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1356 Part X: Malignant Myeloid Diseases Chapter 87: Myelodysplastic Syndromes 1357

decisions. Patients with TP53 mutations may comprise a special group, higher levels if the patient is actively bleeding. Antifibrinolytic agents,
as they have such a poor outlook with conventional therapies that either such as aminocaproic acid or tranexamic acid, can be used in patients
clinical trial enrollment or palliative care may be most appropriate for who have mucosal bleeding despite platelet transfusion or to decrease
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individuals with a TP53 mutant genotype. 315,316 the need of platelet transfusions. This strategy is especially effective in
The calculated prognostic score should not be the sole guide to patients with urinary bleeding or bleeding from arteriovenous malfor-
treatment of a patient, as many patients deviate from the average expec- mations of the gut.
tation of disease behavior. The prognostic scores are based on the aver-
age behavior of large numbers of patients without confidence intervals Antimicrobial Agents
to show the degree of variation, which is substantial. Unexpected pro- Febrile events are common in higher-risk syndromes because of the fre-
gression or evolution of disease may also necessitate changes in treat- quency of moderately severe neutropenia and functional disorders of
ment approach, and patients’ comorbid conditions may preclude use of neutrophils and monocytes. Also, chemotherapy is more likely to be used
specific therapies (e.g., renal failure requires dose adjustment or avoid- in these situations, inducing severe neutropenia. Appropriate cultures
ance of lenalidomide). There is also uncertainty among clinical investi- and use of broad-spectrum antibiotics until and if a specific organism
gators about the optimal therapeutic approach in many situations, such is found is important, with subsequent therapy tailored to microbio-
as for IPSS lower-risk patients with severe cytopenias other than ane- logic data. Chapter 24 discusses an approach to febrile neutropenia. The
mia, anemic IPSS lower-risk patients without del(5q) and with a serum use of prophylactic antimicrobial agents in neutropenic patients is of
erythropoietin level greater than 500 U/L, and IPSS higher-risk patients uncertain usefulness in MDS, but may help prevent infections in those
who are not transplant candidates and for whom azacitidine and decit- who have had previous problems with recurrent infection. In this
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abine have failed. 317 setting, levofloxacin and acyclovir are the best studied. Prophylactic
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Measurement of treatment response in a clinical trial usually antifungal agents are used more frequently in AML patients, and some
involves comparison to the 2006 International Working Group (IWG) guidelines recommend posaconazole or voriconazole in MDS patients
response criteria. Although IWG response criteria focus on improve- who have prolonged neutropenia and are at increased risk for fungal
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ments in specific measurable and objective variables such as hemoglo- infections or who are undergoing induction chemotherapy. 336–339
bin level, the number of abnormal metaphases on karyotyping, and
marrow blast proportion, surveys have shown that what matters most Erythropoiesis-Stimulating Agents
to patients is decreased symptoms, 319,320 improved quality of life, 321–323 RBC transfusion dependency negatively influences clinical outcomes
avoidance of hospitalization and extended survival, which overlap with in MDS. RBC transfusion dependence is a marker of more severe
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but are not identical to numerical disease measurements. Economic marrow failure, increased risk of transformation to AML, and increased
considerations also determine clinical care patterns, and the high cost iron overload from repetitive transfusions. Less-well-defined immuno-
of MDS care is a burden for many patients. 324 modulatory effects of transfusions may contribute to poor outcomes.
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In contrast, some studies found that neither the serum ferritin nor the
THERAPEUTIC APPROACHES TO PATIENTS number of RBC transfusions were associated with survival in clonal
342,343
WITH LOWER-RISK DISEASE sideroblastic anemia.
Erythropoiesis-stimulating agents (ESAs), such as recombi-
All patients, regardless of risk score, deserve “best supportive care.” Sup- nant human erythropoietin analogues, can be used to treat anemia
portive care consists of improving quality of life by treatment of cytope- in patients who are transfusion-dependent, if the serum erythropoi-
nias or their complications (e.g., dyspnea, bleeding, infection) and etin level is lower than optimal for the hemoglobin level. Responses
providing ongoing psychosocial support, while monitoring the patient’s are best in patients with low serum erythropoietin levels, normal
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clinical status at intervals. The inclusion of palliative care can be very blast counts, lower IPSS scores, normal cytogenetics, lower levels
325
345
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helpful to many patients, especially those at higher-risk and does not of inflammatory cytokines, absence of aberrant marker expression
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imply the cessation of treatment. Counseling by experienced palliative by flow cytometry, and in patients who do not require regular RBC
care physicians can provide patients with important support in their transfusions. 309,347 Hemolysis and deficiencies of iron, vitamin B , or
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understanding of the best ways to manage their disabilities and to make folate should be excluded as a cause of anemia before ESA therapy is
therapeutic decisions. started. Iron stores should be kept replete during ESA therapy. 348,349
Epoetin alfa at a dose of 150 to 300 U/kg per day three times per
Red Cell Transfusion week or single weekly doses of 40,000 to 60,000 U are effective. 350–362
Red blood cell (RBC) transfusions should be administered for symp- There is no increase in response with doses exceeding 60,000 U
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tomatic anemia. Often patients will tolerate hemoglobin levels lower weekly. In clinical practice, weekly epoetin is more commonly admin-
than 8 g/dL, but the level at which symptoms develop varies from istered than three times per week, a dosing schedule that was developed
patient to patient. Higher thresholds have been suggested to prevent in the hemodialysis setting. Darbepoetin alfa in various schedules of
cardiac consequences of prolonged anemia, 326,327 while lower thresholds administration (e.g., 500 mcg fixed dose once every 3 weeks) has also
have been recommended based on superior outcomes with restrictive been found effective in increasing hemoglobin levels and in enhancing
RBC transfusion strategies in inpatient populations 328–330 and the need quality of life. 363,364 Meta-analysis has confirmed erythropoietic response
to preserve the blood supply. Patients with MDS may receive hundreds rates are similar for those treated either with epoetin alfa or with the
of units of RBCs over the course of their illness. 331,332 longer-acting darbepoetin alfa. 365
The probability of a response to ESA therapy increases modestly
Platelet Transfusion with duration of therapy, but from a practical standpoint it is difficult to
Thrombocytopenia is common in MDS and has a higher prevalence obtain reimbursement to continue patients on ESA treatment beyond
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in higher-risk IPSS categories. Furthermore, many therapies used in 12 weeks in the absence of an objective response. Unlike in patients
MDS may worsen thrombocytopenia. Hemorrhage is the second most with solid tumors or renal failure, there is no evidence that ESAs
common cause of death in patients with MDS. Platelet transfusions increase thromboembolic disease or accelerate progress to leukemia,
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may be required if the platelet count falls below 10 × 10 cells/L or at but followup in studies to date have been short. Several series have
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