Hematologic Malignancies: Classification, Prevalence, Symptoms, Treatment, Complications

What is Hematologic Malignancy?

Hematologic malignancies are commonly known as blood cancer. The condition includes a wide range of myelomas, lymphomas, and leukemias that originate in the cells of the immune and lymphatic system of the body. The history of hematologic malignancies dates back to the year 1832 when Thomas Hodgkin characterized a type of malignant lymphoma. The disease was named Hodgkin disease and was followed by the discovery of other lymphomas, leukemia, and myeloid neoplasms in the subsequent years.

Classification Of Hematologic Malignancy

There are three broad classifications of hematologic malignancy:

  1. Leukemia: Leukemia is one of the most familiar forms of blood cancer. Leukemia is the rapidly growing class of hematologic malignancy, while the other two ways develop gradually. Leukemia is the condition where malignancy is developed in the white blood cells of the body. Around 44,600 patients in the United States who were diagnosed positive with leukemia in the year 2011. The mortality count due to the disease was 21780.
  2. Lymphoma: Lymphoma is associated with lymphocyte blood cells. The cytogenetic aberrations of the lymphoma cells lead to hematologic malignancies. The lymphoma was the first discovered hematologic malignant disorder, which came to be known as the Hodgkin disease. It erratic development and multiplication of lymphoma cells in the lymph nodes and other tissues give rise to the cancerous condition
  3. Myeloma: Myeloma is also referred to as Plasma Cell Myeloma as it affects the plasma cells of the body. The disease is a result of genomic aberration, where the abnormal myeloma cells intervene in the production of antibodies. It eventually impairs the immune system. The first case of myeloma was reported in 1844.

While there are further sub-classifications of the three types, all other forms of hematologic malignancies fall under these broad terms.(1)

Epidemiology and Prevalence of Hematologic Malignancy

The prevalence of hematologic malignancy or blood cancer can be defined as the fraction of people in a population who have been subjected to cancer diagnosis at least once in their life. The prevalence rate of cancer is figured with the help of data from cancer registries throughout the world. When a study was carried out to study the total prevalence of hematological malignancies in the U.K, it was found that around 19700 people have undergone a prior diagnosis of blood cancer. If we compare it with the total population, about 327,800 people were diagnosed with blood cancer at one time. Further research illustrated that chronic lymphocytic leukemia was most prominent in men, while women have Hodgkin lymphoma as the prevalent condition. In the United States, the hematological malignancies are 10% of the overall diagnosed cancer cases. The patients happened to share epidemiologic risks like a family chronology of hematologic malignancy. (2,3)

Symptoms of Hematologic Malignancy

The symptoms of hematologic malignancies play a significant role in diagnosis as well as taking palliative care of the patients. Some of the commonly observed symptoms in patients suffering from different types of hematologic malignancies are:

  • Lack of energy to perform routine activities
  • Difficulty in getting sound sleep
  • Feeling of drowsiness throughout the day
  • Dry mouth
  • Difficulty in breathing
  • Feeling bloated
  • Severe hair loss
  • Swollen extremities
  • Declining interest in sexual activities or loss of libido
  • Pain while urinating
  • Constipation
  • Weight loss
  • Loss of appetite
  • Loss of sensation or numbness in feet and hands

Besides these physical symptoms, the patient also suffers from psychological distress like the feeling of nervousness, irritation, sadness, worry, etc.(4)

Pathophysiology of Hematologic Malignancies

The condition of hematopoietic homeostasis is sustained throughout the life of an individual. It is regulated with the help of self-renewal properties of the blood stem cells. When the virtue of self-renewal of the hematopoietic cells develops a defect, it leads to irregular differentiation of the blood cells. The accumulation of irregular and abnormal blood cells lead to hematologic malignancies. All the blood cells of the body are considered to be emanated from the progenitor cells or stem cells present in the bone marrow. In the case of hematological malignancy, the leukemia stem cells are also produced from the same progenitor cells. They readily get adapted to the regulatory mechanism as well as develop their mechanism to prevent apoptosis and senescence. This leads to the development of various blood cancers.(5)

