E74b Hematological system: leukemias, lymphomas and myeloma

Topic

Hematologic tumors—namely leukemias, lymphomas, and myeloma—possess a physical characteristic that radically distinguishes them from solid tumors: their growth is not limited by physical space constraints. This is because their tumor cells do not form a compact mass in a single location within the body; instead, they circulate freely or are distributed throughout the bone marrow and peripheral blood.

Free from such spatial constraints, the growth of a hematologic tumor can be purely exponential, lacking the braking mechanisms that cause solid tumors to plateau; this exponential growth continues until normal blood cell production in the bone marrow collapses—that is, until the tumor cells completely displace the healthy cells responsible for producing red blood cells, white blood cells, and platelets.

Acute leukemias, in particular, have doubling times of just a few days, creating the greatest time-sensitivity of any tumor type; this rapid growth rate necessitates initiating treatment for acute leukemia much more urgently than for most other tumors.

These hematologic tumors also possess a fundamental peculiarity shared by no other tumor type: the tumor itself is part of the patient's immune system—or a precursor to that part—because leukemias, lymphomas, and myeloma originate from the very cells that constitute the immune system. This characteristic requires any immunotherapy targeting these tumors to be extremely specific in order to distinguish tumor cells from the patient's normal immune cells, which are nearly identical to one another.

To achieve this specificity, various treatment approaches exist: the patient's own T-lymphocytes can be genetically modified to specifically recognize the tumor cells; There are also bispecific antibodies capable of simultaneously binding to a tumor cell and a T-lymphocyte, bringing them into close proximity; additionally, there are antibody-drug conjugates that bind specifically to the tumor cell and release a cytotoxic drug directly onto it. All three treatment types rely on the presence—on the surface of hematologic tumor cells—of specific proteins that are absent (or present at much lower levels) in most other body tissues, thereby allowing the treatment to be directed selectively against the tumor.

It is this combination of spatially unrestricted growth—which can become purely exponential to the point of collapsing normal blood cell production—and the fact that the tumor itself is part of the patient's immune system that makes hematologic tumors require both greater treatment urgency and a much higher degree of immunological specificity than any solid tumor.

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