Primary BM disorders

Aplastic anemia

Congenital AA

Acquired AA

Definition - decrease in hemopoietic pluripotent stem cells due to aplasia of bone marrow

Recessive

Autoimmune - T lymphocytes suppress hematopoietic stem cells

Secondary - from radiation or chemicals

Tx - anti-thymocyte globulin, cyclosporin, methylprednisolone, BM transplant

Growth retardation, congenital skeletal defects, renal defects, skin defects, mental retardation

10% chance develop AML

Dx - random chromosomal breaks

Tx - androgen, BM transplant

Primary myelofibrosis

Proliferation hematopoietic cell clones (particularly megakaryocytes) --> releases cytokines like fibroblasts --> fibrosis, collagen produciton, osteosclerosis, CD34 cell mobilisation --> hematopoetic tissue replaced by connective tissue and fibrosis

Primary - hematological malignancy

Secondary - irriation due to carcinomatous infiltration or due to PV or ET

CBC - pancytopenia, severity depends on neutrophil count

PS - no normal cells

BM study - hypocellular, hypoplasia (empty bone marrow), mostly fat cells,very little functional cells, cellularity <25%

PS - tear drop cells, BM infiltration with blasts, nucleated RBCs, myelocytes - leukoerythroblastic picture

Myelodysplastic syndrome

Potential for hematological emergencies - can lead to microangiopathic hemolytic anemia due to anemia + thrombocytopenia

BM failure - thrombocytopenia, macrocytic anemia

Causes - 5I

Iatrogenic - chemo drugs, radiation, cytotoxic drugs

Idiopathic

Industrial - benzen

Infections - EBV, HBV, HIV

Immune - SLE

Inherited

Fanconi's anemia

Dyskeratosis congenita

Diamond Blackfan anemia

Schwachman-Diamond syndrome

Congenital amegakaryocytic thrombocytopenia with absent radius (TAR)

X-linked recessive

Progressive BM failure, increased malignancy predisposition

Growth retardation, somatic abnormalities

Cafe au lait spots, hypo/hyperpigmentation

Skeletal abnormalities - absent thumb, radial hypoplasia, scoliosis

Underdeveloped gonads, horseshoe kidneys

Most common type, may be immune related

Proliferation defect of precursor cells, stem cell defects or immune reaction against hemopoietic tissues

Risk of bleeding and infection/sepsis due to pancytopenia

Genetic factors HLA-DR2 and HLA-DR15 may be relevant

Supportive

Curative

Transfusion - red cells, platelets

Prophylactic antibiotics

Immunosuppressive therapy

BM transplant

Primary MDS

Benzene exposure

Cigarette smoking

Inherited syndromal disorder like Fanconi's anemia

Secondary MDS

Chemo or radiation therapy

Classification

Cytopenia lineage - single or multi-lineage

%blasts and %ring sideroblasts

RA - refractory anaemia - unilineage

RARS - refractory anemia with ringed sideroblasts

RAEB-I - refractory anemia with excess blasts, 5-9%

RAEB-II - refractory anemia with excess blasts, 10-19%

RCMD - refractory cytopenia with multilineage dysplasia

Immature blood cells don't mature - non-functioning BM; direct insult of hematopoietic stem cells leading to increased apoptosis or clonal mutation and expansion of an abnormal clone leading to ineffective hematopoiesis

Possible progression to AML due to aberrant growth signals, reduced apoptosis --> uncontrolled blast cell proliferation

Anti-thymocyte globulin (ATG)

Cyclosporin A

Prednisolone

BM aspirate - dry tap

BM trephine - consistent with PMF

CBC - low Hb, high WBC, high platelet, high LDH

Cytogenetics - JAK2, V617F, CALR mutation negative

Clinical px

Anemia symptoms - dyspnea, reduced ET

Hepatosplenomegaly - due to extramedullary hematopoiesis

Classification

PrePMF

Overt PMF

Increase WBC, decrease Hb

Complications

Marrow failure

Leukemic transformation

Heart failure

Ruxolitinib

Transfusion

Splenectomy

Hydroxyurea if high increase in platelet count

Thalidomide/lenalidomide with prednisolone

SCT