Pulmonary Leukemic Infiltration Research Articles

Anatomic Approach to Common and Uncommon Manifestations of Thoracic Leukemias with Radiologic-Pathologic Correlation.

Leukemias are hematopoietic malignancies characterized by the production of abnormal leukocytes in the bone marrow. Clinical manifestations arise from either bone marrow suppression or leukemic organ infiltration. Lymphadenopathy is the most common direct manifestation of intrathoracic leukemia. However, leukemic cells may also infiltrate the lungs, pleura, heart, bones, and soft tissues. Pulmonary complications in patients with leukemia typically include pneumonia, hemorrhage, pulmonary edema, and sequelae of leukemia treatment. However, pulmonary abnormalities can also be related directly to leukemia, including leukemic pulmonary infiltration. The direct, non-treatment-related effects of leukemia on intrathoracic structures will be the focus of this imaging essay. Given the typical anatomic approach for image interpretation, an organ-based depiction of common and less common intrathoracic findings directly caused by leukemic involvement is presented, emphasizing imaging findings with pathologic correlations. Keywords: Leukemia, Pulmonary, Thorax, Soft Tissues/Skin, Hematologic, Bone Marrow © RSNA, 2023.

PULMONARY LEUKEMIC INFILTRATES CAUSING RESPIRATORY FAILURE IN ACUTE MYELOID LEUKEMIA

PULMONARY LEUKEMIC INFILTRATES CAUSING RESPIRATORY FAILURE IN ACUTE MYELOID LEUKEMIA

What Is Different in Acute Hematologic Malignancy-Associated ARDS? An Overview of the Literature.

Background and Objectives: Acute hematologic malignancies are a group of heterogeneous blood diseases with a high mortality rate, mostly due to acute respiratory failure (ARF). Acute respiratory distress syndrome (ARDS) is one form of ARF which represents a challenging clinical condition. The paper aims to review current knowledge regarding the variable pathogenic mechanisms, as well as therapeutic options for ARDS in acute hematologic malignancy patients. Data collection: We provide an overview of ARDS in patients with acute hematologic malignancy, from an etiologic perspective. We searched databases such as PubMed or Google Scholar, including articles published until June 2022, using the following keywords: ARDS in hematologic malignancy, pneumonia in hematologic malignancy, drug-induced ARDS, leukostasis, pulmonary leukemic infiltration, pulmonary lysis syndrome, engraftment syndrome, diffuse alveolar hemorrhage, TRALI in hematologic malignancy, hematopoietic stem cell transplant ARDS, radiation pneumonitis. We included relevant research articles, case reports, and reviews published in the last 18 years. Results: The main causes of ARDS in acute hematologic malignancy are: pneumonia-associated ARDS, leukostasis, leukemic infiltration of the lung, pulmonary lysis syndrome, drug-induced ARDS, radiotherapy-induced ARDS, diffuse alveolar hemorrhage, peri-engraftment respiratory distress syndrome, hematopoietic stem cell transplantation-related ARDS, transfusion-related acute lung injury. Conclusions: The short-term prognosis of ARDS in acute hematologic malignancy relies on prompt diagnosis and treatment. Due to its etiological heterogeneity, precision-based strategies should be used to improve overall survival. Future studies should focus on identifying the relevance of such etiologic-based diagnostic strategies in ARDS secondary to acute hematologic malignancy.

