1. Pei Lin Professor of Pathology Department of Hematopathology
MD Anderson Cancer Center

2. Clinical History
80-year-old man with a history of HTN, neuropathy and chronic anemia
Came to MDACC to see Dr. Garcia-Manero on 8/2/2007 for an outside diagnosis of Refractory anemia or CMML one year ago
Transfusion independent and untreated.
Chronic fatigue, dizziness
PE: o hepatosplenomegaly or peripheral adenopathy

3. Outside BM biopsy (3/7/2007)
WBC 4.7, Hgb 11.1, MCV 93, Platelet 341, Neutrophils 41.3, Lymphs 32.3, Monos 25.3 (abs: 1189), Eos 0.9, Basos 0.2,
Hypercellular bone marrow (70-90%) with left-shifted granulopoiesis, megakaryocytic hyperplasia, dyserythropoiesis and 3% blasts (see comment)

4. Outside BM (comment):
Flow cytometry immunophenotypic analysis of a sample from the bone marrow aspirate at Dianon Systems, Stratford, Connecticut demonstrated non-specific findings including left-shifted granulopoiesis with decreased expression of CD16.

5. Lab (8/2007 MDACC) WBC: 5.7, hemoglobin 12, and platelet 219
Neutrophils 67%, lymphocytes 17%, monocytes 16% (abs: 912)
Ferritin level is 915, Epo: 45.8.

7. RAS mutation negative

8. 5/11/2010
WBC: 7.6, HGB: 9.0, MCV: 94, Platelet: 273, Neutrophils: 68.0, Lymphs: 11.0, Monos: 16.0, Eos: 2.0, Metas: 3.0

9. JAK2 V617F PCR: 41%
RAS mutation: neg

12. Pomalidomide 5/21/2010
Danazol 1/7/2011
JAK2 inhibitor 4/2011

17. Risk Stratification IPSS, International Prognostic Score System
DIPSS, dynamic IPSS
DIPSS, DIPSS plus
MIPSS, Molecular IPS
GPSS, Genetics-Based PSS
1WBC
4 109/L or /L in Lille; WBC /L in IPSS,
DIPSS, DIPSS. 2Platelets /L in DIPSS and
/L in MIPSS. 3DIPSS unfavorable karyotype: complex
karyotype or 1 or 2 abnormalities including 8, 7/7q, i(17q),
5/5q, 12p, inv(3) or 11q23 rearrangement; GPSS high-risk:
complex without MK, 2 abnormalities not included in very high-risk
category, 5q, 8, other autosomal trisomies except 9, and other sole
abnormalities not included in other risk categories; very high-risk: MK,
inv(3), i(17q), 7/7q, 11q or 12p. 4Includes driver mutation status
(JAK2/MPL/CALR), as well as ASXL1 and SRSF2.
Mascarenhas J Looking forward: novel therapeutic approaches in chronic and advanced phases of myelofibrosis in ASH education book: 2015

18. Monocytosis is an adverse prognostic factor for survival in younger patients with primary myelofibrosis
129 patients PMF ≤ 60 yrs.
Range: 18–60, median 52)
WBC: 30 k/uL
Hb: 10 g/dL
PLT 100 k/uL
W, H, P, M
W, H, P
Leukocyte count (30k/uL)
Hemoglobin level (<10 g/dL)
Platelet count (< 100/uL)
Absolute monocyte count of ≥1 × 109 L1 x 10(9)L(-1) WH
M.A. Elliott, S. Verstovsek, D. Dingli, S.M. Schwager, R.A. Mesa, C.Y. Li, A. Tefferi Leuk Res 2007;31:

20. Proposed Diagnosis and Take home points
Dx: Primary myelofibrosis presenting with persistent monocytosis, JAK2 V617F +
Monocytosis may occur as initial presentation of PMF or during the disease course
Persistent monocytosis is associated with an adverse prognosis
May not be associated with RAS mutations or cytogenetic aberrations
Megakaryocytic dysplasia may be diagnostic clue