Page 1262 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 92: Acute Leukemia 869

TABLE 92-4 Common and Most Severe Side Effects from Chemotherapies Induction of Consolidation
a
Used in Treatment of Acute Leukemias (Continued) remission of remission Maintenance
(CR1)
Drug Selected Side Effects
ATRA Leukocytosis (during APL treatment)
Differentiation/retinoic acid syndrome
Pseudotumor cerebri No CR or
Transaminitis relapse
Birth defects if used during pregnancy
Arsenic trioxide Tachycardia
QT interval prolongation
Hypokalemia Induction of
Hyperglycemia Allo-SCT remission
Hypomagnesemia (CR2)
Nausea FIGURE 92-1. General framework for treatment of patients with acute leukemia.
Abdominal pain and diarrhea
Transaminitis
Neuropathy cells that survived induction chemotherapy. There are typically between
one to four cycles roughly 1 month apart. Maintenance therapy is often
Methotrexate Renal and hepatic clearance
Arachnoiditis (with IT administration) given on an outpatient basis and does not typically cause significant
protracted myelosuppression.
Acute neurologic syndrome
Much emphasis is placed on early determination of which individu-
Renal failure als with acute leukemia will benefit from allogeneic stem cell transplant
Pancytopenia
Mucositis (allo-SCT). Ideally the search for a stem cell donor begins once cyto-
genetics and molecular studies are completed as the process of donor
Hepatotoxicity
Nephrotoxicity qualification can take several weeks to a month. Factors in determin-
ing who should be referred for allogeneic SCT are patient, donor, and
Pneumonitis
disease specific. Overall performance status and comorbidities of the
Vincristine Hepatic clearance patient are important in determining who can survive and benefit from
CNS injury/neurotoxicity allo-SCT and what preparative regimens are available to the patient.
Constipation from enteric neuropathy Similarly, the benefit is more likely to outweigh the risk of graft-versus-
Hyperuricemia host disease (GVHD) the better the HLA-match between donor and
Pancytopenia recipient. The better the disease risk profile, the less likely a patient is to
Hepatic venoocclusive disease be referred for transplant. However, it is worth considering allogeneic
Allergic reaction SCT for patients with good risk disease other than APL in first CR if a
Imatinib Dose reduce with renal and hepatic dysfunction well-matched donor is available as the risk of relapse even for good-risk
Hepatotoxicity leukemia is still high.
Edema, including pericardial and pleural effusions
Rash DIAGNOSIS AND MANAGEMENT OF
Nausea and diarrhea ACUTE PROMYELOCYTIC LEUKEMIA
Neutropenia and thrombocytopenia
Dasatinib Pancytopenia The initial management of patients with AML is dependent on the
Edema (superficial) clinical scenario, age, and comorbidities of the patient, and there is some
Pleural effusion flexibility to tailor the induction regimen to the situation. However,
Cardiac dysfunction/CHF careful attention must be made for clues indicating that the subtype of
Rash AML is acute promyelocytic leukemia (APL). This subtype of AML is
Hypophosphatemia, hypokalemia, and hypocalcemia rapidly fatal if misdiagnosed and inappropriately managed, but unique
Diarrhea because if it is properly managed, there is a CR rate of 90% and cure rates
46,48
Hepatotoxicity of up to 80%. The risks facing the patient with APL include fatal CNS
and pulmonary hemorrhage, and effects of differentiation syndrome
a This is not an exhaustive list. The reader is referred to standard pharmacologic references for a more once ATRA therapy is initiated. The intensivist should also be on the
extensive list.
lookout for ATRA syndrome.
APL should be suspected based on the presence of promyelocytes
and in some cases by maintenance (Fig. 92-1). At any point, referral for in the peripheral blood. Patients with newly diagnosed APL typically
allogeneic SCT may be appropriate, although transplant during relapse present with pancytopenia, including leukopenia, and with severe DIC.
is currently only recommended within the context of a clinical trial, and Fibrinogen levels are typically low (<100 mg/dL), D-dimer will be posi-
once a patient has relapsed, the goal is to achieve a complete remission tive and PT and aPTT are increased. More so than for any other group
and rapidly move toward allogeneic SCT if the patient is likely able to of leukemia patients, those with APL tend to have extremely prominent
tolerate the intensive therapy and long-term sequelae. ecchymoses. Any procedure, including minor ones such as venipuncture
The goal of induction chemotherapy is to achieve a complete remis- and bone marrow aspirate and biopsy, is likely to result in protracted
sion (CR). This is defined as the absence of detectable leukemia in the bleeding from the puncture site. Placement of central lines and any other
blood or bone marrow (less than 5% blasts in the bone marrow), rees- more invasive procedures should be avoided until after the coagulopathy
tablishment of normal marrow elements, and normalization of all other has resolved. APL cells contain high levels of tissue factor and “cancer
blood counts for at least 1 month. Failure to achieve a CR is a poor prog- procoagulant” molecules which trigger fulminate DIC when they are
nostic indicator for all types of leukemia. Consolidation chemotherapy released into circulation. The Annexin II receptor is also expressed
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is myelosuppressive therapy designed to eliminate any residual leukemic on the surface of APL cells, and is an activating receptor for tissue-type

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