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| ==Differenting Chronic lymphocytic leukemia from other Diseases== | | ==Differenting Chronic lymphocytic leukemia from other Diseases== |
| ===Differentials based on Biomarkers===
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| * Chronic lymphocytic leukemia must be differentiated from other diseases that cause [[weight loss]], [[night sweats]], [[hepatosplenomegaly]], and palpable [[lymph node]]s, such as [[hairy cell leukaemia]], prolymphocytic leukaemia, [[follicular lymphoma]], and [[mantle cell lymphoma]].
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| * Based on the expression of cell surface markers, the table below differentiates chronic lymphocytic leukemia from other diseases that cause similar clinical presentations:
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| <br>
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| {| style="border: 0px; font-size: 90%; margin: 3px; width: 1000px"
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| | valign="top" |
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| |+
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| ! style="background: #4479BA; width: 600px;" | {{fontcolor|#FFF|'''Differential Diagnosis'''}}
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| ! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|'''Surface Immunoglobulin'''}}
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| ! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|'''CD5'''}}
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| ! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|'''CD22/FMC7'''}}
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| ! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|'''CD23'''}}
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| ! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|'''CD79b'''}}
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| ! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|'''CD103'''}}
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|
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| |-
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|
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| | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
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| '''Chronic lymphocytic leukemia'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Weakly positive'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Positive'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Negative'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Positive'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Negative'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Positive/Negative'''
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|
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| |-
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|
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| | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
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| '''[[Prolymphocytic leukemia]]'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Strongly positive'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Negative'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Positive'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Negative'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Positive'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Negative'''
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|
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| |-
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|
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| | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
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| '''[[Hairy cell leukemia]]'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Strongly positive'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Negative'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Positive'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Negative'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Positive/Negative'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Positive'''
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|
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| |-
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|
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| | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
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| '''[[Mantle cell lymphoma]]'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Positive'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Positive'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Strongly positive'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Negative'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Strongly positive'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Negative'''
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|
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| |-
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|
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| | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
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| '''[[Follicular lymphoma]]'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Strongly positive'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Negative'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Positive'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Negative'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Strongly positive'''
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| | style="padding: 5px 5px; background: #F5F5F5;" align="center" |
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| '''Negative'''
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| |}
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| <br>
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| * Chronic lymphocytic leukemia must also be differentiated from other causes of fever, hepatosplenomegaly, and lymph node swelling such as:
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| :* [[Splenic marginal zone lymphoma]]
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| :* Nodal marginal zone [[lymphoma]]
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| :* [[Lymphoplasmacytic lymphoma]]
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| :* [[Sézary syndrome]]
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| :* Smoldering [[adult T cell leukemia]]
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|
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| ===Other Differentials===
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| The following table differentiates chronic lymphocytic leukemia from other leukemias that may present with similar clinical features such as [[fever]], [[fatigue]], [[weight loss]], recurrent [[infections]] and elevated [[leukocyte counts]]. The following are the differentials:
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|
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| {| class="wikitable"
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| ! align="center" style="background:#4479BA; color: #FFFFFF;" + |Characteristic
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| ! align="center" style="background:#4479BA; color: #FFFFFF;" + |Causes
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| ! align="center" style="background:#4479BA; color: #FFFFFF;" + |Laboratory abnormalities
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| ! align="center" style="background:#4479BA; color: #FFFFFF;" + |Physical examination
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| ! align="center" style="background:#4479BA; color: #FFFFFF;" + |Therapy
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| ! align="center" style="background:#4479BA; color: #FFFFFF;" + |Other associations
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| |-
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| |[[Acute myeloid leukemia|'''Acute myeloid leukemia''']]
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| * [[Chromosomal]] instability
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| * Sporadic [[mutations]]
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| * Prior exposure to [[benzene]]
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| * Prior exposure to alkylating agents
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| * Prior exposure to [[Topoisomerase II|topoisomerase II inhibitors]]
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| * [[Germline]] ''[[RUNX1]]'' [[mutation]]
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| * [[Anemia]]
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| * [[Thrombocytopenia]]
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| * [[Neutropenia]]
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| * Elevated [[LDH]]
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| * Elevated [[uric acid]]
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| * Elevated [[phosphorus]]
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| * Elevated [[potassium]]
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| * Low [[calcium]]
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| * Greater than 20% [[myeloblasts]] on [[bone marrow]] aspirate.
