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WILLIAM'S HEMATOLOGY > 85 Primary Myelofibrosis > Flashcards

85 Primary Myelofibrosis Flashcards

1
Q

TRUE OR FALSE

The the fibrosis in PMF is secondary, not primary

A

TRUE

The the fibrosis in PMF is secondary, not primary

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2
Q

The only cancer in the medical lexicon not so designated; rather, it is named for an epiphenomenon in the extracellular matrix

A

PMF

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3
Q

Central pathologic change in PMF

A

Neoplastic (dysmorphic) megakaryocytopoiesis

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4
Q

Mutations in PMF

A

50% JAK2 gene
25% Calreticulin (CALR) gene
~5%Thrombopoietin receptor (C-MPL) gene

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5
Q

Percentage of triple-negative PMF

A

10%

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6
Q

In infants, the disorder can mimic the classic disease or show certain features but not others, such as ________________

A

Absence of hepatosplenomegaly

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7
Q

TRUE OR FALSE

In young and middle-age adults, PMF is similar to that in older subjects, although the proportion of indolent cases may be higher, and the disease occurs in boys twice as frequently as in girls.

A

FALSE

In young and middle-age adults, PMF is similar to that in older subjects, although the proportion of indolent cases may be higher, and the disease occurs in girls twice as frequently as in boys.

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8
Q

TRUE OR FALSE

In adults, the disease occurs with about equal frequency in men as in women.

A

TRUE

In adults, the disease occurs with about equal frequency in men as in women.

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9
Q

Exposure to high concentrations of __________ or __________________ preceded the development of PMF in a very small number of cases in the past.

A

Benzene
Very-high-dose ionizing radiation

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10
Q

Benzene in exposures greater than __________ is associated with an increased relative risk of acute myelogenous leukemia (AML) but not of chronic myelogenous leukemias.

A

40–200 ppm-years

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11
Q

TRUE OR FALSE

Most lymphocytes, and especially most long-lived T-lymphocytes are formed before acquired JAK2 V617F mutational event and are thus not part of PMF clone.

A

TRUE

Most lymphocytes, and especially most long-lived T-lymphocytes are formed before acquired JAK2 V617F mutational event and are thus not part of PMF clone.

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12
Q

JAK2 gene mutation in exon 12 account for _____ of PMF

A

~1%

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13
Q

JAK2 V617F is a dominant, gain-of-function mutation in the gene residing on chromosome _________

A

Chromosome 9p24

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14
Q

Percentage of JAK2 Mutation in:

PV:
PMF:
ET:

A

Percentage of JAK2 Mutation in:

PV: 98%
PMF: 60%
ET: 55%

Absent in most healthy individuals

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15
Q

A negative regulator of three important pathways in hematopoiesis—JAK2/STAT5, AKT, and MAPK—as well as in inflammation

A

LNK protein

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16
Q

Non-Driver Somatic Mutations that predict an inferior prognosis

A

ASXL1/SRSF2

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17
Q

Non-Driver Somatic Mutations associated with progression to AML from an MPN

A

RUNX1, TP53, NRAS, WT1, FLT3, IDH1/2, and TET2

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18
Q

High levels of fibroblastic factors __________________ resulted in intense fibrosis in animal models.

A

TGF-β 1 and platelet-derived growth factor [PDGF]

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19
Q

Increased ______________ was thought to be the principal cause of osteosclerosis

A

Osteoprotegerin

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20
Q

In PMF, it is the most prominent alteration in this clonal myeloid disease and is responsible for most of its major manifestations

A

Neoplastic megakaryopoiesis

Constitutive mobilization and circulation of CD34+ cells are prominent features of the clonal expansion.

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21
Q

TRUE OR FALSE

Microvessel density and marrow blood flow are increased in patients with PMF.

A

TRUE

Microvessel density and marrow blood flow are increased in patients with PMF.

