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8. Myeloproliferative Disorders

• 8.1 Acute Myeloid Leukaemia
• 8.2 Acute Promyelocytic Leukaemia
• 8.3 Myelodysplastic Syndrome

8.1 Acute Myeloid Leukaemia

Diagnostic Criteria

Core criteria (applicable to all cases):

1. More than 20% blasts cells by flow cytometry, or morphology when the quality of the EDTA sample is sub-optimal (use higher figure) or more than 5% blasts in the presence of a balanced translocation
2. Myeloid lineage demonstrated by immunophenotype
3. The immunophenotype can be one of two patterns:
   • Type A: CD34⁺,CD117⁺,CD13⁺,CD33⁺,HLA-DR⁺,cCD3^-, cCD79^-
   • Type B: CD34^-,CD117⁺,CD13⁺,CD33⁺,HLA-DR^{+ or -}, CD15^var+,cCD3^-,cCD79^-,MPO⁺ (by flow)
   • Intermediate phenotypes occur and are acceptable to define myeloid lineage

Immunophenotypic variants:

1. Probable t(8;21): Type A pattern with CD19⁺, evidence of maturation and variable CD56
2. Monocytic type: Type B phenotype with CD64⁺⁺⁺, CD14^var+,HLA-DR⁺
3. Myelomonocytic type: Monocytic blasts with variable proportion of type A blasts

All cases should be reported initially as AML with further sub-classification when cytogenetics and PCR data are available.

Sub-classification criteria in order of priority:

1. Presence of a balanced translocation
   • Inv16
   • t(8;21)
   • t(15;17) - report as APML
   • 11q23/MLL abnormalities
2. History of chemotherapy or radiotherapy - diagnose as AML probable therapy related. For secondary AML with adverse features - leave diagnosis as therapy-related AML
3. Documented history of MDS or MPD - diagnose as AML arising from transformation of MPD/MDS
4. AML with multi-lineage dysplasia. This requires the same criteria as MDS in the non-blast population. However this is a subjective category of doubtful clinical relevance, especially when cytogenetically normal. This should not be used as a diagnostic term, but features of dysplasia will be mentioned in the body of the text.
5. AML NOS with a comment on the lineage of blast cells as defined by flow cytometry.

Prognostic Factors

AML with favourable prognosis

All balanced translocations except MLL. "Favourable effect of balanced translocation should be interpreted in terms of clinical features" to be appended onto report automatically by HILIS.

AML with adverse cellular features - any one of the following:

Complex karyotype (≥5 abnormalities)

Partial or complete loss of chromosome 5, -7 or 3q abnormalities

Flt-3 ITD-positive

Otherwise AML NOS

Definition of Remission Status

When a blast cell population is detected unequivocally by flow cytometry or PCR this will be reported as not in remission, with the extent of infiltration stated. Where these techniques are not available remission will be defined as a morphological blast count of <5%.

Terms to be Used

Each category can be modified with a comment on prognosis when PCR and cytogenetics results are available.

1. "The favourable effect of the balanced translocation should be interpreted in the context of other biological and clinical prognostic factors" will be appended onto the bottom of the report automatically by HILIS
2. "The adverse prognostic effect of the cellular features should be interpreted in the context of other biological and clinical prognostic factors" will be appended onto the bottom of the report automatically by HILIS

8.2 Acute Promyelocytic Leukaemia

Diagnostic Criteria

All cases must have:

1. CD34^+/-,CD13-hetero⁺,CD33-homo⁺⁺⁺,CD117⁺,CD15^-,HLA-DR^-, MPO⁺⁺⁺ (by flow)
2. Microparticulate pattern with anti-PML
3. Confirmation of t(15;17) by PCR or cytogenetics

Term to be Used

8.3 Myelodysplastic Syndrome

This diagnosis requires the demonstration of multilineage dyshaemopoiesis; at least two lineages must be involved. If the diagnosis is ambiguous by morphology, a diagnosis of "Morphological diagnosis uncertain" or "Suspicious of malignancy" should be made and the bone marrow should be repeated in 6 months if clinically indicated.

Diagnostic Criteria

Typical Cases

1. Hypercellular marrow in the presence of cytopenia
2. Abnormal marrow architecture
3. Erythroid series shows nuclear budding or bridging, vacuolation of late erythroblasts, multinuclear cells, asynchronous haemoglobinisation
4. Myeloid series shows abnormal granulation, pseudo-Pelger change, maturation asynchrony, increased numbers of CD34⁺ myeloblasts, usually >3.5% by flow cytometry. The blasts should have the phenotype CD34⁺,CD45⁺,CD117⁺,CD15^-
5. Megakaryocytes are cytologically abnormal with micro forms and nuclear lobe separation

Variants

1. All above features in a hypocellular marrow
2. 5q- as sole cytogenetic abnormality often with increased abnormal megakaryocytes +/- increased platelets and anaemia
3. Refractory anaemia with ring sideroblasts, requires >15% ring sideroblasts and <5% blasts

Prognostic factors

1. Blast count defines refractory cytopenia with multilineage dysplasia and refractory anaemia with excess blasts (RAEB - blast count 5-20%)
2. International prognostic score incorporating blast count, cytopenia and degree of cytogenetic abnormality. This can only be assessed if PB data is supplied. High risk (IPSS ≥2.5) patients are defined as:
   • Blasts >10% (score 1.5) and high risk cytogenetics (score 1)
   • Blasts >10% (score 1.5), cytopenia affecting 2 or 3 cell lines (score 0.5) and either high risk (score 1) or intermediate risk (score 0.5) cytogenetics

International Prognostic Scoring System (IPSS) for MDS

1. Neutrophil count <1.5, platelets <100, haemoglobin <10g/dl

Differences from WHO

1. Refractory anaemia is an ill defined entity and will not be diagnosed
2. RAEB will not be subdivided
3. Use of IPSS high risk group

Terms to be Used

Any type may occur as hypocellular variant. Cytogenetics will be carried out when a morphological diagnosis of MDS is made. When cytogenetics results are available, the number of IPSS points should be stated in comments. If full data is not available to give the IPSS score, the minimum IPSS should be stated based on the information available. High risk cases will be identified in the comment where information is available.

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