DSA: Leukemias and Lymphomas and White cell disorders (from the end of week 2) Flashcards
Acute Leukemia EOD
- short duration of symptoms, including fatigue, fever, and bleeding
- cytopenias or pancytopenia
- more than 20% blasts in the bone marrow
- blasts in peripheral blood in 90% of patients
What cell is malignant in Acute leukemia?
hematopoietic progenitor cell
What are the clinical findings in acute leukemia due to?
replacement of normal bone marrow elements by the malignant cells
What is AML in relation to acute leukemia?
a myeloblastic subtype of it
-60 years
What is Acute Promyelocytic anemia characterized by?
t(15;17)
What does the t(15;17) make?
PML-RAR-alpha
- blocks retinoic acid…. blocks differntiation
- can be overcome with retinoic acid
What is the lymphoblastic subtype of acute leukemia?
ALL
- acute lymphoblastic leukemia
- mostly childhood
AML
- t(8;21) is the a good diagnosis
- inv(16) is good too
- monosomy 5 or 7 is bad
- FLT3 is bad too
APL
- t(15;17)
- PML-RAR-alpha
- response to non-chemotherapy treatments
ALL
- hyperdiploidy and t(12;21) is good
- hypodiploidy and t(9;22) and t(4;11) is bad
Mixed Phenotype Acute leukemias
- has blasts that lack differentiation along the lymphoid or myeloid lineage or blasts that express both myeloid and lymphoid lineage-specific antigens
- high risk and poor prognosis
How do these acute leukemia patients present?
- bleeding
- infections… we need to treat them or they’ll die
- gum hypertrophy and bone and joint pain
- hyperleukocytosis, elevated blast count, impaired circulation, present as headache, confusion, and dyspnea
- Patients will be pale and have purpura and petechiae
- rectal fissures`
Lab findings of acute leukemia
-pancytopenia and circulating blasts
-bone marrow hypertrophy and dominated by blasts
-pts with ALL with have a mediastinal mass visible on chest radiograph
-Auer rods!!!!! secure the diagnosis
-MPO +
-
What is CD10 known as?
the common ALL antigen
differential diagnosis with AML?
-myeloproliferative disorders, CML, and myelodysplastic syndromes
-left shifted bone marrow recovering from a previous toxic insult
-
Tx of AML?
-anthracycline (rubicin)
-cytarabine
-stem cell transplantation maybe later down the road
-if over 60, bad prognosis
-
Tx of ALL?
chemotherapy
-if Ph chromsome is there, kinase inhibitor like dasatinib
prognosis of AML
-good if under 60
prognosis for ALL
-good if younger than 39 years
Chronic Lymphocytic Leukemia
- B-cell lymphocytosis greater than 5000
- Coexpression of CD19, CD5 on lymphocytes
What is CLL a malignancy of?
B- cells
-it’s usually indolent, slowly progressive accumulation of them
How is CCL manifested clinically?
by immunosuppression, bone marrow failure, and organ infiltration
-the B cells don’t make normal antibody
Symptoms of CLL
- older ppl
- lymphocytosis
- LAD
What is the Rai classification of CLL?
- 0: lymphocytosis only
- 1: +LAD
- 2: +organomegaly
- 3: +anemia
- 4: +thrombocytopenia
In about 5% of cases of CLL, while the systemic disease remains stable, an isolated lymph node transforms into and aggressive large cell lymphoma… what’s that called?
-Richter Syndrome
Lab findings for CLL
-hallmark is lymphocytosis
-WBC >20,000
-distinguished from mantle cell lymphoma by presence of CD23 and absence of Cyclin D1 mutation
-if cells have mutated Ig, that’s good!
