Myeloproliferative Neoplasms

Front 1

What other tyrosine kinase-activating mutation than JAK2 V617F can be found in some cases of polycythemia vera, and perhaps some other MPNs?

Back 1

JAK2 exon 12 mutation

Front 2

Systemic mastocytosis is often associated with what somatic mutations?

Back 2

c-kit

Front 3

In what percent of CML cases is the Philadelphia chromosome found? In the remaining cases, how is the characteristic transcript found?

Back 3

95% of CML cases are BCR-ABL positive. The remainder have to be picked up by FISH or RT-PCR. Prognosis is the same for Ph+ and Ph- CML.

Front 4

What is the significance of major breakpoint cluster region mutations in CML?

Back 4

This is typical CML, and the transcript is called p210BCR-ABL

Front 5

What is the significance of the micro-BCR p230BCR-ABL protein?

Back 5

Found in rare CML variant cases with chronic neutrophilia +/- thrombocytosis. The course is more indolent than typical CML.

Front 6

What is a Pseudo-Gaucher cell?

Back 6

Pseudo-Gaucher cells, which are found in many hematologic abnormalities, including CML, AML, CLL, Hodgkin lymphoma, multiple myeloma, and ITP, cannot be distinguished from Gaucher cells on H&E stained sections. However, Gaucher cells show diffuse iron staining, while pseudo-Gaucher histiocytes are generally negative.4 In pseudo-Gaucher cells, cellular debris accumulates when the capacity of lysosomes is overwhelmed by the material produced from apoptosing cells.

Front 7

What are sea-blue histiocytes?

Back 7

Marcophages that accumulate ceroids and/or lipofuscin in their cytoplasm. They are associated with a high rate of intramedullary cell death or storage diseases. Sea-blue histiocytosis can be observed in patients with genetic lipid metabolic diseases or ceroid storage diseases.

This morphological finding can be associated both with acquired conditions of increased cellular turnover and inborn errors of lipid metabolism

Front 8

What is the significance of the p190BCR-ABL product in CML?

Back 8

Most often found in Ph-positive ALL. It also can be coexpressed with p210 or detected alone in cases associated with monocytosis.

Front 9

Why is RT-PCR preferred for monitoring disease response in CML?

Back 9

FISH for BCR-ABL has a 3% false positive rate

Front 10

What other TK activities are affected by imatinib (other than BCR-ABL)

Back 10

ARG, PDGFRA, PDGFRB, c-kit

Front 11

What is the most common mechanism of resistance to imatinib?

Back 11

50-90% due to point mutations that affect the TK domain of ABL (the site of imitinib binding)

Front 12

What are the significant differences between dasatinib and nilotinib?

Back 12

Dasatinib has no structural similarity to imatinib, whereas nilotinib is an imatinib-derivative with 30-fold greater potency.

Front 13

What is the significance of T315I in CML?

Back 13

It's called the gatekeeper mutation, and is resistant to all 3 TKi's.

Front 14

How should CML patients with myeloid or lymphoid blast crisis be managed after acheiving hematologic response on second generation TKi's.

Back 14

Allogeneic HSCT, until long term data on the second generation drugs are out.

Front 15

What is the definition of accelerated phase in CML?

Back 15

•10 to 19 percent blasts in the peripheral blood or bone marrow
•Peripheral blood basophils ≥20 percent
•Platelets <100,000/microL, unrelated to therapy
•Platelets >1,000,000/microL, unresponsive to therapy
•Progressive splenomegaly and increasing white cell count, unresponsive to therapy
•Cytogenetic evolution (defined as the development of chromosomal abnormalities in addition to the Philadelphia chromosome)

Front 16

What is the definition of blast crisis in CML?

Back 16

•≥20 percent peripheral blood or bone marrow blasts [3]
•Large foci or clusters of blasts on the bone marrow biopsy [4]
•Presence of extramedullary blastic infiltrates (eg, myeloid sarcoma also known as granulocytic sarcoma or chloroma)

Front 17

Which type of CML blast crisis is more likely to respond to chemotherapy (achieve a second chronic phase) AML or ALL?

