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Acute Undifferentiated Leukemia

Acute undifferentiated leukemia (AUL) is a type of leukemia where the immature blasts do not belong to a specific cell lineage, and originate from the hematopoietic stem cell. AUL is a subtype of acute leukemias of ambiguous lineage (ALAL).


Presentation

Acute undifferentiated leukemia (AUL) is a form of acute leukemia of ambiguous lineage (ALAL). In these types of leukemia, there is no distinct cell lineage, either lymphoid or myeloid, with some cells expressing characteristics of more than one cell type. In AUL, the cancer cells cannot be assigned to a specific lineage. Genetic correlation has yet to be ascertained. Due to the rarity of the disease, its natural history and prevalence are not known [1] [2]. Furthermore, AUL and other ALALs have no distinct features, and so cannot be distinguished clinically.

AUL is thought to originate from immature or poorly differentiated hematopoietic stem cells. These blast cells cannot be classified as they do not display lineage specific markers. AUL is seen in various age groups, but is most frequent after the 6th decade. Leukemias that present during this time period are associated with a poor prognosis, with a five year survival rate as low as 3% [3].

AUL presents similarly to other acute leukemias, typically with anemia and several bleeding diatheses. Bleeding may be from the skin, gastrointestinal tract and reproductive system, evidenced by epistaxis, petechiae, ecchymosis, hematuria, and abnormal uterine bleeding. Additional symptoms such as weight loss, malaise, fever and fatigue may be experienced. Individuals may also present with infections, which can be severe. They are more susceptible to infection due to the reduced production of normal white blood cells.

Other possible manifestations are bone pain (from bone involvement), meningitis, lymphadenopathy, hepatomegaly, splenomegaly, and cutaneous lesions (leukemia cutis).

Easy Bruising
  • Acute leukemia of unspecified cell type Corresponding ICD-10 Codes C95.0 Acute leukemia of unspecified cell type Corresponding ICD-10-CM Codes (U.S. only) C95.0 Acute leukemia of unspecified cell type (effective October 01, 2015) Signs and Symptoms Easy[seer.cancer.gov]
Easy Bruising
  • Acute leukemia of unspecified cell type Corresponding ICD-10 Codes C95.0 Acute leukemia of unspecified cell type Corresponding ICD-10-CM Codes (U.S. only) C95.0 Acute leukemia of unspecified cell type (effective October 01, 2015) Signs and Symptoms Easy[seer.cancer.gov]
Anemia
  • The mRNA encoding the major bcr/abl fusion protein then appeared in the stage of sideroblastic anemia. Finally, the mRNA encoding both major and minor bcr/abl was detected in the stage of AUL transformation.[ncbi.nlm.nih.gov]
  • AUL presents similarly to other acute leukemias, typically with anemia and several bleeding diatheses.[symptoma.com]
  • […] undifferentiated leukemia in adults Due to the prolifertation of abnormal white blood cells in the bone marrow of patients with AUL, red blood cell production in the bone marrow is relatively poor leading to leukemia symptoms of weakness and fatigue (from anemia[nethealthbook.com]
  • On admission, the hemogram findings were leucocytosis (110.7 10 9 /L) with 93% blasts in peripheral blood, anemia (6 gm/L), and thrombocytopenia (13 10 9 /L). The bone marrow aspirate was performed and that was hyper cellular with 95% blasts.[omicsonline.org]
  • Clinical stage C: Either one or both of the blood disorders anemia and thrombocytopenia have developed.[cancercenter.com]
Pallor
  • The physical examination revealed mild pallor, purpuric spots over trunk and thighs. In addition, the patient had bilateral cervical lymphadenopathy, bilateral tonsillar enlargement and hepatosplenomegaly.[omicsonline.org]
  • Pallor may be obvious. Signs of infection can be nonspecific. Fever or pneumonia may present. Thrombocytopenia often causes petechiae on the lower limbs. DIC may aggravate the situation and cause larger lesions.[patient.info]
Petechiae
  • Bleeding may be from the skin, gastrointestinal tract and reproductive system, evidenced by epistaxis, petechiae, ecchymosis, hematuria, and abnormal uterine bleeding.[symptoma.com]
  • Corresponding ICD-10-CM Codes (U.S. only) C95.0 Acute leukemia of unspecified cell type (effective October 01, 2015) Signs and Symptoms Easy bruising or bleeding Eczema-like skin rash Fatigue Fever Night sweats Pain or feeling of fullness below the rib s Petechiae[seer.cancer.gov]
  • Thrombocytopenia often causes petechiae on the lower limbs. DIC may aggravate the situation and cause larger lesions. Petechiae are small dots, purpura is larger and ecchymoses are larger bruises. Hepatomegaly and splenomegaly may be found.[patient.info]
Suggestibility
  • A 1.0 kb TCRbeta transcript was expressed in the Kasumi-3 cells, suggesting that TCRbeta rearrangement occurred as Dbeta-Jbeta joining events.[ncbi.nlm.nih.gov]
  • Three cases had no rearrangement of Ig or T beta genes which was suggestive of non-lymphoid origin of these cases. In contrast, 4 cases showed rearrangements of Ig and/or T beta genes.[ncbi.nlm.nih.gov]
  • These findings confirm the heterogeneity of undifferentiated leukemias, and suggest the hypothesis that some AUL's can be induced to express markers of early myeloid cells.[ncbi.nlm.nih.gov]
  • These data suggest that the majority of cases of AUL can be reclassified as either myeloid or lymphoid leukemias, that AUL is associated with a high frequency of chromosomal abnormalities, and that AUL carries a very poor prognosis.[ncbi.nlm.nih.gov]
  • Combined gamma-GT/TdT analysis revealed that both enzyme markers were mutually exclusive in 75% of AUL cases, suggesting that gamma-GT /TdT-blasts are of nonlymphoid origin, and gamma-GT-/TdT blasts are of lymphoid origin.[ncbi.nlm.nih.gov]
Meningism
  • Other possible manifestations are bone pain (from bone involvement), meningitis, lymphadenopathy, hepatomegaly, splenomegaly, and cutaneous lesions (leukemia cutis). The diagnosis of acute undifferentiated leukemia is one of exclusion.[symptoma.com]

