Is this MDS?

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Motivation: In the past few months, I have come across multiple patients with chronic unexplained macrocytosis.  I am often tempted to diagnose MDS and request a bone marrow biopsy.  But, is there a better non-invasive scoring system to triage the likelihood of MDS?  Recently, while searching this topic, I came across this paper that estimates a pre-test likelihood of MDS.

Paper: Rauw, J., Wells, R.A., Chesney, A., et. al.  Validation of a scoring system to establish the probability of myelodysplastic syndrome in patients with unexplained cytopenias or macrocytosis.  Leukemia Research (2011) 35: 1335-38.

Methods: Retrospective review of bone marrow biopsies (2006-2008) at an academic hospital in Toronto, Canada.  Inclusion criteria were anemia (hemoglobin <12 g/dL), thrombocytopenia (platelet < 150), leukopenia (WBC < 4), neutropenia, or macrocytosis (MCV > 96).  Patients with known or suspected hemato-lymphoid diseases (such as lymphoma or widespread lymphadenopathy) were excluded.  BM biopsies were classified as MDS, suspected MDS (met most but not all pathological criteria), or not MDS.

Results:
Scoring System: The authors designed a scoring system with four parameters: (1) age >= 65, (2) RDW > 14.5%, (3) MCV > 96, and (4) LDH  > 250.

Bone Marrow Diagnoses: Of the 313 biopsies reviewed, 100 had MDS, 27 had suspected MDS, and 186 did not have MDS.  Among those not having MDS, 34% were normal, 10% had AML, and the rest had other diagnoses.

Sensitivity and Specificity of Confirmed/Suspected MDS Based on Risk Factors:
Risk Factors              Sensitivity              Specificity
>=1 factor                  95%                       18%
>=2 factors                74%                        46%
>=3 factors                39%                        79%
    4 factors                6%                          96%

Discussion: I liked this paper because it provided a risk assessment of MDS based on parameters that are easily and routinely measured.  Having multiple risk factors should lower the threshold for referral to hematology and having a bone marrow biopsy.  As in other retrospective reviews from tertiary medical centers, the numbers in this paper are affected significantly by referral bias.  In the patients with anemia and macrocytosis getting BM biopsy, probably all had B12 and folate checked and had MCV measured when abstaining alcohol.  In the regular inpatient setting, alcoholism as well as B12 deficiency probably accounts for a significant portion of macrocytosis.  For patients without these other more straightforward explanations, stratifying patients for MDS by these risk factors is a quick clinical tool.