LYMPHOID LEUKEMIA - kau



LYMPHOID LEUKEMIA

Leukemia where the cells affected are of lymphoid origin is classified as Lymphoid Leukemia. The process could either Acute or Chronic.

ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

As the name indicates, this is a leukemia involving lymphoid cells and because it is acute, the cells are very immature lymphoblasts or their progeny. The disease is characterized by the abundance of lymphoid blasts in Bone Marrow (BM) and may be peripheral blood (pb). The presence of blasts in peripheral blood is not always seen. Certain cases of acute leukemia (whether lymphoid or non-lymphoid) do not show blasts in pb. Such cases are known as ALEUKEMIC LEUKEMIA. Generally, ALL could present with the following lab and clinical findings:

WBC count: low, normal, or high. Blasts are usually seen in peripheral blood constituting a wide range from 30-90% (depending on the severity of the case). All WBC other than lymphoid, are usually decreased (in both, pb and BM). The BM is hypercellular showing at least 30% blasts (and up to almost 100% of nucleated BM cells, depending on the severity of the case). Platelets and RBC are usually decreased. Clinically, the patients are usually children under the age of 15, suffering from fatigue, malaise, pallor (depending on the degree of anemia caused by decreased RBC), repeated infections, chills, fever (related to decreased normal WBC function), easy bruising, hemorrhages, petechiae, epistaxis (related to decreased platelets). Gradual weight loss could also be seen, as well as joints and bone pain. Lymphadenopathy, splenomegaly, and/or hepatomegaly, can also be seen.

ALL can also affect adults (known as Adult ALL) and usually the pathogenesis is stronger with a poor prognosis, where as children ALL has the best prognosis of all cases of Acute Leukemias (lymphoid or myeloid) with up to 90% achieving complete remission and up to 60% completely cured.

MORPHOLOGICAL CLASSIFICATION OF ALL:

Lymphoid cells are of variable shapes and sizes, and hence differentiating among these types is essential, so that they do not get confused with other cells. The FAB group classified ALL into three sub-division or types known as L1, L2, and, L3. Table 36.1 (below) describes the differences among the three, morphologically.

L1 is the most common form of ALL, which strikes children especially under 15 years old (74% of cases). Children with this type of ALL have the best prognosis because they respond well to therapy, the majority of which achieve complete remission.

L2 is the second most common form of ALL cases, the majority of which are adolescent people (66% are children above 15 years old).

L3 also known as Burkitt’s type ALL, it is the rarest form of ALL accounting for no more 5% of cases. This type is associated with the worst prognosis.

CYTOCHEMISTRY:

Although cytochemistry is becoming obsolete and outdated (especially when compared with immunophenotyping and molecular technologies), yet cytochemical identification of blast cells is still a major part of any leukemia case characterization.

Lymphoid blasts are Myeloperoxidase NEGATIVE, while myeloblasts may be negative but their more mature forms are strongly positive. Therefore, a positive Myeloperoxidase must eliminate ALL diagnosis. Some lymphoid blasts are weakly positive for Sudan Black.

ACID PHOSPHATASE: not very useful because it is positive in all of ALL cases as well as in myeloid cells. However, the pattern of positivity is different in T-lymphocytes than other cells. In T-lymphs the positive area is localized to the Golgi region where as other cells has a diffused distribution of the dye.

Non Specific Esterase (NSE): important in distinguishing between L2 and M5. Lymphoblasts of L2 have a focal activity (positivity) in their cytoplasm, where as M5 monoblasts have a diffused reaction all over.

Terminal deoxynucleotidyl transferase (Tdt): present in 90% of ALL cases but it is of significant importance in the follow up of CML cases in blastic crisis, suspected to be a lymphoblastic transformation.

Periodic Aid-Schiff (PAS): very useful in distinguishing the sub-types of ALL (i.e., L1, L2, and L3). Positive reaction appears as heavily stained granules or chunks of granules in the cytoplasm. The stain is scored according to the degree of positivity (similar to LAP score) with cells stained heaviest (containing most stained granules) scored as 4+ and cells devoid of any activity scored as zero. According to that scoring system, ALL is categorized as follows:

L1: very high scores

L2: not more than 10%

L3: negative

IMMUNOLOGIC CLASSIFICATION OF ALL:

Using immunophenotying technology such as CD markers (Clusters of differentiation, also known as Clusters of Designation), ALL could be classified into 4 sub-groups. Rather than morphology, this categorization distinguishes ALL according to the cell type involved. Almost all the cases of ALL are caused by the clonal proliferation of one of the following lymphoid cells: pro-B, pre-B, B, or T lymphocytes. However, a very limited number of cases some cells could be carrying markers for both T and B lymphocytes (within the same patient). These cases used to be classified as non-B, non-T ALL (also known as null type ALL).

Immunophenotyping investigations for ALL should include (at least) the following CD markers:

CD 2: sheep erythrocyte receptor found in T cells. The same receptor is the principle behind the historical “sheep erythrocyte rosette formation” test.

CD 22: Surface Immunoglobulin (SIg) found in mature B cells.

CD 10: Common ALL Antigen (CALLA) present in 70% of ALL cases. This is usually positive in pre-B, pro-B, and B but not T cells.

Tdt: present on all lymphoid cells except mature B ones.

HLA-DR: present on all lymphoid cells except T ones.

CD’s 2, 5, and 7: these are specific T-lymphocyte markers.

In addition to the above named CD’s, at least 2 myeloid markers should be included to exclude myeloid origin of the cells investigated, e.g., CD 13, and CD 33.

For more information on the immunologic classification of ALL, see table 36.2, below.

CYTOGENETICS:

A few translocations have been associated with different types of ALL, examples of which include:

t (1; 19) in pre-B ALL

t (8; 14) in B ALL

t (4; 11) in My+ ALL (MY+ is a type of ALL with myeloid markers)

t (9; 22) also known as Philadelphia (Ph1 +ve) in pro-B ALL. The break point of the Ph1 is different from that typically seen in the classical CML.

TREATMENT:

Chemotherapy (whether followed by BMT or not) is the choice treatment for ALL. Chemotherapeutic agents commonly used (usually in combination) include:

Predonisone: lysis of blasts.

Vincristine: inhibits RNA synthesis.

Methotrexate: inhibits DNA synthesis.

6-mercaptopurine: interferes with purine synthesis and hence inhibits RNA and DNA synthesis.

Daunorubicin: binds to DNA and inhibits DNA and RNA synthesis.

BMT is preferred in patients who relapsed but achieved second remission, with allogeneic matched donors being with best chance. If unavailable, autologus marrow that was purged with anti CD 10 monoclonal antibodies could suffice. Recent studies using pb stem cell harvest have been investigated, however, the small amounts of stem cells in pb are usually a limiting factor.

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