Chapter 104. Acute and Chronic Myeloid Leukemia (Part 8)

The hematologic toxicity of high-dose cytarabine-based induction regimens has typically been greater than that associated with 7 and 3 regimens. Toxicity with high-dose cytarabine includes myelosuppression, pulmonary toxicity, and significant and occasionally irreversible cerebellar toxicity. All patients treated with high-dose cytarabine must be closely monitored for cerebellar toxicity. Full cerebellar testing should be performed before each dose, and further high-dose cytarabine should be withheld if evidence of cerebellar toxicity develops. This toxicity occurs more commonly in patients with renal impairment and in those over age 60. The increased toxicity observed with high-dose cytarabine has limited the use of this...
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Chapter 104. Acute and Chronic Myeloid Leukemia (Part 8) Chapter 104. Acute and Chronic Myeloid Leukemia (Part 8) The hematologic toxicity of high-dose cytarabine-based induction regimenshas typically been greater than that associated with 7 and 3 regimens. Toxicitywith high-dose cytarabine includes myelosuppression, pulmonary toxicity, andsignificant and occasionally irreversible cerebellar toxicity. All patients treatedwith high-dose cytarabine must be closely monitored for cerebellar toxicity. Fullcerebellar testing should be performed before each dose, and further high-dosecytarabine should be withheld if evidence of cerebellar toxicity develops. Thistoxicity occurs more commonly in patients with renal impairment and in thoseover age 60. The increased toxicity observed with high-dose cytarabine has limitedthe use of this therapy in elderly AML patients. Supportive Care Measures geared to supporting patients through several weeks ofgranulocytopenia and thrombocytopenia are critical to the success of AMLtherapy. Patients with AML should be treated in centers expert in providingsupportive measures. Recombinant hematopoietic growth factors have been incorporated intoclinical trials in AML. These trials have been designed to lower the infection rateafter chemotherapy. Both G-CSF and granulocyte-macrophage colony-stimulatingfactor (GM-CSF) have reduced the median time to neutrophil recovery by anaverage of 5–7 days. This accelerated rate of neutrophil recovery, however, hasnot generally translated into significant reductions in infection rates or shortenedhospitalizations. In most randomized studies, both G-CSF and GM-CSF havefailed to improve the CR rate, disease-free survival, or overall survival. Althoughreceptors for both G-CSF and GM-CSF are present on AML blasts, therapeuticefficacy is neither enhanced nor inhibited by these agents. The use of growthfactors as supportive care for AML patients is controversial. We favor their use inelderly patients with complicated courses, those receiving intensive postremissionregimens, patients with uncontrolled infections, or those participating in clinicaltrials. Multilumen right atrial catheters should be inserted as soon as patients withnewly diagnosed AML have been stabilized. They should be used thereafter foradministration of intravenous medications and transfusions, as well as for blooddrawing. Antibiotic-impregnated catheters should be considered if the risk of line-related infection is high. Adequate and prompt blood bank support is critical to therapy of AML.Platelet transfusions should be given as needed to maintain a platelet count>10,000–20,000/µL. We believe that the platelet count should be kept at higherlevels in febrile patients and during episodes of active bleeding or DIC. Patientswith poor posttransfusion platelet count increments may benefit fromadministration of platelets from human leukocyte antigen (HLA)-matched donors.RBC transfusions should be administered to keep the hemoglobin level >80 g/L (8g/dL) in the absence of active bleeding, DIC, or congestive heart failure. Bloodproducts leukodepleted by filtration should be used to avert or delayalloimmunization as well as febrile reactions. Blood products should also beirradiated to prevent transfusion associated graft-versus-host disease (GVHD).Cytomegalovirus (CMV)-negative blood products should be used for CMV-seronegative patients who are potential candidates for allogeneic SCT.Leukodepleted products are also effective for these patients if CMV-negativeproducts are not available. Infectious complications remain the major cause of morbidity and deathduring induction and postremission chemotherapy for AML. Prophylacticadministration of antibiotics in the absence of fever is controversial. Oral nystatinor clotrimazole is recommended to prevent localized candidiasis. For patients whoare herpes simplex virus antibody titer–positive, acyclovir prophylaxis is effectivein preventing reactivation of latent oral herpes infections. Fever develops in most patients with AML, but infections are documentedin only half of febrile patients. Early initiation of empirical broad-spectrumantibacterial and antifungal antibiotics has significantly reduced the number ofpatients dying of infectious complications (Chap. 82). An antibiotic regimenadequate to treat gram-negative organisms should be instituted at the onset offever in a granulocytopenic patient after clinical evaluation, including a detailedphysical examination with inspection of the indwelling catheter exit site and aperirectal examination, as well as procurement of cultures and radiographs aimedat documenting the source of fever. Specific antibiotic regi ...