Back 17

With myeloid blast crisis, induction
chemotherapy regimens used for acute myeloid leukemia
(AML) can achieve a second chronic phase in 20% to 30% of patients, whereas regimens for ALL are effective in 40% to
60% of cases with lymphoid blast crisis.

Front 18

What is the response rate, 5-year PFS and OS rate to front-line TKi therapy in CML?

Back 18

Currently, the CCyR rate to frontline
TK inhibitors is 70% to 90%, with 5-year progressionfree
survival and overall survival rates between 80% and
95%.

Front 19

What are the milestones that support the likelihood of achieving a good outcome in CML?

Back 19

• Achieving CHR at 3 months
• Achieving at least an MCyR at 12 months
• Achieving CCyR at 18 months

Front 20

Do CML patients always follow the chronic - accelerated - blast course?

Back 20

Blast crisis may develop suddenly, without
an intervening accelerated phase, in up to one fourth of
chronic-phase patients. By comparison, a sudden transformation
from chronic phase to blast phase occurs in 5%
of patients on IFN therapy. Sudden transformation to
blast phase in patients taking imatinib is observed with
an annual rate of 1% to 2%.

Front 21

What are the characteristic cutaneous findings in systemic mastocytosis?

Back 21

Cutaneous manifestations of mastocytosis typically include
a reddish-brown maculopapular eruption (urticaria pigmentosa)
or, less often, a diffuse erythema, plaques, nodules, or the
classic description of urticaria following stroking of the skin
(Darier sign).

Front 22

What are the first-line treatments in cutaneous mastocytosis?

Back 22

Treatment of CM includes H1 and H2 antihistamines, cromolyn
and other mast cell stabilizers, topical or intralesional
glucocorticoids, and psoralen and ultraviolet A (PUVA) phototherapy.

Front 23

Why are opiod analgesics a problem in patients with mastocytosis?

Back 23

They are known mast cell degranulators and may produce severe
adverse reactions in sensitive individuals

Front 24

What is the treatment approach for patients with systemic mastocytosis with and without bone complications?

Back 24

IFN can be helpful for patients with painful skeletal lesions
or mast cell tumors that threaten bony integrity. Corticosteroids
are generally avoided in this case because of their potential
adverse effects on bone density. Patients with evidence of
end-organ damage without major bony complications should
receive a combination of corticosteroids and IFN.

Front 25

What single-agent chemotherapy regimen is standard in patients with symptomatic systemic mastocytosis?

Back 25

Single-agent cladribine, given
as 5-day treatment cycles every 4 to 6 weeks

Front 26

What is the role of imatinib in treatment of systemic mastocytosis?

Back 26

Some patients without the D816V mutation and with ASM, MCL, or SM-AHNMD may respond to imatinib

Front 27

How common is transition from cutaneous to systemic mastocytosis?

Back 27

Rare. Also, cutaneous involvement in SM appears to confer an indolent
behavior

Front 28

What are the demographic characteristics that are associated with PDGFRA-related neoplasms?

Back 28

considerably more common in men (male-tofemale
ratio, 9:1 to 17:1) and are usually diagnosed between
the ages of 25 and 55 years (median age of onset is late 40s).
PDGFRA-related neoplasms seem to represent approximately
50% of patients with HES

Front 29

What is the most serious complication of PDGRFRA-related neoplasms?

Back 29

endomyocardial fibrosis with ensuing restrictive cardiomyopathy

Front 30

What is the fusion gene in PDGFRA-related neoplasms?

Back 30

FIP1L1-PDGFRA. FISH testing relies on the probe for
the CHIC2 gene, which is uniformly deleted in patients with the FIP1L1-PDGFRA fusion gene. RT-PCR can be used both
for diagnosis and monitoring of disease response and for
minimal residual disease monitoring

Front 31

What are the cell surface markers for activated eosinophils?

Back 31

CD23, CD25, CD69

Front 32

What is the treatment and prognosis for patients with PDGFRA-related neoplasms?

