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Diffuse Alveolar Hemorrhage in Acute Myeloid Leukemia Sowmya Nanjappa, MBBS, MD, Daniel K

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Diffuse Alveolar Hemorrhage in Acute Myeloid Leukemia Sowmya Nanjappa, MBBS, MD, Daniel K Case Series Diffuse Alveolar Hemorrhage in Acute Myeloid Leukemia Sowmya Nanjappa, MBBS, MD, Daniel K. Jeong, MD, Manjunath Muddaraju, MD, Katherine Jeong, MD, Eboné D. Hill, MD, and John N. Greene, MD Summary: Diffuse alveolar hemorrhage is a potentially fatal pulmonary disease syndrome that affects individuals with hematological and nonhematological malignancies. The range of inciting factors is wide for this syndrome and includes thrombocytopenia, underlying infection, coagulopathy, and the frequent use of anticoagulants, given the high incidence of venous thrombosis in this population. Dyspnea, fever, and cough are commonly pre- senting symptoms. However, clinical manifestations can be variable. Obvious bleeding (hemoptysis) is not always present and can pose a potential diagnostic challenge. Without prompt treatment, hypoxia that rapidly progresses to respiratory failure can occur. Diagnosis is primarily based on radiological and bronchoscopic findings. This syndrome is especially common in patients with hematological malignancies, given an even greater propensity for thrombocytopenia as a result of bone marrow suppression as well as the often prolonged immunosuppression in this patient population. The syndrome also has an increased incidence in individuals with hematological malignancies who have received a bone marrow transplant. We present a case series of 5 patients with acute myeloid leukemia presenting with diffuse alveolar hemorrhage at our institution. A comparison of clinical manifestations, radio- graphic findings, treatment course, and outcomes are described. A review of the literature and general overview of the diagnostic evaluation, differential diagnoses, pathophysiology, and treatment of this syndrome are discussed. Introduction 5 patients. The median patient age was 57 years (range, Diffuse alveolar hemorrhage (DAH) is a potentially fa- 51–70 years). Three (60%) patients were women. No tal pulmonary disease that affects individuals with can- congruity was observed on the AML subtype diag- cer and hematological/nonhematological malignan- nosed by pathology. Two (40%) patients had received cies. Clinicians caring for patients with acute myeloid allogeneic hematopoietic stem cell transplantation leukemia (AML) must maintain a high index of sus- (HSCT) with matched unrelated donors in the year picion for DAH, because these patients are immuno- prior to developing DAH, whereas the other 3 patients compromised by their underlying disease process and were receiving induction chemotherapy (7 days stan- subsequently at increased risk because they typically dard-dose cytarabine plus 3 days of daunorubicin). receive treatment with immunosuppressive agents and The 2 patients who received HSCT had prior pulmo- stem cell transplantation. Here we present a case series nary function tests available, with results revealing de- of 5 patients with AML who developed DAH. We also creased diffusing lung capacity for carbon monoxide review the clinical presentation, diagnostic evaluation, of below 80%. Three patients had a history of a prior differential diagnosis, and therapeutic management of or underlying pulmonary disorder, including 1 patient this potentially life-threatening clinical syndrome. with a history of left lower lobe resection, 1 patient with a history of chronic obstructive pulmonary dis- Case Series ease, and 2 patients with a history of cryptogenic-or- Table 1 summarizes the clinical characteristics for the ganizing pneumonia. One patient had a history of an unknown autoimmune disorder affecting his ear. Each patient’s clinical presentation was different. From the Departments of Internal Medicine (SN, KJ, EDH), Radi- One patient presented with fever at the time of diag- ology (DKJ), and Infectious Diseases (JNG), H. Lee Moffitt Cancer Center & Research Institute, Department of Oncologic Sciences nosis of DAH (by bronchoscopy). Four patients devel- (SN, DKJ, EDH), University of South Florida Morsani College of oped hypoxia with increasing oxygen requirements Medicine, Tampa, Florida, and the Department of Critical Care and dyspnea. Three patients complained of cough, and Medicine (MM), SSM St Mary’s Health Center, St Louis, Missouri. 