DIFFUSE ALVEOLAR HEMORRHAGE: A RARE COMPLICATION OF ACUTE MYELOID LEUKEMIA

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary syndrome affecting individuals with hematologic malignancies with increased incidence post bone marrow transplant. We present a rare case of DAH presumably related to pulmonary leukemic infiltration (PLI) in a newly diagnosed Acute Myelogenous Leukemia (AML) patient. CASE PRESENTATION: A 55-year-old female, previously healthy, presented to the emergency room with a 1-week history of dyspnea, cough, and epistaxis. Laboratory data were relevant for leukocytosis (WBC 150,000/mm3) with 84% blasts, thrombocytopenia (platelets 15,000/mm3), and anemia (Hb 8.9 g/dL). CT angiography of the chest was negative for pulmonary embolism but showed scattered bilateral ground-glass opacities (GGO). Peripheral blood flow cytometry revealed AML. She underwent leukapheresis with an appropriate response. On day 5 of admission, she was transferred to the intensive care unit for increased oxygen requirement and required endotracheal intubation the day after. Chest CT showed significant worsening in bilateral GGO and septal thickening. WBC 27,000/mm3, Hb 7.7 g/dL, and platelets 50,000/mm3. Bronchoscopy with serial bronchoalveolar lavages (BAL) showed an increasingly bloody return. BAL cell differential was significant for 75% blasts. She was treated with platelet transfusion, nebulized tranexamic acid, high dose corticosteroids, and empiric antibiotic therapy. Emergent induction chemotherapy (daunorubicin + cytarabine) was started. Repeat bronchoscopy in 48h showed resolution of DAH and undetectable blasts in BAL. She was extubated on day 7 post-intubation, and her respiratory status improved back to baseline. DISCUSSION: Pulmonary opacities in leukemia may be the result of an infectious process, pulmonary edema, drug toxicity, diffuse alveolar hemorrhage, intravascular leukostasis, or pulmonary leukemic infiltrates. Though the timing of pulmonary complications, clinical presentation, and chest CT findings may help identify the etiology, diagnosis is frequently challenging, and early BAL may be of benefit. In this patient, worsening respiratory status and pulmonary infiltrates despite leukapheresis excluded leukostasis and suggested PLI. Hemoptysis is absent in more than one-third of patients with DAH. She had no hemoptysis, and DAH was subsequently diagnosed with bronchoscopy. We believe that early diagnosis of PLI, excellent response to induction chemotherapy, along with other supportive measures led to a favorable outcome. CONCLUSIONS: Early recognition of acute respiratory failure etiology in patients with leukemia and pulmonary infiltrates is essential. Albeit rare, DAH should always be on the differential as early identification and treatment can likely improve outcomes. REFERENCE #1: Nanjappa S, Jeong DK, Muddaraju M, Jeong K, Hill ED, Greene JN. Diffuse Alveolar Hemorrhage in Acute Myeloid Leukemia. Cancer Control. 2016 Jul;23(3):272-7 REFERENCE #2: Nucci M, Nouér SA, Anaissie E. Distinguishing the Causes of Pulmonary Infiltrates in Patients with Acute Leukemia. Clin Lymphoma Myeloma Leuk. 2015 Jun;15 Suppl: S98-103. DISCLOSURES: No relevant relationships by Tony Abdo, source=Web Response No relevant relationships by Samiksha Gupta, source=Web Response No relevant relationships by SYED HUSSAIN, source=Web Response No relevant relationships by Miloni Parmar, source=Web Response

