Although most people associate me with CLL, I spent almost as much of my career on myelodysplastic syndrome (MDS). Even as a young man I was fascinated by this pre-leukemic condition and in my early twenties encountered three patients with what we would now call refractory anemia with sideroblasts who had chromosomal abnormalities (MM, AW and PS). In those days before chromosome banding, we could not identify individual chromosomes and just called them 'C' group chromosomes. In retrospect, chromosomes 7 and 8 were involved.
As a registrar and senior registrar I accumulated a series of unexplained cases, but it wasn't until Dr Mufti came to work for me as a fellow, having previously worked with the late, great, David Galton at the Hammersmith, that we set about identifying what was going on. We wrote an important paper that established that MDS was much more common than people had thought hitherto, and that most of it went undiagnosed. Myelodysplastic syndromes: a scoring system with prognostic significance
G. J. Mufti, J. R. Stevens, D. G. Oscier, T. J. Hamblin*. British Journal of Haematology 1985 59,425–433. We discovered that our hospital 76 cases had been misdiagnosed in the past 5 years. This was the first paper to offer a prognosis based on the initial diagnostic picture and it has since been cited in the medical literature 423 times. Later on we added our data to those of the French, Japanese, Spanish, Germans and a small American series to produce the International scoring system for evaluating prognosis in myelodysplastic syndromes P Greenberg, C Cox, MM LeBeau, P Fenaux, P Morel, G Sanz, M Sanz, T Vallespi, T Hamblin, D Oscier, K Ohyashiki, K Toyama, C Aul, G Mufti and J Bennett Blood 1997, 89, 2079-2088. which is one of the most cited papers in Blood with 1990 citations.
My main interest in MDS has been in diagnosing the very early forms of the disease. Barn door cases need to be distinguished from acute leukemia, but accurate diagnosis of the early cases depends on viewing very good blood films with an expert eye. Abnormalities of nuclear shape and structure, various cytoplasmic inclusions and granulation and overall cellularity are crucial. More can be done diagnostically by looking and the histology of bone marrow trephines and the disposition of the reactive tissue. Unlike CLL, you can't simply stick a sample on a flow cytometer and hope to get an answer. Though you may get clues.
There are certainly similarities between MDS and aplastic anemia, and one of the features of aplastic anemia is the presence of a clone of cells derived from this strange condition, paroxysmal nocturnal hemoglobinuria (PNH), in which the red cells are particularly susceptible to lysis by endogenous complement. It seems that cells lack GPI connected molecules on their surfaces that inhibit complement activity, particularly CD55 and CD59 and they can be tested for by flow cytometry.
The sorts of patients I am talking about are those that have a degree of isolated and unexplained thrombocytopenia, neutropenia or anemia (particularly with a raised MCV). The degrees of myelodysplastic features are too small to label the condition MDS (although Alan Jacobs of Cardiff used to call such cases NQMDS or NYMDS - not quite- or not yet- MDS). The international community has labelled such cases idiopathic cytopenia of undetermined significance (ICUS).
In this month's BJ Haem there is a letter from Japan (Ando et al 2010, 150: 705-707) reporting on PNH cells in ICUS. It is brief and probably premature, but it picks out 2 of the 11 ICUS cases that they studied and suggest that these who had small populations of PNH cells also had very low numbers of megakaryocytes - perhaps making them aplastic anemia forme fruste rather than MDS. However the numbers are too small to be statistically significant.
People complain that hematologists are poor at diagnosing MDS. True, but that underestimates the difficulty.