Myeloproliferative Disorders

1. Chronic myelogenous leukemia (CML)
2. Polycithemia vera (PV)
3. Essential thrombocytemia (ET)
4. Idiopathic myelofibrosis (previously called agnogenic myeloid metaplasia (AMM)

Non Hodgkin's Lymphoma International Prognostic Index

Five Adverse Prognostic Factors

1. Age greater than 60 years
2. Ann Arbor Stage III/IV
3. More than one extranodal site
4. Serum LDH concentration > normal
5. ECOG performance status

Prognostic Index By Risk Group










Age Adjusted Prognostic Index (less or equal 60 years old)

For this adjustment, age and number of extranodal sites are not used










NEJM 1993:329;987-994

Complications After HSCT

Early (0-30 Days)
A.Regimen related toxicity
1.Mucositis (65-70%)
2.Myocarditis & Pericarditis from either cyclophosphamide or TBI (rare)
3.Hemorrhagic Cystitis (10%)
4.Veno-occlusive disease (5-40%)
5.Pneumonitis (10- 20%)
6.Alveolar hemorrhage (5-10%)
B.Infections (75%)
C.Graft Failure (2-10%)
D.Adverse drug reactions from Polypharmacy (Common)

Intermediate (1-3 months)
Acute GVHD (20-50%) (more frequent with non-sibling donors)

Late (Beyond 3 months)
A.Chronic GVHD (20 – 40%)
B.Hypothyroidism (30 – 50%)
C.Growth disturbances in children (common)
D.Sterility/Hypogonadysm (common)
E.Cataracts (25 – 40%)
F.Avascular necrosis of bone and demineralization of bone (5 – 15%)
G.Malignant relapse (Variable)
H.Second Malignancy (2-10%)

WHO Classification of Acute Myeloid Leukemia

Acute myeloid leukemia with recurrent genetic abnormalities

• Acute myeloid leukemia with t(8;21)(q22;q22), (AML1/ETO)
• Acute myeloid leukemia with abnormal bone marrow eosinophils and inv(16)(p13q22) or t(16;16)(p13;q22), (CBF/MYH11)
• Acute promyelocytic leukemia with t(15;17)(q22;q12), (PML/RAR and variants
• Acute myeloid leukemia with 11q23 (MLL) abnormalities

Acute myeloid leukemia with multilineage dysplasia

• Following MDS or MDS/MPD
• Without antecedent MDS or MDS/MPD, but with dysplasia in at least 50% ofcells in 2 or more myeloid lineages

Acute myeloid leukemia and myelodysplastic syndromes, therapy related

• Alkylating agent/radiation–related type
• Topoisomerase II inhibitor–related type (some may be lymphoid)
• Others

Acute myeloid leukemia, not otherwise categorized
Classify as:

• Acute myeloid leukemia, minimally differentiated
• Acute myeloid leukemia without maturation
• Acute myeloid leukemia with maturation
• Acute myelomonocytic leukemia
• Acute monoblastic/acute monocytic leukemia
• Acute erythroid leukemia (erythroid/myeloid and pure erythroleukemia)
• Acute megakaryoblastic leukemia
• Acute basophilic leukemia
• Acute panmyelosis with myelofibrosis
• Myeloid sarcoma

Hypercalcemia of malignancy

- Common (10 - 30% of patients with Ca will have it)
- Most common malignancies re breast, lung and multiple myeloma
- Poor prognosis, particularly if high PTH-rP
- 3 Types:

1. Humoral, PTH-rP mediated, most frequent cause.
2. Local bone destruction, with cytokines produced by tumor (breast, lung, MM) that induce differentiation os fibroblasts in osteoclasts.
3. Overproduction of Vitamin D, most frequent cause in lymphomas and Hodgkins + granulomatous disorders.

- Non specific symptoms: lethargy, confusion, anorexia, nausea, abdominal pain, constipation, polyuria & polydipsia. Usually patients are dehydrated and hypovolemic.

- Laboratory diagnosis is made with ionized calcium; if total serum calcium is used, it shold be corrected for the albumin level. Other electrolytes should be measured. Hypochloremia is suggestive of hypercalcemia of malignancy. Intact PTH is usually low and PTH-rP may be measured for understanding mechanism of hypercalcemia and to predict response to biphosphonates.

