MDS/MPN

Question 1

WHO Criteria for MDS

Answer 1

• Refractory cytopenia of childhood (RCC)
  PB blasts <2%, BM blasts< 5%
• Refractory cytopenia with excess blasts (RAEB)
  PB blasts 2-19%, BM 5-19%
• Refractory cytopenia with excess blasts in transformation (RAEB_T)
  PB and/or BM blasts 20-29%
• MDS/AML

Note that JMML and DS related TAM are separate categories

Question 2

Major differences in adult vs childhood MDS

Answer 2

• RCC often hypocellular in children

- RCC/RAEB can have stable counts for months/years. Median time to progression of RCC to RAEB is 5 y

Question 3

Differential diagnosis of hypoplastic BM

Answer 3

1. Infections: EBV, CMV, HSV, parvo, HIV
2. Vitamin def (B12, folate)
3. Metaboic (MVK deficiency)
4. Rhuem
5. Mitochondrial (Pearson)
6. Inherited BMF syndrome (FA, DC, AMKT, TAR, etc)
7. SAA
8. RCC
9. PNH
10. Prephase to leukemia
11. HLH
12. lymphoproliferative disorders

Question 4

Most common cytogenetic and molecular abnormalities

Answer 4

Cytogenetics:

• Monosomy 7
• Trisomy 8
• complex karyoptype
• 5q- is rare (common in adults)

Molecular

• GATA 2
• ETV6
• RUNX1
• CEBPA

Question 5

JMML criteria

Answer 5

1. Clinical/Heme (all 4 mandatory)
   - monocyte count > 1
   - blast percentage < 20%
   - splenomegaly
   - absence of Ph chromosome
2. Oncogentic (1 is sufficient)
   - somatic mutation in PTPN11 or k-ras or n-ras
   - clinical diagnosis of NF-1 or germline NF-1
   - germline CBL mutation and LOH in CBL
3. For those without oncogenetic criteria, must have 2 of the following:
   - hypersensitivity to GM-CSF
   - monosomy 7 or other chromosomal abn
   - HbF increased
   - myeloid precursors in BM
   - hyperphosphorylation of STAT 5

Question 6

Prognostic factors in JMML

Answer 6

poor prognostic factors:

• Age > 2
• Hb F elevated> 10%
• low plt count < 33

Question 7

Mutations associated with JMML

Answer 7

N-ras
K-ras
PTPN-11
CBL
NF-1

Question 8

Treatment options for JMML

Answer 8

1. Germline n-ras/k-ras/ptpn-11 - Noonan’s related MPD so watch and wait
2. Germline CBL also often self-resolve so watch and wait if well
3. Germline NF-1 - HSCT
4. Somatic PTPN-11 and k-ras or n-ras - HSCT
   * k-ras has high risk of relapse. n-ras less so in the absence of high-risk features may consider watch and wait

Question 9

Essential Thrombasthenia criteria

Answer 9

• Plt > 450
• BM wit mega proliferation and no increase in granulopoesis/erythropoesis
• JAK2V617F or other clone
• Absence of criteria for other MPN
• no reactive cause