DISEASES OF WHITE BLOOD CELLS Premed 3 Dr Roopa

What Is Leukemia?

    Cancer of the white blood cells Acute or Chronic Affects ability to produce normal blood cells Bone marrow makes abnormally large number of immature white blood cells called blasts

History

 Means “white blood” in Greek  Discovered by Dr. Alfred Velpeau in France, 1827  Named by pathologist Rudolf Virchow in Germany, 1845

Leukemias

 ↑ leukocytes Acute leukemias Chronic leukemias 1. Acute Lymphoblastic Leukemia (ALL) 2. Acute Myelogenous Leukemia (AML) 1.Chronic Lymphoblastic Leukemia (CLL) 2. Chronic Myelogenous Leukemia (CML)

Treatment may involve some combination of chemotherapy , radiation therapy , targeted therapy , and bone marrow transplant , in addition to supportive care and palliative care as needed.

The success of treatment depends on the type of leukemia and the age of the person.

Acute Leukemias

     Blast predominate Child or elder Short & drastic course ALL – Lymphoblasts (pre-B or pre-T) AML – Myeloblasts

Chronic Leukemias

     More mature cells Middle age Longer & less devastating course CLL – Lymphocytes CML – Myeloid stem cells

Acute Leukemias

 accumulation of blasts in the marrow

Acute Lymphoblastic Leukemia (ALL)

  

Children Lymphoblasts (pre-B or pre-T)

Neoplastic transformation of the lymphoid stem cells • Progressive accumulation of Lymphoblasts in the bone marrow • Suppression of normal hemopoiesis

ALL

• Primarily a disease of children and old age • B-cell subtype (80%) • T-cell subtype (20%)

ALL - Pathogenesis

• Etiology unknown • Genetic predisposition (some) Down syndrome • Translocations (worse prognosis) t(4;11) t(12;21) t(9;22)

Signs &Symptoms

        Anemia Infection Bleeding Bone pain Arthritis Splenomegaly Lymphadenopathy CNS involvement

ALL

Prognosis: • Age 3-7, pre-B, L1 : > 90% - CR Less favorable ( 2/3 - cure ) • Adults, mature B and T-ALL: Therapy: Chemotherapy ( w/CNS prophylaxis ), supportive care, BMT

ACUTE MYELOGENOUS LEUKEMIA ( AML )

Adults Myeloblasts monoblasts, eosinoblasts, megakarioblasts, proerythroblasts, basophiloblasts Auer rods in the cytoplasm of the cells Very rapidly progressive malignancy

AML

Auer rods in AML

AML - Pathogenesis

Environmental factors: High-dose radiation exposure Myelotoxic agents (benzene, alkylating agents) Genetic abnormalities: Down syndrome, Immunodeficiency diseases

 Differentiation from ALL may be made by microscopy – presence of Auer Rods.

Clinical features based on    Marrow failure –anemia, bleeding, DIC, infection… Leukemic infiltration – bone pain, CNS signs, hepatosplenomegaly, lymphadenopathy… Constitutional upset -- malaise, fever, weakness, polyarthritis.

Course: • Rapidly fatal if untreated (< 2 mo ) • Median survival - 3 years after chem..

• Adverse prognostic factors: Therapy: Age > 60 t(9;21), Previous chemotherapy Leukocytosis > 100,000 /ul Chemotherapy, supportive, BMT

***Remember this*** For Acute leukemias

    acute leukemias = too many blasts in the marrow 2 broad categories: AML vs. ALL a hematologic urgency prognosis is poor in adults; but good in kids with ALL.

CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)

A monoclonal lymphoproliferative disorder characterized by lymphocytosis(>4000/cu.mm), lymphadenopathy and splenomegaly

B - CLL > 95%

T - CLL

CLL

• Most common adult leukemia in Western society (30% of all leukemias) • Monoclonal proliferation of the small lymphocytes… • Age > 40 M:F / 2:1

CLL PB and BM

CLL - Pathology

Blood: • • • • Lymphocytosis ( > 10,000 u/L - diagnostic ) (+) Coombs test (20%) Hypogammaglobulinemia (50-70%) Anemia, thrombocytopenia, neutropenia Bone marrow: • nodular / interstitial infiltrates • diffuse - obliteration of normal hemopoiesis Lymphadenopathy, Hepatosplenomegaly (50-60%)

CLL - Clinical course

Initially: asymptomatic Advanced disease: • bacterial infections, hemorrhage Prognostic factors: • extent of tumor burden • pattern of marrow infiltration • chromosomal abnormalities Median survival: ~ 6 years

Smudge cells - CLL

CLL

 One more peripheral blood findings in CLL is Presence of

Smudge cells



( parachute cells).

