Question

Compare and contrast leukemia, lymphoma, and multiple myeloma 1. 2. Differentiate between Hodgkin's lymphoma, and non-Hodgkin's lymphoma 3.ldentify and differentiate between the different types of transfusion reactions. 4. Which of these reactions are most fatal, and why?

Answer 1

I.Compare and contrast Leukemia, Lymphoma & Multiple Myeloma

To understand these diseases, we must first understand the normal development of the cells they affect. Hematopoiesis is the process by which blood cells form and mature.

All the different types of blood cells arise in the bone marrow from a common pluripotent hematopoietic stem cell, and undergo a series of developmental steps to differentiate into mature cells and assume specific roles in the body. New, immature blood cells may stay in the marrow to mature or may travel to other parts of the body to mature. Normally, blood cells are produced in an orderly, controlled way, as the body needs them. Some circulate throughout our bodies via blood vessels and lymph vessels. Some reside in the Lymphatic tissuesthat are primarily concentrated in lymph nodes, thymus, spleen, and in most of our major organ systems.

Leukemia, lymphoma, and multiple myeloma are all cancers of the blood-forming organs, or hematopoietic neoplasms. They arise due to errors in the genetic information of an immature blood cell. As a consequence of these errors, the cell's development is arrested so that it does not mature further, but is instead replicated over and over again, resulting in a proliferation of abnormal blood cells. Nearly every stage of the hematopoietic process can give rise to a distinct type of cancer.

Historically, scientists and physicians have classified these diseases by their locations in the body, the appearance of affected cells under the microscope, and the natural progression of the diseases. In leukemia, the cancerous cells are discovered circulating in the blood and bone marrow, while in lymphoma, the cells tend to aggregate and form masses, or tumors, in lymphatic tissues. Myeloma is a tumor of the bone marrow, and involves a specific subset of white blood cells that produce a distinctive protein.

Leukaemia can arise in either of two main groups of white blood cell types -lymphocytes or myelocytes. Either type of leukemia can be acute, a rapidly progressing form of the disease in which the affected cells are very immature and unable to serve their proper purpose, or chronic, which progresses more slowly and is distinguished by cells that are relatively well differentiated but still function poorly. Lymphoma involves lymphocytes and can also be subclassified. Non-Hodgkin's lymphoma (NHL) is the more prevalent form of the disease. Among non-Hodgkin's lymphomas, indolent disease progresses slowly and exhibits well-differentiated lymphocytes, while the more aggressive forms are characterized by lymphocytes with far less differentiation. Hodgkin's disease, which is less common than NHL and has different clinical and epidemiological features, has historically been distinguished from NHL by the presence of distinctive cells called Reed-Sternberg cells.

Leukemias, lymphomas, and myelomas share some common features, but there are major differences among them - and there are similarities and differences within each disease group. These cancers actually represent a large number of diseases that vary significantly in their causes, molecular profiles, and natural progression. In the past decade we have a experienced a revolution in the field of molecular biology that has brought new tools that are helping us refine cancer classification in terms of the molecular changes that distinguish a normal cell from a cancerous one, and draw differences between cancerous cells of different types.

II.Differentiate between Hodgkin's Lymphoma and Non- Hodgkin's Lymphoma.

With two similar-sounding names, Hodgkin lymphoma and non-Hodgkin lymphoma can easily be confused. Lymphoma is a form of cancer that affects the lymphocytes, a type of white blood cell that plays an important role in the immune system. The primary difference between these two categories of lymphatic cancer is the type of lymphocyte that is affected. Hodgkin lymphoma is marked by the presence of Reed-Sternberg cells, which a physician can identify using a microscope. In non-Hodgkin lymphoma, these cells are not present.

In addition to the presence or lack of Reed-Sternberg cells, other differences between Hodgkin and non-Hodgkin lymphoma include that:

• Non-Hodgkin lymphoma is more common than Hodgkin lymphoma.
• The majority of non-Hodgkin patients are over the age of 55 when first diagnosed, whereas the median age for diagnosis of Hodgkin lymphoma is 39.
• Non-Hodgkin lymphoma may arise in lymph nodes anywhere in the body, whereas Hodgkin lymphoma typically begins in the upper body, such as the neck, chest or armpits.
• Hodgkin lymphoma is often diagnosed at an early stage and is therefore considered one of the most treatable cancers. Non-Hodgkin lymphoma is typically not diagnosed until it has reached a more advanced stage.

Despite the many differences between these two types of lymphatic cancer, both have similar symptoms, such as enlarged lymph nodes, fatigue, weight loss and fever. If you notice any of these symptoms, it is important to consult with a physician.

What treatment options are available?

Treatment for Hodgkin or non-Hodgkin lymphoma will depend on the type of lymphatic cancer you have, its stage, your overall health and many other factors. At Moffitt Cancer Center, the multispecialty experts that make up our Malignant Hematology Program collaborate as a tumor board to review patient cases, ensuring each patient receives an individualized treatment plan that addresses his or her unique needs.

