Pharmacy Program

Delivering Integrated Care and Cost Management

The IHTC works collaboratively with payors to optimize care. We ensure that the patients and families we serve have access to care and therapies, thereby helping to contain costs and reduce both bleeding events and utilization of resources.

The IHTC Pharmacy’s ability to purchase clotting factor through the Public Health Service 340B discount program and our overall pricing structure benefit payors and patients by dispensing clotting factor at significantly reduced prices.

Myelodysplastic Syndrome

Myelodysplastic syndromes (MDS) is a collection of disorders in which the bone marrow does not properly produce enough blood cells.  Normally the bone marrow produces three major types of blood cells: red blood cells (carry oxygen), white blood cells (help fight infection), and platelets (component of clotting).  MDS is further defined as a neoplastic disease or malignancy of heterogeneous clonal hematopoietic stem cell disorders grouped together because of the presence of the dysplastic changes in one or more of the cell lineages.  Resulting in peripheral cytopenias in combination with hypercellular bone marrow (after correction for age) exhibiting dysplastic changes which are the hallmarks of the disease.  The mean age is 68 years with a slight male preponderance.  MDS is one of the most common causes of peripheral cytopenias among the elderly and patients with preexisting bone marrow injury.

Occupational/Environmental Exposures
Risk for development of MDS has been linked to the following: smoking, benzene, organic chemicals, heavy metals, herbicides, pesticides, fertilizers, and petroleum and diesel derivatives.  Other predisposing factors include prior therapy with chloramphenical, radiation, and chemotherapeutic agents such as melphalan, chlorambucil, cycylophosphamide, or procarbazine.

MDS falls into groups based on features of bone marrow morphology and the proportion of the numbers of myeloblasts.  These categories have prognostic significance.  The categories classification below is defined by the World Health Organization (WHO).  The evolution into Acute Myeloid Leukemia (AML) is defined by WHO as the presence of > 20% m>

Refractory Anemia (RA) Anemia (no blasts)

<5% bp>

<15% reroblasts

RA with ringed Anemia (no blasts) Anemia (no blasts)


<15% eringed sideroblasts

RA with excess blasts – 1 (RAEB-1)


Absense of Auer Rods

5-9% b

<5% b

RA with excess blasts – 2 (RAEB-2)


Auer Rods may be present

<1000/uL monocytes

10-19% b <5% b;

MDS unclassified ( MDS -U)


no blasts

Absense of Auer Rod

Dysplasia in granulocytes

or megakaryocytes

<5% b

MDS with isolate del(5q)


Absense of Auer Rods

Normal or increased megakaryocyte number

del(5q) as the only

Clinical manifestations and syndromes
Anemia and fatigue are present in nearly all of the patients; however, patients can be asymptomatic at diagnosis.  Pallor, easy bruising, bleeding, infections with bacterial infection as the principal cause of death, mouth sores, fever.  Very rare, Sweet Syndrome, is a cutaneous form of MDS and heralds acute leukemia transformation.

Thrombocytopenia is a common feature of MDS.  Mild thrombocytopenia with macrocytosis with or without anemia and neutropenia in an older patient is usual.  Platelets produced by the bone marrow in patients with MDS mature abnormally.  Bleeding in patients with myelodysplasia is almost always due to thrombocytopenia or intrinsic platelet dysfunction.  Platelets vary in size, shape, and granulation.  There are also abnormalities in platelet aggregation.  Thrombocytopenia or platelet dysfunction occasionally precedes diagnostic changes in myeloid cells and can provide a clue to the correct diagnosis.

5q syndrome (deletion of chromosome 5q or monosomy 7 in cytogenetic testing) is characterized by progression to overt leukemia in 25% osp; There is a marked predominance of cases in women (up to 70%).; Red cell transfusion is primary treatment.

Childhood MDS is uncommon, but when it does occur the clinical manifestation is similar to that of adults. Median age of onset is 6 years.  Down syndrome is present in one-third of the pediatric patients.

MDS with Bone Marrow Fibrosis shows a substantial amount of reticulin fibers in the marrow but can be differentiated from the myelofibrosis by the presence of trilineage dysplasia and absence of hepatosplenomegaly.

Chronic Myelomonocytic leukemia (CMML) is characterized by a monocyte count of >1×109 with prominent splenomegaly, and skin or visceral infiltration at diagnosis or that develops during the course of the disease.