Workup

The diagnosis of acute undifferentiated leukemia is one of exclusion. Although AUL cannot be clinically differentiated from other types of acute leukemia, there are several techniques that are available for diagnosis. These include:

  • Immunohistochemistry [4] [5]
  • Cytochemistry [6]
  • Flow cytometric immunophenotyping
  • Microscopy

These tests are used to identify lineage-specific markers, which are lacking in AUL. Leukemic blast cells in AUL express markers that are non-specific. Often, AULs express cluster of differentiation (CD) markers CD7, CD13, and human leukocyte antigen-D related (HLA-DR) [1] [2].

Investigations carried out for acute leukemia include:

  • Full blood count: This will show pancytopenia in the case of an acute leukemia. The presence of large numbers of blast cells is also indicative of acute leukemia.
  • Comprehensive metabolic panel: This may reveal electrolyte derangements and other abnormal parameters, such as hyperuricemia, hypocalcemia, hyper- or hypokalemia, hypoglycemia, high levels of lactate dehydrogenase and elevated liver enzymes.
  • Peripheral smear.
  • Bone marrow biopsy or aspirate.
  • Imaging: Computerized tomography (CT), magnetic resonance imaging (MRI), ultrasound and X-rays are sometimes used to test for central nervous system, chest or abdominal spread of the leukemia.
Blast Cells Present
  • Thus, these two patients had acute erythroblastic leukemia which differs from erythroleukemia (M6 of FAB classification) in which blast cells present myeloblastic characteristics.[ncbi.nlm.nih.gov]

Treatment

  • These results may be direct evidence for the induction of the bcr/abl fusion gene by treatment with an alkylating agent (ifosphamide).[ncbi.nlm.nih.gov]
  • However, the fact that it is an undifferentiated leukemia may affect the decisions regarding further treatment after the initial treatment.[oncolink.org]
  • Clinical features, clonal karyotypes, and responses to treatment were also examined.[ncbi.nlm.nih.gov]
  • Morphological studies in these cases revealed cytological maturation following TPA treatment.[ncbi.nlm.nih.gov]
  • In one case, within 24 days from starting treatment, the leukemic phenotype changed from AUL to acute myelomonocytic leukemia (FAB L1, TdT to FAB M4, TdT-).[ncbi.nlm.nih.gov]

