T-cell prolymphocytic leukemia
Encyclopedia
T-cell-prolymphocytic leukemia (T-PLL) is a mature T-cell leukemia
with aggressive behavior and predilection for blood
, bone marrow
, lymph nodes, liver
, spleen
, and skin
involvement. T-PLL is a very rare leukemia, primarily affecting adults over the age of 30. It represents 2% of all small lymphocytic leukemias in adults. Other names include T-cell chronic lymphocytic leukemia, "knobby" type of T-cell leukemia, and T-prolymphocytic leukemia/T-cell lymphocytic leukemia.
) T-cell.
, generalized lymphadenopathy
, and skin infiltrates.
Due to the systemic nature of this disease, leukemic cells can be found in peripheral blood, lymph nodes, bone marrow
, spleen
, liver
, skin
. A high lymphocyte count (> 100 x 109/L)along with anemia
and thrombocytopenia
are common findings. HTLV-1 serologies are negative, and serum immunoglobins are within normal limits with no paraproteins present.
cytoplasm
with occasional blebs or projections. The nuclei
are usually round to oval in shape, with occasional patients having cells with a more irregular nuclear outline that is similar to the cerebriform nuclear shape seen in Sézary syndrome. A small cell variant comprises 20% of all T-PLL cases, and the Sézary cell-like (cerebriform) variant is seen in 5% of cases.
Marrow involvement is typically diffuse with morphology similar to what is observed in peripheral blood. In the spleen
, the leukemic cell infiltrate both the red pulp and white pulp, and lymph node
involvement is typically diffuse through the paracortex
. Skin infiltrates are seen in 20% of patients, and the infiltrates are usually dense and confined to the dermis
and around the skin appendages.
, CD3
, and CD7
and negative for TdT
and CD1a
. The immunophenotype CD4
+/CD8
- is present in 60% of cases, the CD4+/CD8+ immunophenotype is present in 25%, and the CD4-/CD8+ immunophenotype is present in 15% of cases.
Also, abnormalities of chromosome 8 are seen approximately 75% of patients, including idic (8p11), t(8;8)(p11-12;q12), and trisomy 8
.
T-cell prolymphocytic leukemia is difficult to treat, and it does not respond to most available chemotherapeutic drugs. Many different treatments have been attempted, with limited success in certain patients: purine analogues (pentostatin, fludarabine, cladribine), chlorambucil
, and various forms of combination chemotherapy regimens
, including cyclophosphamide, doxorubicin, vincristine, prednisone
(CHOP), cyclophosphamide, vincristine, prednisone (COP), and vincristine, doxorubicin, prednisone, etoposide, cyclophosphamide, bleomycin (VAPEC-B).
Alemtuzumab
(Campath), an anti-CD52 monoclonal antibody that attacks white blood cells, has been used in treatment with greater success than previous options. In one study of previously treated people with T-PLL, people who had a complete response to alemtuzumab survived a median of 16 months after treatment.
Some patients who successfully respond to treatment also undergo stem cell transplantation to consolidate the response.
, the median survival time was 7.5 months after diagnosis. More recently, some patients have survived five years and more, although the median survival is still low.
leukemia.
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
with aggressive behavior and predilection for blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
, bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
, lymph nodes, liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
, and skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
involvement. T-PLL is a very rare leukemia, primarily affecting adults over the age of 30. It represents 2% of all small lymphocytic leukemias in adults. Other names include T-cell chronic lymphocytic leukemia, "knobby" type of T-cell leukemia, and T-prolymphocytic leukemia/T-cell lymphocytic leukemia.
Etiology
It is postulated that the originating cell line for this disease is a mature (post-thymicThymus
The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
) T-cell.
Signs and symptoms
Patients typically have systemic disease at presentation, including hepatosplenomegalyHepatosplenomegaly
Hepatosplenomegaly is the simultaneous enlargement of both the liver and the spleen . Hepatosplenomegaly can occur as the result of acute viral hepatitis or infectious mononucleosis, or it can be the sign of a serious and life threatening lysosomal storage disease...
, generalized lymphadenopathy
Lymphadenopathy
Lymphadenopathy is a term meaning "disease of the lymph nodes." It is, however, almost synonymously used with "swollen/enlarged lymph nodes". It could be due to infection, auto-immune disease, or malignancy....
, and skin infiltrates.
Due to the systemic nature of this disease, leukemic cells can be found in peripheral blood, lymph nodes, bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
, spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
, liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
. A high lymphocyte count (> 100 x 109/L)along with anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
and thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
are common findings. HTLV-1 serologies are negative, and serum immunoglobins are within normal limits with no paraproteins present.
Morphology
In the peripheral blood, T-PLL consists of medium-sized lymphocytes with single nucleoli and basophilicBasophilic
Basophilic is a technical term used by histologists. It describes the microscopic appearance of cells and tissues, as seen down the microscope, after a histological section has been stained with a basic dye. The most common such dye is haematoxylin....
cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
with occasional blebs or projections. The nuclei
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
are usually round to oval in shape, with occasional patients having cells with a more irregular nuclear outline that is similar to the cerebriform nuclear shape seen in Sézary syndrome. A small cell variant comprises 20% of all T-PLL cases, and the Sézary cell-like (cerebriform) variant is seen in 5% of cases.
