Promyelocytic leukemia is an acute form of leukemia caused by a neoplasia in the red bone marrow. It involves an uncontrolled proliferation of promyelocytes, an immature precursor of white blood cells, leukocytes. Treatment and median survival rates 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 the increased detection of immature white blood cells in the bloodstream. Promyelocytes are bone marrow cells that are not normally found in the blood. However, in PML, this cell type is overproduced in the bone marrow for reasons that are not yet clear and is released into the free bloodstream. This form of neoplasia is characterized by a very specific, characteristic shape of 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. Ethnic and regional frequencies can be observed in the onset of PML, for which, however, there is still no plausible explanation. Mostly adolescents and young adults are affected, because after the age of 60 the incidence of the disease decreases significantly. Women and men are affected by promyelocytic leukemia approximately equally.
Causes
To date, a definite cause attribution for the development and onset of promyelocytic leukemia is not known. A higher incidence can be observed in Central and South America, in Italy, and in Spain, although the reason for this is also unknown. However, there are indications of so-called chromosomal aberrations, which could be directly involved in the development of promyelocytic leukemia. The presence of a specific chromosome translocation or the corresponding fusion gene is considered diagnostic evidence. In addition, other molecular variants have also been identified, although these occur even less frequently. However, these typical chromosomal alterations do not occur in all patients suffering from promyelocytic leukemia. Therefore, this is also insufficient as the sole criterion for determining the cause. The theory of an increased familial clustering of the disease pattern has also been rejected in the meantime. The disease development of PML always begins in the red bone marrow, where independent, autonomous clones develop that produce immature white blood cells in an uncontrolled manner, i.e., typical of a malignant tumor cell.
Symptoms, complaints, and signs
Promyelocytic leukemia is a form of acute leukemia and therefore always a hematologic emergency requiring 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, an increased bleeding tendency occurs early on as the most important diagnostic criterion. This bleeding tendency is also regularly accompanied by a pronounced blood coagulation disorder. Externally, these signs of the disease are already recognizable by very fine, punctate hemorrhages in the skin and mucous membranes, also known as petechiae. Therefore, there is a danger to life, even with the smallest injuries, due to unstoppable bleeding. However, the greater danger for patients with promyelocytic leukemia comes from internal bleeding, especially intracerebral bleeding, which is also a direct consequence of the increased bleeding tendency. If specific therapeutic measures are not taken immediately, the lives of those affected can usually not be saved. In the early stages of the disease, long before there is a visible bleeding tendency, rather non-specific symptoms are in the foreground. These include, for example, pronounced pallor due to anemia, loss of performance, and fatigue.
Diagnosis and course of the disease
The definite diagnosis of promyelocytic leukemia must be made in the hematology laboratory with the assistance of a specialist. Light microscopy reveals a characteristic leukemic picture with masses 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 to be infaust, being a severe clinical picture with a markedly reduced general condition.
Complications
First and foremost, promyelocytic leukemia leads to a markedly increased bleeding tendency in affected individuals. Even minor accidents or cuts result in severe bleeding. In most cases, promyelocytic leukemia also significantly disturbs blood clotting, so that bleeding cannot be stopped easily. As a rule, therefore, even minor bleeding puts the patient’s life at risk if the bleeding cannot be stopped. Internal bleeding can also occur as a result of promyelocytic leukemia and lead to serious complications and discomfort. The affected persons themselves often suffer from fatigue and tiredness, which cannot be compensated by sleep. A permanent pallor also occurs due to promyelocytic leukemia and the resilience of the affected person decreases significantly due to the disease. The treatment of promyelocytic leukemia is usually carried out with the help of medication. There are no complications if the drug is not overdosed. Furthermore, there is also a positive course of the disease. However, whether the life expectancy of the affected person is reduced by promyelocytic leukemia can usually not be predicted.
When should you see a doctor?