Prognosis

  • Clinically, these diagnostic features matched with a poor prognosis, being associated with refractoriness to treatment, relapse and progression of disease, antecedent hematologic abnormality, and other malignancy.[ncbi.nlm.nih.gov]
  • These data suggest that the majority of cases of AUL can be reclassified as either myeloid or lymphoid leukemias, that AUL is associated with a high frequency of chromosomal abnormalities, and that AUL carries a very poor prognosis.[ncbi.nlm.nih.gov]
  • This acute leukemia carries a poor prognosis.[path.upmc.edu]
  • Leukemias that present during this time period are associated with a poor prognosis, with a five year survival rate as low as 3%. AUL presents similarly to other acute leukemias, typically with anemia and several bleeding diatheses.[symptoma.com]

Epidemiology

  • Eczema-like skin rash Fatigue Fever Night sweats Pain or feeling of fullness below the rib s Petechiae Shortness of breath Weakness Diagnostic Exams Immunophenotyping Lumbar puncture Molecular testing Peripheral blood smear Progression and Transformation None Epidemiology[seer.cancer.gov]
  • Epidemiology These rare leukemias account for less than 4% of all cases of acute leukemia and occur in all age groups but are more frequent in adults.[wiki.clinicalflow.com]
  • BCR-ABL1 Mixed phenotype acute leukemia with t(v;11q23); MLL rearranged Mixed phenotype acute leukemia, B/myeloid, NOS Mixed phenotype acute leukemia, T/myeloid, NOS Mixed phenotype acute leukemia, NOS rare types Other acute leukemias of ambiguous lineage Epidemiology[pathologyoutlines.com]
  • Using the database of the Surveillance, Epidemiology, and End Results registry (SEER), 313 patients with mixed phenotype acute leukemias were identified and compared them with 14,739 patients with acute lymphoblastic leukemia and 34,326 patients with[mycology.imedpub.com]
  • Epidemiology AML is the most common acute leukaemia in adults. The incidence of the AMLs in European adults is 5-8 cases per 100,000.[patient.info]
Sex distribution
Age distribution

Prevention

  • Collaborative overview of randomised trials of antiplatelet therapy, I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. ‎[books.google.de]
  • NCT01137643 Recruiting 18 - 120 Years old NO Healthy Volunteers NO Placebo Refractory Acute Myeloid Leukemia Clinical Trial This phase II trial studies how well selective T cell depletion works in preventing graft-versus-host disease (GVHD) in patients[patientwing.com]
  • They now understand that in normal conditions, SET "masks" histones by wrapping itself around the ends of the protein chains, helping to prevent random commands from using the histones on the DNA to activate genes inappropriately – and therefore protecting[sciencedaily.com]
  • This mutated cell, called a blast because it is not a fully grown cell (thus the word "Blastic" in Blastic Plasmacytoid Dendritic Cell Neoplasm), then proliferates through the bone marrow and blood stream, preventing normal development of other cells[yippee-leukemia.blogspot.com]
  • […] doxorubin, melphalan, and mitoxantrone Exposure to high doses of radiation Certain blood disorders such as myeloproliferative disorders (for example, chronic myelogenous leukemia) A parent, brother, or sister who has had AML Although there is no way to prevent[webmd.com]

References

Article

  1. Shende AC, Bonagura VR, Cheah MS, Lanzkowsky P. Acute undifferentiated leukemia (AUL): a case report and a proposed system of classification. Am J Hematol. 1992;40(3):234-237.
  2. Bassan R, Biondi A, Benvestito S, et al. Acute undifferentiated leukemia with CD7+ and CD13+ immunophenotype. Lack of molecular lineage commitment and association with poor prognostic features. Cancer. 1992;69(2):396-404.
  3. Dores GM, Devesa SS, Curtis RE, Linet MS, Morton LM. Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007. Blood. 2012;119(1):34-43.
  4. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405.
  5. Arber DA, Borowitz MJ, Cessna M, et al. Initial diagnostic workup of acute leukemia: guideline from the College of American Pathologists and the American Society of Hematology. Arch Pathol Lab Med. 2017 Feb 22.
  6. Porwit A, Béné MC. Acute leukemias of ambiguous origin. Am J Clin Pathol. 2015;144(3):361-376.

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Last updated: 2018-06-21 18:23