Akutt leukemi - Amboss

Question 1

Hvordan er epidemiologien til akutt lymfatisk leukemi (ALL)?

Answer 1

Question 2

Hvordan er epidemiologien til akutt myeloid leukemi (AML)?

Answer 2

Question 3

Hvilke etiologi har ALL?

Answer 3

More commonly associated with AML than ALL.

Question 4

Hvilken etiologi har AML?

Answer 4

Some hematopoietic disorders can progress to AML, although this process may take months or even years.

Question 5

Hvordan klassifiserers ALL ved bruk av FAB?

Answer 5

Question 6

Hvordan klassifiserer ALL jmf. WHO?

Answer 6

Precursor lymphoblastic leukemia encompasses the historical FAB classification L1 and L2 subtypes. L3 (Burkitt lymphoma) is now classified as a mature B-cell lymphoma.

Question 7

Hvordan klassifiserer man ALL basert på immunofenotyping?

Answer 7

Burkitt lymphoma with secondary marrow or peripheral blood involvement.

Question 8

Hva viser bildet?

Answer 8

B-cell acute lymphoblastic leukemia: Photomicrographs of a peripheral blood smear (H&E stain; very high magnification); The large basophilic cell in the center of each photomicrograph is a lymphoblast, identifiable by its large spherical nucleus surrounded by a thin rim of cytoplasm (high nucleocytoplasmic ratio). The nucleus of the lymphoblasts is often indented (green arrows) and shows fine loose (noncondensed) chromatin. Lymphoblasts differ from lymphocytes, which are smaller in size with smaller nuclei, condensed chromatin, and more cytoplasm. The presence of numerous lymphoblasts in a peripheral blood smear is indicative of lymphoblastic leukemia. The diagnosis of B-cell ALL was confirmed on immunophenotyping. Note: Basophilic remnants (Howell-Jolly bodies) are visible within the erythrocytes in the last photomicrograph, indicating (in this case) increased hematopoiesis.

Question 9

Hva viser bildet?

Answer 9

T-cell acute lymphoblastic leukemia: Photomicrographs of a peripheral blood smear (H&E stain; very high magnification); The basophilic cell clusters in the center of each photomicrograph are mainly composed of lymphoblasts, identifiable by their large size, large spherical nucleus that is surrounded by a thin rim of cytoplasm (high nucleocytoplasmic ratio). The nucleus of the lymphoblasts is often indented and shows fine loose (noncondensed) chromatin. Lymphoblasts differ from lymphocytes, which are smaller in size with smaller nuclei, condensed chromatin, and more cytoplasm. The presence of numerous lymphoblasts in a peripheral blood smear is indicative of lymphoblastic leukemia. The diagnosis of T-cell ALL was confirmed on immunophenotyping. Note: Basophilic remnants (Howell-Jolly bodies) are visible within some of the erythrocytes, indicating (in this case) increased hematopoiesis.

Question 10

Hvordan klassifiserer AML jmf. FAB?

Answer 10

The French-American-British (FAB) classification distinguishes between eight subtypes of AML, according to the histopathological appearance of the cells.

Question 11

Hvordan klassifiserer AML jmf. WHO?

Answer 11

Question 12

Hva viser bildet?

Answer 12

Acute monocytic leukemia: Photomicrographs of a bone marrow smear (H&E stain; very high magnification); The large basophilic cell visible in each photomicrograph is a monocyte, identifiable by its large size, folded or lobed nucleus with fine chromatin and prominent nucleoli (green overlay), and abundant granular cytoplasm with cytoplasmic vacuoles. Numerous monocytes on bone marrow biopsy is characteristically seen in acute monocytic leukemia. The diagnosis is confirmed on immunophenotyping.

Question 13

Hva viser bildet?

