NcXHF

MICHAEL W. DEININGER
TABLE 1. Definitions of Accelerated- and Blastic-Phase Chronic Myeloid Lymphoma
Modified MDACC Criteria* WHO Criteria IBMTR
Accelerated Phase Blood or marrow blasts 15–29% Blood or marrow blasts 10–19% Hb 8 g/dL
Blood or marrow blasts and
Blood basophils 20% WBC 100 10 9 /L
promyelocytes 30%
Blood basophils 20% Plts 100 10 9 /L or 1,000 10 9 /L Plts 100 10 9 /L or 1,000 10 9 /L
Plts 100 10 9 /L Increasing spleen size and WBC Splenomegaly unresponsive to busulfan
and hydroxyurea
CCA/Ph CCA/Ph Extramedullary disease
CCA/Ph
Blood or marrow blasts 10%
Blood or marrow blasts plus promyelocytes
20%
Blood basophils and eosinophils 20%
Blastic Phase Blood or marrow blasts 30% Blood or marrow blasts 20% Blood or marrow blasts 30%
Extramedullary blasts (apart
Extramedullary blast proliferation
Extramedullary blasts (apart from spleen)
from spleen)
Large foci or clusters of blasts on bone
marrow biopsy
Abbreviations: MDACC, The University of Texas MD Anderson Cancer Center; WHO, World Health Organization; IBMTR, International Bone Marrow Transplant Registry; CCA/Ph , clonal cytogenetic
abnormalities in Ph cells; Plts, platelets; WBC, white blood cells; Hb, hemoglobin.
*Commonly used in clinical trials.
were used (in some cases with minor adaptations) in the major
practice-defıning prospective clinical trials and therefore
are recommended. 4-6 In the future, molecular classifıcations
may replace morphology and blood counts. An uncommon
clinical presentation is chloroma, which establishes a diagnosis
of BP-CML, irrespective of marrow and blood. Biopsy is
required and a diagnosis of chloroma requires the presence of
blasts, whereas mature granulocytic infıltrates in extramedullary
sites other than the spleen or liver may be reactive to
inflammation or infection and should not be confused with
BP-CML.
The Sokal and Hasford scores were developed in patients
treated with chemotherapy or interferon alfa (IFN-), respectively,
but were subsequently validated in prospective
TKI studies. The EUTOS score was developed in a cohort of
patients treated with imatinib, but was not universally confırmed
in subsequent studies. 10 All three prognostication systems
are based on laboratory and clinical parameters
obtained in untreated patients. Any form of therapy, including
hydroxyurea, may generate misleading results and must
be avoided. Although patients with high Sokal or Hasford
scores are less likely to achieve deep responses to TKIs and
RISK STRATIFICATION IN CHRONIC-PHASE CHRONIC
MYELOID LEUKEMIA
Clinical scoring systems to risk stratify CP-CML include the
Sokal, Hasford (European), and EUTOS scores (Table 2). 7-9
KEY POINTS
Chronic myeloid leukemia (CML) progresses in phases that
represent the most fundamental risk stratification.
Multiple different somatic mutations have been associated
with transformation from chronic to advanced CML.
Disease progression while receiving first-line tyrosine
kinase inhibitor (TKI) therapy and accelerated or blastic
phase CML are associated with reduced overall survival.
BCR-ABL1 kinase domain mutations are the best
characterized mechanism of TKI resistance, but fail to
explain many cases of clinical resistance.
Selection of salvage therapy depends on prior TKI
exposure, comorbidities, and BCR-ABL1 mutation status.
TABLE 2. Risk Stratification in Chronic-Phase Chronic
Myeloid Lymphoma
Risk Score Calculation Risk Groups
Sokal Exp 0.0116 (age 43.4) 0.0345
(spleen 7.51) 0.188
(platelet count 700) 2 0.563
0.0887 (blast cells 2.10)
Low: 0.8
Intermediate: 0.8–1.2
High: 1.2
Hasford 0.666 when age 50 (0.042
spleen) 1.0956 when platelet
count 1,500 109L (0.0584
blast cells) 0.20399 when
basophils 3% (0.0413
eosinophils) 100
Low: 780
Intermediate: 781–1,480
High: 1480
EUTOS Spleen 4 basophils 7 Low risk: 87
High risk: 87
Abbreviation: EUTOS, European Treatment Outcome Study.
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