Chapter 29: Pt 3 Leukemias, lymphomas, plasma cell malignancies

malignant disorders of blood and blood forming organs that exhibit uncontrolled proliferation of malignant leukocytes through overcrowding in bone marrow and decreased production and function of normal hematopoietic cells

leukemias

Classification of leukemias include

myeloid vs lymphoid and acute vs chronic

Cell lines affected in AML

proerythroblast, myeloblast, monoblast, megakaryoblast

cell lines affected in ALL

lymphoblast

Cell lines affected in CML

eosinophilic myelocyte, neutrophilic myelocyte, basophilic myelocyte

cells affected in CLL

small b cells

cells affected in MM

plasma cells

Acute leukemia

presence of un-differentiated immature cells with rapid onset and short survival of patient

chronic leukemia

predominant cells is mature but does not function normally, slow progression

Risk factors for leukemias

cigarrette smoking, exposure to benzene, ionizing radiaiton, HIV, Hep C, human T-lymphotropic virus type 1, drugs that cause bone marrow depression, pancytopenia, accumulation disorders

Symptoms of AML and ALL

fatigue, anemia, easy bleeding, amboninal fullness, hepatosplenomegaly, leukopenia, increased infections, lymphadenopathy, pain and tenderness in bones

Peripheral blood smear of aml will show

myeloblasts

peripheral blood smear of all will show

lymphoblasts

Bone marrow biopsy of aml and all will show

increased blast cells

greater than 30% lymphoblasts in bone marrow or blood

acute lymphocytic leukemia

Acute Lymphocytic Leukemia (ALL)

most common childhood leukemia, genetic anomaly of philadelphia chromosome, reciprocal translocation results in abnormal chromosomes 9 and 22

Risk factors for children for all

prenatal x-ray exposure, postnatal exposure to high does radiation, chemotherapy, genetic disorders, sibiling with ALL

most common adult leukemia

AML

AML results from

alterations of expression and function of transcription factors that cause diverse chromosomal translocations, arrest in cellular differentiation

risk factors for AML

exposure to radiation, benzene, chemotherapy, hereditary

Chlinical manifestations of leukemias

fatigue, bleeding, fever, anorexia, diminished sensitivity to sour and sweet tastes, muscle atrophy, central nervous system involvement

Tests done for Leukemias

peripheral blood smear and bone marrow tests

treatment of leukemias

chemotherapy, supportive measures: blood transfusions, antibiotics, antifungals, antivirals, stem cell transplantation, bone marrow transplant

Complications of Leukemias

anemia, netropenia, low wbc count

treatments of anemia, neutropenia, and low wbc from leukemia

anemia -\> blood products
neutropenia -\> granulocyte colony stimulating factors
low WBC count -\> colony stimulating factors to prevent infections

lymphoid neoplasm that arises from hematopoietic stem cells, philedelphia chromosome is often present but can also be linked to BCR-ABL1

chronic myelogenous leukemia

what age range in CML usually diagnosed in

adults 5th to 6th decades

lymphoid neoplasm that affects monoclonal b lymphocytes and expresses increased levels of proapoptotic proteins

chronic lymphocytic leukemia

CLL suppresses what

anti-apoptotic proteins

Clinical manifestations of CLL

Asymptomatic at time of dx, Lymphadenopathy, Suppresses humoral immunity and increases infection with encapsulated bacteria

In CML cells \__ vs in CLL cells

divide too quickly, don't die as they should

Symptoms of CML and CLL

fatigue, easy bleeding, more infections, hepatoplenomegaly (CML), lymphadenopathy (CLL)

Clinical manifestations of CML

infections, fever, weight loss

chronic phase of CML

2-5 years, symptoms may not be present

accelerated phase of CML

6-18 montsh, primary symptoms develop, splenomegaly

terminal blast phase CML

'blast crisis' survival only 3-6 month

tests for CML and CLL

blood and bone marrow tests

treatment of bothCLL and CML

chlorambucil with or without steroid, chemotherapy

treatment of CML

no cure, combined chemotherapy, biologic response modifiers, allogenic stem cell transplantation

CLL treatment

treat infection, hemorrhage, immunologic complicaitons

Rapid progression, often in children, 91% survival rate, primary cells: greater than 30% lymphoblasts and B cells

ALL

slow progression, more common in adults, 85% survival rate, primary cell monoclonal B

CLL

Rapid progression, more common in adult, 24% survival rate, primary cells precursor myeloid cells

AML

slow progression, found mostly in adults, no cure, primary cells neutrophilic or eosphinophilic or clonal that arise from hematopoietic stem cells

CML

Local lymphadenopahty indicates

drainage of an inflammatory lesion located near the enlarged node

generalized lymphadenopathy incidates

malignant or nonmalignant diseases such as mononucleosis, cytokines increase inflammation