LEUKEMIC PULMONARY INFILTRATION: A RARE COMPLICATION OF ACUTE LYMPHOBLASTIC LEUKEMIA

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Fellow Case Reports INTRODUCTION: We report a rare case of pulmonary leukemic infiltration that posed a diagnostic dilemma. CASE PRESENTATION: A 61 year old female presented with weeks of weakness, nausea, vomiting, diarrhea. Initial laboratory evaluation revealed hyperleukocytosis of >100,000 cells/microliter with 86% blasts and thrombocytopenia. A bone marrow biopsy revealed B cell type ALL. Hydroxyurea was initiated for cytoreduction. On hospitalization day 3 she developed hypoxemia requiring 2-3 L supplemental oxygen. Chest radiograph revealed mild patchy airspace opacities. Extensive non-invasive infectious work up was negative. Over next week she developed worsening dyspnea and hypoxemia, with near tandem progression of radiographic airspace disease, despite antibiotics and stabilization of blood count. CT chest revealed diffuse patchy ground glass opacities, small pleural effusion and adjacent atelectasis. Bronchoscopy showed bloody secretions, with BAL differential showing abundant atypical cells with irregular nuclear contours, fine chromatin and prominent nucleoli, consistent with lymphoblastic leukemic blast cells. Concern was for pulmonary leukemic infiltration vs DAH with peripheral blood blast spillage. High dose corticosteroids were initiated. Her clinical condition deteriorated requiring endotracheal intubation and ICU admission. Due to her critically ill status, she was treated dose reduced, moderate intensity Cyclophosphamide and Vincristine chemotherapy. A repeat BAL revealed similar findings of ~30% blasts on differential. Subsequently her respiratory status improved, she was extubated and discharged on low supplemental oxygen. Bone marrow restaging 4 weeks after initial treatment showed persistent B acute lymphoblastic leukemia in the bone marrow. Her oncology team is planning for mini-HOP induction with Larson consolidation. DISCUSSION: Thoracic involvement of leukemia is varied, from leukemic pulmonary infiltration, hyperleukocytopathic reaction, leukostasis, DAH, lymphadenopathy, pleural effusion etc. CT findings of leukemic pulmonary infiltration are nonspecific, however leukemic cells have a tendency to involve the perilymphatic interstitium, producing smooth or nodular thickening of the bronchovascular bundles and interlobular septa. Nodules are also common and may be peribronchovascular, centrilobular, or random in distribution. Ground-glass and consolidative opacities are less common, predominately in peribronchial regions, by infiltration of the parenchyma adjacent to the perilymphatic interstitium. Accurate diagnosis usually requires bronchoalveolar lavage or lung biopsy to rule out other common etiologies. Response to primary chemotherapy usually depends on primary leukemia and patient's clinical status, but usually portends a poor prognosis. CONCLUSIONS: Clinicians need to thoroughly investigate pulmonary infiltrates in a leukemic patient in order to ensure appropriate therapy. REFERENCE #1: Shroff, G. S., et al (2019). Leukemic involvement in the thorax. Radiographics, 39(1), 44-61. DISCLOSURES: No relevant relationships by Jyotirmayee Lenka, source=Web Response No relevant relationships by Naman Sharma, source=Web Response

CT classification of acute myeloid leukemia with pulmonary infiltration.

To characterize and categorize the CT findings of pulmonary leukemic infiltration (PLI) in patients with acute myeloid leukemia (AML). Among 435 patients with AML, 20 patients with PLI were retrospectively selected, and clinical characteristics and CT findings were analyzed. PLI was categorized into four patterns according to CT findings: type A, multiple nodules and/or masses; type B, bilateral perihilar airspace opacities (GGA or consolidation) without any nodules or masses; type C, mixture of type A and B; and type D, PLI without visible abnormal lung opacity. The difference in overall survival among four CT patterns was also examined. The frequency of complex karyotypes was higher in AML patients with PLI than in whole AML patients. Percentages of patients with CT findings of type A, B, C, and D were 35%, 20%, 35%, and 10%, respectively. There was a clear difference in the localization of opacities according to the type of infiltrates, i.e., nodules/masses were mainly detected in the lower/peripheral portion. Conversely, GGA was mainly located in the upper/central portion. The median overall survival from diagnosis of PLI was 262days (range 12-1148). The CT pattern was not significantly associated with survival (p = 0.3), with the exception of patients with type C tending to have significantly better outcomes compared to patients with type B (p = 0.05). This classification can contribute in accurate non-invasive diagnosis and possibly in the estimation of prognosis.

Imaging Features of Pulmonary Leukemic Infiltration With Comparison of Lymphoid and Myeloid Leukemias

PurposeTo describe the imaging findings of lung infiltration by leukemia and differential findings of lymphoid and myeloid leukemias. Materials and MethodsThrough a search of electronic medical records from 2005 to 2017, we identified 21 patients with pathologically proven lung involvement by leukemia. Concurrent CT findings were analyzed by 2 chest radiologists in consensus for ground glass or consolidative opacities, septal thickening, bronchovascular bundle thickening, pulmonary nodules, pulmonary masses, and hilar and mediastinal lymphadenopathy. ResultsThere were 13 cases of lymphoid leukemias and 8 of myeloid leukemias. Nodules and masses were the most common imaging feature (n = 13, 62%). Bronchovascular bundle thickening and hilar lymphadenopathy were exclusively seen in lymphoid leukemias (P = 0.01 and P = 0.006). Centrilobular nodules were also exclusively seen in 3 patients with chronic lymphocytic leukemia. ConclusionLung infiltration by leukemia presents most commonly with nodules or masses, but interstitial abnormalities such as bronchovascular bundle thickening were seen as well. Radiologists should consider leukemic infiltration in the differential diagnosis for nodules, including centrilobular nodules, in these patients.

