Lymphoid leukemia

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Lymphoid leukemia
Other namesLymphocytic, lymphogenous, lymphoblastic leukemias
Specialty Oncology, hematology

Lymphoid leukemias are a group of leukemias affecting circulating lymphocytes, a type of white blood cell. The lymphocytic leukemias are closely related to lymphomas of the lymphocytes, to the point that some of them are unitary disease entities that can be called by either name (for example, adult T-cell leukemia/lymphoma). Such diseases are all lymphoproliferative disorders. Most lymphoid leukemias involve a particular subtype of lymphocytes, the B cells.

Contents

Classification

Historically, they have been most commonly divided by the stage of maturation at which the clonal (neoplastic) lymphoid population stopped maturing:[ citation needed ]

However, the influential WHO Classification (published in 2001) emphasized a greater emphasis on cell lineage. To this end, lymphoid leukemias can also be divided by the type of cells affected:

The most common type of lymphoid leukemia is B-cell chronic lymphocytic leukemia.

B-cell leukemias

B-cell leukemia describes several different types of lymphoid leukemia which affect B cells.

Comparison of most common B-cell leukemias Incidence Histopathology Cell markers Comments
B-cell chronic lymphocytic leukemia
(ICD-O: 9823/3)		30% of all leukemias. Also 3 to 4% of lymphomas in adults [1] Small resting lymphocytes mixed with variable number of large activated cells. Lymph nodes are diffusely effaced [1] CD5, surface immunoglobulin [1] Occurs in older adults. Usually involves lymph nodes, bone marrow and spleen. Most patients have peripheral blood involvement. Indolent. [1]
Precursor B-cell lymphoblastic leukemia
(ICD-O: 9835/3-9836/3)		85% of acute leukemias in childhood, [1] Less common in adults [1] Lymphoblasts with irregular nuclear contours, condensed chromatin, small nucleoli and scant cytoplasm without granules. [1] TdT, CD19 [1] Usually presents as acute leukemia [1]

Other types include (with ICD-O code):

T-cell leukemias

T-cell leukemia describes several different types of lymphoid leukemias which affect T cells.[ citation needed ]

The most common T-cell leukemia is precursor T-cell lymphoblastic leukemia. [1] It causes 15% of acute leukemias in childhood, and also 40% of lymphomas in childhood. [1] It is most common in adolescent males. [1] Its morphology is identical to that of precursor B-cell lymphoblastic leukemia. [1] Cell markers include TdT, CD2, CD7. [1] It often presents as a mediastinal mass because of involvement of the thymus. [1] It is highly associated with NOTCH1 mutations. [1]

Other types include:

In practice, it can be hard to distinguish T-cell leukemia from T-cell lymphoma, and they are often grouped together.

NK cell leukemia

Aggressive NK-cell leukemia (ANKL) is a lymphoid leukemia that is a deficiency NK cells. Not very much is known about this disease due to its rarity, but it is highly aggressive. A majority of patients with NK cell leukemia die within a year of diagnosis, and for ANKL in particular, half of patients die within two months. [2]

Diagnosis

The requirements for diagnosing ANKL are as follows: [3]

  1. Immature-looking NK cells
  2. Certain immunophenotypes [4]
  3. Germline configuration genes: TCR-β and IgH
  4. Restricted cytotoxicity

The T-cell receptor (TCR) is an important factor when ANKL is being diagnosed along with T-cell leukemia. The TCR gene transcripts are normally positive for ANKL. [5] Current Research is attempting to find the causation of ANKL. So far, the researchers have concluded that lineage of the T-cell receptor gene does not predict the behavior of the disease.

Treatment

ANKL is treated similarly to most B-cell lymphomas. Anthracycline-containing chemotherapy regimens are commonly offered as the initial therapy. Some patients may receive a stem cell transplant. [6] [7]

Overall survival depends on the stage of the cancer when treatment is initiated, and on a composite of numerous risk factors. The median time from diagnosis to death is less than 1 year in patients overall. Patients diagnosed early and/or with fewer risk factors can sometimes enter complete remission and expect much longer survival. [2]

Diagnosis

Flow cytometry is a diagnostic tool in order to count/visualize the amount of lymphatic cells in the body. T cells, B cells and NK cells are nearly impossible to distinguish under a microscope, therefore one must use a flow cytometer to distinguish them.

