1. MYELOPROLIFERATIVE DISEASES:
Clonal stem cell disorders that lead to uncontrolled hematopoiesis. These related diseases can transform into each other.
POLYCYTHEMIA VERA
ESSENTIAL THROMBOCYTHEMIA
MYELOFIBROSIS
CHRONIC MYELOGENOUS LEUKEMIA

2. POLYCYTHEMIA VERA
Increased red cell mass that is associated with increases in white cell and platelet cnt.
Normal red cell mass: F – ml/kg
M – ml/kg

3. Polycythemia Vera: Pathogenesis
Clonal disorder involving stem cell
Autonomous proliferation of the erythroid, myeloid & megakaryocytic cell lines.
PV progenitor cells are more resistant to apoptosis.
Chromosomal abnormality: 20q-, trisomy 8/9
Unknown

4. PV: Clinical Mx
Consequence of hyperviscosity: plethora, poor CNS & coronary circulation
Abnormal platelet function: venous thrombosis/ thromboembolism, hemorrhage
Increase myeloproliferation: splenomegaly, pruritus (increase histamine release)

5. PV: Labs Increase Hb & Hct= increase total red cell mass
Leucocytosis – granulocytosis
Thrombocytosis
BM hyperplasia

6. PV: Diagnostic Criteria
Category A:
1. T red cell mass: M > 36 ml/kg
F > 32 ml/kg
2. Arterial O2 sat. > 92%
3. Splenomegaly

7. PV: Dx Category B: 1. Thrombocytosis (PC.> 400T)
2. Leucocytosis (WBC > 12T)
3. Increase LAP score
4. Serum B12 conc. >900 pg/ml
Dx: A1+A2+A3 or A1+A2+ any 2 frm B

8. PV: Complications Erythromelalgia- erythema, warmth, pain
“digital infarction”
Thrombosis – 15-60% ; MR – 10-40%
Hemorrhage – 15-35%; MR – 6-30%
Peptic Ulcer disease
Pancytopenia & myelofibrosis – “spent
phase” – 30-70%
Acute leukemic transformation- 1%

9. PV: Mgt Reduction of Hyperviscosity - phlebotomy ( target Hct- 47%)
<50 y.o. – 1 U (450 ml) q other day
> 70 y.o. – ml TIW +
myelosuppressive
therapy(hydroxyurea/interferon)
erythrocytosis=thrombosis
Aspirin/Salicylates – erythromelalgia
Splenomegaly

10. LEUKEMIAS
Neoplastic expansion of hematopoietic cells in blood and bone marrow
*ACUTE Leukemia- expansion of
immature cells
* CHRONIC Leukemia- expansion of
mature cells
Incidence: 4 –5% of cancer among all age
group.

11. AML: Etiology 1. Radiation – genetic damage; immunosuppression
2. Chemicals – benzene
3. Viruses – human T-cell leukemia virus
RNA
4. Hereditary influences
5. Non random chromosome abnormalities

12. AML CLINICAL MANIFESTATION: * Infiltration of organs
* granulocytopenia
* thrombocytopenia

13. AML: FAB Classification
M1- AML without differentiation
M2 – AML with differentiation
M3- Acute Promyelocytic Leukemia
50% of cases
Chromosomes +8, -5,-7
T(8;21)
Multiple AUER RODS
FIBRINOLYSIS common
T(15:17) / 10% of cases

14. AML: FAB Classification
M4 – Acute Myelomonocytic Leuk
M5-Acute Monocytic Leukemia
M6-Acute Erythroleukemia (erythremic myelosis)
M7 Acute Megakaryocytic
Leukemia
15% of cases
Frquent extramedullary dss
Children/young adults
10% cases
Gum,CNS,LN, extramedullary infiltration
Long prodromal prd.
5% of cases
DRY TAP coz myelofibrosis
AML of DOWNs Syndrome

15. ACUTE LYMPHOCYTIC LEUKEMIA
Clonal proliferation of lymphoid progenitor cells originating in the marrow

16. ALL: FAB Classification
SIZE
L1- small, uniform
CYTPLSM
Scanty, basophilia
NUCLEUS
Regular shape,inscnpcous nucleoli
AGE
C- 85%
A- 31%
L2-large, non-uniform
variable
Irreglr shape, prmnt nucleoi
C- 14%
A-60%
L3- large, uniform
Abundant, deep basophilia
Reglr shape
Promnt nucleoli
C- 1%
A- 9%

17. ALL: Classification by IMMUNOPHENOTYPING
Early pre-B
Pre-B
B-cell
T-cell

18. ACUTE LEUKEMIA: Treatment
1. Bone Marrow Transplant
a. Allogeneic BMT yrs old with histocompatible sibling ( 50% long term dss free survival)
Cx: graft vs. host dss.
intestinal pneumonitis
Relapse rate: %

19. 2. Autologous BMT- individuals own marrow for reinfusion
* up to 60 yrs. Old
* MR: <10%
Cx: potential for reinfusion of leukemic
cells
Long term dss-free survival –50%

20. ACUTE Leukemia: Treatment
1. Induction Chemotherapy: over all
remission rate- 65%
2. Post Remission Therapy:
* Consolidation
* Maintenance
* CNS Prophylaxis
Sanctuary Sites: CNS & Testes

21. Treatment: Supportive Care
1. Antimicrobials:
Infection- main threat to absolutely
neutropenic pts.
High Risk Group:
a. prior high dose steroid
b. protracted granulocytopenia
c. previous fungal sepsis

22. Acute Leukemia: Treatment
2. Transfusion therapy
- component therapy: pRBC,
platelet concentrate
3. Hematopoietic growth factors

23. ALL: Treatment Complications
1. DIC – common in APL – cells lyse & release of thrombogenic materials
2. Hyperleukocytic leukemia- leukostasis
3. Meningeal Leukemia- ALL & Monocytic variant AML
4. Tumor Lysis Syndrome
a. hypocalcemia
b. hyperkalemia
c. hyperphosphatemia
d. hyperuricemia
e. increasre crea, BUN; LDH

25. Prognostic Factors in Childhood ALL
PARAMETER
GOOD
POOR
White cell cnt
Low (<50T)
High
Age
Young (1-10)
Oldr (>10)
CALLA
presnt
absnt
Lymp cell type
Early B cell
T cell
Cytogenetics
normal
abnormal
FAB class L1 L2