ACUTE MYELOMONOCYTIC LEUKEMIA PRESENTING AS PULMONARY INFILTRATES SECONDARY TO LEUKEMIC INFILTRATION

SESSION TITLE: Lung Pathology 1 SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Malignant infiltration of pulmonary parenchyma is a rare complication of acute myeloid leukemia and commonly found on autopsy of patients without prior clinical pulmonary symptoms. We present a case of a 75-year-old female with acute myelomonocytic leukemia presenting as rapidly progressive respiratory failure with pulmonary leukemic infiltration. CASE PRESENTATION: The patient presented to her local hospital after 2 weeks of fevers, chest pain, dyspnea, and a non productive cough. CT angiogram of her chest revealed bilateral diffuse pulmonary infiltrates, loculated pleural effusions, and no evidence of pulmonary embolism. She underwent a left thoracentesis that yielded 13ml of an exudative effusion with following counts (RBCs 16 k/uL, WBCs 5.8 k/uL with 41% neutrophils, 8% lymphocytes, 6% monocytes, 43% macrophages & 2% mesothelial cells), as well as negative cultures and cytology. Due to progression of respiratory failure despite broad spectrum antimicrobials over the next 5 days, and new onset of atrial fibrillation, she was transferred to our hospital. Initial blood counts revealed abnormal peripheral monocytosis (AMC 1.8 k/uL, 32%) with a normal WBC count at 5.6 k/uL. Peripheral smear revealed premature monocytes. Her respiratory failure continued to progress requiring mechanical ventilation. She underwent exploratory thoracoscopy, lung wedge resection and intraoperative bronchoalveolar lavage. Lavage was significant for a WBC count of 400 per uL, 66% of which were monocytes. Lavage and pleural fluid cytologies were negative for malignant cells. Follow up blood counts showed progression of her monocytosis with appearance of promonocytes and peripheral blasts. Peripheral blood flow cytometry revealed 6% atypical myeloblasts and 45% atypical monocytic cells. Pleural and lung biopsies revealed an atypical interstitial mononuclear cell infiltrate with monocytic differentiation consistent with involvement by myeloid leukemia. Faced with refractory shock, multiorgan failure, and the most likely diagnosis of of acute leukemia, her family elected to transition to comfort measures and refused a bone marrow biopsy for diagnostic confirmation. She was palliatively extubated and passed away 4 days after her transfer. Autopsy was performed and confirmed acute myelomonocytic leukemia with leukemic infiltration of lungs, pleura, pericardium and spleen. DISCUSSION: Malignant infiltration of the lung is a rare manifestation of acute myeloid leukemia. We presented a case of progressive respiratory failure secondary to pulmonary and pleural involvement as an early presentation of acute myelomonocytic leukemia with a fatal outcome. CONCLUSIONS: Although uncommon, leukemic lung infiltration remains in the differential of acute pulmonary infiltrates in setting of blood dyscrasias suggestive of acute myeloid leukemia and can cause profound respiratory failure before a leukemia diagnosis is established. Reference #1: Wu Y-K, Huang Y-C, Huang S-F, Huang C-C, Tsai Y-H. Acute respiratory distress syndrome caused by leukemic infiltration of the lung. J Formos Med Assoc. 2008;107(5):419-423. Reference #2: Koh TT, Colby TV, Müller NL. Myeloid leukemias and lung involvement. Semin Respir Crit Care Med. 2005;26(5):514-519 Reference #3: Hildebrand FL, Rosenow EC, Habermann TM, Tazelaar HD. Pulmonary complications of leukemia. Chest. 1990;98(5):1233-1239 DISCLOSURES: No relevant relationships by Abdallah Abboud, source=Web Response No relevant relationships by Timothy Dwyer, source=Web Response No relevant relationships by Kathryn Gillen, source=Web Response No relevant relationships by Joel Mermis, source=Web Response No relevant relationships by Mitchell Tener, source=Web Response

