as the CLL. When it did, it is called “clonally related.” When it did not, it is “clonally unrelated” and tends to behave like a DLBCL that started on its own.

In many cases, the new lymphoma grows from the CLL cells themselves after they pick up further genetic changes, such as damage to a gene called TP53, that let them grow much faster. In other cases, a separate lymphoma appears alongside the CLL. These changes happen in the cancer cells during a person’s life. They are not inherited, and the condition is not contagious.

Doctors know some features of CLL that make transformation more likely, such as very large lymph nodes and certain gene changes, but they cannot predict who will get it, and nothing a person did causes it. It can happen in people who never needed CLL treatment and in people who have had it. Newer CLL medicines called BTK inhibitors have not lowered how often it happens.

The usual warning signs are a lymph node that suddenly grows quickly, fevers that keep coming back, soaking night sweats or losing weight without trying. These changes need a prompt check with the care team rather than waiting for the next routine visit.

The only way to confirm it is a biopsy, which means taking a piece of the growing node or tissue to look at under a microscope. A PET scan, which shows the most active areas, can help doctors choose which node to sample. The biopsy also tells doctors whether it is the DLBCL or the Hodgkin type.

Treatment usually starts soon after diagnosis. The first step is often a combination of chemotherapy with an antibody medicine, similar to the treatment for DLBCL. Doctors may also use targeted CLL medicines, and joining a clinical trial is encouraged because no single approach works well for everyone.

For clonally related disease that responds, European expert guidance lists a donor (allogeneic) stem cell transplant as a standard next step for suitable patients. The aim is to keep the lymphoma from coming back. In a large transplant registry study, results were best in people whose lymphoma had responded fully first.

CAR-T cell therapy is another option for some people. It uses the person’s own T cells, changed in a lab to attack the lymphoma. People with Richter transformation were left out of the main trials of CAR-T for large B-cell lymphoma, so what we know comes from registry studies; it helps some people, but in many the lymphoma comes back. The Hodgkin type and clonally unrelated disease tend to have a better outlook, closer to the same lymphoma starting on its own.

Many people have lived with CLL for years, sometimes without needing treatment. Being told it has changed into an aggressive lymphoma can be a shock, and decisions come quickly. It can help to bring someone to appointments and to ask the team what each step is meant to do.

Chemotherapy can mean hospital stays, a higher risk of infection and tiredness. CAR-T is given at specialist centers, with close watching for side effects such as high fevers or confusion. A donor transplant means months of recovery, close follow-up, a caregiver and care for graft-versus-host disease, where donor immune cells attack the body.

A donor transplant for Richter transformation uses blood-forming cells from another person. European expert guidance lists a matched brother or sister, a well-matched unrelated volunteer, and a partly matched or half-matched donor as standard choices for clonally related disease. The same guidance notes that, in most lymphomas, studies looking back at past transplants show similar results with matched sibling, well-matched unrelated and half-matched family donors.

That means an unrelated volunteer from a registry can be the donor who makes a transplant possible. Not everyone with Richter transformation will need a donor, and joining a registry cannot promise a match for a particular person. CAR-T and a transplant with a person’s own cells use their own cells, not a registry donor’s.

When a transplant from a donor is planned, the team usually tests brothers and sisters first. Each full sibling has about a one in four chance of being a full match.

Most patients do not have a matched relative. In the words of NMDP, the U.S. registry, “75% of patients don’t have a fully matched donor in their own family.” The team then searches registries of volunteer donors around the world and banks of donated cord blood. In some transplants, a half-matched parent, child or sibling can also be the donor.

Matching depends on inherited tissue markers called HLA, so a patient is most likely to match someone who shares their ancestry. Every person who joins makes the search a little more likely to succeed, especially for patients from groups that are underrepresented on registries.