Marrow involvement is typically diffuse with morphology similar to what is observed in peripheral blood. In the spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
, the leukemic cell infiltrate both the red pulp and white pulp, and lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
involvement is typically diffuse through the paracortex
Paracortex
Paracortex is the portion of a lymph node immediately surrounding the medulla. Unlike the cortex, which has mostly immature T cells, or thymocytes, the paracortex has a mixture of immature and mature T cells...
. Skin infiltrates are seen in 20% of patients, and the infiltrates are usually dense and confined to the dermis
Dermis
The dermis is a layer of skin between the epidermis and subcutaneous tissues, and is composed of two layers, the papillary and reticular dermis...
and around the skin appendages.
Immunophenotype
T-PLL has the immunophenotype of a mature (post-thymic) T-lymphocyte, and the neoplastic cells are typically positive for pan-T antigens CD2CD2
CD2 is a cell adhesion molecule found on the surface of T cells and natural killer cells.It has also been called T-cell surface antigen T11/Leu-5, LFA-2, LFA-3 receptor, erythrocyte receptor and rosette receptor....
, CD3
CD3
CD3 or CD-3 may be:* CD3 , an antigen, cluster of differentiation protein , part of the T cell receptor complex on a mature T lymphocyte* Ford CD3 platform* MediaMax CD-3, copy protection scheme* MiniCD, a 3-inch CD...
, and CD7
CD7
CD7 is a human protein encoded by the gene.-External links:...
and negative for TdT
TDT
TDT may refer to:* TDT , a digital television station in Tasmania, Australia* Terminal deoxynucleotidyl transferase, a specialized DNA polymerase expressed in immune cells* Terrestrial Dynamical Time, an obsolete name for Terrestrial Time...
and CD1a
CD1A
CD1a is a human protein encoded by the gene.-Further reading:...
. The immunophenotype CD4
CD4
CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...
+/CD8
CD8
CD8 is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor . Like the TCR, CD8 binds to a major histocompatibility complex molecule, but is specific for the class I MHC protein. There are two isoforms of the protein, alpha and beta, each encoded by a different gene...
- is present in 60% of cases, the CD4+/CD8+ immunophenotype is present in 25%, and the CD4-/CD8+ immunophenotype is present in 15% of cases.
Genetic findings
Clonal TCR gene rearrangements for the γ and δ chains are typically found. The most frequent chromosomal abnormality is the inversion of chromosome 14, specifically inv 14(q11;q32). This is found in 80% of cases, while 10% of cases show a reciprocal translocation of chromosome 14 (t(14;14)(q11;q32)).Also, abnormalities of chromosome 8 are seen approximately 75% of patients, including idic (8p11), t(8;8)(p11-12;q12), and trisomy 8
Trisomy 8
Trisomy 8 is a human chromosomal disorder caused by having three copies of chromosome 8. It can appear with or without mosaicism.-Characteristics:...
.
Treatment
Most patients with T-cell prolymphocytic leukemia require immediate treatment.T-cell prolymphocytic leukemia is difficult to treat, and it does not respond to most available chemotherapeutic drugs. Many different treatments have been attempted, with limited success in certain patients: purine analogues (pentostatin, fludarabine, cladribine), chlorambucil
Chlorambucil
Chlorambucil is a chemotherapy drug that has been mainly used in the treatment of chronic lymphocytic leukemia...
, and various forms of combination chemotherapy regimens
Chemotherapy regimens
A fundamental philosophy of combination cancer therapy is that different drugs work through different cytotoxic mechanisms. Because they have different dose-limiting adverse effects, they can be given together at full doses in chemotherapy regimens....
, including cyclophosphamide, doxorubicin, vincristine, prednisone
CHOP
CHOP is the acronym for a chemotherapy regimen used in the treatment of non-Hodgkin lymphoma. CHOP consists of:* Cyclophosphamide, an alkylating agent which damages DNA by binding to it and causing cross-links...
(CHOP), cyclophosphamide, vincristine, prednisone (COP), and vincristine, doxorubicin, prednisone, etoposide, cyclophosphamide, bleomycin (VAPEC-B).
Alemtuzumab
Alemtuzumab
Alemtuzumab is a monoclonal antibody used in the treatment of chronic lymphocytic leukemia , cutaneous T-cell lymphoma and T-cell lymphoma...
(Campath), an anti-CD52 monoclonal antibody that attacks white blood cells, has been used in treatment with greater success than previous options. In one study of previously treated people with T-PLL, people who had a complete response to alemtuzumab survived a median of 16 months after treatment.
Some patients who successfully respond to treatment also undergo stem cell transplantation to consolidate the response.
Prognosis
T-PLL is an aggressive disease, and patients are not expected to live normal lifespans. Before the recent introduction of better treatments, such as alemtuzumabAlemtuzumab
Alemtuzumab is a monoclonal antibody used in the treatment of chronic lymphocytic leukemia , cutaneous T-cell lymphoma and T-cell lymphoma...
, the median survival time was 7.5 months after diagnosis. More recently, some patients have survived five years and more, although the median survival is still low.
Epidemiology
About four men are diagnosed with this disease for every three women. Despite its overall rarity, it is also the most common type of mature T cellT cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
leukemia.