{Onc: Blood CA}

Leukemia

Background

1. Type of cancer of blood or bone marrow (hematological neoplasms)
• Abnorm incr WBCs
2. Spectrum of diseases
• Acute leukemias
• Acute lymphocytic
• Acute myelogenous
• Chronic leukemias
• Chronic lymphocytic
• Chronic myelogenous
• Hairy cell, T-cell prolymphocytic, juvenile myelomonocytic
3. From mutations of DNA d/t radiation exposure, chemicals, viruses

Pathophysiology

1. Spectrum of neoplasms of blood-forming cells
• Acute: rapid incr in immature blood cells
• Commonly in children
• Immediate Tx required to prevent/contain spread
• Chronic: excessive accumulation abnorm mature WBCs
• Commonly in adults
• Months-years; pt can be monitored to ensure max effective Tx
2. Acute Nonlymphocytic (myelogenous) Leukemia (AML)
• 80-90% of all adult leukemias
• 30-60yo
• Signs/Sx
• Weakness/fatigue (anemia)
• Bleeding/bruising (low plts)
• Fever (neutropenia)
• Bone pain, hepatosplenomegaly, confusion
• Progression over days-wks
• Dx: blasts in periph blood & 30% in bone marrow
• Tx:
• Intensive combo chemo w/daunorubicin & cytarabine
• Autologous bone marrow transplant
• Acute promyelocytic leukemia
• High incidence of DIC
• Dramatic response to all-trans retinoic acid
3. Acute Lymphocytic Leukemia (ALL)
• Predominately in children (2-10 yo)
• Signs/Sx
• Weakness, fatigue, bleeding, fever (like AML)
• Lymphadenopathy, hepatocyte selection medium (HSM), bone pain
• Intracerebral leukostasis: confusion, lethargy, incr ICP
• Tx:
• Whole brain radiation
• Leukapheresis
• Hydroxyurea PO
• Urate nephropathy: hydration, alkalinize, allopurinol
• Induction Tx (vincristine, L-asparaginase, prednisone) followed by consolidation or bone marrow transplant
• Intrathecal methotrexate (MTX) & radiation as prophylaxis
• Children 80% cure; adults 40% cure
4. Chronic Lymphocytic Leukemia (CLL):
• Usually asymptomatic or fatigue if anemic
• Elderly (median 65 yo)
• Signs/Sx
  • Lymphadenopathy, HSM in advanced stages
  • Lymphocytosis >10,000, w/40% lymphs in bone marrow
• No Tx if asymptomatic, normal exam, normal Hgb & plts
• Tx if Sx, cytopenias, LN's
• Chlorambucil/prednisone; CAP or CVP to nonresponders
• Pneumovax
• Immune hemolytic anemia or immune thrombocytopenia as complication Tx w/glucocorticoids
5. Chronic Myelogenous Leukemia (CML)
• Signs/Sx:
• Massive splenomegaly
• > 100,000 WBC's
• Dx: Philadelphia chromosome t(9:22)
• Tx:
• Imatinib (Gleevec) +/- TK inihibitors (ie, dasatinib, nilotinib)
• CNS Sx from leukostasis: leukopheresis, hydroxyurea
• Urate nephropathy: allopurinol, hydration
• Chemo: interferon alpha-2a, cytarabine
• Combo chemo for blast crisis (mimics AML)
• Bone marrow transplant for pts <55yo
6. Hairy Cell Leukemia
• Men, 40-60 yo
• Signs/Sx
• Splenomegaly, pancytopenia
• Dx: hairy cells in blood & bone marrow
• Tx:
• 90% remission w/single agent chemo: CdA
• Other options include interferon alpha, DCF, 2CAA

Diagnosis

1. History
• Fatigue/weakness (chronic or acute)
• Hyperviscosity
• Immunocompromised
• Infection (especially with granulocytes <0.5 K [0.5 x10^9/L])
• Skin, gingival, perirectal, lung, urine
• Gram-negative, gram-positive cocci, Candida sepsis
• Treatment: gentamicin & 3rd gen cephalosporin
2. Physical Exam/Signs & Sx
• Ocular manifestations (eg, orbital inflammatory processes, orbital vessel occlusions)
• Leukemic retinopathy
• Hepatomegaly, splenomegaly, leukemic meningitis, lymphadenopathy
• Bleeding when pancytopenic
3. Labs/Tests
• Leukostasis when WBC >100,000 [100 x10^9/L]
• Anemia & pancytopenia
• Peripheral smear usually distinguishes between acute & chronic
• Lymph node biopsy/Bone marrow aspirate
• Confirm dx & classify disease by immunophenotype & cytogenics
4. Imaging
• CT/MRI (brain), X-ray (bones), ultrasound (kidneys, spleen, liver)
• Degree of organ damage d/t disease progression/chemo
• CT can be used to check lymph nodes in chest
• Fluorescein angiography for ocular manifestations
• Optical coherence tomography (OCT) to confirm macular exudative detachment
• OCT useful in pt therapy monitoring
5. Differential Dx
• Anemia
• Bone marrow failure
• Lymphoma
• Orbital cellulitis
• Central retinal vein occlusion

Treatment

1. Hematology/Oncology eval for Tx plan
• Chemo, radiation & BMT possible
2. Symptomatic Tx can be started in ER
3. Multidisciplinary approach
• Routine ophthalmic eval to prevent ocular Sx

Disposition

1. Outpt vs inpt work-up depending upon Sx, stability of pt
2. Decision in conjunction w/pt, consultants & primary physician

References

1. Gambacorti-Passerini, C.; Antolini, L.; Mahon, F. -X.; Guilhot, F.; Deininger, M.; Fava, C.; Nagler, A.; Della Casa, C. M. et al. (2011). "Multicenter Independent Assessment of Outcomes in Chronic Myeloid Leukemia Patients Treated with Imatinib". JNCI Journal of the National Cancer Institute 103 (7): 553-561.

Contributor(s)

1. Ho, Nick, MD

Updated/Reviewed: November 2011