Leukemic Pulmonary Infiltration with Tracheobronchial Involvement in a Patient with Chronic Lymphocytic Leukemia

Leukemic Pulmonary Infiltration with Tracheobronchial Involvement in a Patient with Chronic Lymphocytic Leukemia

A Flow Cytometric Analysis of Bronchoalveolar Lavage Fluid Cells in the Diagnosis of Leukemic Pulmonary Infiltration in a 63-year-old Female with Adult T Cell Leukemia

A Flow Cytometric Analysis of Bronchoalveolar Lavage Fluid Cells in the Diagnosis of Leukemic Pulmonary Infiltration in a 63-year-old Female with Adult T Cell Leukemia

気管支肺胞洗浄が腫瘍細胞浸潤と Pneumocystis Carinii 肺炎の早期診断に有用であった急性転化型成人 T 細胞白血病の 1 例

気管支肺胞洗浄が腫瘍細胞浸潤と Pneumocystis Carinii 肺炎の早期診断に有用であった急性転化型成人 T 細胞白血病の 1 例

Respiratory events at the earliest phase of acute myeloid leukemia

Acute myeloid leukemia (AML) can result in acute respiratory failure (ARF) during the first days, requiring intensive care unit (ICU) admission in half the cases. We describe three leukemia-specific syndromes responsible for ARF: leukostasis, pulmonary leukemic infiltration (PLI) and acute lysis pneumopathy (ALP). We retrospectively analyzed clinical and laboratory data from 114 patients admitted to a medical ICU within 10 days after a diagnosis of AML. Respiratory events (REs) occurred in 95 patients and were leukemia-specific in 58 patients (61%). Day-28 mortality was 34.5% in patients with leukemia-specific REs (leukostasis, 41%; PLI, 23%; and ALP, 31%) and 48.6% in patients with other REs. By multivariate analysis, independent risk factors for death were age > 50 (odds ratio, 13; 95% confidence interval, 3–51), Eastern Cooperative Oncology Group (ECOG) status ≥ 2 (5.4; 1.8–17) and need for invasive mechanical ventilation (19; 5–75). Dexamethasone therapy was protective (0.26; 0.09–0.8), suggesting a role as a preventive treatment in patients with AML-related non-infectious pulmonary involvement.

Bilateral Leukemic Pulmonary Infiltrate: A Rare Manifestation of Acute Myeloid Leukemia

Acute myeloid leukemia (AML) often presents with nonspecific symptoms of fatigue, anemia or infection. Pulmonary involvement is common in AML during the course of the disease and is usually caused by infection, hemorrhage, leukemic pulmonary infiltrates and leukostasis. Symptomatic leukemic pulmonary infiltrates as a first manifestation of AML is very uncommon but potentially life threatening if not diagnosed and treated in a timely manner. Here we present a rare case of AML with symptomatic bilateral leukemic infiltrates as a first manifestation with peripheral blasts 77%. Common infectious etiologies were ruled out. The pulmonary infiltrates dramatically improved with standard induction chemotherapy. Even though leukemic pulmonary infiltrates in AML is a diagnosis of exclusion but must be considered in the differential diagnosis when a patient present with pulmonary symptoms with blast cell > 40% and suspected acute leukemia. J Med Cases. 2014;5(3):137-139 doi: http://dx.doi.org/10.14740/jmc1651w

Infiltrations pulmonaires spécifiques à la phase initiale des leucémies aiguës myéloïdes: le poumon leucémique du diagnostic au traitement

Patients with acute myeloid leukemia (AML) can develop acute respiratory failure (ARF) during the first days of the disease, leading to admission to the intensive care unit in half of the cases. Even though infections are the most frequent causes of ARF, some of the patients may develop a specific leukemic pulmonary involvement. Different kinds of respiratory involvement can be distinguished: leukostasis, pulmonary leukemic infiltration, and acute lysis pulmonary disease. In this review, we describe these three different entities based on the literature and our experience. However, consensus remains limited and further studies are warranted to establish diagnostic criteria. Finally, we present specific management guidelines, based on collaboration between hematologists and intensivists.