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22
Q

Causes of anemia in PMF

A
  • Decreased erythropoiesis
  • Shortened red cell survival
  • Effects of splenomegaly on the distribution of red cells in the circulation
  • Hemolysis
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23
Q

Synonym for PMF

A

Megakaryocytic myelosis
Chronic megakaryocytic leukemia

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24
Q

Four of the five major types of collagen are present in normal marrow:

A
  • Type I in bone
  • Type III in blood vessels
  • Types IV and V in basement membranes
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25
Q

The fine reticulin fibers that appear after silver impregnation of marrow are principally _________ collagen

A

Type III collagen

They do not stain with trichrome dyes

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26
Q

The thicker collagen fibers are principally ____________ collagen and stain with trichrome dyes, but do not impregnate with silver.

A

Type I collagen

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27
Q

Collagen types I, III, IV, and V are increased in PMF , but _______________ is increased uniformly and preferentially.

A

Type III collagen

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28
Q

In terms of fibroplasia, all are increase except for

A

Collagenase
Plasma level of matrix metalloprotein III

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29
Q

Marrow fibrosis in PMF is most closely correlated with _____________________.

A

Increased neoplastic and dysmorphic megakaryocytes in the marrow

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30
Q

TRUE OR FALSE

The increased pathologic emperipolesis (the entry of neutrophils and other marrow cells into the canalicular system of megakaryocytes), evident in human PMF and in mouse models, suggests this may be an additional mechanism of α-granule injury and release of TGF-β and PDGF.

A

TRUE

The increased pathologic emperipolesis (the entry of neutrophils and other marrow cells into the canalicular system of megakaryocytes), evident in human PMF and in mouse models, suggests this may be an additional mechanism of α-granule injury and release of TGF-β and PDGF.

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31
Q

TRUE OR FALSE

The fibroblastic proliferation in marrow is not an intrinsic part of the abnormal clonal expansion of hematopoiesis.

A

TRUE

The fibroblastic proliferation in marrow is not an intrinsic part of the abnormal clonal expansion of hematopoiesis.

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32
Q

Extramedullary hemopoiesis is almost always present in what organs

A

Liver and spleen

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33
Q

Pathophysiology of extramedullary hematopoiesis

A

Escape of progenitor cells from marrow and their lodgment in other organs

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34
Q

TRUE OR FALSE

Reversion of the liver and spleen to their fetal hematopoietic functions (metaplasia) is a major factor in extramedullary hematopoiesis, and quantitatively significant, effective hematopoiesis occur outside of the marrow

A

FALSE

Reversion of the liver and spleen to their fetal hematopoietic functions (metaplasia) is NOT a MAJOR factor in extramedullary hematopoiesis, and quantitatively significant, effective hematopoiesis DOES NOT occur outside of the marrow

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35
Q

The most frequent self-reported complaint and is disproportionate to the degree of anemia.

A

Fatigue

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36
Q

Severe left upper quadrant or left shoulder pain can occur from __________________

A

Splenic infarction and perisplenitis

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37
Q

Occasionally, bone pain is prominent, especially in the ________________.

A

Long bones of the lower extremities

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38
Q

Fatigue, weight loss, cachexia, night sweats, and bone pain are more frequent later in the course of the disease and are related to the ______________________ that are a key feature of the disease

A

Increase in circulating inflammatory cytokines

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39
Q

TRUE OR FALSE

Splenomegaly is present on palpation or imaging studies in some of patients at the time of diagnosis, and hepatomegaly is detectable in two-thirds of patients.

A

FALSE

Splenomegaly is present on palpation or imaging studies in almost ALL patients at the time of diagnosis, and hepatomegaly is detectable in TWO-THIRDS of patients.

