The last essays “multiple myeloma 1&2” may help you understand malignancy or “cancer” of mature B lymphocyte and plasma cell.

Under the physiological condition, mature B lymphocytes and plasma cells produce and secret astronomically diverse clones of immunoglobulin molecules, IgM of the former and the other immunoglobulin isotypes , such as IgG, IgA, IgE and IgD of the latter. Each clone of immunoglobulin has the specific function of antibody against any antigenic substance, like a key and key hole for it.

However, malignancy of each of those cells means production of only one type of immunoglobulin molecule, which is called “Monoclonal protein” or M protein. It still has a certain antibody specificity. M protein of IgM increases in the blood, then this type of malignancy is diagnosed as essential macroglobulinemia, or Waldenstroem’s macro- globulinemia, because of bigger gammaglobulin of IgM molecule, such as around one million molecular weight of IgM. So M protein can be used as a tumor marker of its malignancy. In this case, malignant cells are derived from mature B lymphocyte. Generalized lymph nodes are involved and infiltration of malignant cells is observed in the bone marrow.

On the other hand, if M protein derives from other than IgM, such a M protein is produced by malignant growth of plasma cell in the bone marrow. Many growth sites of malignant cells in the bone marrow destruct bone tissue leading to pathological fracture or strong bone pain. This state is diagnosed as multiple myeloma. M protein could easily be detected in the serum by immunological laboratory test. In health examination, this is often recognized as reverse value of A/G ratio, which is very popular to check the ratio of albumin by globulin. As G value is increasing, this is called hyperglobulinemia, or hypergammaglobulinemia. This is the first step for diagnosis of multiple myeloma or Waldenstroem’s macroglobulinemia.

As I described in the last essay, this monoclonal immunoglobulin consists of two pairs of heavy chain and light chain, such as kappa (κ) or lambda(λ). If a certain case of multiple myeloma shows M protein IgGκ in the serum, abnormal protein composed of two light chains of κ can be seen in the serum and urine. This abnormal protein is called Bence-Jones protein, BJP in short. Since the molar weight of BJP is small, it can be found in urine as proteinuria. In general, immunoglobulin in the blood does not go into urine, because of bigger molecular weight of immunoglobulin than filter size of the glomerular filtration “sieve”.

In general, health screening includes urine protein measurement, which is mainly to detect albumin, major protein in the blood, abnormally going out to urine through renal glomerulus from the blood plasma. This test is mainly to check illness at the glomerulus. Therefore if a diagnosis of “hypergammaglobulinemia” is given, BJP screening should be taken. This is why one should take detail examination, if one can be found with some abnormality at blood or urine test of general health screening.

The major sign of multiple myeloma is pains at multiple bone sites. If one faces those cases, having an examination by orthopaedist or physician would be recommended. Detail examination may include blood test, urine test, and X-ray examination. Multiple sites of bone are occupied by growth sites of malignant plasma cells, called myeloma site, and the size of them progress very slowly. But there are some cases progressing rapidly, therefore, seeing a medical specialist periodically is very important. Increase and decrease of M protein in blood is important to check the progress of this illness. At present, various good medicines have been developed, for example, bortozemib, thalidomaide or melphalan.

Thalidomaide was once used as hypnosis, or medicine to alleviate morning sickness. But it was stopped selling because it may be inducing inborn deformity-phocomelia. But now this medicine is attracting attentions as anticancer drug, which is especially effective for multiple myeloma. In addition, some bone stiffener has been developed.

The effect of BioBran on multiple myeloma was reported by a researcher of the US, and its ability to activate NK cells is attracting attentions. Now medical team in Slovakia is conducting basic research and clinical trials on this effect.

From the practical point of view, it is usually difficult to evaluate effects of anticancer drug. The method to check it can be divided into two kinds, such as double-blind control study and case-control study. The former is as follows. In order to compare two groups statistically, it is important to gather patients with same demography and disease stage as many as possible and to divide them into two groups. Anticancer drug is administered to one group and not to the other. And statistical comparisons are made between those two groups. It is easy to set up two groups theoretically, but it is quite hard or almost impossible to carryout this comparison for these patients.

The latter is to administered anticancer drug to each patient, and record the effect one by one. The latter is easier to practice, but it is not accepted by medical authority from the viewpoint of lack in objectivity and “anecdotal” record.

Treatment strategies for multiple myeloma include alleviating pains at bone, preventing bone fracture, and reducing M protein in blood and BJP in urine. In many cases, stagnation of abnormal proteins may cause troubles at kidney functions called myeloma kidney, and sometimes result in serious conditions like death.

Anyway, the most problematic point of this cancer is that it shows no direct relations with lifestyle-related diseases and at present preventive measures against this disease remains to be found.

For reference I introduce a research reported on “New England Journal of Medicine” which is highly appreciated internationally. Nowadays, it is internationally used as Velcade for patients with multiple myeloma.

Richardson PG et al: A Phase 2 study of Bortezomib in relapsed, refractory myeloma. N Eng J Med 2003; 348:2609-17

In next essay, I will talk about head and neck cancer. Esophagus cancer, thyroid cancer, cancer of pharynx, laryngopharynx and rhinopharynx cancer may be mentioned because they are related with life-style diseases. Brain tumor will not be mentioned.