Treatment

Targeted therapy

Several molecular tumor profiling protocols have been initiated in Europe (e.g., MOSCATO-01, iTHER, and ESMART) to identify actionable lesions for targeted treatment in specific subgroups of patients. [8]

NK cell therapy

Natural killer (NK) cell therapy is used in pediatrics for children with relapsed lymphoid leukemia. These patients normally have a resistance to chemotherapy, therefore, in order to continue on, must receive some kind of therapy. In some cases, NK cell therapy is a choice. [9]

NK cells are known for their ability to eradicate tumor cells without any prior sensitization to them. [10] One problem when using NK cells in order to fight off lymphoid leukemia is the fact that it is hard to amount enough of them to be effective. [10] One can receive donations of NK cells from parents or relatives through bone marrow transplants. There are also the issues of cost, purity and safety. [11] Unfortunately, there is always the possibility of Graft vs host disease while transplanting bone marrow.

NK cell therapy is a possible treatment for many different cancers such as Malignant glioma. [12]

Related Research Articles

<span class="mw-page-title-main">Leukemia</span> Blood cancers forming in the bone marrow

Leukemia is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called blasts or leukemia cells. Symptoms may include bleeding and bruising, bone pain, fatigue, fever, and an increased risk of infections. These symptoms occur due to a lack of normal blood cells. Diagnosis is typically made by blood tests or bone marrow biopsy.

<span class="mw-page-title-main">Lymphoma</span> Hematologic cancer that affects lymphocytes

Lymphoma is a group of blood and lymph tumors that develop from lymphocytes. The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph nodes, fever, drenching sweats, unintended weight loss, itching, and constantly feeling tired. The enlarged lymph nodes are usually painless. The sweats are most common at night.

<span class="mw-page-title-main">Chronic lymphocytic leukemia</span> Medical condition

Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes. Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, night sweats, or weight loss for no clear reason may occur. Enlargement of the spleen and low red blood cells (anemia) may also occur. It typically worsens gradually over years.

<span class="mw-page-title-main">Tumors of the hematopoietic and lymphoid tissues</span> Tumors that affect the blood, bone marrow, lymph, and lymphatic system

Tumors of the hematopoietic and lymphoid tissues or tumours of the haematopoietic and lymphoid tissues are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues are all intimately connected through both the circulatory system and the immune system, a disease affecting one will often affect the others as well, making aplasia, myeloproliferation and lymphoproliferation closely related and often overlapping problems. While uncommon in solid tumors, chromosomal translocations are a common cause of these diseases. This commonly leads to a different approach in diagnosis and treatment of hematological malignancies. Hematological malignancies are malignant neoplasms ("cancer"), and they are generally treated by specialists in hematology and/or oncology. In some centers "hematology/oncology" is a single subspecialty of internal medicine while in others they are considered separate divisions. Not all hematological disorders are malignant ("cancerous"); these other blood conditions may also be managed by a hematologist.

<span class="mw-page-title-main">Acute lymphoblastic leukemia</span> Blood cancer characterised by overproduction of lymphoblasts

Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruising, enlarged lymph nodes, or bone pain. As an acute leukemia, ALL progresses rapidly and is typically fatal within weeks or months if left untreated.

Acute leukemia or acute leukaemia is a family of serious medical conditions relating to an original diagnosis of leukemia. In most cases, these can be classified according to the lineage, myeloid or lymphoid, of the malignant cells that grow uncontrolled, but some are mixed and for those such an assignment is not possible.

<span class="mw-page-title-main">Interleukin 7</span> Growth factor secreted by stromal cells in the bone marrow and thymus.

Interleukin 7 (IL-7) is a protein that in humans is encoded by the IL7 gene.

Large granular lymphocytic (LGL) leukemia is a chronic lymphoproliferative disorder that exhibits an unexplained, chronic elevation in large granular lymphocytes (LGLs) in the peripheral blood.

<span class="mw-page-title-main">Aggressive NK-cell leukemia</span> Medical condition

Aggressive NK-cell leukemia is a disease with an aggressive, systemic proliferation of natural killer cells and a rapidly declining clinical course.

Richter's transformation (RT), also known as Richter's syndrome, is the conversion of chronic lymphocytic leukemia (CLL) or its variant, small lymphocytic lymphoma (SLL), into a new and more aggressively malignant disease. CLL is the circulation of malignant B lymphocytes with or without the infiltration of these cells into lymphatic or other tissues while SLL is the infiltration of these malignant B lymphocytes into lymphatic and/or other tissues with little or no circulation of these cells in the blood. CLL along with its SLL variant are grouped together in the term CLL/SLL.

T cell receptor delta locus, also known as TCRD or TRD@, is a protein that in humans is encoded by the TRD gene. It contributes the delta (δ) chain to the larger TCR protein.

Biphenotypic acute leukaemia (BAL) is an uncommon type of leukemia which arises in multipotent progenitor cells which have the ability to differentiate into both myeloid and lymphoid lineages. It is a subtype of "leukemia of ambiguous lineage".

