Chronic myeloid disorders

Chronic myeloid disorders can be a confusing group of diseases to understand. There is overlap between conditions, making diagnosis challenging at times and many conditions have multiple names. Today we discussed a case of myelodysplastic syndrome, which is very likely a case of myelofibrosis. Here, we describe a general approach to these conditions and some of the clinical features.

Chronic myeloid disorders is an umbrella term encompassing multiple conditions: chronic myeloid leukemia (CML), myelodysplastic syndrome (MDS), chronic myeloproliferative disease and atypical chronic myeloid disorders. Chronic myeloproliferative disorders can be broken into polycythemia vera (PRV), essential thrombocytosis (ET) and idiopathic myelofibrosis (IMF). I think that confusion arises as a result of the multiple subgroups within each category of disease. You need to read about each entity separately to gain a better understanding of its differences.

MDS is as a result of ineffective and disordered hematopoeisis in one or more cell lines. Despite low peripheral counts, bone marrow evaluation reveals normal or hypercellularity. This is generally a disease of the elderly, where the majority of patients are over 65. It can be seen earlier, increasingly if caused by an external chemical exposure (ex. benzene). Clinical features are those associated with low blood counts; infection, bruising, fatigue etc. Some additional hints towards a diagnosis include an increased number of band neutrophils on the smear, the so called "pseudo-Pelger-Huet" anomaly, a result of premature cells being pushed into the blood.

The classification of myelodysplastic syndromes (MDS) changed in 2001. The World Health Organization changed the previous French-American-British (FAB) definition to improve the diagnosis of AML. MDS are a group of myeloid neoplasms, that impact on the proliferation of hematopoietic cells. Patients can present in a myriad of ways, and are generally classified into multiple categories:

1. Refractory cytopenia with unilineage dyslpasia- low RBCs or low platelets or low neutrophils
2. Refractory cytopenia with multilineage dysplasia- multiple low cell lines
3. Anemia with ringed sideroblasts- sideroblasts are abnormal mitochondria that are visibly different as a result of increased iron content
4. Refractory anemia with excess blasts - two stages based on percentage blasts (5-10%, 10-20%)
5. MDS from 5q deletion- a specific genetic variant
6. MDS otherwise unclassified

Prognosis varies depending on the subtype of MDS. Twenty percent of patients with MDS will die from AML, however those with 5q deletion are less likely to convert, and have a more indolent course.

Myelofibrosis (IMF), aka agnogenic myeloid metaplasia, is a different disease. This is a clonal stem cell disorder with progressive bone marrow fibrosis. An abnormal precursor is thought to produce factors that result in fibroblast proliferation and collagen deposition. Premature fibrosis pushes precursor cells into the periphery resulting in deposition of these cells in distant tissues. This leads to hematopoeisis outside the marrow. Cells can deposit in many different organs, including the lungs, pericardium, spleen, bowel, liver etc. IMF is less common than MDS, present in only 0.5 people per 100,000. The clinical presentation includes fatigue, splenomegaly, constitutional symptoms, and complications of bone marrow failure. Counts are often increased initially because of compensatory extramedullary hematopoeisis. Blood smear will often show premature WBCs, teardrop cells, giant platelets, termed a leukoerythroblastic pattern. Up to 60% of these patients will have a testable mutation in a gene called JAK-2. Occasionally,  can be difficult to distinguish IMF, from burnt out ET or PRV.

The prognosis in IMF is poor, with 10% of patients transforming to AML, having an average survival of 2-5 years. Unfortunately there are few successful treatments for this condition. In young individuals, allogeneic stem cell transplant can be considered, but in the elderly there is little that can be done. Blood counts can be controlled with various chemotherapy, and low counts managed with transfusion.

Two reviews for each of these conditions are listed below.

MDS review - NEJM
Myelofibrosis and NEJM