Diagnosis of Hematologic Malignancies

The most daunting challenge of hematologic malignancies is its diagnosis. The differentiation of the hematopoietic stem cells gives rise to various forms of clinically distinct cancerous conditions. The genetic DNA sequence is no more a prominent cause of the variation. Instead, the alternation in the genomic structure like chromosomal translocation, deletions, and mutations are the causative agents of hematological malignancies. Morphological evaluation is followed by the examination of molecular markers to diagnose blood cancer. One such crucial diagnostic procedure is molecular diagnosis. Gene expression profiling is a genomic technique that acts as a tool of molecular diagnosis for blood cancer patients. The gene profiling has helped to segregate the clinical diversity of different blood cancers. It is based on the theory that a fraction of genes in each cell are vigorously transcribed into the messenger RNA. It helps to trace the lineage of the cell, its stage of differentiation, movement of intracellular regulatory trails, etc. It deciphers the distinction between normal blood cells and malignant blood cells. Gene expression profiling gives a robust framework for the molecular diagnosis of hematological malignancies.(6)

Treatment of Hematologic Malignancies

There are a large number of treatment modalities that have evolved over the years to treat blood cancer patients. The most popular method of treatment of blood cancer is the transfusion of blood cells to the patients. The other frequently administered therapy included chemotherapy and immunosuppressant medication in the patients having self-destructive antibodies. Many patients were subjected to radiotherapy to destroy the malfunctioning blood stem cells to cease the production of malignant blood cells. (7)

Target Therapy For Hematologic Malignancy

The management of hematological malignancies has witnessed swift progress with the current molecular target therapy. The customized target therapy focuses on squaring the development of malignant cells. It deprives the cell of particular molecules required for carcinogenesis or the formation of tumors. The target molecule therapy is an excellent achievement in the file of genomics. The molecular target therapy has received approval from the US Food and Drug Administration as a personalized therapy for blood cancer patients. The targeted therapy is effective in myeloma, chronic leukemia, and lymphoma. It is a choice of treatment for geriatric patients. The therapeutic comorbidities associated with the old age of the patients restrict the use of standard chemotherapy. But target treatment with imatinib and rituximab has provided superior results than conventional chemotherapy. The common molecules used for target therapy to treat hematological malignancy are as follows:

Ulocuplumab, sorafenib, sunitinib, enasidenib, navitoclax, vosaroxin, panobinostat, vorinostat, rituximab, blinatumomab, imatinib, dasatinib, nilotinib, bosutinib, and ibrutinib are some known molecules for target therapy in blood cancer patients.(8)

Immunotherapy For Hematologic Malignancy

The immunotherapy for cancer treatment has expedited over the recent years and has evolved to provide promising therapies. Immunotherapy has transformed the scenario of malignancy treatment throughout the world. Hematological malignancies are well treated with immunotherapy as they have a well-poised target for the immune cells to invasion. The different types of immunotherapy for blood cancer patients are discussed below:

Monoclonal Antibodies: The first monoclonal antibody that was approved by the US FDA for treating malignant disorders is Rituximab. Falling in the steps with Rituximab, other antibodies like Obinutuzumab and Ofatumumab were developed to treat B cell malignancy. Daratumumab was recently developed to treat multiple myeloma.

Antibody-Drug Conjugates: With further development, the monoclonal antibodies transformed into more effective agents. The antibody was conjugated with a cytotoxic agent to facilitate a direct drug delivery system. The meta-analysis of antibody-drug conjugate showed improved survival rates in patients with acute myeloid leukemia as well as reduced chances of relapse. Similar results were achieved with Brentuximab as it effectively treated the relapse of Hodgkin Lymphoma. Inotuzumab ozogamicin is another antibody-drug conjugate that has shown promising results to treat hematological malignancies.

