Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (356 page)

Cytogenetic studies are recommended not only to determine prognosis but most importantly to rule out CML through the absence of BCR-ABL translocation.

   
Coagulation
: PT or PTT may be prolonged and laboratory evidence of DIC is occasionally found.

   
Leukocyte alkaline phosphatase
(LAP) is increased (not routinely recommended).

   
Other
: LDH, serum uric acid, and vitamin B
₁₂
are often increased.

Suggested Readings

Levine RL, Gilliland DG. Myeloproliferative disorders.
Blood.
2008;112:2190–2198.

Mascarenhas J, Hoffman R. A comprehensive review and analysis of the effect of ruxolitinib therapy on the survival of patients with myelofibrosis.
Blood.
2013;121:4832–4837.

Tam CS, Abruzzo LV, Lin KI, et al. The role of cytogenetic abnormalities as a prognostic marker in primary myelofibrosis: applicability at time of diagnosis and later during disease course.
Blood.
2009;113:4171–4178.

MYELODYSPLASTIC SYNDROME (MDS)

   Definition

MDS is a group of clonal disorders of the hematopoietic system, characterized by ineffective hematopoiesis. Dysplasia (abnormal morphology) involving at least 10% of a specific myeloid lineage, peripheral blood cytopenias, and increased risk of transformation into acute myeloid leukemia. Approximately two thirds of patients present initially with low-risk disease. Higher grade disease categories tend to progress to acute myeloid leukemia. Refractory cytopenias are the principal cause of mortality and morbidity. The differential diagnosis of MDS includes various causes of macrocytic or refractory anemias, alcohol consumption, and thyroid disease.

   Who Should Be Suspected?

An elderly patient, presenting with cytopenia(s) discovered by routine CBC, or with symptoms resulting from anemia (fatigue, weakness, exercise intolerance, new angina), less frequently infections, bruising, or bleeding. Splenomegaly and lymphadenopathy are absent. The presence of monocytosis is suggestive of chronic myelomonocytic leukemia (CMML). Previous exposure to environmental toxins such as benzene, radiation therapy, or treatment with alkylating agents or topoisomerase II inhibitors may result in secondary MDS. Alternatively, young patients with an inherited hematologic disorder are predisposed to develop MDS.

   Classification

   The WHO classification has proved helpful for prognosis and in selection of therapy and is updated periodically. The 2008 WHO classification of MDS contains eight entities:

  1.  Refractory cytopenias with unilineage dysplasia (RCUD).

  2.  Refractory anemia (RA): <5% bone marrow blasts, ≤1% blasts in the peripheral blood; <15% of erythroid precursors are ringed sideroblasts (characterized by at least five granules of iron that encircle the nucleus of erythroid precursors).

   Refractory neutropenia (RN)

   Refractory thrombocytopenia (RT)

  3.  Refractory anemia with ringed sideroblasts (RARS): similar to RA, but with ≥15% ringed sideroblasts in the bone marrow. Erythroid dysplasia only.

  4.  Refractory cytopenias with multilineage dysplasia (RCMD): dysplasia in ≥10% of cells in two or three lineages and <5% bone marrow blasts; ±15% ringed sideroblasts.

  5.  Refractory anemia with excess blasts-1 (RAEB-1): 5–9% blasts in the bone marrow but no Auer rods. Cytopenia(s) but <5% blasts in peripheral blood.

  6.  Refractory anemia with excess blasts-2 (RAEB-2): 10–19% blasts in bone marrow, Auer rods ±; 5–19% blasts in peripheral blood, cytopenia(s).

  7.  Myelodysplastic syndrome unclassified (MDS-U): <5% blasts in bone marrow; dysplasia in <10% of cells when accompanied by a cytogenetic abnormality is considered presumptive evidence for a diagnosis of MDS; cytopenias and ≤1% blasts in peripheral blood.

  8.  MDS associated with isolated del (5q) (the 5q
⁻
syndrome). Bone marrow: normal or increased mononuclear megakaryocytes with spherical nuclei; <5% blasts; no Auer rods; del(5q) as the only cytogenetic abnormality. Peripheral blood: anemia, normal or increased platelet count, and no or rare blasts (<1%).

   Syndromes with mixed features of myelodysplastic–myeloproliferative disorders are classified separately as MDS/MPS. The prototype is CMML.