Decision Making for Older Patients with High-Risk MDS
- Background: A 72-year-old male was referred by his primary care physician (PCP) to a hematologist after he was found anemic by his PCP on annual physical. Because of macrocytosis, folate and B12 deficiency have been excluded by laboratory testing. Patient had recently undergone a colonoscopy without pathologic findings and 3 submitted stool guaiac cards were negative. In 2 serial exams 6 weeks apart, his anemia worsened and was accompanied by thrombocytopenia. PCP referred him to hematologist.
- Chief Complaint/Describe Presenting Characteristics: In hematologist’s office, patient reported being out of breath and having palpitations on exertion. His wife also noted his pallor but attributed it to winter. On more pointed questioning, the patient’s progressive lack of energy was noted by the patient for some time, but it was attributed by him to “getting old.”
- History: Patient has annual physical exam appointments and 1 year ago his blood counts were normal. Patient has diabetes and is currently on insulin regimen. Patient has also history of hypertension but has been always well controlled on 25 mg atenolol per day. He takes multivitamins and vitamin D. His thyroid studies were normal.
- Differential Diagnosis: The presence of reticulocytopenic anemia thrombocytopenia and mild neutropenia is suggestive of a generative bone marrow failure syndrome. The presence of hypogranulated and macrocytosis is highly suggestive of myelodysplastic syndrome (MDS). Given the age of the patient and the exclusion of most common nutritional deficiencies, MDS is the most likely diagnosis and makes the diagnosis of aplastic anemia less likely. Patient does not have any features of myeloproliferative neoplasm (MPN) or MDS/MPN overlap syndromes as these are associated with normo- or microcytic anemia, may have leukocytosis, leukoerythroblastic changes and splenomegaly, all the features absent in this patient. The absence of circulating blasts makes acute myelogenous leukemia (AML) unlikely. Of course, differential diagnosis includes secondary marrow failure due to disease affecting blood production such as lymphoma or myeloma. CBC was as follows:
- WBC 2.80 cells/L
- Hemoglobin 13.4 g/dL
- MCV 107.9 fL
- Platelet count 87,000/uL
- Neut% 43.9
- Lymph% 35.0
- Mono% 18.3
- Eosin% 2.5
- Baso% 0.3
- Abs Neut (ANC) 1290/uL
- Retic 0.1%
- Hypogranulated neutrophils
At this point patients was transfused 2U RBC and a bone marrow exam was performed confirming the diagnosis of MDS.
Mildly hypercellular marrow (approximately 50%) with trilineage hematopoiesis, granulocytic left-shift, 6% blasts and increased monocytes. Erythroid and myeloid series dysplastic, micromegakaryocytes.
- Initial Treatment Plan: Patient has advanced MDS with IPSS Int-2 [6% of blasts (score value 0.5), del7 (karyotype=poor, score value 1.0), severe anemia (two cytopenias: ANC and platelet count low, score value 0.5); Total score: 0.5+1.0+0.5=2.0, Intermediate-2]; he has symptomatic anemia and will likely become transfusion dependent. IPSS Int-2 and poor-risk cytogenetics (monosomy-7) suggest high chance of progression and need for treatment. Erythropoietin is not indicated in advanced MDS. Patient does not have sibling donor (his only brother is not alive) and following a bone marrow transplant consult, he elected not to pursue the transplant, a decision that is not unreasonable given the advanced age and comorbidities. Similarly, this patient is not candidate for intensive therapy. When the option of clinical trials was discussed, the patient indicated that he did not wish to participate at this time. According to the NCCN guidelines for MDS, the patient could receive either decitabine (NCCN, category 2A) or 5-Azacytidine (NCCN, preferred, category 1). A decision was made for 5-Azacytidine at 75mg/m2 sc. x 6days q4 weeks.
- Outcome of the case. Initial 2 cycles of 5-Azacytidine resulted in a transient worsening of thrombocytopenia and neutropenia but the therapy was continued through this complication and patient’s anemia eventually improved after 4 cycles of therapy. At that point MDS peripheral blood panel was performed showing 25% of cells with monosomy-7.
- Follow up: Because this patient achieved a hematologic improvement, the therapy with 5-Azacytidine was continued with additional 5 cycles of 5-Azacytidine administered. Patients with MDS who achieve response will invariably relapse without maintenance therapy and thus attempts should be made to continue the treatment as long as tolerated. He continued to have a mild neutropenia which worsened following each cycle. Patient reported having hard time (very tired) for around 10 days following each cycle and thus he requested ‘a break.’ The cycles were stretched out to every 6 weeks, a measure which improved the tolerance.
- Discussion and Summary: This is a typical patient with MDS who presented early with advanced disease as assessed by IPSS int-2 and who showed poor-risk cytogenetics and RAEB1. He also developed cytopenia, most significantly anemia, for which he already needed a transfusion. In such a scenario, therapy with hypomethylating agents is indicated, including either 5-Azacytidine or decitabine. The 5-day regimen of decitabine may produce more myelotoxicity and therefore 5-Azacytidine was selected. This patient showed an excellent hematologic response, but also a persistence of monosomy-7 by FISH suggested a high risk for relapse and lack of complete cytogenetic response. Therefore, maintenance therapy as long as possible and tolerated is needed to maintain a response. Periodic discussions regarding the clinical trials should be discussed with the patient.
Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89(6):2079-2088.