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40
Q

Proportion of splenomegaly

Mildly:
Moderately enlarged:
Massive:

A

Mildly: one-fourth
Moderate: half
Massive: one-fourth

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41
Q

A syndrome that closely mimics the raised and tender plaques of Sweet syndrome

A

Neutrophilic dermatosis

  • The dermatopathology of neutrophilic dermatosis is different from leukemia cutis and is unrelated to infection or vasculitis.
  • The predominant histologic lesion is an intense polymorphonuclear neutrophilic infiltrate.
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42
Q

These cutaneous lesions in PMF may have myeloid cells with giant cells carrying ________ markers characteristic of megakaryocytes

A

CD61

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43
Q

Percentage of patient with Prefibrotic Primary Myelofibrosis

Without overt reticulin fibrosis in the marrow

A

25%

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44
Q

Constant finding in prefibrotIc PMF

A

Thrombocytosis

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45
Q

The most important distinction or prefibrotIc PMF with ET

A

In PMF, bizarre changes are evident with wide variation in megakaryocyte size, from very small to giant size cells.

Nuclear lobulation is abnormal, with bulky multilobulation, hypolobulation, and free megakaryocyte nuclei in the marrow spaces.

In ET, megakaryocytes are increased, but they do not display the dysmorphia observed in PMF.

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46
Q

Symptoms or signs leading to diagnosis of Extramedullary (Fibrohematopoietic) Tumors

A

(1) identification of a mass on imaging regardless of location

(2) appearance of signs or symptoms of an effusion in the thorax or abdomen

(3) unexpected neurologic signs

(4) another finding that appears unexpected in a patient with PMF

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47
Q

TRUE OR FALSE

Portal vein thrombosis is a complication of PMF and occasionally precedes disease onset.

A

TRUE

Portal vein thrombosis is a complication of PMF and occasionally precedes disease onset.

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48
Q

TRUE OR FALSE

Abnormalities of humoral immune mechanisms have been observed in as much as half of patients with PMF.

A

TRUE

Abnormalities of humoral immune mechanisms have been observed in as much as half of patients with PMF.

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49
Q

Causes of nonclonal secondary myelofibrosis

A

Lupus erythematosus, Vasculitis, polyarteritis nodosa, ulcerative colitis, scleroderma, biliary cirrhosis, Sjögren syndrome, and acute reversible myelofibrosis responsive to glucocorticoids

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50
Q

Imaging that can uncover evidence of new bone formation and periosteal thickening (osteosclerosis)

A

MRI

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51
Q

Imaging that provide evidence for increased bone formation, bone thickening, and higher proportions of cancellous and of woven bone.

A

Lumbar spine dualenergy x-ray absorption studies and quantitative computed tomography

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52
Q

Approximately _____ of patients with PMF will experience a significant thrombotic event during the ___________ of the disease.

A

10%

First four years

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53
Q

The two principal risk factors for thrombosis are :

A

Elevated leukocyte count and age

Not platelet count

The combination of the JAK2 mutation, leukocytosis, and age predicted the highest incidence of thrombosis.

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54
Q

The JAK2 mutational analysis is positive in: (%)

Idiopathic hepatic vein thrombosis:
Idiopathic portal vein thrombosis:

A

Idiopathic hepatic vein thrombosis: 35%

Idiopathic portal vein thrombosis: 25%

55
Q

TRUE OR FALSE

Normocytic–normochromic anemia is present in all patients with PMF

A

FALSE

Normocytic–normochromic anemia is present in most, but not all, patients

Anisocytosis and poikilocytosis are a constant finding.

56
Q

TRUE OR FALSE

In some cases, teardrop-shaped red cells (dacrocytes) are present in sufficient number to be found in few oil immersion field

A

FALSE

In all cases, teardrop-shaped red cells (dacrocytes) are present in sufficient number to be found in every oil immersion field

57
Q

Approximately ________% of patients present with pancytopenia because of severe impairment of hematopoiesis affecting each cell lineage, coupled with sequestration in a massively enlarged spleen.

A

10%

Pancytopenia usually is associated with intense marrow fibrosis.

58
Q

The________________________in the blood is correlated with the extent of marrow reticular fiber density

A

Frequency of hematopoietic progenitor cells in the blood

Megakaryocytes also are present in the systemic venous blood.

59
Q

An (Increase/Decrease) in blood CD34+ cells is very characteristic of PMF, and the concentration of these cells lends weight to the diagnosis.