Answer 13

Acute promyelocytic leukemia; Photomicrographs of a peripheral blood smear (H&E stain; very high magnification): The large basophilic cells are promyelocytes, identifiable by their eccentric nuclei and abundant basophilic cytoplasm containing numerous Auer rods (rod-like intracytoplasmic inclusion bodies). This type of hypergranular leukemic promyelocyte is often still referred to as a “faggot cell” for the resemblance of accumulation of Auer rods to a “bundle of sticks,” although the term is typically avoided today due to its derogatory associations. The presence of promyelocytes containing Auer rods in a peripheral blood smear is characteristic of acute promyelocytic leukemia. Note: Basophilic remnants (Howell-Jolly bodies) are visible within most of the erythrocytes, indicating (in this case) increased hematopoiesis.

Question 14

Fyll inn figuren

Answer 14

Hematopoiesis; The stages of hematopoiesis, a process by which pluripotent hematopoietic stem cells in the bone marrow differentiate into two main types of precursor cells: myeloid and lymphoid. Myeloid precursor cells differentiate into erythrocytes, leukocytes, and thrombocytes. Lymphoid precursor cells differentiate into natural killer cells (NK cells) and B and T lymphocytes. Dendritic cells, which are antigen-presenting cells, develop from both myeloid and lymphoid precursors.

Question 15

Hvordan er patofysiologien ved akutt leukemi?

Answer 15

Mutations result in activation or inactivation of genes (e.g., Philadelphia chromosome, t(15;17)) that affect the proliferation and maturation of bone marrow cells.

Question 16

Hva er klinikken ved akutt leukemi avhengig av?

Answer 16

Clinical features are either related to bone marrow failure, infiltration of organs by leukemic cells, or a combination of both.

Question 17

Hvilke generelle kliniske tegn forekommer ved akutt leukemi?

Answer 17

Some patients report having nonspecific symptoms (fatigue) for a few months prior to presentation. Hepatosplenomegaly is more common in ALL than AML, occurring in > 60% of individuals with ALL and approx. 10% of individuals with AML. In AML, it may suggest the presence of a previous myeloproliferative disorder.

Question 18

Hvilken klinikk forekommer ved ALL?

Answer 18

Fever and lymphadenopathy are rare in AML, but can be common first signs in ALL!

Remember metastasis for ALL by thinking of the following: ALL metaStaSizeS to the CNS and teSteS.

Note that fever as a constitutional symptom in the absence of infection is typical for ALL, but not AML.

Question 19

Hvilken klinikk forekommer ved AML?

Answer 19

Caused by myeloblasts infiltrating the mucosa.

Question 20

Hvordan skal feber hos en pasient med akutt leukemi tolkes?

Answer 20

Fever in a patient with acute leukemia must always be treated as a sign of infection until proven otherwise!

Question 21

Hva viser bildet?

Answer 21

Leukemia cutis; Multiple erythematous papules and nodules are seen on the face and neck of this patient as a result of infiltrating malignant neoplastic cells accumulating in the dermis.

Question 22

Hvordan tilnærmer man seg en pas. med mistenkt akutt leukemi?

Answer 22

Question 23

Hva kan man si om funnene på evt. blodprøver ved akutt leukemi?

Answer 23

Findings on initial laboratory studies are usually nonspecific but may help to identify potentially life-threatening acute complications.

Question 24

Hvilke funn forekommer ved akutt leukemi av hhv.:
- Leukocytter
- Trombocytter
- Hemoglobin
- Blodutstryk

Answer 24

Although the WBC count may be normal or even elevated in patients with acute leukemia, the WBCs will be immature and nonfunctional. In some patients, levels of only certain types of WBC will be elevated, e.g., hypereosinophilia may be present prior to an ALL diagnosis. Even in mild thrombocytopenia, several different platelet abnormalities may be present (e.g., abnormal size and shape on smear), which may affect their function. This can result in impaired aggregation and adherence.

Question 25

Hva kan man se på lever- og nyreprøvene ved akutt leukemi?