2 patients presented with bleeding at other sites in the Address correspondence to Sowmya Nanjappa, MBBS, MD, and John N. Greene, MD, Moffitt Cancer Center, 12902 Magnolia Drive, form of epistaxis. One patient had hemoptysis and that Tampa, FL 33612. E-mails: [email protected] and patient was neither hypoxic nor dyspneic at the time. [email protected] All patients were thrombocytopenic and anemic. Submitted February 17, 2016; accepted March 4, 2016. On radiological imaging, all 5 patients had bilateral, No significant relationships exist between the authors and the com- panies/organizations whose products or services may be referenced ground-glass pulmonary opacities on computed tomog- in this article. raphy (CT). In 3 patients, the findings of bronchoalveo- 272 Cancer Control July 2016, Vol. 23, No. 3 lar lavage (BAL) on bronchoscopy confirmed the diag- tor VII. Three patients died due to hypoxic respiratory nosis of DAH by retrieving progressively bloody effluent failure within 30 days of confirming the DAH diagno- on BAL. DAH was suspected in 1 patient by her clinical sis by bronchoscopy. The other 2 patients did not re- syndrome and pinkish effluent on BAL, and 1 patient quire intubation and were weaned off supplemental had suspected DAH based on documentation of bloody oxygen and discharged home in stable condition. secretions noted from bronchoscopy performed at a dif- ferent institution. Although none of the cultures taken Discussion during bronchoscopy in the 5 patients revealed an un- DAH is a clinical syndrome defined by a disturbance of derlying infectious process, all patients were being em- the alveolar-capillary basement membrane that causes pirically given broad-spectrum antibiotics. bleeding into the pulmonary alveoli.1 It is a final, com- All 5 patients were treated with high-dose steroids mon pathway for a variety of underlying issues affect- and 1 patient also received aminocaproic acid and fac- ing the lungs, including autoimmune vasculitides, drug Table 1. — Select Clinical Characteristics of Study Patients Patient Sex Age, Malignancy Oncological Pulmonary Exposure Symptoms Bleeding at Available Vitals WBC, Hemo- Platelet y Therapy Disease to Antico- Other Sites on Presentation 103/ globin, Count, at DAH History agulants mcL g/dL 103/mcL Diagnosis 1 M 63 AML 7 + 3 induction COP No Cough Epistaxis BP: 124/78 mm Hg 3.74 7.4 14 (FAB, M5a) LLL resection Dyspnea HR: 102 beats/ Unknown Fever minute autoimmune Hypoxia RR: 20 breaths/ disorder minute Temp: 98.8 °F 2 F 51 AML MUD COP Prophy- Cough Epistaxis BP: 121/80 mm Hg 0.02 8.1 35 (FAB, M1 Allogenic COPD lactic Fever Hemoptysis HR: 109 beats/ in relapse) HSCT dalteparin minute Rhinovirus (5000 U) Hemoptysis RR: 20 breaths/ minute O2 saturation: 96% on room air Temp: 98.7 °F 3 M 70 ALL Reinduction Nodular No Dyspnea No BP: 99/51 mm Hg 0.03 7.4 5 (WHO, MEC pneumonia Hypoxia HR: 76 beats/ therapy- Suspected minute related sleep apnea myeloid RR: 17 breaths/ neoplasms) minute Temp: 97.7 °F 4 F 57 AML MUD None No Dyspnea No BP: 127/71 mm Hg 0.30 9.8 15 (WHO, with Allogenic Hypoxia HR: 78 beats/ myelodys- HSCT minute plasia-related Left chest changes) wall pain RR: 30 breaths/ minute O2 saturation: 97% on room air Temp: 97.8 °F 5 F 56 AML 7 + 3 induction None No Cough No BP: 139/88 mm Hg 95.10 7.1 20 (FAB, M4) Dyspnea HR: 109 beats/ Hypoxia minute RR: 22 breaths/ minute O2 saturation: 95% on room air Temp: 99.3 °F continued on the next page July 2016, Vol. 23, No. 3 Cancer Control 273 Table 1. — Select Clinical Characteristics of Study Patients, continued Patient Pro- BAL CMV Cultures Medical Antibiotic Treatment Intubation Mortality Length calcitonin, Appearance PCR Treatment of ng/mL Respiratory Sputum Blood for DAH Given on Duration Hospital Admission Stay, d 1 NR Bloody Negative Negative No Negative Steroids None NA Yes Deceased 15 results 2 NR Bloody Negative Negative No VRE Aminocaproic Yes 41 d Yes Deceased 41 results Candida acid Received for glabrata Factor VII prolonged Steroids neutropenia, treatment of bacteremia 3 NR Bloody No Negative No Strepto- Steroids Yes 32 d No Alive 32 results results coccus Empiric mitis antibiotics for Strepto- neutropenia, coccus treatment of oralis bacteremia 4 0.23 Bloody No Negative No Negative Steroids Yes 10 d No Deceased 12 results results Empiric antibiotics for neutropenia 5 1.21 Pinkish No Negative No Negative Steroids Yes 22 d No Alive 22 results results Initially started for treatment of pneumonia Continued for prophy- laxis after prolonged neutropenia 7 + 3 = 7 days standard-dose cytarabine plus 3 days of daunorubicin, ALL = acute lymphocytic leukemia, AML = acute myeloid leukemia, BAL = bronchoal- veolar lavage, BP = blood pressure, CMV = cytomegalovirus, COP = cryptogenic organizing pneumonia, COPD = chronic obstructive pulmonary disease, DAH = diffuse alveolar hemorrhage, F = female, FAB = French American British classification, HR = heart rate, HSCT = hematopoietic stem cell transplantation, LLL = left lower lobe, M = male, MEC = mitoxantrone/etoposide/intermediate-dose cytarabine, MUD = matched unrelated donor, NR = not reported, PCR = polymerase chain reaction, RR = respiratory rate, Temp = temperature, VRE = vancomycin-resistant enterococci, WBC = white blood count, WHO = World Health Organization classification. toxicities, infections,
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