Back 32

Treatment is with imatinib, which is extremely effective. 5-year survival is now ~80%.

Front 33

What is the usual presentation of PDGFRB-related neoplasms?

Back 33

Patients with PDGFRB-related neoplasms tend
to present with features characteristic of chronic myelomonocytic
leukemia with associated eosinophilia

Front 34

What is the fusion gene product in PDGFRB-related neoplasms?

Back 34

t(5;12) translocation involving ETV6(12p13) and
PDGFRB (5q33)

Front 35

What is the treatment and prognosis for PDGFRB-related neoplasms?

Back 35

Treatment is imatinib. Although there are only
small case series on the impact of imatinib on the survival of
patients with PDGFRB-related neoplasms, these studies suggest
a similar benefi t to that seen in patients with PDGFRArelated
neoplasms, with median survivals exceeding 5 years.

Front 36

What are the 3 different ways in which FGFR1-related neoplasms can present?

Back 36

FGFR1-related
neoplasms can present as classic MPNs, precursor B- or T-cell
lymphoblastic leukemia, or AML. Median age is 32.

Front 37

What is the most common genetic aberration in FGFR1-related neoplasms?

Back 37

The
most common chromosomal translocation associated with
FGFR1-related neoplasms is t(8;13)(p11;q12), which results
in expression of the ZNF198-FGFR1 fusion TK.

Front 38

What is the treatment and prognosis of FGFR1-related neoplasms?

Back 38

Early intensive therapy followed by allogeneic SCT remains
the only potential curative therapy for patients with FGFR1-

Front 39

What is required for diagnosis of chronic eosinophilic leukemia-NOS?

Back 39

The revised 2008 WHO criteria
also require the presence of eosinophilia (1.5  109/L);
presence of clonal cytogenetic or molecular abnormality or
blasts cells 2% in the peripheral blood or 5% in the bone
marrow; lack of BCR-ABL1, PDGFRA/PDGFRB, or FGFR1
rearrangements; bone marrow blasts 20%; and absence of
inv(16)(p13.1q22).

Front 40

What are the four body systems affected by CES-NOS other than the heart?

Back 40

Peripheral and central nervous system fi ndings
can include mononeuritis multiplex, peripheral neuropathy,
and paraparesis, as well as cerebellar involvement, epilepsy,
dementia, cerebral infarction, and eosinophilic meningitis.
Pulmonary involvement includes idiopathic infi ltrates, fi brosis,
pulmonary effusions, and pulmonary emboli. Skin manifestations
are common and can take many forms, including
angioedema, urticaria, papulonodular lesions, and erythematous
plaques. Gastrointestinal involvement by eosinophilia
can result in ascites, diarrhea, gastritis, colitis, pancreatitis,
cholangitis, or hepatitis

Front 41

What is the treatment approach to CES-NOS?

Back 41

First line = steroids, then hydroxyurea
Second line = vincristine-etoposide
Also consider anti-IL-5 antibody for rapid response. Campath has been reported successful in 2 case reports.

Front 42

What is the genetic aberration in PV? In what percentage of cases is it found?

Back 42

JAK2 V617F is found in 90-95% of cases.

Front 43

What is the most common genetic aberration in PV patients who are JAK2 V617F-negative?

Back 43

JAK2 exon 12 mutations are specifi c to JAK2
V617F–negative PV and are most often identified in patients
with erythrocytosis without associated thrombocytosis or
leukocytosis.

Front 44

What are the granulocyte and platelet abnormalities associated with PV?

Back 44

Qualitative platelet defects including acquired vWF disease, and inappropriate granulocyte activation.

Front 45

How can Budd-Chiari syndrome mask a diagnosis of PV?

Back 45

Liver dysfunction can lead to fluid overload, which causes a normal hematocrit despite an elevated red cell mass. However, in the acute setting, hepatic necrosis can be
associated with transiently elevated EPO levels, misleadingly
suggesting a secondary, EPO-driven erythrocytosis

Front 46

In addition to kidney and liver tumors, what other tumors can produce EPO?