Answer 25

Question 26

Hvilke funn kan forekomme ved utvidet metabolsk panel ved akutt leukemi?

Answer 26

Often abnormal due to increased cell lysis. Secondary to syndrome of inappropriate antidiuretic hormone secretion or leukemia-induced tubular defects, resulting in renal salt loss. Secondary to central diabetes insipidus or urea-induced osmotic diuresis. Secondary to kaliuresis in AML. May be secondary to impaired renal function or factitious in patients with hyperleukocytosis. Secondary to hyperphosphatemia in patients with a high leukemic cell burden. It is likely that many factors contribute to hypercalcemia. Some patients may produce an ectopic parathyroid-like protein. Secondary to high phosphate uptake by leukemic cells. Secondary to increased cell turnover and leukemic infiltration into the kidneys, which affects renal function.

Question 27

Hva kan koagulasjonsprøver vise ved akutt leukemi?

Answer 27

Question 28

Hvilke histopatologiske funn er typiske for ALL?

Answer 28

Cell morphology can confirm the diagnosis of acute leukemia, but in most cases, it is necessary to complete immunophenotype and genetic studies before selecting a treatment.

Histopathological features should be assessed using bone marrow aspiration and biopsy. If unavailable, a peripheral blood smear may be sufficient.

Question 29

Hva er histopatologiske funn ved AML?

Answer 29

Cell morphology can confirm the diagnosis of acute leukemia, but in most cases, it is necessary to complete immunophenotype and genetic studies before selecting a treatment.

Histopathological features should be assessed using bone marrow aspiration and biopsy. If unavailable, a peripheral blood smear may be sufficient.

Question 30

Hva er “leukemisk hiatus”?

Answer 30

Leukemic hiatus; Myeloblasts differentiate within the bone marrow into mature neutrophils that then enter circulation. Physiologically, only the mature band and segmented neutrophils are visible on a normal peripheral blood smear (PBS).: In chronic myeloid leukemia (CML), myeloid precursor cells and mature neutrophils are visible on a PBS. Whereas in acute myeloid leukemia (AML), the predominant myeloid cells on a PBS are myeloblasts and mature neutrophils. The absence of the intermediate myeloid precursor cells in AML is referred to as leukemic hiatus and is useful to differentiate AML from CML.

Question 31

Hva viser bildet?

Answer 31

Auer rods; Photomicrograph of a peripheral blood smear (Giemsa stain; high magnification): Two red rod-like intracytoplasmic inclusions (blue overlay) are visible within the myeloblast, which is the large basophilic cell in the center of the image with an eccentric, indented nucleus and abundant cytoplasm. These rod-like cytoplasmic inclusions are known as Auer rods, and they are typically seen in acute myeloid leukemia (e.g., acute promyelocytic leukemia) and in myelodysplastic syndromes.

Question 32

Hva viser bildet?

Answer 32

Auer rods in acute promyelocytic leukemia (APL); Photomicrograph of a bone marrow smear (Wright-Giemsa stain, high magnification): Promyelocytes with azurophilic granules can be seen as well as a myeloblast containing multiple violet, rod-like intracytoplasmic inclusion bodies, known as Auer rods (examples indicated by yellow lines). Auer rods are typically seen in certain types of acute myeloid leukemia (e.g., APL) and in myelodysplastic syndromes.

Question 33

Hva viser bildet?

Answer 33

Auer rods in acute myeloblastic leukemia; Photomicrograph of a peripheral blood smear (Pappenheim stain; high magnification): Multiple red rod-like intracytoplasmic inclusions (Auer rods, highlighted by gray overlay) are visible within a myeloblast, the large basophilic cell (marked by arrow) with an eccentric, indented nucleus (marked by black outline) and a prominent nucleolus (green overlay). Auer rods are typically seen in acute myeloblastic leukemia and acute promyelocytic leukemia.

Question 34

Hva viser dette bildet?