A

Increase

The height of the CD34+ cell count is correlated with the extent of disease and disease progression.

60
Q

A concentration greater than __________ blood CD34+ cells is virtually diagnostic of PMF

A

15 × 10 6 /L

61
Q

Patients with greater than ___________ CD34+ cells have more rapid progression of disease than patients with fewer CD34+ cells.

A

Greater than 300 × 10 6 /L CD34+ cells

62
Q

CD34+ cells have impaired in vitro differentiation to natural killer cells, which appears to be related to a dysregulation in control of _______

A

IL-15

63
Q

Stain for collagen fibrosis; characteristically stains green

A

Gomori trichrome stain

64
Q

Characteristic of megakaryocytes in BMA of PMF

A

Giant megakaryocytes and micromegakaryocytes, abnormal nuclear lobulation, and naked megakaryocyte nuclei

65
Q

Thrombopoietin receptors are (decreased/increased) on megakaryocytes and platelets.

A

Decreased

66
Q

Characteristic of granulocytes in BMA of PMF

A

Hyperlobulation and hypolobulation of the nucleus, acquired Pelger–Huët anomaly, nuclear blebs, and nuclear–cytoplasmic maturation asynchrony

67
Q

Microvessel density is significantly (decreased/increased) in approximately 70% of patients

A

Increased

68
Q

Scale used in grading of the degree of PMF

A

Bauermeister scale (0-4)
European grading scale (0–3)

69
Q

Marrow finding in prefibrotic stage

A

Increased proportion of late neutrophil precursors (myelocytes, metamyelocytes, bands)
Myeloblasts and CD34+ cells are inconspicuous
Erythropoiesis may be slightly decreased
Increased and abnormal megakaryocytopoiesis :hallmark of this phase

70
Q

Chromosome abnormalities of hematopoietic cells are evident in approximately______of patients at the time of diagnosis.

A

40%

71
Q

Most frequent cytogenetic findings

A
  • partial trisomy 1q
  • Interstitial deletion of a segment of the long arm of chromosome 13
  • del(13)(q12–22), which bears the retinoblastoma gene
  • del 20q
  • trisomy 8
72
Q

The______abnormality is more prevalent in PMF than any other MPNs.

A

5q–

73
Q

Cytogenetic findings that are associated with PMF but are not exclusively seen in patients with PMF.

A

del(13) and der(6)t(1;6)(q21–23;p21.3)

74
Q

15% of patients present with unfavorable karyotypes namely:

A

Three or more abnormalities
+9
–7/7q–
5/5q–
i(17q)
inv(3)
12p–
11q23

75
Q

An unfavorable karyotype is associated with a ___________greater risk of acute leukemic transformation than a favorable karyotype.

A

Sixfold

76
Q

Finding on MRI of PMF as cellularity and fibrosis progress

A

Hypointensity of T1-weighted and T2-weighted images

77
Q

TRUE OR FALSE

MRI can identify the uncommon periosteal reactions that usually occur in the distal femur, proximal tibia, or ankle.

A

TRUE

MRI can identify the uncommon periosteal reactions that usually occur in the distal femur, proximal tibia, or ankle.

The reactions represent expansion of marrow cellularity into normally inactive regions of long bones or extramedullary spaceoccupying lesions of fibrohematopoietic tissue.

78
Q

MRI finding of patchy or diffuse osteosclerosis

A

“sandwich vertebrae”

The findings of sodium-fluoride positron emission tomography can be virtually specific for osteosclerosis of PMF

79
Q

INCREASE OR DECREASE:

Serum levels of uric acid, lactic dehydrogenase, bilirubin, alkaline phosphatase, and high-density lipoprotein

A

INCREASE

80
Q

INCREASE OR DECREASE

Serum levels of albumin and cholesterol

A

DECREASE

81
Q

Serum________________ is often decreased and is a negative prognostic factor

A

Cholesterol

82
Q

INCREASE OR DECREASE

Thrombopoietin and IL-6
Serum-soluble IL-2 receptor and serum VEGF
Urinary excretion of calmodulin

A

INCREASED

Thrombopoietin and IL-6 do not correlate with either platelet or megakaryocyte mass.