Causes of lymphadenopathy

neoplastic disease, immunologic or inflammatory conditions, endocrine disorder, lipid storage diseases, unknown

diverse group of neoplasms that develop from proliferation of malignant lymphocytes in the lymphoid system

malignant lymphomas

Two major categories of lymphomas

hodgkin lymphoma or non-hodgkin lymphoma

Lymphoma can result from

genetic mutations, viral infection

cells in lymphnode that are necessary for diagnosis but not specific to hodgkin lymphoma, derived from malignant B cells that become binucleate

reed-sternberg cells

spread of hodgkin lymphoma

contiguous

types of hodgkin lymphoma

classic and nodular lymphocyte-predominant

b cell in germinal center has unsuccessful immunoglobulin gene rearragement, cells should undergo apoptosis but survive and likely have major histocompatibility type 1

hodgkin lymphoma

clinical manifestation of hogkin lymphoma

enlarged painless neck lymphnodes, lymphadenopathy causing pressure or obstruction, mediastinal mass, fever, weight loss, night sweats, pruritus, fatigure

tests done for hogkin lymphoma

chest x-ray, lymphangiography, biopsy

bimodal age distribution of hodgkin lymphoma shows peaks in

20s and \>60

approximate cure rate of hodgkin lymphoma

75%

treatment of hodgkin lymphoma

radiation therapy, chemotherapy, bone marrow or stem cell transplantation, monoclonal antibodies, nonmyeloablative allogenic stem cell transplantation

Other names for non-hodgkin lymphoma

b cell neoplasm, t-cell neoplasm, NK neoplasm

non-hodgkin lymphoma is linked to

chromosomal translocations

clonal expansion of b cells, t cells and/or nk cells, changes in proto-oncogenes and tumor suppressor genes contribute to cell immortality and thus an increase in malignant cells

non-hodgkin lymphoma

clinical manifestations of non-hodgkin lymphoma

localized or generalized painless lymphadenopathy, nodal enlargement and transformation over months to years, retroperitoneal and abdominal masses, ascites and leg swelling

Tests for Non-Hodgkin Lymphoma

biopsy

survival of nonhodgkin lymphoma

extended periods but less than hodgkin's lymphoma

treatment of non-hodgkin lymphoma is dependent on

type of cell, tumor stage, histologic status, symptoms, age, comorbidities

Treatment of Non-Hodgkin's lymphoma

chemotherapy, radiation, monoclonal antibodies, radioimmunotherapy

highly aggressive b-cell non-hodgkin lymphoma

burkitt lymphoma

presentation of burkitt lymphoma in africa vs us

fast growing tumor of jaw and facial bones vs abdominal swelling

more than 90% of cases of burkitt lymphoma are linked to

EBV

treatment of burkitt lymphoma

chemotherapy, adjuvant monoclonal antibody therapy

variant of non-hodgkin lymphoma from blastic cells, clones or relatively immature t cells become malignant in thymus

lymphoblastic lymphoma

more than 85% of lymphoblastic lymphoma

have t cell origins

First sign of lymphoblastic lymphoma

Painless lymphadenopathy in the neck

treatment of lymphoblastic lymphoma

Combined chemotherapy with multiple drugs

end stage cell of humoral immune response

plasma cell

types of plasma cell malignancy

precursors to malignant myeloma, waldenstrom macrohlobulinemia

plasma cell disorders primarly occur in which age group

elderly

malignant plasma cells produce abnormally large amounts of one class of immunoglobulin, M protein overproduction, bence jones proteins can pass through glomerulus and damage renal tubular cells

multiple myeloma

Clinical manifestations of multiple myeloma

hypercalcemia, renal failure, anemia, lytic lesions, skeletal pain, hyperviscosity syndomre, recurring infections

Tests for multiple myeloma

Radiographic and laboratory studies; bone marrow biopsy

acronym for multiple myeloma

CRAB

multiple myeloma is an increase in

any plasma cell line

prognosis of multiple myeloma

poor

treatment of multiple myeloma

-combinations of chemotherapy, drug therapy, targeted therapy, biologic therapy, radiation, plasmapheresis
- high dose chemotherapy with blood-forming stem cell transplantation
-tandem transplate thalidomide or both
- bisphosphonates to reduce skeletal damage
- hydration and diuretics
- antibiotics

splenomegaly is typically from

sequestration of rbcs

hypersplenism

overactive spleen

congestive splenomegaly

occurs with hepatic cirrhosis

infiltrative splenomagaly

engorgement by macrophages with indigestible material from various 'storage diseases'

splenomegaly can be a manifestation of

anemia from rbc destructions

treatment of splenomegaly

removal, should be last resort

Hemostasis is dependent on

adequate numbers of platelets and coagulation factors

consequences of diminished hemostasis

internal or external hemorrhage

purpura could be from

diffuse hemorrhage into skin tissues

thromboembolic disorders are

clotting disorders

thrombocytopenia is a platelet count of less than

100,000

a platelet count of

hemorrhage from minor trauma

platelet count less than 15,000

spontaneous bleeding

platelet count

severe bleeding that can be fatal

Heparin-induced thrombocytopenia (HIT)

immune-mediated adverse drug reaction caused by IgG antibodies against heparin-platelet factor 4, can lead to thrombosis