Along with increased number of normal appearing lymphocytes.

Chronic Myelogenous Leukemia (CML)

 Excessive development of mature neoplastic granulocytes in the bone marrow   Move into the peripheral blood in massive numbers Ultimately infiltrate the liver and spleen 8/12/2009 35

Chronic Myelogenous Leukemia

    Philadelphia chromosome 9 and 22 translocation almost specific to CML Produces BCR/c-abl fusion oncogene   The chromosome abnormality that causes chronic myeloid leukemia (CML) (9 &22) Genetic marker Chronic, stable phase followed by acute, aggressive (blastic) phase 8/12/2009 36

 i.e – mainly uncontrolled proliferation of myeloid cells.

 Males more than females  Splenomegaly – sometimes massive..

**Philadelphia chromosome**

  Hybrid chromosome with translocation between the long arm of chr. 9 and long arm of chr.22 . --- t(9:22).

May be present in granulocyte, RBC or platelet precursors in more than 95% of CML..

CML - Pathology

Bone marrow:

• Hypercellular / predominant

hyperplasia granulocytic

• Increased megakaryocytes (small forms) • Normal to decreased erythroid precursors

Peripheral blood: • Granulocytosis immature cells,

(>25,000/cmm), with

• Basophilia,

eosinophilia,

Extramedullary hemopoiesis: Spleen,

nodes liver, lymph

CML - Clinical Features

15 - 20% of all leukemias; age 25-60 Symptoms: - non-specific - related to hypermetabolism (high cell turnover) - related to splenomegaly Course: - chronic phase (mean survival, 3-4y) - accelerated phase - blast crisis / myeloid or lymphoid Therapy: chemotherapy; BMT (survival, < 1y)

Hodgkin’s lymphoma

    a lymphoid neoplastic disorder of B cell origin A disease marked by chronic enlargement of the lymph nodes, often local at the onset and later generalized.

characterized by the presence of Reed Sternberg cells (or variants of RS cells) in the affected tissues Enlargement of the spleen and often of the liver is also present.

Reed-Sternberg cells

 Considered to be a malignant neoplasm of lymphoid cells of uncertain origin.  Owl – Eye appearance  These cells have mirror-image nuclei.

 Young adults and elderly

Signs & Symptoms

      Enlarged painless nodes – mostly neck & axilla Fever, wt.loss, pruritis & night sweats.

Pel – Ebstein Fever – fever alternating with long periods (15-28days).

Anemia Cachexia Hepatosplenomegaly

Hodgkin’s disease: Summary

     a lymphoid neoplasm of B cell origin characterized histologically by Reed Sternberg cells (or variants) commonly presents with lymphadenopathy or mediastinal mass in young adults treatment modality depends on stage curable in most

Non Hodgkin's Lymphoma

   These include all lymphomas without Reed-Sternberg cells.

Most are B-cell proliferations Extra nodal involvement is there..

Signs & Symptoms

       Often symptomless Lymphadenopathy, wt.loss..

Extra nodal spread – skin, bone, gut, CNS, lung..

Pancytopenia may be there Infections are very common.

Fatigue, unexplained fever, sweats Enlarged Tonsils and adenoids

FOLLICULAR LYMPHOMA

      Follicular lymphoma’s – most common in US Derived from B lymphocytes t (14:18) Affects middle age Not very aggressive – mean survival 7-10 yrs Rarely they may transform in to aggressive type of lymphomas

Burkitt’s Lymphoma

      

A Lymphoblastic lymphoma mainly in African children.

Mostly associated with EBV infection.

Involves facial bones ( Jaw), ovaries, and abdominal lymph nodes.

Undifferentiated stem cells with scattered pale macrophages containing nuclear debris. Isolated histiocytes on background of abnormal lymphoblasts (STARRY SKY APPERANCE) t (8:14) High incidence in AIDS pt’s

Burkitts lymphoma