Back 46

cerebellar hemangiomas, uterine
myomas, ovarian tumors, parotid tumors, lymphomas, and
adrenal tumors can be associated with pathologic EPO production.

Front 47

Is there a role for phlebotomy in secondary polycythemia?

Back 47

In secondary polycythemia, phlebotomy
may occasionally be indicated to decrease blood viscosity
and improve oxygenation when symptoms occur or
prophylactically, especially when hematocrit values exceed
60%.

Front 48

Describe the types of "ambiguous" cases related to possible PV.

Back 48

10-40% of patients with an elevated RCM, normal or near-normal EPO level and no obvious cause for secondary polycythemia will go on to have features of PV, while most cases will spontaneously resolve. Some JAK2 exon 12 positive patients will have idiopathic erythrocytosis that persists for years without progressing.

Front 49

What labs are helpful in diagnosing JAK2-negative PV patients?

Back 49

Elevated LAP score, elevated B12 level, elevated LDH, elevated uric acid, EEC growth, PRV1
granulocyte overexpression, decreased c-Mpl expression, marrow hypercellularity with megakaryocyte clustering

Front 50

What is the prognosis for patients with polycythemia vera?

Back 50

Once the diagnosis is secure, treatment with phlebotomy,
with aspirin, and with or without cytoreductive agents
results in a near-normal life span for the average patient who
is diagnosed at a median of 60 to 65 years of age. However,
although it exceeds 10 years, the median survival of individuals
diagnosed with PV before 40 years of age is considerably
shorter than the life expectancy for a healthy person of similar
age, even with active management

Front 51

Describe postpolycythemic myelofibrosis. What is the incidence of AML in these patients?

Back 51

Postpolycythemic myelofi brosis is characterized by
progressive hepatosplenomegaly due to extramedullary
hematopoiesis, advanced marrow fi brosis, and pancytopenia
with leukoerythroblastosis. The median survival time in
patients with postpolycythemic myelofi brosis is 3 years. At
least 25% to 50% of patients with postpolycythemic myelofi
brosis develop AML, although it is important to note that
not all PV patients who transform to AML will progress
through a postpolycythemic myelofi brosis phase.

Front 52

Which PV therapies are leukemogenic and which are not?

Back 52

Phosphorus-32
(32P) treatment, chlorambucil, busulfan, and alkylating agent
combinations are associated with up to 15-fold increase in transformation to AML. Hydroxyurea, IFNa and anagrelide are not leukemogenic.

Front 53

How should patients with PV be managed in a perioperative setting?

Back 53

Up to 80% of patients with PV who undergo
surgery in the context of a hematocrit and/or platelet count
markedly above the normal range will suffer a thrombohemorrhagic
event. The hematocrit and platelet count should be normalized for
several weeks prior to elective surgery to minimize the risk of
perioperative thrombosis and bleeding in patients with PV.
Postoperative thrombosis prophylaxis should be given whenever
possible.

Front 54

What are the phlebotomy goals for patients with PV?

Back 54

Generally accepted goals include a hematocrit of 45% for
men, 42% for women, and 37% for pregnant women late
in gestation

Front 55

When should immunosupressive therapy accompany phlebotomy in PV?

Back 55

Aggressive initial phlebotomy without adjunctive myelosuppressive therapy may be associated
with a higher risk of thrombosis, particularly in the
elderly and those with a prior history of thrombosis; this has
been hypothesized to be the result of new platelet formation
in response to the thrombopoietic stimulus of rapid phlebotomy.
Based on these clinical observations, myelosuppressive
therapy is recommended as part of the initial treatment of
patients 60 years of age and younger patients with thrombotic
risk factors, particularly a history of thrombosis

Front 56

How should high-risk women of childbearing age be treated for PV?

Back 56

IFNa

Front 57

Describe the ECLAP trial as relates to the treatment of PV.