83
Q

TRUE OR FALSE

In PMF, the white cell count usually is less than 30 × 109/L at the time of diagnosis.

A

TRUE

In PMF, the white cell count usually is less than 30 × 10 9 /L at the time of diagnosis.

In CML, the white cell count is usually greater than 30 × 10 9 /L in almost all patients and greater than 100 × 10 9 /L in half of patients.

84
Q

Condition characterized by intense marrow fibrosis and an increase in marrow polyclonal T and B lymphocytes.

A

Primary autoimmune myelofibrosis

85
Q

Conditions that can induce reactive marrow fibrosis and occasionally simulate PMF

A
  • Metastatic carcinoma, especially a primary carcinoma of breast or prostate
  • Disseminated mycobacterial infection
86
Q

TRUE OR FALSE

All clonal hematopoietic diseases (AML, CML, oligoblastic myelogenous leukemia [myelodysplastic syndrome], lymphomas) may have increased marrow reticulin fibers but only infrequently have collagen fibrosis.

A

TRUE

All clonal hematopoietic diseases (AML, CML, oligoblastic myelogenous leukemia [myelodysplastic syndrome], lymphomas) may have increased marrow reticulin fibers but only infrequently have collagen fibrosis.

87
Q

Leukemia accompanied by intense marrow fibrosis

A

Acute megakaryoblastic leukemia

88
Q

Transition into PMF

PV:
ET:

A

Transition into PMF

PV: 15%
ET: 7-15%

89
Q

The principal initial reasons for therapy

A

Constitutional symptoms, anemia, thrombocytopenia, and splenomegaly

90
Q

Predictors of more rapid progression of disease

A
  • Hemoglobin less than 100 g/L
  • White blood cell count less than 4.0 × 10 9 /L or greater than 30.0 × 10 9 /L
  • Patelet count under 100 × 10 9 /L
  • Bllasts above 1% of total leukocytes
91
Q

Staging prognostic systems used in PMF

A

Dynamic international prognostic scoring system (DIPSS plus)

92
Q

Componennt of Dynamic international prognostic scoring system (DIPSS plus)

A
  • Age older than 65 years
  • Constitutional symptoms
  • White blood cell count over 25 × 10 9 /L
  • Hemoglobin less than 100 g/L
  • Blood blasts greater than 1%
  • Unfavorable karyotype, including +8, -7/7q-, i(17q), -5/5q-, 12p-, inv(3), or 11q23 rearrangement
  • Transfusion dependency;
  • Platelet count lower than 1 × 10 9 /L
93
Q

Options for treatment of anemia in PMF

A
  • BT
  • Recombinant erythropoietin
  • Luspatercept
  • Androgen therapy
94
Q

TRUE OR FALSE

Use of erythropoietin for anemia is usually disappointing in over 50% of PMF patients.

A

TRUE

Use of erythropoietin for anemia is usually disappointing in over 50%of PMF patients.

Patients selected by their inappropriately low serum erythropoietin levels (<125 U/L) for the degree of anemia—beneficial effects can result.

95
Q

A recombinant protein that is composed of a modified extracellular domain of activin receptor type IIb linked to the IgG1 fc domain. It inhibits several ligands in the TGF-β superfamily.

This inhibition results in an accelerated maturation and proliferation of LATE erythroid precursors.

A

Luspatercept

Administered subcutaneously in doses up to 1.75 mg/kg every 21 days

96
Q

Side effects of Luspatercept

A

High blood pressure (11%)
Bone pain (8%)
Diarrhea (4%)

97
Q

TRUE OR FALSE

Severe anemia may improve with androgen therapy in some patients but, generally, it is less effective than erythropoietin.

A

TRUE

Severe anemia may improve with androgen therapy in some patients but, generally, it is less effective than erythropoietin.