<span class="mw-page-title-main">Blastic plasmacytoid dendritic cell neoplasm</span> Medical condition

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy. It was initially regarded as a form of lymphocyte-derived cutaneous lymphoma and alternatively named CD4+CD56+ hematodermic tumor, blastic NK cell lymphoma, and agranular CD4+ NK cell leukemia. Later, however, the disease was determined to be a malignancy of plasmacytoid dendritic cells rather than lymphocytes and therefore termed blastic plasmacytoid dendritic cell neoplasm. In 2016, the World Health Organization designated BPDCN to be in its own separate category within the myeloid class of neoplasms. It is estimated that BPDCN constitutes 0.44% of all hematological malignancies.

<span class="mw-page-title-main">Childhood leukemia</span> Medical condition

Childhood leukemia is leukemia that occurs in a child and is a type of childhood cancer. Childhood leukemia is the most common childhood cancer, accounting for 29% of cancers in children aged 0–14 in 2018. There are multiple forms of leukemia that occur in children, the most common being acute lymphoblastic leukemia (ALL) followed by acute myeloid leukemia (AML). Survival rates vary depending on the type of leukemia, but may be as high as 90% in ALL.

Adoptive cell transfer (ACT) is the transfer of cells into a patient. The cells may have originated from the patient or from another individual. The cells are most commonly derived from the immune system with the goal of improving immune functionality and characteristics. In autologous cancer immunotherapy, T cells are extracted from the patient, genetically modified and cultured in vitro and returned to the same patient. Comparatively, allogeneic therapies involve cells isolated and expanded from a donor separate from the patient receiving the cells.

Autologous immune enhancement therapy (AIET) is a treatment method in which immune cells are taken out from the patient's body which are cultured and processed to activate them until their resistance to cancer is strengthened and then the cells are put back in the body. The cells, antibodies, and organs of the immune system work to protect and defend the body against not only tumor cells but also bacteria or viruses.

Clonal hypereosinophilia, also termed primary hypereosinophilia or clonal eosinophilia, is a grouping of hematological disorders all of which are characterized by the development and growth of a pre-malignant or malignant population of eosinophils, a type of white blood cell that occupies the bone marrow, blood, and other tissues. This population consists of a clone of eosinophils, i.e. a group of genetically identical eosinophils derived from a sufficiently mutated ancestor cell.

Epstein–Barr virus–associated lymphoproliferative diseases are a group of disorders in which one or more types of lymphoid cells, i.e. B cells, T cells, NK cells, and histiocytic-dendritic cells, are infected with the Epstein–Barr virus (EBV). This causes the infected cells to divide excessively, and is associated with the development of various non-cancerous, pre-cancerous, and cancerous lymphoproliferative disorders (LPDs). These LPDs include the well-known disorder occurring during the initial infection with the EBV, infectious mononucleosis, and the large number of subsequent disorders that may occur thereafter. The virus is usually involved in the development and/or progression of these LPDs although in some cases it may be an "innocent" bystander, i.e. present in, but not contributing to, the disease.

<span class="mw-page-title-main">T-cell acute lymphoblastic leukemia</span> Type of acute lymphoblastic leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is a type of acute lymphoblastic leukemia with aggressive malignant neoplasm of the bone marrow. Acute lymphoblastic leukemia (ALL) is a condition where immature white blood cells accumulate in the bone marrow, subsequently crowding out normal white blood cells and create build-up in the liver, spleen, and lymph nodes. The two most common types of ALL are B-lymphocytes and T-lymphocytes, where the first protects the body against viruses and bacteria through antibody production which can directly destroy target cells or trigger others to do so, whilst the latter directly destroy bacteria or cells infected with viruses. Approximately 20% of all ALL patients are categorized specifically to suffer from T-ALL and it is seen to be more prevalent in the adult population in comparison to children, with incidences shown to diminish with age. Amongst T-ALL cases in the pediatric population, a median onset of age 9 has been identified and the disease is particularly prominent amongst adolescents. The disease stems from cytogenic and molecular abnormalities, resulting in disruption of developmental pathways controlling thymocyte development, tumor suppressor development, and alterations in control of cell growth and proliferation. Distinct from adult T-cell leukemia where T-cell lymphotropic virus Type I causes malignant maturation of T-cells, T-ALL is a precursor for lymphoid neoplasm. Its clinical presentation most commonly includes infiltration of the central nervous system (CNS), and further identifies mediastinal mass presence originating from the thymus, along with extramedullary involvement of multiple organs including the lymph node as a result of hyperleukocytosis.

