Promyelocytic leukemia is an acute form of leukemia caused by red bone marrow neoplasia. This leads to an uncontrolled proliferation of promyelocytes, an immature precursor of white blood cells, leukocytes. Treatment and mean survival chances of promyelocytic leukemia are still considered poor.
What is promyelocytic leukemia?
Promyelocytic leukemia, PML, is a special form of acute myeloid leukemia, AML. It is characterized by an increased number of immature white blood cells being detected in the bloodstream. Promyelocytes are bone marrow cells that are not normally found in the blood. See gradphysics for Femoral Head Necrosis in English.
In PML, however, this cell type is overproduced in the bone marrow and released into the free bloodstream for reasons that are not yet clear. This form of neoplasia is characterized by a very specific, characteristic shape of the immature white blood cells, also called blasts.
Within all new diagnoses of acute myeloid leukemia, promyelocytic leukemia accounts for only about five percent, so this form of leukemia is rare. When PML breaks out, ethnic and regional frequencies can be determined for which, however, there is still no plausible explanation.
Adolescents and young adults are mainly affected, because after the age of 60 the incidence rate decreases significantly. Women and men are about equally affected by promyelocytic leukemia.
Causes
A clear causal assignment for the development and the onset of promyelocytic leukemia is not known to this day. A higher incidence can be observed in Central and South America, in Italy and in Spain, but the reason for this is also unknown. However, there are indications of so-called chromosomal aberrations that could be directly involved in the development of promyelocytic leukemia.
The presence of a specific chromosome translocation or the corresponding fusion gene is regarded as diagnostic proof. In addition, other molecular variants have also been identified, which, however, occur even more rarely. However, these typical chromosomal changes do not occur in all patients suffering from promyelocytic leukemia.
This is therefore insufficient as the sole criterion for determining the cause. The theory of an increased family accumulation of the disease has now been rejected again. The development of PML always begins in the red bone marrow, where independent, autonomous clones develop, which produce immature white blood cells uncontrolled, i.e. typical of a malignant tumor cell.
Symptoms, Ailments & Signs
Promyelocytic leukemia is a form of acute leukemia and is therefore always a haematological emergency that requires immediate medical intervention. Due to the neoplasia of immature white blood cells in the bone marrow, the production of thrombocytes, blood platelets, is largely suppressed.
Therefore, there is an increased tendency to bleed early on, which is the most important diagnostic criterion. This tendency to bleed is also regularly associated with a pronounced blood clotting disorder. Externally, these symptoms are already recognizable by the finest, punctiform bleeding in the skin and mucous membranes, also referred to as petechiae.
Therefore, there is a risk of death, even with the smallest of injuries, due to uncontrollable bleeding. However, the greater risk for patients with promyelocytic leukemia comes from internal, especially intracerebral, bleeding, which is also a direct result of the increased tendency to bleed.
If specific therapeutic measures are not taken immediately, the lives of those affected cannot usually be saved. In the early stages of the disease, long before there is a visible tendency to bleed, the focus is on non-specific symptoms. These include, for example, pronounced paleness due to anemia, a drop in performance and tiredness.
Diagnosis & course of disease
The reliable diagnosis of promyelocytic leukemia must be made in the haematological laboratory with the assistance of a specialist. Under the light microscope, a characteristically leukaemic picture is seen with massive occurrences of promyelocytes in the peripheral blood.
Biopsies of the bone marrow as well as human genetic and coagulation tests can confirm the diagnosis at an early stage. The course of the disease is considered infaust, since it is a severe disease with a significantly reduced general condition.
Complications
First and foremost, promyelocytic leukemia leads to a significantly increased tendency to bleed in those affected. Even minor accidents or cuts can cause severe bleeding. Blood coagulation itself is also clearly disrupted by promyelocytic leukemia in most cases, making it difficult to stop the bleeding. As a rule, even minor bleeding can be life-threatening if the bleeding cannot be stopped.
Internal bleeding can also occur due to promyelocytic leukemia and lead to serious complications and symptoms. Those affected often suffer from exhaustion and fatigue, which, however, cannot be compensated for with the help of sleep. Permanent paleness also occurs as a result of promyelocytic leukemia and the resilience of those affected decreases significantly as a result of the disease.
Promyelocytic leukemia is usually treated with medication. There are no complications if there is no overdose of the drug. Furthermore, there is also a positive course of the disease. However, it cannot usually be predicted whether the life expectancy of the person affected will be reduced by promyelocytic leukemia.
When should you go to the doctor?