Long-Term Remission in a Juvenile Myelomonocytic Leukemia Patient After Graft Rejection of Unrelated Bone Marrow Transplantation

Abstract 4962Juvenile myelomonocytic leukemia (JMML) is an aggressive clonal malignancy and mixed myeloproliferative and myelodysplastic disorder. Although cure in most cases requires hematopoietic stem cell transplantation (HSCT), the major cause of treatment failure is relapse. However, in some cases, symptoms improve without treatment. We report a case of a patient with JMML who sustained remission after graft rejection of an unrelated bone marrow transplantation (UBMT). CaseAn 18-month-old girl presented with marked splenomegaly and hemorrhagic diathesis. Laboratory blood tests revealed the following: white blood cell (WBC) count 12. 2 × 109/L, monocytes 22. 0%, hemoglobin 7. 6 g/dL, platelets 10. 0 × 109/L, and fetal hemoglobin 12. 8%. A bone marrow aspirate revealed a hypercellular marrow with mild dysplastic changes and 4. 4% blast cells. The BCR–ABL fusion gene was not detected. Following a diagnosis of JMML, she subsequently developed respiratory failure due to leukemic infiltration of the lungs, and was referred to our hospital. On admission, she developed severe thrombocytopenia due to splenic sequestration of platelets, and she needed frequent transfusions. She received chemotherapy with cytarabine and 6-mercaptopurine. Pulmonary leukemic infiltration improved, but transfusion frequency could not be reduced. After she had undergone splenectomy, platelet transfusion was not needed. When her clinical condition had improved, KRAS mutation was investigated by bone marrow aspiration, and the KRAS 13G>D mutation was detected. Five months after diagnosis, she was transplanted with major mismatch blood type, HLA-A 1-allele mismatch, from an unrelated female donor. The conditioning regimen consisted of busulfan (BU; 16 mg/kg), fludarabine (Flu; 120 mg/m2), and cyclophosphamide (CY; 120 mg/kg). Short-term methotrexate and tacrolimus (FK506) were administered for the prevention of graft-versus-host disease. The level of infused donor marrow cells was 1. 18 × 108/kg. Recovery of peripheral blood count was rapid, and no regimen-related toxicity was observed. Chimerism by short tandem repeat analysis of bone marrow mononuclear cells on day 28 after UBMT was 100% recipient type, indicating graft rejection with autologous hematopoietic cell recovery. FK506 was then discontinued. From day 48 after UBMT until the current day, WBC count has been almost 10. 0 × 109/L. Despite graft rejection, the KRAS 13G>D mutation was not detected by bone marrow aspiration on day 219, and her peripheral blood counts were normalized. Four years after diagnosis, the KRAS 13G>D mutation in the peripheral blood, nails, buccal mucosa, and hair was not detected, but the KRAS13G>D mutation was not. She has been managed without treatment and remained in complete remission for over 5 years since receiving UBMT. DiscussionIn JMML patients with specific RAS mutations, spontaneous improvement in hematologic abnormalities has been reported. HSCT was needed in this case because the patient developed respiratory failure due to pulmonary infiltration of JMML cells. In JMML patients with gene mutation, JMML-specific gene mutations could not be detected after engraftment of HSCT. In contrast, most JMML cases relapse and need a second HSCT after rejection of the first. However, this patient's condition normalized after rejection of UBMT. Nowadays, minimal residual disease in JMML is analyzed by detection of JMML cell-specific gene mutations. The KRAS mutation can be detected in spontaneously regressed JMML following hematological improvement. We suggest that a myeloablative conditioning regimen including BU, Flu, and CY could eradicate JMML clones, and in some JMML cases, this could prevent the need for a second HSCT after rejection of the first. Disclosures:No relevant conflicts of interest to declare.

