Leukemia

Stem Cells

                     Multipotential                                                                                     Mulipotential

                     Hematopoietic Cells                                                                           Lymphocytic Cells

            Differentiate & mature into                                                                 Differentiate & mature into

            6 types of blood cells                                                                              3 types of blood cells

Red Cells                             Basophils                                                                      T lymphocytes

Neutrophils                        Monocytes                                                                    B lymphocytes

Eosinophils                         Platelets                                                                        Natural Killer Cells

Exposure to benzene and other organic solvents; herbicides/pesticides (CLL)

Smoking

Radiation exposure - Hiroshima, Chernobyl

Viruses - HTLVI and T cell ALL

Oncogenes

Hyperleukocytosis - leukostasis in lungs, CNS

Pancytopenia - Red blood cells (RBCs), White blood cells (WBCs), platelets

RBCs - anemia, fatigue, weakness, shortness of breath

WBCs - infection (bacterial, fungal)

Platelets - bleeding

Organ infiltration - lymph nodes. Liver/spleen, testes, CNS, gums

Metabolic - hyperuricemia, hypercalcemia, renal failure

Signs and symptoms (may be silent)

Examination of patient, peripheral blood, bone marrow (CSF, lymph nodes)

Morphology (myeloid vs. lymphoid)

Cytochemistry/flow cytometry (CD 33)

Cytogenetics [Ph+, t(15;17)]

Molecular genetics (Bcr-abl)

Goals are complete remission and cure

Chemotherapy

Radiation

Stem cell transplantation

New approaches

Acute vs. Chronic Leukemia

Complete remission

Relapse - disease has come back

Minimal residual disease

Disease-free survival (cure)

Refractory or resistant disease - disease that does not respond to chemotherapy

0.1% of bone marrow cells

Also present in umbilical cord blood

Can be mobilized into peripheral blood

Unique properties

Continuously replenish the pool

Mature into all the circulating blood cells

HLA antigens - tissue transplantation Ags

Autologous - using patients own stem cells

Allogeneic - using stem cells from someone else but the are identical

Matched Related Donor/Matched Unrelated Donor (MRD/MUD)

Non-myeloablative (mini transplant) - treatment used is not used to completely wipe out the bone marrow

Bone marrow - pancytopenia

GI tract-nausea/vomiting, diarrhea

Skin and hair

Reproductive function

Renal failure from tumor lysis

Hickman catheter (RAC)

Transfusions

Cytokines (G-CSF, Erythropoietin)

TPN - total parentural nutrition

Air filtration/low bacteria diets

DNA/genes

Tumor activator genes promote cell growth or prevent apoptosis (programmed cell death)

Tumor suppressor genes inhibit cell growth or promote apoptosis

Translocations

Deletions

 

3,500 new cases/year in US

1800 in children <15 yrs

Most common type of leukemia <15 yrs

Long-term remission (cure) in about 75-80% of children, 20-30% of adults

FAB L1, L2, L3

Immunopheotype - Pre-B, T, B cell

Risks: age <2, >10 yrs; age >30 yrs

WBC >25K in adults, >50K in peds, >100K T cell

Cytogenetics: Ph+, t(4;11), other

Extramedullary disease - leukemia outside of the bone marrow

>4 weeks to achieve CR (complete remission)

Chemotherapy

Induction (V, P, D, L-asp)

Post-remission (intensification, consolidation)

Maintenance

CNS prophylaxis (IT chemo, radiation)

Allogeneic in 1^st complete remission for high risk ALL

MUD/MRD for Ph+ in 1^st CR; any >1^st CR

Autologous in 2^nd or greater CR

Incidence - 10,100 new cases/year, mostly adults; 6,900 deaths/year

Possible causes - organic solvents, radiation, chemotherapy for breast cancer, Hodgkin's; Down syndrome, Fanconi's anemia

Classification:

FAB M0-M7

Specific cytogenetic abnormalities

t(8;21) in M2

t(15;17) in M3

abnormal 16 in M4

AML Risk Factors:

WBC >100K

Age >60 (especially with high risk cytogenetics)

Cytogenetics:

Good risk; t(15;17), t(8;21)

Poor risk; Ph+, +8, del 5, 7

Intermediate risk; normal

Treatment of AML:

Induction chemotherapy (Ara-C, Idarubicin)

Consolidation chemotherapy (CALGB)

35% Disease Free Survival for best groups

Stem cell transplant in 1^st CR (allo vs. auto)

65% DFS for best groups

Incidence - 7800-8100 new cases/year; 5100 deaths/year

Twice as common as CML

Only 2% of patients with chronic leukemia are children

Risks - herbicide/pesticide exposure; first degree relatives

Incurable

Lymphocytosis

Enlarged lymph nodes, liver, spleen

Hypogammaglobulinemia (low IgG)

Autoantibodies (AIHA, ITP)

Infections

Richter's transformation

Rai Stage                 Features                              Survival (med)

0                                 High WBC                         10 yrs

1                                 Lymph nodes                    10 yrs

2                                 Liver/spleen                      6 yrs

3                                 Anemia                                 2 yrs

4                                 Low platelets                      2 yrs

Observation until clinically indicated

Chemotherapy with: Fludarabine or 2-CDA, Chlorambucil +/ Prednisone

Radiation to large spleen or lymph nodes

Stem cell transplantation

Alpha-interferon (Roferon A, Intron A)

Homoharringtonine

Hydroxyurea (Hydrea)

Cytarabine (Cytosar-U)

Busulfan (Myleran)