Back 57

The ECLAP study, a double-blind randomized trial, compared
low-dose aspirin with placebo among 518 patients who
had no indication for anticoagulation and no preexisting
clear indication or contraindication to aspirin therapy and
demonstrated that low-dose aspirin (eg, 100 mg/d) reduces
the rate of thrombosis and cardiovascular deaths in patients
with PV receiving standard phlebotomy and supportive care.
The aspirin-treated group suffered 60% fewer major thromboses
and cardiovascular deaths

Front 58

How is PV-related pruritis (unresponsive to phlebotomy or hydroxyurea) managed? Painful splenomegaly and/or hypercatabolic symptoms?

Back 58

Antihistamines, PUVA, cholestyramine, or selective
serotonin reuptake inhibitors (eg, paroxetine) may provide
symptomatic relief. Cytoreductive therapy with hydroxyurea
or IFN may help in refractory cases. Painful splenomegaly
and unacceptable hypercatabolic symptoms also usually
require treatment with hydroxyurea or IFN. Splenectomy
or splenic irradiation may be necessary for palliation in
selected patients who are intolerant of or unresponsive to
cytoreductive agents.

Front 59

In addition to talking to patients about the (at least) hypothetical increase in risk for AML, what other adverse effects of hydroxyurea should be discussed?

Back 59

Cytopenias
and, less commonly, chronic mucocutaneous ulcers

Front 60

What are the main adverse effects of anagrelide?

Back 60

Anagrelide is a vasodilator; adverse effects, including headache, palpitations, diarrhea,
and fl uid retention, may be avoided or minimized by starting
at a lower dose and titrating up.

Front 61

What is the role of Phosphorous-32 in treatment of PV?

Back 61

32P has been demonstrated in randomized
trials to increase the risk of hematologic and nonhematologic
malignancies, particularly when combined with
alkylating agents or hydroxyurea. However, it is well tolerated
in the short term, and responses after a single treatment may
last several months. Recent studies indicate that lower-dose
32P may be equally effective as conventional doses, but with
reduced and delayed risk of malignancy development. Therefore,
low-dose 32P is a reasonable palliative option for patients
70 years of age and may be especially useful in patients
whose blood counts are diffi cult to control with hydroxyurea.

Front 62

What roles does HSCT have in treatment of PV?

Back 62

Currently, the high risks of morbidity and mortality
with myeloablative allogeneic transplantation and the
baseline favorable prognosis with PV restrict the use of SCT
to younger patients with a poor prognosis

Front 63

What is the difference between the two general types of familial polycythemic states?

Back 63

They can be either truncating EPO receptor
mutations (low endogenous EPO level) or VHL/HIF2A mutations
(high endogenous EPO level).

Front 64

What percentage of patients with ET are JAK2 positive, and what are the clinical implications for these patients?

Back 64

Patients with
ET who have JAK2 V617F have a higher median hemoglobin
concentration and neutrophil count than those who lack the
mutation, and they may have more thromboembolic events
and require more cytoreductive therapy

Front 65

How are ET and PV different in terms of presenting signs and symptoms?

Back 65

hypercatabolic signs and constitutional symptoms
are uncommon in ET

Front 66

Which hematologic malignancies have to be excluded before making a diagnosis of ET?

Back 66

MPNs (especially PV and CML) and MDS [especially 5q–
syndrome, chromosome 3(q21;q26) abnormalities, or refractory
anemia with ringed sideroblasts associated with marked
thrombocytosis (RARS-T)].

Front 67

How does the LAP score help sort various MPNs?

Back 67

The LAP score is typically elevated in ET, like PV but unlike
CML

Front 68

What are the causes of Howell-Jolly bodies?

Back 68

Common causes of asplenia are splenectomy following trauma to the spleen, and autosplenectomy caused by sickle cell anemia. Ten percent of patients with Coeliac disease also present with splenic atrophy with subsequent Howell-Jolly bodies. Other causes are radiation therapy involving the spleen, such as that used to treat Hodgkin lymphoma. Howell-Jolly bodies are also seen in: severe hemolytic anemia, megaloblastic anemia, hereditary spherocytosis, and myelodysplastic syndrome (MDS).