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| * [[Pyrexia]]
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| * Evidence of [[infection]]
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| * [[Pallor]]
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| * [[Mucosal]] [[bleeding]] (less common than in [[acute promyelocytic leukemia]])
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| * [[Bruising]] (less common than in [[acute promyelocytic leukemia]])
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| * [[Cytarabine]]
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| * [[Anthracycline]]
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| * [[Enasidenib]]
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| * [[Liposomal]] [[daunorubicin]] plus [[cytarabine]]
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| * [[Gemtuzumab ozogamicin|Gemtuzumab ozogamycin]]
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| * [[Midostaurin]]
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| * [[Enasidenib]]
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| * Ivosidenib
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| * [[Stem cell transplant]]
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| * Variable [[prognosis]] based on [[cytogenetic]] and molecular profile
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| * Five new [[Food and Drug Administration|FDA]]-approved therapies became available in 2017-2018
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| |-
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| |[[Acute promyelocytic leukemia|'''Acute promyelocytic leukemia''']]
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| * Prior exposure to alkylating agents
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| * Prior exposure to [[topoisomerase II]] inhibitors
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| * [[Chromosomal translocation|Translocation]] between [[Chromosome 15 (human)|chromosomes 15]] and [[Chromosome 17 (human)|17]]
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| * Creation of PML-RAR''alpha'' [[gene]] product
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| * Differentiation block in [[myeloid cells]]
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| * Low [[white blood cell]] count (typically)
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| * [[Anemia]]
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| * [[Neutropenia]]
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| * [[Thrombocytopenia]]
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| * Low [[fibrinogen]]
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| * Elevated prothrombin time (PT)
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| * Elevated partial thromboplastin time (PTT)
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| * [[Mucosal bleeding]]
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| * [[Petechiae]]
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| * [[Ecchymoses]]
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| * Evidence of [[infection]]
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| * [[Pallor]]
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| * [[Thrombosis]]
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| * [[All-trans retinoic acid|All-''trans'' retinoic acid]] (ATRA)
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| * Arsenic trioxide
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| * [[Cytarabine]]
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| * [[Anthracycline]]
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| * Presence of [[Auer rods]] in promyelocytes
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| * High risk for early death from [[hemorrhagic]] complications
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| |-
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| |[[Acute lymphoblastic leukemia|'''Acute lymphoblastic leukemia''']]
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| * [[Chromosomal]] instability
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| * Sporadic [[mutations]]
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| * [[Anemia]]
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| * [[Thrombocytopenia]]
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| * [[Neutropenia]]
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| * Elevated [[LDH]]
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| * Elevated [[uric acid]]
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| * Elevated [[phosphorus]]
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| * Elevated [[potassium]]
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| * Low [[calcium]]
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| * Greater than 20% [[lymphoblasts]] on [[bone marrow]] aspirate
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| * [[Neurological|Neurologic]] deficits
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| * [[Pallor]]
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| * [[Lymphadenopathy]]
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| * HyperCVAD ([[cyclophosphamide]], [[vincristine]], [[doxorubicin]], [[dexamethasone]])<ref name="pmid28665419">{{cite journal| author=Terwilliger T, Abdul-Hay M| title=Acute lymphoblastic leukemia: a comprehensive review and 2017 update. | journal=Blood Cancer J | year= 2017 | volume= 7 | issue= 6 | pages= e577 | pmid=28665419 | doi=10.1038/bcj.2017.53 | pmc=5520400 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28665419 }} </ref>
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| * R-HyperCVAD (inclusion of [[rituximab]])
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| * Peg-asparaginase
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| * [[Intrathecal]] [[methotrexate]]
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| * [[Intrathecal]] [[cytarabine]]
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| * [[Blinatumomab]] (bispecific [[T cell]] engager)
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| * [[Inotuzumab ozogamicin|Inotuzumab]] ozogamycin (anti-CD22 antibody)
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| * [[Tisagenlecleucel]] (chimeric antigen receptor T (CAR-T) cell therapy)
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| * [[Stem cell transplant]]
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| * Sanctuary sites include the [[central nervous system]] ([[CNS]]) and [[testes]]
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| |-
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| |[[Chronic myelogenous leukemia|'''Chronic myeloid leukemia''']]
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| * [[Translocation]] between [[Chromosome 9 (human)|chromosomes 9]] and [[Chromosome 22|22]]
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| * Creation of [[Bcr-abl|BCR-Abl]] [[gene]] product
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| * Elevated [[white blood cell]] count
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| * Presence of [[white blood cell]] precursors at various stages of maturation
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| * Presence of excess metamyelocytes, [[basophils]], [[eosinophils]], and [[band cells]]
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| * [[Splenomegaly]]
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| * [[Abdominal tenderness]]
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| * [[Pallor]]
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| * Evidence of [[infection]]
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| * [[Imatinib]]
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| * [[Nilotinib]]
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| * [[Dasatinib]]
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| * [[Bosutinib]]
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| * [[Ponatinib]]
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| * [[Omacetaxine]]
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| * High response rate to [[tyrosine kinase inhibitors]]
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| * Risk for development of T315I [[kinase]] domain [[mutation]]
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| * Typically does not require [[stem cell transplant]]
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| * Three phases include chronic, accelerated, and blast phase
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| |-
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| |-
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| |[[Chronic lymphocytic leukemia|'''Chronic lymphocytic leukemia''']]
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| * Chromosomal instability
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| * Sporadic [[mutations]]
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| * [[Infections]]
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| * Elevated absolute [[lymphocyte]] count (in all stages)
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| * Presence of >5000 clonal [[B cells]] per microliter in peripheral blood
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| * Anemia (in Rai stage III)
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| * [[Thrombocytopenia]] (in Rai stage IV)
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| * [[Lymph node enlargement]] in Rai stage I
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| * [[Splenomegaly]] in Rai stage II
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| * [[Hepatomegaly]] in Rai stage II
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| * [[Pallor]]
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| * [[Bleeding]]
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| * Fludarabine
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| * Cyclophosphamide
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| * Rituximab
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| * Obinutuzumab
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| * Ofatumumab
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| * Ibrutinib
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| * Venetoclax
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| * Associated with [[autoimmune hemolytic anemia]], which occurs in 10-25% of patients with CLL
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| * Associated with [[immune thrombocytopenia purpura]]
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| * Associated with [[pure red cell aplasia]]
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| * Treatment with corticosteroids or anti-leukemic therapy will correct the autoimmune complications of CLL
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| |}
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| ==References== | | ==References== |