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Aplastic Anemia MPD
Aplastic Anemia MPD
- Aplastic anemia
- Myelodysplastic syndrome (MDS)
- Pure red cell aplasia (PRCA)
- Myelophthisis (20 myelofibrosis)
Aplastic anemia
- BM failure that arises from injury to or abnormal
expression of the stem cell
(hypoplastic BM/pancytopenia)
- Men and women are affected equally, but biphasic age
distribution (with the major peak in the teens and twenties
and a second rise in older adults).
- mechanisms:
- an antibody directed against an antigen on stem cells
or
- an immune mechanism
(T- lymphocytes suppress/destroy stem cell proliferation).
- Causes: - congenital
- SLE
- chemotherapy/radiotherapy
- toxins: benzenes, tolune, insecticides
- drugs: CAF, phenylbutazone, Au, sulfa
- viruses
• hepatitis (non-A, non-B, & non-C)
• EBV
• Parvovirus 19
• HIV-1 (AIDS)
- immune diseases
- pregnancy
- PNH
- idiopathic
Clinical features
- Bleeding: the most common
early sx
- Sx of anemia
- Infection: unusual 1st sx
- Restriction of sx to
hematologic system
- Laboratory features
aplastic anemia (severe)if >1:
• neutrophil <500/mcL
• platelets <20,000
• BM cellularity <20%
• cRetic count <1%
- Large RBCs (MCV)
- BM readily aspirated but
dilute
- Dx: pancytopenia + fatty BM
Pancytopenia
causes
BM disorder
Aplastic anemia
MDS
acute leukemia
MF
infiltrative diseases (lymphoma, myeloma, Ca)
megaloblastic anemia
nonmarrow disorders
hypersplenism
SLE
infections (TB, AIDS, leishmaniasis, brucellosis)
Treatment
supportive (most)
• transfusion (RBC, platelets)
• antibiotics
in severe cases + young <50: allogenic BMT
(HLA-matched)
elderly (>50): - immunosuppressive + anti-thymocyte
globulin (ATG) + cyclosporin (or tacrolimus)
high dose immunosuppressive with
cyclophosphamide, 200mg/kg
androgens (oxymetholone) 2-3mg/d
- treatment
- blood transfusions + Fe chelation
- myeloid granulocyte factors (G-CSF) + EPO 30,000 U, sc
- Cytotoxic drugs
- Lenalidomide, 10mg/d
- Azacitidine
- Decitabine
- immunosuppressive (ATG, cyclosporin, anti-CD52 monoclonal antibody – Campath)
- allogenic stem cell transfusion – curative
- hematopoeitic growth factors (HGF)
Course & prognosis
- Ultimately fatal
- cure rate: 30-60%
- most die of infection/ bleeding
- pts with refractory anemia may survive many yrs
(risk of leukemia: <10%)
- Those with excess blasts or CMML: short survival
(<2 yrs) & higher (20-50%) risk of developing
acute lekemia
- full deletion of C5 and C7: poor prognosis
Pure red cell aplasia
- Rare
- autoimmune disease against erythroid precursors
- the unaffected lineages (myeloid & platelet) appear
quantitatively and qualitatively normal
- idiopathic
- SLE, CLL, lymphoma, thymoma
- drugs: phenytoin, CAF
- in response to viral infection
- papovirus
- anemia: often severe, NCNC
- low/absent reticulocytes
- RBC morphology : N
-BM: normocellular, erythroid precursors are markedly
reduced or absent
- treatment:
• stop offending drug
• resection of the tumor( eg, thymoma)
• high –dose iv Ig (eg, papovirus – related)
• immunosuppressive therapy:
o glucocorticoids
o ATG + cyclosporine (tacrolimus)
o anti-CD20 monoclonal antibody (Daclizumab)
- The presence of erythroid colonies has been considered
predictive of response to immunosuppressive therapy in
idiopathic PRCA.