Front 69

What is the general prognosis for patients with ET?

Back 69

Life expectancy in the first decade after diagnosis is similar to age-matched controls. Transformation to AML is also rare in the first decade but increases after 2-3 decades.

Front 70

How does platelet count relate to risk of thrombotic or hemorrhagic complications in ET?

Back 70

Although some studies have
found an increased risk of bleeding in ET patients with a
platelet count of 1,500,000/L, there are no data to suggest
that absolute platelet number is clearly predictive of thromboembolic
complications in the absence of other clinical risk
factors. Nevertheless, controlling the platelet count may be
protective, and studies with hydroxyurea (targeted at maintaining
the platelet count at 600,000/L) and anagrelide
(targeted at maintaining the platelet count at 400,000/L)
have shown that these drugs decrease the risk of primary or
recurrent thrombotic events (from 24% to 3.6% during the
27-month observation period).

Front 71

What are the two major risk factors in ET, and how should this group be treated?

Back 71

Age > 60 and/or history of thromboembolic event = high risk.
Patients with ET at high risk of thrombosis
should be treated with low-dose aspirin and hydroxyurea
with a goal platelet count of 400,000 to 600,000/L.
Anagrelide should be reserved for patients with an insuffi cient
response to hydroxyurea or with intolerable hydroxyureaassociated
adverse effects.

Front 72

How is treatment of pregnant patients, or patients who desire pregnancy, different between PV and ET?

Back 72

It isn't. Both use IFNa, either standard or pegylated form.

Front 73

What is the general treatment approach in terms of thromboemolism prophylaxis in ET?

Back 73

Platelet-lowering agents and low-dose aspirin are indicated
for high-risk patients with ET. Hydroxyurea should be the fi rst
choice because it is superior to anagrelide at preventing most
thrombohemorrhagic events. Anagrelide can be a useful
second-line agent. Low-dose aspirin alone should be used
for low-risk patients and may effectively treat vasomotor
symptoms.

Front 74

Which cell surface marker has some prognostic value in PMF?

Back 74

The number of circulating CD34
cells in PMF patients can be 50-fold higher than in PV or ET.
Higher levels of circulating CD34
cells in PMF are associated
with more advanced bone marrow fi brosis and other
disease characteristics. One study observed shorter survival
and earlier transformation to AML among PMF patients
with circulating CD34
cell counts >300/microL

Front 75

What are the two hallmarks of PMF?

Back 75

marrow fi brosis and extramedullary
hematopoiesis;

Front 76

What percentage of patients with PMF are JAK2 positive?

Back 76

50%

Front 77

In JAK2 V617F-negative PMF and ET patients, what mutation can activate JAK2 in up to 5-10% of patients?

Back 77

MPL

Front 78

What are the general requirements for diagnosing PMF (not the acutal diagnostic criteria)?

Back 78

increased bone marrow
reticulin or collagen fi brosis, leukoerythroblastic peripheral
blood fi ndings, and splenomegaly, in the absence of a secondary
cause for these fi ndings or of features better fitting ET or
PV or CML

Front 79

How can certain autoimmune conditions mimic PMF?

Back 79

Secondary marrow changes of increased reticulin
fibrosis with megakaryocytic hyperplasia resembling PMF
have been associated with systemic lupus erythematosus,
Sjögren syndrome, psoriatic arthritis, and other chronic
autoimmune diseases, most commonly in the absence of
splenomegaly or signifi cant leukoerythroblastic peripheral
blood findings

Front 80

What are the four features of the leukoerythroblastic peripheral blood smear?

Back 80

immature myeloid cells,
nucleated red blood cells, teardrop erythrocytes, and large
platelets.

Front 81

Describe the prefibrotic or "cellular" stage of PMF.

Back 81

Approximately 20% to 30% of patients with PMF are
believed to present in the prefi brotic stage. The early prefi -
brotic stage of PMF, also referred to as the “cellular” or “proliferative”
stage, may be associated with thrombocytosis and
modest leukoerythroblastosis but may be diffi cult to distinguish
from ET. This condition may cause diagnostic diffi culties
in the absence of clear evidence of megakaryocyte atypia
on bone marrow biopsy

Front 82

Risk of developing AML is increased in PMF patients with what hematologic abnormalities?