<span class="mw-page-title-main">Cellular adoptive immunotherapy</span> Cellular adoptive immunotherapy

Cellular adoptive immunotherapy is a type of immunotherapy. Immune cells such as T-cells are usually isolated from patients for expansion or engineering purposes and reinfused back into patients to fight diseases using their own immune system. A major application of cellular adoptive therapy is cancer treatment, as the immune system plays a vital role in the development and growth of cancer. The primary types of cellular adoptive immunotherapies are T cell therapies. Other therapies include CAR-T therapy, CAR-NK therapy, macrophage-based immunotherapy and dendritic cell therapy.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Table 12-8 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN   978-1-4160-2973-1. 8th edition.
  2. 1 2 Suzuki R, Suzumiya J, Yamaguchi M, Nakamura S, Kameoka J, Kojima H, Abe M, Kinoshita T, Yoshino T, Iwatsuki K, Kagami Y, Tsuzuki T, Kurokawa M, Ito K, Kawa K, Oshimi K (May 2010). "Prognostic factors for mature natural killer (NK) cell neoplasms: aggressive NK cell leukemia and extranodal NK cell lymphoma, nasal type". Ann. Oncol. 21 (5): 1032–40. doi: 10.1093/annonc/mdp418 . PMID   19850638.
  3. ↑ Oshimi K (July 2003). "Leukemia and lymphoma of natural killer lineage cells". Int. J. Hematol. 78 (1): 18–23. doi:10.1007/bf02983235. PMID   12894846. S2CID   24785150.
  4. ↑ Landay AL, Muirhead KA (July 1989). "Procedural guidelines for performing immunophenotyping by flow cytometry". Clin. Immunol. Immunopathol. 52 (1): 48–60. doi:10.1016/0090-1229(89)90192-x. PMID   2656019.
  5. ↑ Hong M, Lee T, Young Kang S, Kim SJ, Kim W, Ko YH (May 2016). "Nasal-type NK/T-cell lymphomas are more frequently T rather than NK lineage based on T-cell receptor gene, RNA, and protein studies: lineage does not predict clinical behavior". Mod. Pathol. 29 (5): 430–43. doi: 10.1038/modpathol.2016.47 . PMID   27015135.
  6. ↑ Mercadal S, Briones J, Xicoy B, Pedro C, Escoda L, Estany C, Camós M, Colomo L, Espinosa I, Martínez S, Ribera JM, Martino R, Gutiérrez-García G, Montserrat E, López-Guillermo A (May 2008). "Intensive chemotherapy (high-dose CHOP/ESHAP regimen) followed by autologous stem-cell transplantation in previously untreated patients with peripheral T-cell lymphoma". Ann. Oncol. 19 (5): 958–63. doi: 10.1093/annonc/mdn022 . PMID   18303032.
  7. ↑ Reimer P, Schertlin T, Rüdiger T, Geissinger E, Roth S, Kunzmann V, Weissinger F, Nerl C, Schmitz N, Müller-Hermelink HK, Wilhelm M (2004). "Myeloablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation as first-line therapy in peripheral T-cell lymphomas: first results of a prospective multicenter study". Hematol. J. 5 (4): 304–11. doi:10.1038/sj.thj.6200359. PMID   15297846.
  8. ↑ Cordo V, Meijerink J (January 2021). "T-cell Acute Lymphoblastic Leukemia: A Roadmap to Targeted Therapies". Blood Cancer Discovery. 2 (1): 19–31. doi: 10.1158/2643-3230.BCD-20-0093 . PMC   8447273 . PMID   34661151.
  9. ↑ Rubnitz JE, Inaba H, Kang G, Gan K, Hartford C, Triplett BM, Dallas M, Shook D, Gruber T, Pui CH, Leung W (August 2015). "Natural killer cell therapy in children with relapsed leukemia". Pediatr Blood Cancer. 62 (8): 1468–72. doi:10.1002/pbc.25555. PMC   4634362 . PMID   25925135.
  10. 1 2 Sakamoto, N; Ishikawa, T; Kokura, S; Okayama, T; Oka, K; Ideno, M; Sakai, F; Kato, A; Tanabe, M; Enoki, T; Mineno, J; Naito, Y; Itoh, Y; Yoshikawa, T (2015). "Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer". Journal of Translational Medicine. 13: 277. doi: 10.1186/s12967-015-0632-8 . PMC   4548900 . PMID   26303618.
  11. ↑ Bachanova, Veronika; Miller, Jeffrey S. (2014). "NK Cells in Therapy of Cancer". Critical Reviews in Oncogenesis. 19 (1–2): 133–41. doi:10.1615/CritRevOncog.2014011091. PMC   4066212 . PMID   24941379.
  12. ↑ Ogbomo, Henry; Cinatl, Jindrich; Mody, Christopher H.; Forsyth, Peter A. (2011). "Immunotherapy in gliomas: Limitations and potential of natural killer (NK) cell therapy". Trends in Molecular Medicine. 17 (8): 433–41. doi:10.1016/j.molmed.2011.03.004. PMID   21507717.
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