Melphalan for Amyloidosis

In severe cases of amyloidosis, there is still a small but definite survival benefit for early diagnosis. However, in milder or early stages of the disease, there is little to no survival benefit.

Amyloidosis is a group of blood and bone marrow disorders in which abnormal, abnormal blood-derived materials accumulate in various tissues and organs of the human body. A protein called amyloid is involved in causing amyloidosis.\n

The American Cancer Society estimates there will be 910 new cases of AL amyloidosis, 910 cases of LG-AL amyloidosis, 630 cases of AG-AL amyloidosis and 15,090 new cases of other AL amyloidosis and 4,100 new cases of other LG-AL amyloidosis. In 2017, 26,000 Americans are expected to have AL amyloidosis with a prevalence of 7 per 100,000. For LG-AL, the average age in 2017 is around 70. For AG-AL it is around 50. For other amyloidosis it is around 65.

About one third of all patients die from amyloidosis and one third succumb to amyloidosis related illnesses; 20 times out of 25 is usually due to kidney failure. Treatment of amyloidosis has long been controversial, for various reasons including lack of strong scientific evidence that amyloidosis is the result of an underlying disease and that amyloidosis treatment is effective in preventing progression of the disease and preventing mortality, as well as being harmful. More aggressive treatment that slows the progression of symptoms will improve outcomes in patients with early-stage amyloidosis. Treatment options that improve quality of life or prolong life in patients with late-stage amyloidosis are less clear.

There is a range of non-specific signs and symptoms of amyloidosis. These signs may include fatigue, unexplained weight loss and anemia. In addition, amyloidosis has many clinical manifestations of which heart palpitations are a prominent one. A specific test for the disease can be done when there are no other specific signs of the syndrome.

Amyloidosis is caused by a primary systemic amyloid precursor protein disease, where both amyloid A and amyloid B are involved in the etiology of the disease. Amyloid is also found, but less commonly, in renal disease in general. These conditions are related, which is reflected in the fact that amyloidosis can cause some renal manifestations of the disease.

Melphalan is a highly effective treatment for amyloidosis in most countries. However, for people who have kidney failure, this substance should be avoided, as there is evidence that it may increase risk of kidney failure. In particular, the use of any chemotherapeutic agent, with or without haematological impairment, including melphalan for treatment of amyloidosis may increase risk of kidney failure.

Melphalan is a drug that can produce skin lesions that look similar to myeloma. Myeloma patients have low levels of serum protein, low levels of serum albumin, low calcium levels, high levels of Bence Jones protein and low levels of other proteins. In myeloma patients, high levels of serum calcium, increased albumin and increased total protein level in serum seem to exist, which is the indication of the use of melphalan among myeloma patients in the treatment of low body weight. Also, this method could help treat amyloidosis patients by improving nutritional status for patients. But the result will be the same as Bence Jones protein.

Clinicians should be aware of the limitations and pitfalls of clinical trial evidence for systemic therapies for amyloidosis beyond current treatments. Importantly, patients with advanced disease or in whom clinical trials evaluating targeted therapies may help direct therapy warrant careful consideration and a rigorous discussion of the potential clinical benefits and the potential risks of such trials in patients with advanced amyloidosis.

Patients with AA amyloidosis tend to come from a family of end stage renal disease regardless of renal function and are usually of a young age at the time of diagnosis. The most frequent type of amyloid protein is a monoclonal form of plasma cell dyscrasias. Therefore, in patients of AA amyloidosis, renal failure is due to glomerular amyloid deposition rather than to amyloid accumulation in the kidney itself. In a subset of patients with renal failure of unknown origin, it is found to be secondary to amyloid deposition in the kidneys.

Melphalan may be particularly useful in combination with other, more novel agents for aggressive amyloidoses of the AL and AL wild-type with a high amyloid constituent: CHOP, in the case of amyloidosis with AL wild-type with a low amyloid content (sporadic, or AL with no detectable amyloid in routine pathology). Such combinations may be particularly useful for patients with no detectable amyloid components, although these patients carry a real risk of relapse and should be treated accordingly. This may be particularly urgent for the treatment of AL amyloidosis with a high amyloid constituent.