-if they have ZAP-70, we need to worry
-del 17p (TP53) is the worst prognosis
-
Tx pf CLL
- most cases no specific therapy, observation
- if bad, cyclophosphamide and fludarabine
- in older ppl, chlorambucil with obinutuzumab
- if relapsed or refractory disease, ibrutinib and idelalisib
When should Fludarabine be avoided?
in patients with autoimmune hemolytic anemia
-it could exacerbate it
prognosis of CLL?
pretty good if it isn’t stage 3 or 4
EOD for CML
- elevated white blood count
- markedly left-shifted myeloid series but with a low percentage of promyelocytes and blasts
- Presence of bcr/abl gene (Philadelphia chromosome)
What is CML?
it’s just an overproduction of myeloid cells
-remember (9;22)
What happens if CML is untreated?
it progresses to an accelerated and then acute blast phase… indistinguishable from acute leukemia
Symptoms of CML
- middle age
- fatigue, night sweats, fevers
- enlarged spleen
- sternal tenderness from marrow overproduction
CML lab findings
- myeloid left shift!!! immature cells
- hypercellular bone marrow
- bcr-abl gene
- the blast phase of CML is diagnosed when blasts are more than 20%
tx of CML
- not emergent
- tyr kinase inhibitor
- imantinib
NHL EOD
- often present with painless LAD
- Pathologic diagnosis of lymphoma is made by pathologic examination of tissue
What translocation does Burkitt lymphoma have?
t(8;14)
-c myc!
Follicular lymphomas translocation
t(14;18)
-BCL2
Once pathologic diagnosis is established, what do we do next?
STAGE IT using whole body PET/CT scan, a bone marrow biopsy, and lumbar puncture if they are really bad
Lab findings with NHL
-paratrabecular monoclonal lymphoid aggregates in bone marrow
What lab finding has an influence on the prognosis of NHL?
serum LD
Tx of indolent NHL
- follicular, marginal zone, and small lymphocytic lymphoma (CLL)
- depends on stage
- localized radiation
- if disseminated, treat only if symptoms come up
Tx of aggressive NHL
- DLBCL
- short course immunotherapy if localized RCHOP + radiation or 6 cycles of immunochemotherapy without radiation
- peripheral T-cell lymphomas don’t respond as well to radiation
What are factors that mean bad prognosis in NHL?
- > 60
- elevated serum LD
- Stage 3 or 4 disease
- more than one extranodal site of disease
- poor performance state
In treatment of AML, what do we use for induction, consolidation, and maintenance?
- induction: 5+7 (anthracycline and Ara-C)
- Consolidation: High dose Ara-C (HDAC)
- Maintenance: All trans retinoic acid (ATRA)… remember that this is for APL ONLY
What is APL again?
- Acute promyelocytic leukemia
- accumulation of granulocytes called promyelocytes
- M3 subtype of AML
- responds well to ATRA
In treatment of ALL, what do we use for induction, consolidation, and maintenance?
- induction: vincristine+prednisone
- consolidation: multiple agents+ CNS prophylaxis (MTX or Ara-C)
- Maintenance: 6MP and MTX
Hairy Cell Leukemia
- indolent B-cell lymphoma
- middle aged males
- CD103 is the “unique” hairy cell antigen
- BRAF mutation
- high levels of IL-2 in serum
- severe monocytopenias, so infections happen
- pancytopenia and splenomegaly
- TRAP resistant
- treat with 2-Chlorodeoxyadenosine (cladribine)
Go through the Rai staging system again.
0: Lymphocytosis only
1: +LAD
2: +HSM
3: +anemia
4: +thrombocytopenia
- remember, this is for CLL
EOD of Gastric Lymphoma
- symptoms of dyspepsia, weight loss, or anemia
- variable abnormalities on upper GI series or endoscopy including thickened folds, ulcer, mass, or infiltrating lesions; diagnosis established by endoscopic biopsy
- abdominal CT and EUS require for staging
What kinds of lymphomas are Gastric lymphomas usually?
- Non hodgkin B cell lymphoma
- believed to arise from MALT
What is an important risk factor the development of primary gastric lymphoma?
-infections with H. pylori
clinical findings for Gastric lymphoma
- ab pain, weight loss, or bleeding
- looks like ulcer
What should probably be performed if we have Gastric lymphoma?
