Hematology, Oncology & Immunology · Topic 22 of 28

Lymphoma, Chronic Leukemias & Myeloproliferative Disorders

Tap any line to see why it matters

Hematology-oncology · chronic blood cancers

Lymphoma, Chronic Leukemias & Myeloproliferative Disorders

Painless nodes need a biopsy. Then recognize B symptoms, CLL's lymphocyte count, CML's Philadelphia chromosome and polycythemia vera's hematocrit target.

01 · B symptomsFever, night sweats, > 10% weight loss in 6 mo

02 · Suspect CLLLymphocytes above 5,000/µL, clonal on flow

03 · PV targetPhlebotomy to hematocrit below 45%

Lymphoma: diagnosis

Diagnose on tissue: open or core biopsy; FNA often inadequate

Accessible node: open biopsy

Deep lesion: image-guided core biopsy

FNA is often inadequate for diagnosis and classification

B symptoms: fever, night sweats, unintentional weight loss

B-symptom weight loss: more than 10% of body weight in 6 months

B symptoms carry prognostic and staging weight

B symptoms suggest internal node, visceral or marrow involvement

Reed-Sternberg cells: large, binucleated, CD15+, CD30+, CD20− classic Hodgkin

Reed-Sternberg cells sit in a mixed inflammatory infiltrate

Classic Hodgkin: typically painless cervical nodes

Classic Hodgkin peaks at ages 15–40 and over 60

Non-Hodgkin: screen for HIV and hepatitis B and C at diagnosis

CLL: recognize it

Suspect with absolute lymphocytosis above 5,000/µL; flow cytometry confirms

Peripheral flow confirms clonal B cells: CD5, CD19, CD20, CD23

Marrow biopsy is not required

A smaller clone is monoclonal B-cell lymphocytosis

Hypogammaglobulinemia and neutropenia bring infections

DAT-positive autoimmune hemolytic anemia, immune thrombocytopenia

CLL infections: use bactericidal antibiotics

Consider immunoglobulin: ≥ 2 severe infections in 6 months plus hypogammaglobulinemia

CLL: when to treat

CLL is incurable, so withhold therapy until one of these

Constitutional symptoms

Significant organomegaly or nodes

Recurrent infections

Symptomatic cytopenias

Lymphocyte rise of ≥ 50% in 2 months

Lymphocyte doubling time under 6 months

CML: recognize and stage

Philadelphia chromosome t(9;22) makes BCR::ABL tyrosine kinase

BCR::ABL kinase drives myeloid overgrowth, blocks apoptosis; TKIs inhibit it

Suspect CML: high granulocytes with immature forms

Basophilia, eosinophilia, normal or high platelets

Splenomegaly in 60–70%

Granulocytes: usually under 50,000/µL if asymptomatic

Granulocytes: can reach 200,000–1,000,000/µL when symptomatic

Confirm by cytogenetics, FISH or RT-PCR

About 85% present in chronic phase

Accelerated phase: cytopenias, spleen growth, blasts up to 19%

Blast phase: ≥ 20% blasts, sepsis and bleeding like acute leukemia

Polycythemia vera: recognize it

JAK2 mutation with low or low-normal erythropoietin

Suspect PV: hemoglobin above 16.5 g/dL (men), 16.0 g/dL (women)

Test JAK2 V617F (over 95%), then exon 12

PV: erythropoietin low or low-normal

High erythropoietin suggests secondary erythrocytosis, the more common cause

Thrombosis is the leading cause of morbidity and death in PV

Stroke, MI, DVT, retinal occlusion, splenic infarct

Merck differs: JAK2 V617F 90%, exon 12 5%; hematocrit target below 42% in women (CYTO-PV and current reviews use below 45% for all); aspirin only for microvascular symptoms, with no reduction in macrovascular events (ECLAP and current reviews recommend it for all without a contraindication); peginterferon or ruxolitinib preferred, hydroxyurea restricted over leukemia concerns.

