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What is double hit lymphoma (DHL)?

DHL is an uncommon subtype of diffuse large B-cell lymphoma (DLBCL), making up about 5% of DLBCL cases. In DHL, the lymphoma cells have abnormalities (called mutations or rearrangements) on two significant genes – the MYC gene and either the BCL2 or BCL6 genes. Most lymphoma cells have a rearrangement on one only or none of these genes.

  • MYC gene

MYC regulates approximately 15% of human genes and has a role in the progression of the cell cycle, apoptosis (programmed cell death) and cellular transformation through protein synthesis and metabolism. In DHL, changes to this gene result in rapid growth of lymphoma cells.

  • BCL2 gene

BCL2 regulates cell death (apoptosis) by either inducing it or inhibiting it. In DHL, changes in this gene result in an anti-apoptotic effect in lymphoma cells, leading to their prolonged survival.

  • BCL6 gene

BCL6 has a role in regulating activation, survival, DNA damage response and cell cycle arrest. Click here for more information.


DHL may be identified as the original diagnosis, but also may occur in people with a past history of a slower growing (low grade or indolent) lymphoma, called follicular lymphoma. In this case, the follicular lymphoma ‘transforms’ into DHL and is suspected when a lymph node mass starts to grow rapidly.

Most DHLs are rapidly growing lymphomas as the MYC and (most commonly) BCL2 re-arrangements lead to the growth of lymphoma cells that survive for longer than normal.

Diagnosing DHL

Identifying the type of DHL relies on staining the lymphoma cells using a process called IHC (Immunohistochemistry) and/or another complex test called FISH (Fluorescent In Situ Hybridisation).

How is DHL treated?

Combination chemotherapy is the main form of treatment for DHL. The names of different drug combinations often are derived from the first letter of each of the drugs used. The protocol used will be determined by your particular situation and careful consideration by your doctor.

Chemotherapy is given in several ways:

  • through a vein (intravenously or IV) usually in the arm or hand;
  • in tablet form (orally); or
  • occasionally, as an intrathecal infusion (IT) – into the fluid around the spinal cord.

stem cell transplant may be offered to some people with DHL after a response to their initial treatment.


DHL is a challenging condition to treat. You should speak to your doctor about the specific nature of your case (e.g., DHL mutations, and the extent of your lymphoma) and the implications of this for you. Only your doctor has all your medical information regarding your particular situation.

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Last updated on May 22nd, 2024

Developed by the Leukaemia Foundation in consultation with people living with a blood cancer, Leukaemia Foundation support staff, haematology nursing staff and/or Australian clinical haematologists. This content is provided for information purposes only and we urge you to always seek advice from a registered health care professional for diagnosis, treatment and answers to your medical questions, including the suitability of a particular therapy, service, product or treatment in your circumstances. The Leukaemia Foundation shall not bear any liability for any person relying on the materials contained on this website.