STEPTRACKERHEMATOLOGY + ONCOLOGY | PATHOLOGY | HIGH-YIELD REVIEW

Chronic Leukemias

Mature-looking clonal cells that build up slowly — CLL, hairy cell leukemia, CML and HTLV-1 adult T-cell leukemia.

FOCUS ON
CLL: older adult, smudge cells, CD5⁺ CD23⁺; dies of infection; may transform (Richter). Hairy cell: massive spleen, dry tap, TRAP⁺/CD11c/CD25/CD103, BRAF V600E, cladribine. CML: t(9;22), basophilia, imatinib. ATLL: HTLV-1, hypercalcemia, flower cells.
TYPE
CELL · MARKERS
GENETICS · FEATURES
CLUE · TREATMENT
CLL / SLL
most common adult leukemia
Small mature B cells: CD5⁺, CD23⁺, CD19⁺, dim CD20; smudge cells.
Lymphocytes > 5000/µL; SLL when nodes dominate · del(13q) good, del(17p)/TP53 poor
Often found on routine CBC in a 70-year-old · ibrutinib (BTK), venetoclax
CLL complications
Immune dysregulation from the clone.
Hypogammaglobulinemia (infections — leading cause of death), warm AIHA, ITP
Richter transformation → DLBCL: rapidly growing node, B symptoms
Hairy cell leukemia
middle-aged men
Mature B cells with hair-like projections: TRAP⁺, CD11c, CD25, CD103, annexin A1.
BRAF V600E; red-pulp spleen infiltration; marrow fibrosis
Massive splenomegaly, pancytopenia, dry tap, no lymphadenopathy · cladribine
CML
myeloproliferative
All granulocyte stages, basophilia, ↓ LAP.
t(9;22) BCR-ABL; chronic → accelerated → blast crisis (2/3 AML, 1/3 ALL)
Splenomegaly · imatinib and other TKIs
Adult T-cell leukemia/lymphoma
CD4⁺ CD25⁺ T cells with cloverleaf ("flower") nuclei.
HTLV-1 (Japan, Caribbean, West Africa); Tax oncoprotein
Lytic bone lesions, hypercalcemia, skin lesions; aggressive
Sézary syndrome
leukemic phase of MF
Circulating CD4⁺ T cells with cerebriform nuclei.
Mycosis fungoides spread to blood
Generalized erythroderma — page 6.07
T-LGL leukemia
Clonal cytotoxic large granular lymphocytes (CD8, CD57).
STAT3 mutations
Neutropenia + splenomegaly in a patient with RA

Mechanism — accumulation, not arrest

Mature cloneEscapes apoptosis
→
Slow accumulationBlood, marrow, spleen, nodes
→
Immune failureLow Ig, autoimmunity
→
TransformationRichter (CLL), blast crisis (CML)

Unlike acute leukemias, the cells mature — the problem is that too many survive.

Marker summary

DISEASE
KEY MARKERS
CLL
CD5⁺, CD23⁺, dim CD20; smudge cells
Mantle cell lymphoma
CD5⁺, CD23⁻, cyclin D1 (t(11;14))
Hairy cell leukemia
CD11c, CD25, CD103, TRAP, BRAF V600E
CML
BCR-ABL; ↓ LAP; basophilia
ATLL
CD4, CD25; HTLV-1
Sézary
CD4; cerebriform nuclei

How it's tested

COMMON CONFUSIONCLL and mantle cell lymphoma are both CD5⁺. CD23 and cyclin D1 tell them apart.
THE TRAPA middle-aged man has a huge spleen and pancytopenia, but no lymphadenopathy, and the marrow aspirate is dry. That is hairy cell leukemia, not CML or myelofibrosis — check TRAP and BRAF.
YOUR APPROACHAge + spleen + nodes + smear (smudge, hairy, flower) → marker → genetic hook → treatment.

If you see… think…

70-year-old, lymphocytes 40,000, smudge cells, CD5⁺ CD23⁺ → CLL
CLL patient with spherocytes and positive Coombs → warm AIHA
CLL with one rapidly enlarging node and fevers → Richter transformation
Massive spleen, pancytopenia, dry tap, TRAP⁺ → hairy cell leukemia — cladribine
WBC 180,000 with all myeloid stages and basophilia → CML
CML patient with blasts now > 20% → blast crisis
Caribbean adult, hypercalcemia, lytic lesions, flower cells → ATLL (HTLV-1)
Recurrent pneumonias in CLL → hypogammaglobulinemia
RA with neutropenia and large granular lymphocytes → T-LGL leukemia