An increased bleeding tendency should be understood as an alarm signal of the organism. If even minor injuries cannot be stopped by standard methods of hemostasis, increased vigilance is called for. A visit to the doctor should be made as soon as possible, because if the course of the disease is unfavorable, promyelocytic leukemia will lead to premature death of the patient. Timely and comprehensive medical care is essential in dealing with the disease. This includes early diagnosis and a visit to the doctor at the first sign of health impairment. In addition, open wounds pose a risk of sepsis and thus blood poisoning. A pale complexion, rapid exhaustion and increased fatigue are signs of a disorder. If the complaints occur suddenly or develop gradually, a doctor is needed. If there is an increasing need for sleep, apathy as well as apathy, there is a need for action. If there are changes in behavior, leisure activities are reduced, or a lack of interest becomes apparent, a doctor should be consulted. Disturbances in attention or concentration are cause for concern. They indicate a health irregularity that needs to be investigated and treated. A mental as well as physical decline in the usual level of performance must be discussed with a physician. A decrease in resilience or an increase in the experience of stress are clues that should be followed up.
Treatment and therapy
Causal, or cause-related, treatment of promyelocytic leukemia is not yet possible. All elements of therapy focus on stopping the autonomous neoplasia of immature white blood cells in the bone marrow. For this purpose, high-dose chemotherapies with so-called anthracyclines are initially administered. However, since the patients’ lives are in danger due to the increased bleeding tendency, a substitution therapy with coagulation factors must take place in parallel. To increase the platelet count, additional selective platelet concentrates are administered intravenously. Newer treatment strategies result from the administration of all-trans-retinoic acid, ATRA, it 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 blasts into mature and functional white blood cells, neutrophilic granulocytes. In addition to high-dose chemotherapy as well as treatment with ATRA, arsenic compounds are always included in the treatment regimen. The antileukemic efficiency of certain arsenic molecules in the treatment of acute leukemias is well documented. However, because of the enormous toxicity of arsenic as a heavy metal, any form of overdose must be strictly avoided.
Prevention
If a patient survives five years after initial diagnosis of promyelocytic leukemia, the recurrence rate is remarkably low compared with other bone marrow neoplasms. Close monitoring of blood counts and coagulation values is essential.There is no direct prevention against the occurrence of promyelocytic leukemia. However, healthy patients in middle age can be advised to have their blood count checked regularly by their family doctor as part of their preventive checkups. Leukemic changes would thus be noticed at an early stage, even if no symptoms were present yet.
Follow-up
After treatment for promyelocytic leukemia, long-term monitoring of patients is recommended. Follow-up continues for a period of at least ten years. During this time, patients are seen once a year for follow-up. Follow-up examinations focus on the detection of late recurrence. The term refers to a recurrence of the disease several years after treatment. Recurrence of promyelocytic leukemia after successful therapy is very rare in the period up to five years. However, late recurrences after more than ten years have been observed in isolated cases. This explains the long period of follow-up examinations. Regular follow-up examinations can detect late effects of the therapy and detect the occurrence of secondary leukemias or other malignant tumors. Part of the follow-up for patients with promyelocytic leukemia is regular examination of the bone marrow at three-month intervals over a period of 12 to 18 months. The duration of follow-up depends on whether patients are classified as standard-risk or high-risk. The aim of this follow-up is to detect any residual leukemia cells remaining in the body. Timely therapy in the event of a positive finding can detect and treat relapse at an early stage.
What you can do yourself
Promyelocytic leukemia has a good prognosis with adequate treatment. However, the patient’s cooperation is very important for this. In consultation with the physician, the patient should be treated in a specialized leukemia center. There, all known complications can either be prevented or quickly treated by certain measures. In order to detect leukemia in time, the patient should definitely consult the doctor in case of unclear symptoms such as permanent extreme fatigue, pallor of the skin, fever, constant abdominal pain, increased bleeding tendency, bruises, swelling of the lymph nodes, joint pain and other strange changes. In this way, a quick start of the therapy is possible. The patient can also obtain extensive information from self-help groups, the Deutsche Krebshilfe e.V. (German Cancer Aid) or the Deutsche Leukämie- und Lymphom-Hilfe e. V. (German Leukemia and Lymphoma Aid) and thereby also reduce fears. Many patients are helped by membership in a self-help group, where various experiences in dealing with the disease are exchanged. This is a great relief for many of those affected. The certainty that a cure is possible can additionally accelerate the healing process. But even in more severe cases, this exchange can have a very positive impact on the quality of life. Often, the use of psychological counseling also helps to prevent depression and other psychological sequelae of leukemia. Despite severe disease, a healthy lifestyle with a balanced diet and spending time in the fresh air also supports recovery.