An increased bleeding tendency is to be understood as an alarm signal from the organism. If even minor injuries cannot be stopped with the usual methods of stopping bleeding, increased vigilance is required. A doctor should be consulted as soon as possible, since promyelocytic leukemia can lead to premature death in the event of an unfavorable course of the disease. Timely and comprehensive medical care is essential when dealing with the disease. This also includes early diagnosis and a visit to the doctor at the first signs of health impairment.
In addition, there is a risk of sepsis and thus blood poisoning with open wounds. A pale complexion, rapid exhaustion and increased tiredness are signs of a disorder. If the symptoms appear suddenly or develop gradually, a doctor is needed. If there is an increasing need for sleep, apathy and apathy, there is a need for action. If there are changes in behavior, leisure activities are reduced or there is a lack of interest, a doctor should be consulted.
Disturbances in attention or concentration are worrisome. They indicate a health irregularity that needs to be investigated and treated. A mental and physical decline from the usual level of performance must be discussed with a doctor. A decrease in resilience or an increase in stress are indications that should be followed up.
Treatment & Therapy
A causal, i.e. cause-related treatment of promyelocytic leukemia is not yet possible. All elements of therapy are focused on stopping the autonomic neoplasia of immature white blood cells in the bone marrow. For this purpose, high-dose chemotherapy with so-called anthracyclines is initially carried out.
However, since the patients are in mortal danger due to the increased tendency to bleed, substitution therapy with coagulation factors must take place at the same time. To increase the platelet count, selective platelet concentrates are also administered intravenously. Newer treatment strategies result from the administration of all-trans retinoic acid, ATRA, which is a derivative of vitamin A acid.
This substance, which is not a chemotherapeutic agent, acts at the molecular level and induces the maturation of immature blast cells into mature and functional white blood cells, neutrophilic granulocytes. In addition to high-dose chemotherapy and treatment with ATRA, arsenic compounds are always included in the treatment concept.
The antileukemic efficacy of certain arsenic molecules in the treatment of acute leukemia is well documented. Due to the enormous toxicity of arsenic as a heavy metal, however, any form of overdose must be strictly avoided.
Prevention
If a patient has survived five years after the initial diagnosis of promyelocytic leukemia, the recurrence rate is surprisingly low compared to other bone marrow neoplasms. Close checks of blood count and coagulation values are essential. There is no direct prevention against the occurrence of promyelocytic leukemia.
However, healthy middle-aged patients can be advised to have blood counts checked regularly as part of preventive medical check-ups. Leukemic changes would be noticed early on, even if there were no symptoms yet.
Aftercare
After treatment of promyelocytic leukemia, long-term monitoring of patients is recommended. Follow-up care runs for a period of at least ten years. During this time, the patients are examined once a year for control purposes. The follow-up examinations focus on the determination of a late recurrence.
The term refers to a recurrence of the disease several years after treatment. A recurrence of promyelocytic leukemia after successful therapy is very rare within a period of up to five years. However, late recurrences after more than ten years have occasionally been observed. This explains the long period of follow-up examinations.
With the regular check-ups, long-term consequences of the therapy can be recorded and the occurrence of secondary leukemia or other malignant tumors can be determined. Part of the follow-up for patients with promyelocytic leukemia is regular bone marrow examination at three-monthly intervals for a period of 12 to 18 months.
The length of follow-up depends on whether patients are classified as standard-risk or high-risk. The aim of this follow-up examination is to detect any residual leukemia cells that may remain in the body. Timely therapy when the findings are positive can allow a relapse to be recognized and treated early.
You can do that yourself
With adequate treatment, promyelocytic leukemia has a good prognosis. However, patient support is very important. In consultation with the doctor, the patient should be treated in a specialized leukemia center. There, all known complications can either be prevented or treated quickly by taking certain measures. In order to recognize the leukemia in good time, the patient should definitely see a doctor if they have unclear symptoms such as permanent extreme tiredness, pale skin, fever, constant abdominal pain, increased tendency to bleed, bruises, swollen lymph nodes, joint pain and other strange changes. This makes it possible to start therapy more quickly.
The patient can also contact self-help groups, the German Cancer Aid Association or the German Leukemia and Lymphoma Aid Association. V. provide extensive information and thereby also reduce fears. Membership in a self-help group, where different experiences in dealing with the disease are exchanged, helps many patients. This is a great relief for many of those affected. The certainty that healing is possible can also accelerate the healing process. But even in more severe cases, this exchange can have a very positive impact on the quality of life.
Taking advantage of psychological counseling often helps to prevent depression and other psychological consequences of leukemia. Despite a serious illness, a healthy lifestyle with a balanced diet and staying in the fresh air also supports recovery.