What is the difference between leukemia and lymphoma?

Leukemia and lymphoma are the two most common blood cancers. Blood cells consist of three main types: red blood cells (RBCs), white blood cells (WBCs), and platelets (Figure 1). All three are derived from hematopoietic stem cells (HSCs). Blood cancers typically affect white blood cells and their progenitors. 

The differences between leukemias and lymphomas can be subtle, but in broad terms they are distinguished by location (bone marrow versus lymph nodes), and position in lineage (affecting stem or progenitor cells versus more mature lymphocytes). These distinctions can be blurred because lymphocytes in the lymph nodes can return to the bone marrow while stem and progenitor cells can differentiate and leave the bone marrow. Indeed chronic lymphocytic leukemia and small lymphocytic lymphoma refer to the same disease with a diagnosis of the former if the cancer is mainly found in the bone marrow and the latter if the cancer is predominantly in the lymph nodes (link).

Leukemias can be acute or chronic, and involve lymphoid (lymphocyte) or myeloid (RBCs, macrophages, neutrophils, mast cells, platelets) lineages giving rise to 4 main classes: acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), acute lymphocytic leukemia (ALL), or chronic lymphocytic leukemia (CLL).

Lymphomas are classified as Hodgkin (HL) or Non-Hodgkin (NHL) lymphoma. HL is characterized by the presence of Reed-Sternberg cells, which are large abnormal multi-nucleate cells that originate from mature B-cells. As many as 40% of HL cases are associated with presence of Epstein-Bar Virus (EBV) whose role in the cancer is not known. NHLs are a more heterogeneous collection of cancers; about 85% are B-cell type with the remaining 15% being T-cell or NK-cell type (link). 

In terms of age of onset, leukemia and lymphoma are the most common cancers among children and young adults, although the risk is very low. The incidence rate decreases in the 20s, 30s, and 40s, and then increases again past 55 with age being a major risk factor similar to the vast majority of cancers. For example, more than half of NHL patients are 65 or older when first diagnosed.

The symptoms of both leukemia and lymphoma are relatively non-specific and include fever, fatigue, frequent infections, weight loss, swollen lymph nodes, enlarged liver or spleen, easy bleeding and bruising, excessive sweating, bone pain, and itchy skin. Numerous other conditions share these symptoms, so that a more informative diagnostic test is needed.

An abnormal complete blood count (CBC) is an important indicator of leukemia or lymphoma with either a high WBC or low WBC count raising red flags along with low RBC and platelet counts. These suspicions can be followed up with a biopsy of lymph nodes or bone marrow looking for proliferation of cancerous cells which can lead to a more definitive diagnosis. In addition, imaging can provide an idea of the extent and spread of the disease. 

 

The good news is that treatments for both leukemia and lymphoma have been improving steadily. There have been refinements of standard chemotherapy protocols which include developing more effective combinations. In addition, scientists have achieved a better molecular understanding of certain leukemias/lymphomas such as delineating the underlying genetic changes. These insights have led to targeted therapies that specifically inhibit oncogenic proteins that drive the cancer. Finally, the two main types of immunotherapies, PD-1 inhibitors and CAR-T, have had success with both leukemias and lymphomas. Indeed, CAR-T has had the most success against blood cancers and comparably less success against solid tumors.

As a result of this progress, the five-year survival rate for all types of leukemia is 65 percent, and the five-year survival for Hodgkin lymphoma is 90% and for Non-Hodgkin lymphoma is 73% depending on the type and stage (Mayo Clinic). The earlier the cancer is diagnosed, the better the chances. 

Hopefully we can continue progressing toward an eventual effective cure of leukemia, lymphoma, and other blood cancers.

Figure 1. Lineage of hematopoietic stem cell (HSC) shows early development in bone marrow followed by later maturation in blood stream and lymph nodes. Generally speaking, leukemia develops earlier in the lineage in bone marrow whereas lymphoma develops later in the lineage in lymph nodes and blood.