A 62-year-old male with a history of acute myeloid leukemia and allogeneic hematopoietic stem cell transplantation (HSCT) 2 months ago presents with cough, dyspnea on exertion, and fevers for 1 week. On examination, his temperature was 100.9°F, heart rate 100 beats/min, respiratory rate 20 breaths/min, and blood pressure 120/80 mm Hg. He appeared chronically ill with bibasilar crackles on auscultation. His white blood cell count was 3400 cells/µL and his chest radiograph showed bilateral lower lobe infiltrates.
Differential diagnosis includes all of the following EXCEPT:
Correct Answer: A
Allogeneic HSCT is used to treat a variety of hematologic malignancies and nonmalignant disorders. Pulmonary complications occur in up to onethird of patients after HSCT and may be either infectious or noninfectious. The types of complications also vary based on the time after HCST.
Pulmonary complications associated with the preengraftment phase (<30 days after HSCT) can occur because of neutropenia, mucositis, cardiotoxic effects of medications, and copious fluid administration. These include bacteria, viral, and fungal pneumonia. Patients are also at increased risk for aspiration as mucositis from the conditioning regimen can lead to swallowing difficulties. Pulmonary edema may occur due to cardiac dysfunction (from chemotherapy or chest irradiation) or be of noncardiac origin (sepsis, aspiration, viral infection, hyperacute graft-versus-host disease). Periengraftment respiratory distress syndrome typically develops 7 to 11 days after HSCT and is characterized by fever, rash, noncardiogenic pulmonary edema, and hypoxemia. It is more frequently seen in autologous HSCT and is believed to be due to diffuse capillary leakage associated with the release of cytokines and influx of neutrophils into the lungs with engraftment. Treatment is supportive though consideration should be given to using high-dose corticosteroids in symptomatic patients.
In the immediate postengraftment phase (30-100 days after HSCT), cellular immunity is impaired. Patients continue to be at risk for bacterial, fungal, and viral infections. The median onset time of Aspergillus infection is 100 days post HSCT. Infection with Pneumocystis jirovecii should be suspected in patients with a lapse in their prophylaxis. Diffuse alveolar hemorrhage (DAH) and idiopathic pneumonia syndrome (IPS) are two causes of respiratory failure after HSCT that should be considered once infection is ruled out. Chemotherapeutic agents (eg, busulfan, cyclophosphamide, sirolimus) and radiation used for preparative conditioning can cause lung toxicity and injury. Acute radiation pneumonitis can develop 4 to 12 weeks after chest or whole-body radiation. Late or fibrotic radiation pneumonitis can develop 6 to 12 months after radiation.
Late pulmonary complications are those that occur >100 days post HSCT. Humoral and cellular immunity are impaired. Patients are at risk for infection with encapsulated bacteria (Haemophilus influenzae, Streptococcus pneumoniae) as well as Nocardia, Legionella, and Actinomyces. The risk of cytomegalovirus (CMV) pneumonitis is highest in CMVseropositive recipients with seronegative donors. Late noninfectious pulmonary complications include bronchiolitis obliterans, cryptogenic organizing pneumonia, and posttransplant lymphoproliferative disorder.
A 67-year-old male who presented with severe back pain and bilateral lower extremity weakness is admitted to the intensive care unit after emergent surgical spinal decompression and fixation. Bone marrow biopsy shows >10% clonal plasma cells.
Other criteria for the diagnosis of multiple myeloma include all the following EXCEPT:
Correct Answer: C
Multiple myeloma is a neoplasm of plasma cells resulting in a monoclonal immunoglobulin. It is distinguished from premalignant forms, monoclonal gammopathy of undetermined significance (MGUS), and smoldering multiple myeloma (SMM), by the presence of certain clinical features. Clinical symptoms of multiple myeloma result from the infiltration of plasma cells into bone or other organs or kidney damage from excess light chains.
To make the diagnosis of multiple myeloma (see Table below for diagnostic criteria for multiple myeloma), a bone marrow biopsy or aspirate must show >10% clonal plasma cells or biopsy-proven plasmacytoma plus presence of organ or tissue damage related to the plasma cell proliferative disorder. The myeloma-defining clinical features are hypercalcemia, renal failure, anemia, and bone lesions (CRAB).
Diagnostic Criteria for Multiple Myeloma:
In 2014, the International Myeloma Working Group updated the diagnostic criteria for multiple myeloma with three biomarkers to identify those patients who are at imminent risk of progression of their malignancy to intervene prior to the development of end-organ damage. The biomarkers are:
A 73-year-old male with a history of multiple myeloma presents with symptoms of nausea, abdominal pain, and lethargy. His serum calcium is 15 mg/dL.
Which of the following statements about the management of hypercalcemia is FALSE?
Correct Answer: B
Hypercalcemia is one of the myeloma-defining events and is caused by the osteolytic tumor lesions. Symptoms of hypercalcemia include nausea, vomiting, weakness, abdominal pain, constipation, confusion. Severe hypercalcemia (defined at serum calcium >14 mg/dL) can result in cardiac arrhythmias and coma.
Treatment of hypercalcemia includes hydration with isotonic saline with possible use of loop diuretics to both augment excretion of calcium as well as inhibit calcium reabsorption in the thick ascending limb. Calcitonin decreases bone resorption and works within 4 to 6 hours to lower calcium levels. However, because of tachyphylaxis, its efficacy is limited to about 48 hours. Bisphosphonates also decrease bone resorption by inhibiting osteoclasts but its onset of action is 24 to 72 hours. Zoledronic acid or pamidronate are can be given intravenously and are recommended for hypercalcemia due to malignancy. Oral third-generation bisphosphonates such as risedronate and alendronate are not recommended for the treatment of severe or acute hypercalcemia. Denosumab is a monoclonal antibody that inhibits RANKL and decreases osteoclast activity. It is recommended for the treatment of hypercalcemia in patients who do not respond to bisphosphonates. Unlike bisphosphonates, it is not cleared by the kidney and can be used in patients with kidney disease. Its onset of action is 4 to 10 days. Hemodialysis may be needed in patients with severe hypercalcemia and neurologic symptoms (eg, coma) or in patients with renal failure or heart failure who cannot tolerate aggressive volume expansion.
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