Iatrogenic (therapy-related) myelodysplasia can occur when exposed to myelotoxic agents and radiation and increases the risk of acute myeloid leukemia.  Development is typically 4-7 years after treatment and carries a poor prognosis.  Prior splenectomy also increases the risk for developing MDS.
Diagnosis-relies on morphologic findings in a patient with clinical evidence of impaired hematopoiesis as manifested by anemia, neutropenia, thrombocytopenia, or a combination of cytopenias.  CBC reveals macrocytosis and low reticulocyte count.  On peripheral smear, there may be oval macroctyic red cells, hypogranular granulocytes with pseudo-Pelger-Huet anomaly (neutrophils with only two nuclear lobes), and giant platelets.  Bone Marrow biopsy is needed for diagnosis and reveals normal or increased cellularity.  Abnormalities include megaloblastic red cell precursors with multiple nuclei or asynchronous maturation of the nucleus and the cytoplasm.  Ringed sideroblast—erythroid precursors with iron-laden mitochondria are occasionally identified.  There is often a predominance of immature myeloid cells and granulocytic precursors showing asynchronous maturation of the nucleus and cytoplasm.  Mature granulocytes are often hypogranular and hypovulated.  Megakaryocytes may have few nuclear lobes and are often small.

Standard of care is generally accepted to be supportive.  Patients with an indolent course make up the majority of cases and may have a long asymptomatic survival.  Rarely, some patients with a poor prognosis may have a survival of <1yr, similar to patients with AML.

Supportive therapy involves blood transfusions when symptoms develop and if frequency of transfusions increase to 1-2 every month, a trial of vitamins, androgens, or erythropoietin alone or in combination with immunomodulatory therapy may be indicated.  Transfuse platelets when <10,000 or if the patient experiences bleeding or upcoming surgery is required.  Granulocyte colony-stimulating factors or granulocyte-macrophage colony-stimulating factor has improved neutropenia but is historically not effective.

Low-dose cytarabine has been used and has a response rate of 10-15%, val is not improved.  AML-like regimens typically have a remission rate of 40-60%, 20-40%.&mp;mp;mp;mp;mp;mp;mp;mp;mp;mp;mp;mp;bsp; Patients most likely to benefit from AML-like regimens are younger than 50 years, have normal karyotype, and refractory anemia with excess blast transformation.  Ara-C plus doxorubicin are most commonly used.  Novel agents such as topotecan can be used and have a role in poor prognosis patients (older with poor cytogenetics).

Bone Marrow Transplantation
Allogeneic stem cell transplantation is the only hope for cure in a small subset of patients.  The restrictions: < 50 years with HLA-matched donors and comorbities.  Mortality rate is 40% a-free period is estimated at 45% a/>
Among age-comparable groups, 3 year complete response and survival rates were similar with intensive chemotherapy vs. allogeneic stem cell transplant.  Therefore treatment is largely supportive.

Evolution to AML occurs in 10-50% o MDS.  In RAEB, the rate is 20-55%.&mp;mp;mp;mp;mp;mp;mp;mp;mp;mp;mp;mp;bsp; In RARS 0-29%.&mp;mp;mp;mp;mp;mp;mp;mp;mp;mp;mp;mp;bsp; RAEB has a median survival of 5-12 months where as RARS has a median survival of 3-6 years.  Prognosis can be roughly gauged by the International Prognostic Scoring System for MDS.

International Prognostic Scoring System by MDS Risk Level

0 <5% Good 0 or 1
0.5 5-10% Intermediate 2 or 3
1.0 Poor 2 or 3
1.5 11-20%
2.0 21-30%


Low (0) 5.7
Intermediate-1 (0.5-1.0) 3.5
Intermediate-2 (1.5-2.0) 1.2
High (>2.5) 0.4



The Washington Manual, Subspecialty Consult Series: Hematology and Oncology Subspecialty Consult; Lippincott, Williams, & Wilkins, 2004.

Bethesda, Handbook of Clinical Hematology; Rodgers, Griffin, Young, Neal, 2005.

Disorders of Hemostasis & Thrombosis, Second Edition; Goodnight, Scott, Jr., Hathaway, William, 2001.

The Myelodysplastic Syndromes: A Review for Patients, Families, Friends, and Healthcare Professionals; Bennett, M.D., University of Rochester Cancer Center,

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