Proposed criteria for measurement of disease progression in adult MDS/MPN
| Combination of 2 major criteria, 1 major and 2 minor criteria, or 3 minor criteria from list . |
|---|
| Major criteria |
| Increase in blast count* |
| <5% blasts: ≥50% increase and to >5% blasts |
| 5-10% blasts: ≥50% increase and to >10% blasts |
| 10-20% blasts: ≥50% increase and to >20% blasts |
| 20-30% blasts: ≥50% increase and to >30% blasts† |
| Evidence of cytogenetic evolution‡ |
| Appearance of a previously present or new cytogenetic abnormality in complete cytogenetic remission via FISH or classic karyotyping |
| Increase in cytogenetic burden of disease by ≥50% in partial cytogenetic remission via FISH or classic karyotyping |
| New extramedullary disease |
| Worsening splenomegaly |
| Progressive splenomegaly that is defined by IWG-MRT: the appearance of a previously absent splenomegaly that is palpable at >5 cm below the left costal margin or a minimum 100% increase in palpable distance for baseline splenomegaly of 5-10 cm or a minimum 50% increase in palpable distance for baseline splenomegaly of >10 cm |
| Extramedullary disease outside of the spleen |
| To include new/worsening hepatomegaly, granulocytic sarcoma, skin lesions, etc. |
| Minor criteria |
| Transfusion dependence§ |
| Significant loss of maximal response on cytopenias ≥50% decrement from maximum remission/response in granulocytes or platelets |
| Reduction in Hgb by ≥1.5g/dL from best response or from baseline as noted on complete blood count |
| Increasing symptoms as noted by increase in ≥50% as per the MPN-SAF TSS|| |
| Evidence of clonal evolution (molecular)¶ |
| Combination of 2 major criteria, 1 major and 2 minor criteria, or 3 minor criteria from list . |
|---|
| Major criteria |
| Increase in blast count* |
| <5% blasts: ≥50% increase and to >5% blasts |
| 5-10% blasts: ≥50% increase and to >10% blasts |
| 10-20% blasts: ≥50% increase and to >20% blasts |
| 20-30% blasts: ≥50% increase and to >30% blasts† |
| Evidence of cytogenetic evolution‡ |
| Appearance of a previously present or new cytogenetic abnormality in complete cytogenetic remission via FISH or classic karyotyping |
| Increase in cytogenetic burden of disease by ≥50% in partial cytogenetic remission via FISH or classic karyotyping |
| New extramedullary disease |
| Worsening splenomegaly |
| Progressive splenomegaly that is defined by IWG-MRT: the appearance of a previously absent splenomegaly that is palpable at >5 cm below the left costal margin or a minimum 100% increase in palpable distance for baseline splenomegaly of 5-10 cm or a minimum 50% increase in palpable distance for baseline splenomegaly of >10 cm |
| Extramedullary disease outside of the spleen |
| To include new/worsening hepatomegaly, granulocytic sarcoma, skin lesions, etc. |
| Minor criteria |
| Transfusion dependence§ |
| Significant loss of maximal response on cytopenias ≥50% decrement from maximum remission/response in granulocytes or platelets |
| Reduction in Hgb by ≥1.5g/dL from best response or from baseline as noted on complete blood count |
| Increasing symptoms as noted by increase in ≥50% as per the MPN-SAF TSS|| |
| Evidence of clonal evolution (molecular)¶ |
Blasts as measured from the bone marrow.
Patients with development of acute myeloid leukemia from MDS/MPN; 20-30% blasts may be allowed on some clinical trials for patients with MDS/MPN.
Increase in cytogenetic burden of disease by ≥50% (via FISH or classic karyotyping). Given variability of fluorescent probes used in FISH, cytogenetic normalization via FISH will depend on specific probes used.
Transfusion dependency is defined by a history of at least 2 U of red blood cell transfusions in the past month for a hemoglobin level <8.5 g/dL that was not associated with clinically overt bleeding. Cytopenias resulting from therapy should not be considered in assessment of progression.
MPN-SAF TSS validation among patients with MDS/MPN is currently under way (R.A. Mesa, personal communication, 2014).
The identification of new abnormalities using single nucleotide polymorphism arrays or sequencing or a clearly significant increase in mutational burden of a previously detected abnormality. Precise criteria for defining new abnormalities and what exactly constitutes a significant increase in mutational burden are open to interpretation; we suggest that this criterion should be used conservatively based on current evidence.