III.Identify and differentiate between the different types of transfusion reactions.

Introduction

Transfusion reactions are defined as adverse events associated with the transfusion of whole blood or one of its components. These may range in severity from minor to life-threatening. Reactions can occur during the transfusion (acute transfusion reactions) or days to weeks later (delayed transfusion reactions) and may be immunologic or non-immunologic. A reaction may be difficult to diagnose as it can present with non-specific, often overlapping symptoms. The most common signs and symptoms include fever, chills, urticaria (hives), and itching. Some symptoms resolve with little or no treatment. However, respiratory distress, high fever, hypotension (low blood pressure), and red urine (hemoglobinuria) can indicate a more serious reaction.

Typess of transfusion reactions include the following:

1. Acute hemolytic
2. Delayed hemolytic
3. Febrile non-hemolytic
4. Anaphylactic
5. Simple allergic
6. Septic (bacterial contamination)

Transfusion-related acute lung injury (TRALI) Transfusion-associated circulatory overload (TACO). All suspected reactions should result in immediately stopping the transfusion and notifying the blood bank and treating clinician.

Etiology

Immune-mediated transfusion reactions typically occur due to mismatch or incompatibility of the transfused product and the recipient. They include naturally occurring antibodies in the blood recipient (such as anti-A, anti-B which are typically responsible for acute hemolytic transfusion reactions) as well as antibodies made in response to foreign antigens (alloantibodies). These alloantibodies account for many reactions including mild allergic, febrile non-hemolytic, acute hemolytic and anaphylactic. Antibodies present in the blood donor can also cause reactions and are thought to be involved in transfusion-associated lung injury (TRALI).

Non-immunologic reactions are usually caused by the physical effects of blood components or the transmission of disease. Bacterial contamination, for example, results in septic transfusion reactions and is caused by bacterial and/or endotoxin contamination of a blood product. This may happen at the time of collection due to inadequate blood donor arm disinfection, the presence of bacteria in the donor’s circulation at the time of collection, or due to improper product handling after collection.

Transfusion reactions can also occur unrelated to factors intrinsic to the blood. Examples of these include transfusion-associated volume overload (TACO) and hypothermia.

Epidemiology

Transfusion reactions range in frequency from relatively common, (mild allergic and febrile non-hemolytic reactions) to rare (anaphylaxis, acute hemolytic, and sepsis). Fatal adverse events have been reported to occur most commonly with TRALI, and long-term or later adverse events are typically the result of disease transmission.

The severity and incidence vary depending on the type of transfusion reaction, the prevalence of disease in the donor population, and the extent of follow-up care the patient receives. Due to advances in donor screening, improved testing, and automated data systems, the risks and fatalities associated with the transfusion of blood products continue to decrease.

Pathophysiology

The pathophysiology varies based on the transfusion reaction.

Acute Transfusion reactions

Mild allergic: Attributed to hypersensitivity to a foreign protein in the donor product.

Anaphylactic: Similar to a mild allergic reaction, however resulting in a more severe reaction. Sometimes this can occur in a patient with IgA deficiency who makes alloantibodies against IgA and then receives blood products containing IgA.

Febrile non-hemolytic: Generally thought to be caused by cytokines released from blood donor leukocytes (white blood cells).

Septic: Caused by bacteria or bacterial byproducts (such as endotoxin) which may contaminate blood.

Acute hemolytic transfusion reactions: Can result in intravascular or extravascular hemolysis, depending on the specific etiology (cause). Immune-mediated reactions are often a result of recipient antibodies present to blood donor antigens. Non-immune reactions are possible, and occur when red blood cells are damaged before transfusion (e.g., by heat or incorrect osmotic conditions).

Transfusion-associated circulatory overload (TACO): Occurs when the volume of the transfused component causes hypervolemia (volume overload).

Transfusion-related acute lung injury: Acute lung injury is due to antibodies in the donor product (human leukocyte antigen or human neutrophil antigen) reacting with antigens in the recipient. The recipient’s immune system responds and causes the release of mediators that lead to pulmonary edema. Possibly contributing to this are clinical conditions that predispose the patient including infection, recent surgery, or inflammation.

Delayed Transfusion Reactions

Delayed hemolytic transfusion reaction: Typically caused by an anamnestic response to a foreign antigen that the patient was previously exposed to (generally by prior transfusion or pregnancy).

Transfusion-associated graft-versus-host disease: Results from engraftment of donor lymphocytes (commonly found in cellular blood products) into an immunocompromised recipient’s bone marrow. The donor lymphocytes recognize the patient as foreign and react against the recipient’s body. The patient’s immune system is unable to clear the foreign lymphocytes. This is rare but often fatal.

IV. Which of these reactions are more fatal and Why?

Most severe and fatal reactions result from inadvertent transfusion of group AB or group A red cells to a group O recipient. Renal failure and disseminated intravascular coagulation (DIC) are potential complications for patients who survive the initial acute reaction. [Acute hemolytic reactions].