98
Q

Dose of Danazol

A

Danazol 600–800 mg/day orally for up to 6 months

The drug is tapered to the minimum effective dose or discontinued if no significant response occurs.

99
Q

TRUE OR FALSE

Androgens are less effective in splenectomized patients or those with less splenic enlargement.

A

FALSE

Androgens are more effective in splenectomized patients or those with less splenic enlargement.

100
Q

Patients undergoing androgen therapy should have periodic assessment of ________ size by physical examination, measurement of_________ and, if appropriate, ultrasonographic imaging

A

Liver

Liver function tests

101
Q

TRUE OR FALSE

Evaluation of male patients for prostatic enlargement or cancer is prudent before starting androgen therapy.

A

TRUE

Evaluation of male patients for prostatic enlargement or cancer is prudent before starting androgen therapy.

102
Q

Patients with significant hemolytic anemia may benefit from

A

Glucocorticoid therapy

Prednisone 25 mg/m2 per day

If tolerated, the dose can be continued for 1–2 months and then tapered gradually.

In children, high-dose glucocorticoid therapy can ameliorate marrow fibrosis and improves hematopoiesis.

103
Q

The most striking and consistent effect with JAK2 V617F Kinase Inhibitors

A

Decrease in spleen size and reversal of constitutional symptoms

104
Q

JAK2 Inhibitors often suppress blood cell counts, and _______________& can be dose-limiting.

A

Thrombocytopenia

105
Q

In 2011, _____________, an oral JAK2 inhibitor, was approved by the FDA for use in patients with intermediate- or high-risk PMF.

A

Ruxolitinib

106
Q

Ruxolitinib should not be administered if platelet counts fall to less than ______________

A

50 × 10 9 /L

Drug not FDA approved for starting platelet counts of 50–100 × 10 9 /L

107
Q

Dose of Ruxolitinib

PC >200

A

20 mg BID

108
Q

Dose of Ruxolitinib

PC 100-200

A

15 mg BID

109
Q

Dose of Ruxolitinib

PC 50-100

A

5 mg twice daily

Increasing each month by 5 mg daily until maximal splenic size reduction, only if platelet count stays above 40 × 109/L

110
Q

JAK32 inhibitor that crosses the brain barrier and unlike in ruxolitinib therapy, Wernicke encephalopathy has been encountered with this therapy, and thiamine deficiency needs to be ruled out before initiation of therapy

A

Fedratinib

111
Q

If encephalopathy is suspectedin Fedratinib, ____________ therapy must be initiated

A

Parenteral thiamine

112
Q

Indications for using Hydroxyurea

A
  • Exaggerated accumulation of platelets
  • Occasional very high leukocyte counts
  • Troublesome areas of extramedullary hematopoiesis
  • Symptomatic splenomegaly
113
Q

Dose of Hydroxyurea in PMF

A

0.5–1.0 g/day or 1–2 g orally 2-3 times per week

114
Q

Patients on HU should be evaluated for dose adjustment at least _____________ and, if appropriate, eventually extended to evaluation every 3 months.

A

Every week for one month

115
Q

TRUE OR FALSE

Thalidomide is poorly tolerated at optimal doses of approximately 800 mg/day.

A

TRUE

Thalidomide is poorly tolerated at optimal doses of approximately 800 mg/day.

  • Most patients receive about half that amount and are tapered to the lowest effective dose.
  • In subsequent studies, lower doses of thalidomide (50 mg/day) administered together with prednisone were more tolerable
116
Q

Drug has also been useful in patients with PMF who have a 5q– cytogenetic abnormality

A

Lenalidomide

117
Q

Most troubling side effects of Lenalidomide

A

Neutropenia and thrombocytopenia

118
Q

Although largely ineffective in later stages of PMF, it has shown efficacy in the early myeloproliferative stage of PMF with mild to moderate marrow fibrosis

A

Interferons

119
Q

Uses of Cytarabine in PMF

A

Ascites resulting from peritoneal hematopoietic implants has been treated with intraperitoneal cytarabine.