Back 82

Severe anemia and high number of circulating immature myeloid cells.

Front 83

What is the treatment of choice for PMF patients with hypercatabolic symptoms, painful splenomegaly, leukocytosis or thrombocytosis?

Back 83

Hydroxyurea.

Front 84

Which patients with PMH are most likely to respond to therapy with EPO?

Back 84

Those with endogenous EPO level of < 120 who have not yet progressed to transfusion dependence.

Front 85

How is thalidomide used in PMF?

Back 85

Low-dose (50 mg/d), with or without a tapering dose of oral prednisone

Front 86

How is PMF-associated hemolytic anemia treated?

Back 86

May rarely respond to
corticosteroids, danazol, or cyclophosphamide

Front 87

What is the role of splenectomy in treatment of PMF?

Back 87

Splenectomy is indicated for
palliation of portal hypertension, refractory anemia, and
symptoms not controlled by cytotoxic agents. With the conventional
laparotomy approach in experienced centers, postoperative
mortality is approximately 10%, and the median
survival is approximately 1 to 2 years

Front 88

What are the risk factors for post-splenectomy thrombosis in PMF patients, how is this managed, and how is post-splenectomy hepatomegaly addressed?

Back 88

Patients at increased risk of thrombocytosis
are those with preoperative platelet counts 50,000
to 100,000/L; 18% to 50% of such patients will achieve
postoperative levels 600,000/L. In this setting, hydroxyurea
or anagrelide should be started or the dose increased the
moment the postoperative platelet count exceeds the normal
range. Massive hepatomegaly resulting from accelerated
extramedullary hematopoiesis develops in 16% to 24% of
patients after splenectomy. This complication may be diffi cult
to control but may respond to cladribine

Front 89

What is the role of radiation therapy in treatment of PMF?

Back 89

Irradiation can effectively palliate pain in 90% of
patients, and treatment can be repeated if necessary. Benefits may last several months, but irradiation
carries a substantial risk of severe, prolonged cytopenias,
which cannot be predicted by baseline blood counts or by the dose of radiation. Local
irradiation can be effective for palliation of painful or threatening
focal areas of extramedullary hematopoiesis (eg, with
spinal or retroperitoneal myeloid tumors).

Front 90

What is the role of HSCT in PMF?

Back 90

Myeloablative allogeneic SCT should be considered for
patients 55 years of age with poor prognostic features who
have an HLA-compatible donor. Nonmyeloablative allogeneic
SCT may benefi t selected patients who are older or who are not
candidates for conventional SCT.

Front 91

What is AHNMD?

Back 91

Systemic mastocytosis (SM) is a myeloproliferative disease affecting multipotent and/or mast cell-committed hematopoietic progenitor cells. In a significant subgroup of patients (10–35%), an associated clonal hematologic non-mast cell lineage disorder (AHNMD) occurs. These AHNMDs can be classified according to recently established WHO criteria. Most AHNMDs resemble myeloid malignancies such as acute myeloid leukemia, myeloproliferative disorders or myelodysplastic syndromes. In only a few cases, lymphoproliferative disorders are diagnosed. Patients with SM-AHNMD have a less favorable prognosis concerning survival when compared to indolent SM. No general guidelines for the treatment of patients with SM-AHNMD have been established so far. A reasonable straightforward approach may be to treat the AHNMD in those patients in the same way as if no coexisting SM exists

Front 92

What are the cutoffs for CMML-1 and CMML-2?

Back 92

CMML-1 = <5% peripheral blasts and <10% bone marrow blasts.
CMM-2 = 5-19% peripheral blasts and 10-19% bone marrow blasts.

Front 93

What enzyme can contribute to hypokalemia in CMML?

Back 93

Muramidase/lysozyme can be a factor but does not account for all cases of hypokalemia in CMML.