Myeloproliferative Disorders

CML

Adult CML:

ACML is a disorder which appears to affect a single progenitor cell which gives rise to all cell lines.

Presentation:  Patients present with anemia, splenomegaly, constitutional symptoms, abdominal pain, bleeding, and rarely leukestasis.  After about 3-6 years, patients enter an accelerated phase which culminates in a blast crisis which is more often myeloid than lymphoid.
Laboratories at Diagnosis:  WBCs of more than 100,000/uL, platelets of more than 400,000/uL.  PMNs, metamyelocytes are present peripherally, with a maximum of about 10% blasts.  Bone marrow shows granulocyte hyperplasia, sea blue histiocytes, and sometimes megakaryocyte hyperplasia.  The leukocyte alkaline phosphatase and vitamin B12 levels are low.  The decreased LAP helps differentiate it from a leukamoid reaction (additionally, in a leukamoid reaction, blasts are not seen in peripheral smears and all cell lines are not elevated).  Decreased LAP is also associated with paroxysmal nocturnal hematuria.
Genetic:  Associated with a t(9;22) which yields a bcr-abl fusion protein of 210 kDa (versus the 185 kDa product in ALL.
Treatment:  Alkylating agents (busulfan), cell cycle blockade (hydroxyurea), biological response modifiers (alpha-IFN), adoptive immunotherapy, stem cell transplant.

Juvenile CML

Presentation:  Fever, immunodeficiency, hepatosplenomegaly, rash, xanthomata, bleeding.
Laboratories at Diagnosis:  Elevated WBCs (about 100,000/uL), immature myeloid cells in the peripheral smear, bone marrow is hyperplastic with decreased megakaryocytes, increased plasma triglycerides, very increased fetal hemoglobin.  The marrow should have less than 25% blastsGrowth in culture associated with GMCSF.
Genetic:  No known mutation.  Associated wth NF-1, a ras GTPase activator protein.
Treatment:  Stem cell transplant.

Polycythemia Vera

In PV, erythroid progenitors replicate regardless of erythropoetin; it is very unusual in children.  In both PV and primary polycythemia, there is increased cell mass.  In secondary polycythemia (which results from increased erythropoetin due to either hypoxia or tumor), there is decreased plasma volume and normal cell mass.

Presentation:  Symptoms relate to hyperviscosity, hypermetabolism, and increased blood volume.  Increased blood pressure, splenomegaly, sometimes hepatomegaly, cyanosis, venous pooling, coagulopathy, stroke, MI, and DVTs.
Laboratories at Diagnosis:  Hypercellular marrow, often increased WBC and platelets.  Giant platelets are often seen in the peripheral circulation.
Special Tests for Diagnosis:

red cell volume and mass (using radiolabeled RBCs)
PaO2
P50 (the PaO2 at which SaO2 = 50%)

Treatment:  Phlebotomy

Essential Thrombocytosis

ET is a diagnosis of exclusion.  Other causes of thrombocytosis including all of the other myeloproliferative disorders must be ruled out.
Laboratories at Diagnosis:  Platelets greater than 600,000/uL, hemoglobin not greater than 13g/dL, normal iron stores, no Philadelphia chromosome, no collagen fibrosis of the marrow.

Agnogenic Myeloid Metaplasia

(myelofibrosis with myeloid metaplasia)

Symptoms:  Bleeding, infection, portal hypertension.
Laboratories at Diagnosis:  leukoerythroblastosis, dacryocytes, extramedullary hematopoesis, myelofibrosis on marrow biopsy, Pelger-Huet cells.