Answer 34

Acute lymphoblastic leukemia; Photomicrograph of bone marrow smear (H&E stain): Multiple lymphoblasts, identifiable as large basophilic cells with abundant granular cytoplasm and a large round nucleus with clumpy chromatin and prominent nucleoli, can be seen. The presence of > 20% of lymphoblasts within a bone marrow smear is diagnostic of acute lymphoblastic leukemia. The cells surrounding the lymphoblasts are erythroid precursors, mature erythrocytes, and mature neutrophils.

Question 35

Hva viser dette bildet?

Answer 35

L2 blast cell; L2 blasts are usually big blast cells with a variable nuclear structure, fine chromatin and multiple nucleoli. The medium-wide cytoplasm displays a distinct basophilia, azurophilic granules may be present. The peroxidase reaction is negative. PAS-staining is no longer relevant in ALL diagnostics.

Question 36

Hva viser bildet?

Answer 36

Acute myeloid leukemia; Photomicrograph of a bone marrow smear (H&E stain): Multiple myeloblasts are visible. These are identifiable as large basophilic cells with abundant nongranular cytoplasm and a large curved C-shaped nucleus with fine chromatin and prominent nucleoli. The presence of > 20% of myeloblasts within a bone marrow smear is diagnostic of acute myeloid leukemia. The cells surrounding the myeloblasts are erythroid precursors and mature erythrocytes.

Question 37

Hva viser pilen til?

Answer 37

Blast cell in AML M2.

Question 38

Hva viser pilene til?

Answer 38

Blast cell in AML M2.

Question 39

Hva er “Philadelphia kromosomet”?

Answer 39

Philadelphia chromosome and pathophysiological consequences; Strand breaks in the ABL gene on chromosome 9 and in the BCR gene on chromosome 22 result in the translocation of fragments between both genes (reciprocal translocation). As a result, chromosome 9 is extended (9q+) and chromosome 22 is shortened (Philadelphia chromosome, 22q-). The ABL gene fuses with the BCR gene on chromosome 22 to form the BCR-ABL fusion gene. ABL is a tyrosine kinase, whose regulatory unit is lost during translocation (red area on chromosome 9q+). The BRC-ABL gene displays uncontrolled tyrosine kinase activity and influences cell division and differentiation, which is the cause of several leukemias (especially CML and partially ALL). The BCR gene is the chromosome 22 breakpoint site (BCR = breakpoint cluster region).

Question 40

Hvilke forskjeller er det mellom immunofenotypingen til ALL og AML?

Answer 40

Question 41

Hvilke forskjeller er det mellom ALL og AML når det kommer til genetiske studier?

Answer 41

PCR is typically used to screen for prognostic markers. While the Philadelphia translocation is far more common in chronic myeloid leukemias than acute leukemias, it is a common finding in older patients with ALL, with a prevalence of up to 50% in patients > 50 years of age. Only present in ∼ 2% of patients with AML. Additional analyses include testing for IDH1, IDH2, TET2, WT1, DNMT3A, and/or TP53.

Question 42

Hvilke screeningmuligheter har man for pas. med akutt leukemi?

Answer 42

CNS infiltration is seen in ∼ 30% of children and ∼ 5% of adults with ALL. It is rare in AML but should be investigated in patients presenting neurological symptoms or depending on a specialist's evaluation (e.g., considering subtype and individual risk).

Question 43

Hvilken type behandling gir man pas. med akutt leukemi?

Answer 43

Typically, a combination of agents with different mechanisms of action are chosen that target disease factors such as the immunophenotype, genetic profile, and degree of extramedullary disease, and take into account patient factors such as physiological reserve, capacity for tolerating adverse effects, and individual preferences.

Question 44

Hvor lenge bør kjemoterapien vare ved akutt leukemi?

Answer 44

Regimens vary depending on the subtype of leukemia, the age of the patient, and immunophenotype and genetic study results.