Intrasplenic cytarabine administered via a splenic artery catheter has resulted in significant improvement in a patient

120
Q

Used in bone pain in PMF

A

Etidronate 6 mg/kg per day on alternate months

Clodronate 30 mg/kg per day for several months

121
Q

Indications for radiotherapy

A
  • Severe splenic pain (splenic infarctions)
  • Massive splenic enlargement with contraindication to splenectomy (eg, thrombocytosis)
  • Treating ascites resulting from myeloid metaplasia of the peritoneum
  • Focal areas of severe bone pain (periostitis or the osteolysis of a myeloid sarcoma)
  • Extramedullary fibrohematopoietic tumors, especially of the epidural space

Repeated doses of 0.5–2.0 Gy to the spleen can ameliorate the pain.

122
Q

Splenic radiation can result in further cytopenias or worsening cytopenias, especially thrombocytopenia, referred to as

A

Abscopal effect

123
Q

Major indications for splenectomy

A

(1) painful enlarged spleen (~50% of patients)
(2) excessive transfusion requirements or refractory hemolytic anemia (~25% of patients)
(3) portal hypertension (~15% of patients)
(4) severe thrombocytopenia (~10% of patients)

124
Q

Splenectomy in PMF

Perioperative mortality:
Postoperative morbidity:
Infection, especially pneumonia:

A

Perioperative mortality: 10%
Postoperative morbidity: 30 %
Infection, especially pneumonia: 10%

125
Q

Useful for exaggerated thrombocytosis post splenectomy

A

Hydroxyurea or aspirin and anagrelide

126
Q

Leukemic blast transformation occurs in approximately _______of patients after splenectomy.

A

15%

127
Q

Median survival after splenectomy

A

18 months

128
Q

The only curative approach to PMF.

A

Hematopoietic cell transplantation

129
Q

Patients usually considered for transplantation

A
  • Younger than age 50 years, with a DNA-based matched-sibling donor
  • Progressive disease
  • Poor prognostic findings, such as :
  • Hemoglobin less than 100 g/L
  • Blast cells greater than 1% of blood cells
  • Unfavorable cytogenetics (eg, abnormalities involving chromosome 5, 7, or 17, or cells with three or more abnormalities)
130
Q

The rate of disease progression is associated with at least 16 variables measured at the time of diagnosis, namely:

A

1. Older age
2. Severity of anemia
3. Exaggerated leukocytosis (>25 × 10 9 /L) or leukopenia (<4.0 × 10 9 /L)
4. Constitutional symptoms of fever, sweating, or weight loss at the time of diagnosis
5. Proportion of blast cells in the blood (≥1%)

  1. Male gender
  2. Severity of thrombocytopenia
  3. Proportion of CD34+ cells in the blood
  4. The presence of the V617F mutation in JAK2
  5. Monocytosis
  6. A decreased proliferating cell nuclear antigen index and a decreased apoptotic index by in situ end labeling
  7. Degree of liver enlargement
  8. Extent of marrow fibrosis
  9. Postsplenectomy spleen histology
  10. WT1 expression in CD34+ cells; and
  11. Certain clonal cytogenetic abnormalities, especially involving chromosome 5, 7, or 17, or with three or more abnormalities

The most consistent predictive variables appear to be advanced age, severity of anemia, and higher-risk clonal cytogenetic abnormality at the time of diagnosis, each of which represents a poor prognostic indicator.

131
Q

The major causes of death in PMF

A

Infection, hemorrhage, postsplenectomy mortality, and acute leukemic transformation

132
Q

Months of survival

Low risk:
Low-intermediate risk:
High-intermediate risk:
High risk:

A

Low risk: 135 months
Low-intermediate risk:95 months
High-intermediate risk: 48 months
High risk: 27 months

133
Q

Gene mutations have been associated with prognosis in patients with PMF, either overall survival or risk of conversion to AML

A

IDH, EZH, ASXLI, and SRSF2

WILLIAM'S HEMATOLOGY (109 decks)

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