Double-hit lymphoma (MYC and BCL2 rearranged)

Lymphoma is a cancer of lymphocytes, white blood cells that help fight infection. Double-hit lymphoma is an aggressive lymphoma of B cells, the lymphocytes that make antibodies. Under the microscope it often looks like diffuse large B-cell lymphoma (DLBCL), though in some cases the cells are medium-sized or look more like other fast-growing lymphomas.

What sets it apart is a test result, not the look of the cells. In a lab test called FISH, two genes, MYC and BCL2, are found broken and rejoined to other DNA. This is called a rearrangement. The World Health Organization now names this condition “diffuse large B-cell lymphoma/high-grade B-cell lymphoma with MYC and BCL2 rearrangements.”

A few related terms cause confusion. “Double-expressor” lymphoma means the MYC and BCL2 proteins are high, but the genes are not rearranged; that is a different finding. Lymphomas with rearranged MYC and BCL6, but not BCL2, are no longer grouped here. “Triple-hit” lymphoma, with all three genes rearranged, still has the MYC and BCL2 rearrangements that define this group.

MYC and BCL2 normally help control how B cells grow. When both are rearranged in the same B cell, that control is lost and the lymphoma can grow quickly. These changes happen in the lymphoma cells during a person’s life.

They are not inherited from a parent and are not passed to children. The lymphoma is not contagious. Some cases grow out of an earlier, slower lymphoma called follicular lymphoma, while others appear without one.

People often notice swollen lymph nodes, sometimes in many places. Fevers, night sweats and weight loss are common. The lymphoma often starts outside the lymph nodes and is usually at an advanced stage by the time it is found.

It often reaches the bone marrow, and it can spread to the brain and spinal cord. That is why doctors may do extra tests and discuss whether treatment to lower that risk makes sense. A recent population-based study found this spread was less common than older reports suggested.

There is no single standard first treatment. Many doctors use more intensive chemotherapy combined with rituximab, an antibody medicine, because studies suggest the usual regimen called R-CHOP works less well here. Those studies were not randomized trials, so the best approach is still not settled, and a clinical trial is often worth asking about. The US National Cancer Institute also notes a clear benefit from a newer regimen called Pola-R-CHP in double-hit lymphoma.

If the lymphoma does not respond to first treatment or comes back within about a year, CAR-T cell therapy is now a standard option for people who are well enough. CAR-T uses the person’s own T cells, collected from their blood and changed in a lab to attack lymphoma. European transplant experts include double-hit lymphoma with the other large B-cell lymphomas in this advice.

If the lymphoma comes back later and responds to more chemotherapy, high-dose chemotherapy followed by a transplant of the person’s own stem cells is an option. European transplant guidance does not recommend that kind of transplant as a routine part of first treatment, although some UK teams may offer it after a good first response. A donor (allogeneic) transplant is considered only in selected people, usually after CAR-T or an own-cell transplant has not worked.

Treatment usually has to start quickly, and intensive chemotherapy can mean hospital stays of several weeks. Tiredness, a higher risk of infection and other side effects depend on the regimen. A fever during treatment needs a call to the care team straight away.

CAR-T is given at specialist centers. The team watches closely for cytokine release syndrome, a strong immune reaction that can cause high fevers, and for confusion or other nerve-system effects. A transplant with a person’s own cells means collecting stem cells first, then high-dose treatment and several weeks of recovery while blood counts return.

Most treatment for double-hit lymphoma does not use a donor. A transplant with a person’s own stem cells uses their own blood-forming cells. Approved CAR-T treatments also start with the person’s own cells, but these are T cells changed to fight lymphoma, not a new marrow.

A registry donor is needed only if a donor (allogeneic) transplant is chosen, which European experts list as an option for eligible people after CAR-T or an own-cell transplant has not worked. Then a brother or sister, an unrelated volunteer or a half-matched relative may be considered. Registry volunteers help patients with many conditions, including people with this lymphoma who do need a donor.