- Treatment
Hydration (aggressive) with NS
Diuretics only when euvolemia has been reached
Biphosphonates (Pamidronate 60 - 90mg IV infusion in 2-4h, Zoledronic acid 4mg if in 15min)
Glucocorticoids (most useful when Vitamin D is involved (Hodgkin's, NHL)
Calcitonin (IM or SC, intranasal doesn't work for hypercalcemia)(usually short lived effect)

- Prevention of recurrence:
Therapy of underlying malignancy; adequate hydration; interminttent biphosphonates (particularly if bony mets); stop meds that raise Ca++; stop oral sources of phosphate

Sickle Cell Anemia Complications

I) Hematologic:
- Anemia:
- Chronic hemolytic,
- Iron deficiency can happen, particularly in young menstruating women.

- Hematologic crises:
1. Hyperhemolysis: decreased Hb, increased bilirubin, increased LDH and increased reticulocytes. Can be caused by infection, coexistent G6PD deficiency, delayed hemolytic reaction.
2. Aplastic crisis: decreased Hb and reticulocyte count. Usually caused by viral infection (ParvoB19)
3. Megaloblastic crisis: Usually when Folate deficiency occurs.

II) Acute chest syndrome:
- MOST FREQUENT CAUSE OF DEATH IN SSA.
- 2nd most common reason for admission
- May be caused by pneumonia, rib or sternal infarction, fat or bone marrow embolism, pulmonary infarcts, PE.
- History:
Chest pain, Fever, Dyspnea, Hypoxia, Pulmonary infiltrates, Worsening anemia,
- Labs/Images
CXR, Cultures, ABGs, Hemoglobin levels, V/Q scans and LLE Dopples US's,
- Management
ATB, Total blood exchange in severe cases, Treatment of cause, Supportive care

III) Musculoskeletal:
- Leg ulcers: more frequent in men, rare when HCT high and with alpha deletions
- Avascular necrosis: higher in alpha deletion
Femoral head, Humoral head, Vertebral bodies

IV) CNS (occur in 25% if sickle cell patients, more common in SS than others)
- CVA (ischemic in children and hemorrhagic in adults)
- Seizures
- Retinopathy. More frequent in SC disease. Amenable to photocoagulation in early course

V) Cardiac:
- High output failure
- Right side failure
- Hemosiderosis
- Ischemia and infarction

VI) Hepatobiliary:
- 2/3 have hepatomegaly
- 75% gave cholelithiasis
- Acute hepatic sequestration of erythrocytes can happen
- Hepatic crisis: intrahepatic cholestasis
RUQ pain, Progressive hepatomegaly, Increasing bilirubin (indirect), PT and PTT prolongation
Increased transaminases
May require total blood exchange if severe (very high bilurubin, PT) and is continued until HbS is less than 30% & Pt is normalized

VII) Genitourinary:
- Intrarrenal sickling can cause intramedullary infarction (hematuria, hyposthenuria)
- Impaired acidification - renal tubular acidosis
(These changes can happen in both homozygous and heterozygous patients)
- Hematuria
- Hyperkalemia:impaired Potassium excretion, 2ary to hyperchloremic acidosis
- Priaprism: tricorporal or bicorporal involvement
Can be acute or chronic: Acute: Prolonged painful erection of several hours' duration, usually does not respond to exchange transfusion and requires surgery, impotence is frequent complication. Chronic (stuttering): usually after intercourse, reversible, reponds well to diazepam or pseudoephedrine. Impotence can happen.
- Nephrotic syndrome
- Glomerular enlargement and focal & segmental glomerulosclerosis
- ACE inhibotors can be used

VIII) Immune:
- Functional asplenia: need for vaccinations against polysaccharide encapsulated bacteria.
- Impaired cellular immunity secondary to iron overload
- Salmonella typhimurium osteomyelitis is classic association, but Staphylococcal can happen.

IX) Splenic sequestration

Diagnosis of AML (WHO)

- More than 20% of blasts in BM or blood

- Clonal, recurring cytogenetic abnormalities, regardless of blast %
1. t(18;21) (q22;q22)
2. inv(16) (p13q22)
3. t(16;16) (p13;q22)
4. t(15;17) (q22;q12)