CAR T Cells: The development and refinement of CAR T cell therapy have accelerated the treatment prospective of hematological malignancies. The treatment focuses on targeting antigens directly to the tumor cells and boosting the action of targeted immune effectors. CAR T cells are modified forms of autologous cells that express chimeric antigen receptors against an antigen of tumor cells. There is already a natural abundance of T cells in areas where blood cancer is located. It helps the CAR T cells to move straightforwardly to the site of action.(9)

Challenges In The Treatment Of Hematologic Malignancy

Although the field of cancer treatment has seen advancements in treatment and a new therapeutic approach, a majority of patients with hematological malignancies survive with an incurable condition. The drugs and treatment modalities might have increased the survival rates in some types of blood cancer patients, but the quality of life remains unaltered in the majority of the patients. The toxicity of chemotherapy and radiotherapy renders the body susceptible to various secondary side effects that further weakens the immune system. Anemia is the most familiar side effect of hematological malignancy in patients. It is associated with fatigue and exhaustion, thereby decreasing the quality of life in patients. While conditions like Hodgkin’s disease is curable even with treatment for relapse, malignancies like indolent lymphoma is a chronic blood cancer condition. The main challenge in the treatment of hematological treatment is to reduce the side effects of therapy in patients with incurable diseases so that they can have a better quality of life.(10)

The Impact of Anemia in Patients With Hematologic Malignancy

The most critical side effect of hematological malignancy is the development of the anemic condition in the patient. It is due to the fact that blood cancers interfere with the normal erythropoietin process of the body. Anemia sets in with functional impairment of organs and is also associated with hemoglobin loss. Patients with hematological malignancies have neoplastic cell infiltration of the bone marrow. The infiltration of the bone marrow cells leads to hemolysis. The chemotherapy-induced suppression of bone marrow is also observed along with nutritional deficiencies in the patient. Anemia in blood cancer patients reduces the lifespan of red blood cells. The production of the blood cells is not enough to compensate for the hemolysis, and thus, the condition aggravates. Anemia negatively impacts the health of blood cancer patients by increasing morbidity and reducing the quality of life. Therefore, the management of anemia is a critical part of the overall treatment of hematological malignancies.(11)

Complications Associated With Hematologic Malignancy

Patients with hematological malignancies are likely to encounter hemorrhagic and thrombotic conditions. The correlation between cancer and thrombosis can be traced back to 1856 when it was first reported. The manifestation of bleeding and abnormal homeostasis in blood cancer patients is a major reason for morbidity and mortality. The complications that develop bleeding complications are:

Platelet Abnormalities: Platelet abnormalities like thrombocytopenia and platelet dysfunction are common in blood malignancy patients. It leads to extended clotting time; thus; the bleeding occurs profusely leading to great blood loss.

Bleeding in Leukemia Patients: Patients with leukemia face the problem of hemorrhage that is the most reported cause of morbidity. The most common sites of bleeding in leukemia patients are skin surface, eyes, mucosal membranes, gum bleeding, and gastrointestinal bleeding.

Acquired Coagulation Disorders: Patients with hematological malignancies have reported various acquired coagulation disorders. The most common symptom of the disorder is a reduction in the synthesis of blood clotting factors. The vitamin K dependent factors have reduced production due to liver failure after chemotherapy or due to neoplastic liver infiltration. The immediate treatment is the administration of Vitamin K orally to stop bleeding.(12)

Conclusion

Blood cancer or hematological malignancy has emerged as one of the common forms of cancer in the world. While the prevalence is quite high, it greatly impacts the life of patients due to side effects of treatments. Some of the conditions are incurable, and thus the medication focuses on improving the quality of life of the sufferers. There are various treatment options like blood transfusion, molecular target therapy, immunotherapy, radiotherapy, and chemotherapy for the treatment of blood malignancies. Still, anemia is a severe side effect that negatively impacts the health of patients. An additional drawback of the disease is hemorrhage and bleeding complications.

References:

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