Response criteria for myelofibrosis

International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) response criteria

CategoryDefinition
Complete remission (CR)All of the following criteria should be met:

  • Complete resolution of disease-related symptoms and signs including palpable hepatosplenomegaly
  • Peripheral blood count remission (hemoglobin ≥ 11 g/dL, platelets ≥ 100 x109/L, neutrophils ≥ 1.0 x109/L), all 3 blood counts should also be no higher than upper limit of normal
  • Normal white cell differential including absence of nucleated red cells, blasts, and immature myeloid cells on the blood film, in the absence of splenectomy (1)
  • Histologic remission on bone marrow trephine: normocellular for age, ≤ 5% myeloblasts, and osteomyelofibrosis grade ≤ 1 (2)
Partial remission (PR)All CR criteria met except bone marrow histologic remission
Clinical improvement (CI)At least one of the following for at least 8 weeks, in the absence of progressive disease, or complete or partial remission:

  • ≥ 2 g/dL increase in hemoglobin or achievement of transfusion independence (only applies to patients with baseline hemoglobin ≤ 10 g/dL) (3)
  • ≥ 50% reduction in palpable splenomegaly (if spleen ≥ 10 cm at baseline) OR spleen no longer palpable (if 5 - 10 cm at baseline) (4)
  • ≥ 100% increase in platelet count AND platelet count ≥ 50 x109/L (only applies to patients with baseline platelet count < 50 x109/L)
  • ≥ 100% increase in neutrophil count AND neutrophil count ≥ 0.5 x109/L (only applies to patients with baseline neutrophil count < 1.0 x109/L)
Progressive disease (PD)At least one of the following: (5)

  • Progressive splenomegaly: palpable splenomegaly > 5 cm below left costal margin if no prior palpable splenomegaly, OR ≥ 100% increase in palpable splenomegaly if baseline 5 - 10 cm, OR ≥ 50% increase if baseline splenomegaly > 10 cm
  • Leukemic transformation confirmed by bone marrow blast count ≥ 20%
  • ≥ 20% increase in peripheral blood blast percentage lasting for ≥ 8 weeks
Stable diseaseNone of the above
RelapsePatient previously meeting criteria CI, PR or CR no longer meets criteria for CI
Notes
(1) Because peripheral blood film analysis is subjective, CR does not require absence of morphologic abnormalities of red cells, platelets, and neutrophils

(2) In patients with CR and a pre-existing cytogenetic abnormality, complete cytogenetic response is defined as failure to detect the abnormality in at least 20 metaphases. Partial cytogenetic response is defined as ≥ 50% reduction in abnormal metaphases. Major molecular response is defined as absence of a previously-positive specific disease-associated mutation in peripheral blood.

(3) Transfusion-dependence is defined as a transfusion of at least 2 units of red blood cells in the previous month for a hemoglobin < 8.5 g/dL not due to clinically overt bleeding. During therapy within clinical trials, transfusions for a hemoglobin ≥ 8.5 g/dL is therefore discouraged unless clinically indicated.

(4) In splenectomized patients, palpable hepatomegaly is substituted, with the same measurement criteria.

(5) Worsening cytopenias were not included as a criterion for progressive disease because of the difficulty differentiating between disease-associated cytopenias and drug-induced myelosuppression. However, ≥ 2 g/dL decrease in hemoglobin, ≥ 100% increase in transfusion requirement, or new development of transfusion dependence, each lasting for > 3 months after discontinuation of protocol therapy, can be considered disease progression.