Myeloproliferative Disorders
- share an origin in a multipotent hematopoietic
progenitor cell
- overproduction of one or more of the formed elements
- without significant dysplasia
- a predilection to extramedullary hematopoiesis, myelofibrosis
- transformation at varying rates to acute leukemia
- Classification (WHO)
• Chronic myelogenous leukemia (CML), bcr-abl–positive
• Chronic neutrophilic leukemia (CNL)
• Chronic eosinophilic leukemia (CEL), not otherwise specified
• Polycythemia vera (PV)
• Primary myelofibrosis (PMF)
• Essential thrombocytosis (ET)
• Mastocytosis
• Myeloproliferative neoplasms, unclassifiable
PV
• overproduction of all the 3 hematopoeitic cells lines (most RBC)
• autonomous production of erythroid cell in the BM
• independent of EPO
• mutation in JAK2 autoinhibitory, pseudokinase domain of the
tyrosine kinase, 95%
Clinical features
- Sxs related to expanded plasma volume & increased blood
viscosity
- headache, dizziness, tinnitus, blurred vision, fatigue
- aquagenic pruritus
- epistaxis
- male predominance (60%)
- median age: 60yrs
- plethora & engorged retinal vessels,
- spleen always enlarged (75% palpable)
- thrombosis is the commonest complication
- high incidence of acid-peptic disease
Lab features
- Hct >60%
- WBC 10,000-20,000/mcL
- platelets > 1,000,000/mcL
- basophilia + eosinophilia
- BM: hypercellular
panhyperplasia
absent Fe store
- Vit B12
- hyperurecemia
Treatment
- Phlebotomy
- 1 unit/week
- target : Hct <45% in men & <42% in women
- myelosuppressive therapy
- indication: - high phlebotomy requirement
- thrombocytopenia
- intractable pruritus
- HU, 500-1500mg/d
- anaglinide
- aspirin (75-81mg)
- allopurinol: uric acid >10mg%
- antihistamines
Prognosis
- survival : 11-15 years
- may arrest MF/CML
- AML (5%)
ET
other designations:
essential thrombocythemia
Idiopathic thrombocytosis
primary thrombocytosis,
hemorrhagic thrombocythemia
- Uncommon
- unknown cause
- marked proliferation of megakaryocytes in BM leading to elevation of the platelet count
- mutation of JAK2 (50%)
Clinical features
- median age of presentation: 50-60 yrs
- wt loss, low-grade fever, weakness
- headache, dizziness
- increased platelet count
- thrombosis most common
- erythromelalgia
- splenomegaly 25%
Lab
- Platelet 2,000,000/mcL
- WBC <30,000/mcL + immature myeloid forms
- Hct: N
- BF: large platelets
- BM: megacaryocytes
Treatment
- HU 0.5-2g/d
- anaglide 1-2mg/d
- aspirin
- plateletphresis
Course & prognosis
- Indolent
- average survival: >15yrs
- late course fibrotic BM + massive splenomegaly
- 10-15% risk of progression to MF after 15 yrs, 1-5% to AML over
20 yrs
ET- BM
PMF
other designations :
idiopathic myelofibrosis
agnogenic myeloid metaplasia
agnogenic myeloid metaplasia
myelofibrosis with myeloid metaplasia
• a clonal disorder of a multipotent hematopoietic
progenitor cell
• of unknown etiology
• characterized by marrow fibrosis, extramedullary
hematopoiesis, and splenomegaly
- the least common chronic MPD
- night sweats, fatigue, and weight loss are common
presenting complaints
- In adults >50
- usually insidious in onset
- present with fatigue (anemia), abdominal fullness (splenomegally)
- unusual: bleeding, bone pain
- splenomegally invariable & massive
- heptomegaly 50%
- anemia + progressive thrombocytopenia bleeding
- Exuberant extramedullary hematopoiesis can cause:
• ascites
• portal, pulmonary,intracranial hypertension
• intestinal or ureteral obstruction
• pericardial tamponade
• spinal cord compression
• skin nodules
Lab
- Anemia
- WBC variable
- platelet variable
- peripheral blood
- significant poikilocytosis
- tear drop forms
- nucleated RBC
- myeloid features shifted to immature forms
- platelet morphology bizzare (giant degranulated form)
- megakaryocyte fragments
- BM: - dry tap
- fibrosis, reticulum fibers
collagen
- No specific chromosomal
abnormality.
50% express the JAK2 mutation
Treatment
- Mild form: no Rx
- transfusion
- thalidomide / lenalidomide
- allogenic BMT
- EPO
- splenectomy
Course & prognosis
• increasing marrow failure with transfusion dependent anemia and
increasing organomegaly
• can evolve from a chronic phase to an accelerated phase
• About 10% transform to an aggressive form of acute leukemia
• prognostic factors for disease acceleration:
o anemia, leukocytosis, thrombocytopenia,
o the presence of circulating myeloblasts,
o older age,
o the presence of complex cytogenetic abnormalities, and
o constitutional symptoms (unexplained fever, night sweats, or weight loss).