The following cases and commentary, which address hematology/oncology, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP15).
Case 1: New symptoms in a patient with chronic lymphocytic leukemia
A 72-year-old man is hospitalized because of dyspnea, anginal chest pain and new-onset anemia. Chronic lymphocytic leukemia was diagnosed two years ago. He has not received specific therapy and has never required a blood transfusion.
On physical examination, the patient appears pale. Blood pressure is 110/80 mm Hg, pulse rate is 112/min, and respiration rate is 24/min. Diffuse cervical, axillary and inguinal lymphadenopathy is present. There is no jugular venous distention. The lungs are clear. Abdominal examination reveals splenomegaly. There is no peripheral edema.
Laboratory studies reveal the following: hemoglobin level, 6.0 g/dL (60 g/L); leukocyte count, 55,000 cells/µL (55 × 109 cells/L) with 90% lymphocytes; platelet count, 115,000 cells/µL (115 × 109 cells/L); reticulocyte count, 12% of erythrocytes; total bilirubin level, 2.8 mg/dL (47.9 µmol/L); direct bilirubin level, 0.6 mg/dL (10.26 µmol/L); direct antiglobulin, positive for IgG (Coombs test); and ABO/Rh blood type, A positive.
A peripheral blood smear shows microspherocytes.
Corticosteroid therapy is begun, and a cross-match for two units of packed erythrocytes is ordered. However, no compatible units are available in the blood bank.
Which of the following is the most appropriate management at this time?
A. Begin erythropoietin.
B. Schedule splenectomy.
C. Transfuse one unit of A-positive packed erythrocytes.
D. Transfuse one unit of O-negative packed erythrocytes.
E. Withhold transfusion until a compatible unit of blood is available.
Case 2: Abrupt onset of left upper-extremity weakness
A 63-year-old woman is evaluated in the emergency department after the abrupt onset of left upper-extremity weakness. The patient does not report any weight loss, headache, nausea, or vomiting. Until today, she has been active and able to completely care for herself.
Medical history is significant for stage IIB non-small-cell lung cancer (characterized by involvement of three of six peribronchial lymph nodes) diagnosed one year ago, for which she underwent right upper lobectomy followed by adjuvant cisplatin and vinorelbine chemotherapy. Mediastinoscopy results at the time were negative, and positron emission tomography showed no metastatic disease.
On physical examination, temperature is normal, blood pressure is 158/98 mm Hg, pulse rate is 96/min, and respiration rate is 22/min; BMI is 19. Cardiopulmonary examination is unremarkable. The patient is right-handed. Neurologic examination shows weakness of the left arm with hyperreflexia of the brachioradialis stretch reflex. Mental status, speech, visual fields and gait are normal.
Results of the complete blood count are normal. An MRI of the brain demonstrates a right parietal lesion measuring 1.5 cm, with evidence of significant edema. Further evaluation reveals no other evidence of extracranial disease.
Dexamethasone is initiated.
Which of the following is the most appropriate next step in management?
A. Best supportive care.
B. Initiation of erlotinib.
C. Initiation of temozolomide followed by radiation therapy.
D. Surgical resection of metastasis.
Answers and commentary
Correct answer: C. Transfuse one unit of A-positive packed erythrocytes.
This patient with symptomatic anemia has severe autoimmune hemolytic anemia secondary to chronic lymphocytic leukemia (CLL) confirmed by positive direct antiglobulin (Coombs) test results and the peripheral blood smear showing microspherocytes. In the absence of pregnancy and previous blood transfusions, the likelihood of alloimmunization to erythrocyte antigens is extremely low.
Because of the broad specificity of autoantibodies in patients with autoimmune hemolytic anemia, most donor erythrocytes will be incompatible on cross-match. In this situation, transfusion of ABO-/Rh-specific, but otherwise incompatible, blood is necessary and can be life-saving. The transfused donor erythrocytes will survive as long as the patient's own erythrocytes and will provide oxygen-carrying capacity until definitive therapy, such as corticosteroids, becomes effective.
Erythropoietin is not indicated in patients with an appropriate reticulocyte response.
Splenectomy may be used to treat idiopathic autoimmune hemolytic anemia in a patient who does not respond to corticosteroid therapy. However, surgery is rarely indicated for patients with autoimmune hemolytic anemia secondary to CLL because therapy for the leukemia also treats the anemia.
Transfusion of O-negative (“universal”) blood is generally reserved for emergency situations in which the patient's ABO/Rh type is not known.
- Because severe autoimmune hemolytic anemia can be life-threatening, an incompatible blood transfusion should not be withheld in a patient with this disorder.
Correct answer: D. Surgical resection of metastasis.
This patient likely has recurrent non-small-cell lung cancer with a solitary, surgically accessible metastasis to the brain, and surgical resection of the metastasis is the most appropriate next step in management. Patients with good performance status and a surgically accessible single (or few) metastatic lesion(s) to the brain and minimal or no evidence of extracranial disease are most likely to benefit from surgical intervention. Surgical resection of this patient's brain metastasis is required for quick symptomatic relief, to control progression of brain metastases, and to provide histologic confirmation of metastasis. This approach is now appropriate for a wider range of patients with brain metastases owing to the improved safety associated with neuroanesthesia and the procedure itself.
Following surgery, this patient may also receive radiation therapy to the lesion, either with external-beam radiation or stereotactic surgery. Although combined-modality treatment with radiation therapy does not prolong survival compared with surgery alone, it does reduce the incidence of recurrent disease and the need for repeated therapy. Retrospective series have suggested that some patients without evidence of other systemic disease have prolonged survival following resection of brain metastases.
Highly chemosensitive cancers, such as metastatic testicular germ-cell tumors and central nervous system lymphoma, will respond to chemotherapy alone. However, non-small-cell lung cancer does not respond well to chemotherapy. Because this patient is symptomatic, she should not receive chemotherapy with erlotinib alone but should undergo surgical resection.
Temozolomide is an alkylating agent used in the treatment of primary and metastatic brain tumors. The combination of temozolomide followed by whole-brain radiation therapy may prove to be more effective than radiation alone in the treatment of metastatic tumors and is currently undergoing evaluation in clinical studies. However, radiation therapy is generally reserved for patients with surgically inaccessible tumors or tumors that are not otherwise appropriate for surgical resection and is not the best therapy for this patient.
Best supportive care (comfort care without chemotherapy or surgery) is not appropriate for this patient because of her previously intact performance status and evidence of a surgically accessible solitary site of recurrence, both of which make her eligible for surgical resection and its potentially positive impact on symptoms, metastatic progression and survival.
- Surgical excision of a solitary brain metastasis should be considered for patients with good performance status, minimal or no evidence of extracranial disease, and a surgically accessible, single brain metastasis amenable to complete excision.