EUS
- endoscopic ultrasound
- gives us the stage
Tx of Gastric lymphoma
- eradicate H. pylori
- Endoscopic surveilence every 6 months
- if we see mutations, radiation maybe required
- don’t do surgical resection, radiation and chemotherapy will do just fine
EOD for Hodgkin Lymphoma
- often painless LAD
- constitutional symptoms may or may not be present
- Pathologic diagnosis by lymp node biopsy
Clinical findings with HL
- RS cells
- bimodal age distribution
- painless mass, commonly in neck
- constitutional symptoms are fever, weight loss, drenching night sweats and stuff like that
- pain in lymph node following alcohol ingestion
- spreads in orderly fashion
- don’t confuse it with reactive lymphocytosis
What is the Ann Arbor staging thing for HL?
- 1: 1 lymph node region involved
- 2: involvement of 2 or more lymph node regions on one side of the diaphragm
- 3: lymph node regions involved on both sides of diaphragm
- 4: disseminated disease with extranodal involvement
- it’s “A” if there are no constitutional symptoms
- “B” if there is 10% weight loss over 6 months, fever, or drenching night sweats
Tx of HL
- Chemotherapy: ABVD
- doxorubicin, bleomycin, vinblastine, dacarbazine
- remember that fibrosis happens with bleomycin
What are the 7 things that influence the prognosis of HL?
- Age
- Stage
- gender
- Hgb
- albumin
- WBC count
- lymphocyte count
What does the prognosis work for HL?
- 75% if 0-2 risk factors
- 55% when 3 or more
When do we see a bad prognosis for HL?
- older
- bulky disease
- lymphocyte depletion or mixed cellularity on histologic exam
What is a normal peripheral WBC count?
7500
What is a Leukamoid reaction
WBC >50,000
-can be from infections
What are some secondary causes of Leukocytosis?
- Chronic Inflammation
- Ciggarette smoking
- Stress (catecholamines release marginated pool)
- Drug induced
- nonhematologic malignancy
- marrow stimulation from destructin of RBCs and platelets
What is it called when non hematopoietic entities invade the bone marrow?
-myelophthisis
What are some primary causes of Neutrophilia?
- Hereditary neutrophilia (constant G-CSF on auto dominant)
- Pelger Huet: looks like a left shift but not
- Down syndrome: GATA1 mutation
- Leukocyte Adhesion Deficiency (LAD): delayed separation of umbilical cord
- Familial Cold Urticaria: rash and hurts when cold
- post splenectomy
How do we tell CML apart from a leukamoid reaction
CML has abnormalities in more than one cell line
-t(9;22)
-low LAP (leukocyte alkaline phosphatase) score in CML
-
What is Monocytosis defined as?
> 500
What is eosinophilia defined as?
> 400
What is neutopenia defined as?
<1500
Does benign or ethnic familial neutropenia show any increased risk for infection?
no
What is Cyclic neutropenia?
- periodic neutropenia that lasts about 3-5 days and occurs at 21 day intervals
- neturophil elastase gene probs
Schwachman Diamond syndrome
- isolated neutropenia at first
- skeletal and pancreas problems
- SBDS gene: regulation of ribosomal RNA
- increased risk for leukemic transformation
Fanconi Anemia
- mutations involved in DNA repair
- takes more time for marrow failure to develop
- short, upper limb anomalies, hyperpigmented cafe au lait spots
Dyskeratosis congenita (DKC)
- nail dystrophy, leukoplakia, and skin pgmentation
- neutropenia
Chediak-Higashi syndrom
- albinism and neutropenia
- defects in vesicular trafficking
- LYST gene
what is the most common cause of neutropenia?
drug induced neutropenia
-neutrophil recovery is speeded by G-CSF
What complement molecule renders neutrophils more adherent and thereby prone to aggregation within the pulmonary vasculature?
C5a
- this happens with pts suffering burns and transfusion rxns
- PNH
What is the characteristic finding in the setting of megaloblastic anemia?
hypersegmentation of the neutrophil
What is standard treatment for CML?
Imatinib mesylate
Splenomegaly, cytopenia, and nonaspirable bone marrow in a middle aged man… what do we think of?
HCL
What is CLL characterized by?
lymphocyte counts that range from 5,000-600,000
*if they have autoimmune hemolytic anemia superimposed onto it, the erythroid hyperplasia can be masked by the lymphocyte infiltration of the bone marrow