Myelodysplastic syndrome

Older patient with refractory cytopenias: suspect MDS

Refractory anemia, usually macrocytic

Refractory neutropenia or thrombocytopenia

Exclude B12, folate and copper deficiency, drugs, autoimmune causes

Confirm with marrow and cytogenetics

Red flags

Bulky lymphoma nodes present acutely by compression

SVC syndrome from lymphoma nodes consult heme-onc

Tracheobronchial compression from lymphoma nodes consult heme-onc

Epidural cord compression from lymphoma nodes consult heme-onc

Obstructive jaundice, hydronephrosis or bowel obstruction from nodes consult heme-onc

Aggressive lymphoma, especially Burkitt: tumor lysis with treatment IV hydration, allopurinol

G6PD deficiency precludes rasburicase: check G6PD first no rasburicase

CML with fever or marked lymphadenopathy is ominous ominous

Budd-Chiari or portal vein thrombosis, even with a normal hematocrit test for PV

Tumor lysis: IV hydration and allopurinol, often rasburicase. See the SVC, cord compression and Tumor Lysis Syndrome sheets.

Drug hazards

Rituximab boxed warning: hepatitis B reactivation screen first

Rituximab hepatitis B reactivation can cause fulminant hepatitis, death

Ibrutinib warnings: hemorrhage, infection, arrhythmia

Ibrutinib warnings: cardiac failure, sudden death, hypertension

Ibrutinib major hemorrhage: 3.1% without antithrombotics

Ibrutinib major hemorrhage: 6.1% with an anticoagulant

Weigh the risks before adding an anticoagulant to ibrutinib

Treatment

CLLobserve first

Withhold therapy until a treatment trigger appears

CMLoral TKI

Imatinib

Oral tyrosine kinase inhibitor, such as imatinib

5-year survival in chronic phase exceeds 90%

PhlebotomyPV mainstay

Keep hematocrit below 45%

A 45–50% target brought more thrombosis and cardiovascular death (CYTO-PV)

AspirinPV, low dose

Aspirin 81–100 mg daily

Give unless contraindicated: eases microvascular symptoms, lowered thrombotic events (ECLAP)

Avoid with acquired von Willebrand disease, which can arise with platelets above 1,000,000/µL

Cytoreductionhigh-risk PV

Hydroxyurea

Age over 60 or prior thrombosis: add to phlebotomy and aspirin, classically hydroxyurea

Interferon is an alternative; ruxolitinib treats hydroxyurea intolerance or resistance

Transformation, late effects and MDS

About 2–10% of CLL transforms to diffuse large B-cell lymphoma (Richter syndrome)Exclude transformation histologically at relapse before restarting therapy

Essential thrombocythemia: platelets above 450,000/µLNormal red cell mass, adequate iron, and no reactive cause, Philadelphia chromosome or myelofibrosis

Essential thrombocythemia treatment: most take aspirinHigh-risk patients get platelet-lowering therapy

Hodgkin late effects: doxorubicin and mediastinal radiationCardiomyopathy, coronary and valvular disease

Hodgkin late effects: bleomycin causes lung injury

Hodgkin late effects: second cancersRadiation raises solid tumor risk; chemotherapy raises leukemia risk from years 3 to 10

MDS transforms to acute myeloid leukemia in 10–30%Azacitidine or decitabine may slow transformation

MDS: chronic transfusion causes iron overloadAllogeneic stem cell transplant is the only cure

Hodgkin or non-Hodgkin lymphoma?

	Hodgkin lymphoma	Non-Hodgkin lymphoma
Nodes	Usually one localized group	Usually more than one group
Spread	Orderly and contiguous	Noncontiguous
Mesenteric nodes	Usually spared	Commonly involved
Extranodal disease	Infrequent	Frequent
Stage at diagnosis	Often early	Usually advanced

Pearl

Hodgkin spreads node to neighboring node; non-Hodgkin skips around and is usually advanced at diagnosis.