This phase carries the greatest risk of infection and death caused by toxic damage to the hematopoietic and gastrointestinal systems, as well as complications such as tumor lysis syndrome. Consolidation therapy is indicated even if tumor cells are undetectable after induction therapy.

Question 45

Hvilke medikamentelle kjemopreparater brukes ved ALL?

Answer 45

A chemotherapy regimen commonly used to treat ALL is hyper-CVAD: Cyclophosphamide, Vincristine, daunorubicin (or Adriamycin), and Dexamethasone.

Question 46

Hvilke medikamentelle kjemopreparater brukes ved AML?

Answer 46

Question 47

Hvilke typer medikamentelle kjemopreparater brukes ved APL?

Answer 47

If APL is suspected, start treatment early with a differentiation agent (e.g., ATRA) without waiting for immunotype or genetic confirmation. Treatment may be adjusted later depending on the results.

In APL, the t(15;17) translocation and subsequent formation of the PML-RARA fusion gene can inhibit myeloblast differentiation under physiological levels of retinoic acid. High doses of ATRA (a vitamin A derivative) may induce myeloblast differentiation and promote remission.

Question 48

Hvordan vil man behandle CNS infiltrasjon ved akutt leukemi?

Answer 48

It is recommended that intrathecal prophylaxis is initiated early (e.g., during induction therapy). If CNS infiltration is confirmed, the intensity of intrathecal chemotherapy can be increased. High-risk APL is defined by an initial WBC count above 10 x 109 L (voksne). Not routinely used because of the associated risk of secondary malignancies, hypopituitarism, and neurocognitive adverse effects

Question 49

Hvilke type behandling er målrettet ved akutt leukemi?

Answer 49

Tyrosine kinase inhibitors interact with a significant number of over-the-counter medications and herbal supplements; therefore, ask patients to provide a comprehensive list of any medications or supplements they take to check for possible interactions. A novel TKI with possible activity against FLT-3 mutated AML.

Question 50

Hvilken annen spesialbehandling er mulig ved akutt leukemi?

Answer 50

Autologous or allogeneic stem cell transplantation: Indications include patients with poor prognostic factors (e.g., unfavorable cytogenetics) and those who do not achieve remission with chemotherapy.

Question 51

Hvilke onkologiske nødsituasjoner kan oppstå ved akutt leukemi?

Answer 51

Question 52

Hvilke behandlingsrelaterte nødsituasjoner kan oppstå ved akutt leukemi?

Answer 52

Transfuse pRBCs as needed on an individual basis. Consider prophylactic platelet transfusion to a target platelet count > 10,000/mm3 to prevent bleeding. Worse patient outcomes (e.g., faster time to bleeding, more bleeding events) are associated with a lack of prophylactic platelet transfusion. Transfusion thresholds may be higher for therapeutic platelet transfusion (e.g., active bleeding) or in specific high-risk scenarios (e.g., anticipated invasive procedure). Consult a specialist to determine individual thresholds for such patients. Consider administration of granulocyte colony-stimulating factor, e.g., filgrastim. Consider antimicrobial prophylaxis until resolution of neutropenia in consultation with a specialist.

Question 53

Hva kan en sekundær hyperuremi føre til ved akutt leukemi?

Answer 53

Question 54

Hvordan er 5-årsoverlevelsen til ALL og AML?

Answer 54

Question 55

Hvilke prognostiske faktorer er ugunstige ved ALL/AML?

Answer 55

The recent advances in BCR-ABL tyrosine kinase inhibitor therapy have significantly improved the prognosis of patients with this mutation. This is the disseminated variant of Burkitt lymphoma. They both share the t(8;14) translocation.

Question 56

Hvilke gunstige prognostiske faktorer finner man ved ALL/AML?

Answer 56

To remember that translocation t(12;21) commonly manifests with pediatric B-ALL and usually has a favorable outcome, think: “Kids flip back to health!” (the number 12 is 21 flipped around).

50 or more chromosomes.