Leukemic Infiltration of Lung Mimicking Fungal Pneumonia

Leukemic infiltration of lung may be seen in acute leukemia especially in those with high white cell counts. However, it is difficult to diagnose antemortem as it mimics infections or pulmonary hemorrhage which are much more common complications. We present an unusual patient who had a fatal outcome due to leukemic progression in the lung despite blood and marrow response to induction chemotherapy. Twenty-eight year old female presented with fever and lymphadenopathy for 4 weeks. Investigations: Hemoglobin: 6.7 g/dL; Thrombocyte count: 0.92 × 109/L; white blood cell (WBC) count: 4.1 × 109/L with 65 % blasts confirmed as precursor B acute lymphoblastic leukemia on bone marrow studies. At baseline, patient was afebrile with a normal chest radiograph (Fig. 1a). By day 7 of therapy (only Prednisolone 60 mg/m2 for the first 1 week as per BFM 95 protocol) her WBC count had dropped to 0.6 × 109/L and her peripheral blood had cleared blasts. However, she developed high grade fever and her general condition deteriorated; infection was suspected and empiric antibiotics were started. The day 8 chemotherapy was modified (only Vincristine was delivered, Daunorubicin was omitted). After initial stabilization, the patient had recurrent fever spikes and worsening respiratory status. Patient’s chest radiograph showed lung infiltrates and nodular shadows which made us suspect fungal pneumonia (Fig. 1b). A bone marrow exam was done which showed hypocellular marrow hence all leukemic therapy was withheld and we started her on 2nd line antibiotics and antifungal therapy (voriconazole). She continued to remain febrile and had persistent pancytopenia. Bleeding manifestations precluded any attempt at tissue diagnosis from lung lesions. Repeat chest imaging (Fig 1c) showed further worsening of pulmonary infiltrates. On day 22, she developed progressive respiratory failure and expired. Post mortem lung biopsy showed extensive leukemic infiltration of lung (Fig. 1d, e). No fungal pathogen/infection could be found. Fig. 1 Chest X-ray before starting chemotherapy (a). Chest X-ray showing path infiltrates in both lung fields (b).Chest X-ray showing progression of lung infiltrates (c). Low magnification (×20) view showing leukemic infiltrates in lung (d). Higher magnification ... Pulmonary involvement in acute leukemia can manifest as pulmonary leukostasis, leukemic infiltrates, alveolar hemorrhage, pulmonary nodules, or pleural infiltrates [1–3]. Clinical presentation can vary from asymptomatic pulmonary infiltrates on imaging to acute respiratory distress syndrome—like features. Various radiological findings based on computed tomography of lung have been described for pulmonary leukemic infiltrates [4] but we could not do any imaging other than chest X-ray as patient was too sick to be transferred. We suspected fungal pneumonia in our patient as she was profoundly neutropenic and was not responding to antibiotics. However, postmortem lung biopsy proved that it was leukemic pulmonary infiltrates rather than infection which caused death in our patient. Most of the reported literature of involvement of lung in leukemic patients is in cases of acute leukemia in pre-treatment setting. However postmortem series have shown pulmonary infiltrates in 31–66 %. It’s very intriguing that our patient had a dramatic response with clearance of blasts while the disease progressed in the lungs. The tissue diagnosis of pulmonary infiltrates in leukemic patients can bring about significant changes in management. However, the procedure can be risky especially where patients have significant bleeding tendencies, as in our patient. This led to empiric therapy which resulted in a negative outcome in our patient. We report this case to create awareness about the possibility of leukemic infiltrates being an important cause of respiratory failure during acute leukemia induction even when there is apparent response in the bone marrow.

Pulmonary involvement by chronic lymphocytic leukemia/small lymphocytic lymphoma is a specific pathologic finding independent of inflammatory infiltration

Pulmonary infiltrates in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are usually secondary to infection, but a subset is due to pathologic infiltration of malignant lymphocytes into the lung parenchyma. In cases with both CLL/SLL and inflammatory infiltrates, it is unknown whether the CLL infiltrate represents a nonspecific “passenger effect” secondary to ongoing inflammation or pathologic leukemic pulmonary infiltration (LPI). We reviewed 49 lung biopsies taken from 38 patients with CLL/SLL. LPI was found in 2 of 21 cases (9.5%) with acute inflammation, 0 of 10 cases of chronic inflammation and in 7 of 18 cases (38.8%) without any pathologic findings of acute or chronic inflammation (p = 0.01). These results demonstrate that LPI identified in biopsies with concurrent inflammation is uncommon, and that most inflammatory infiltrates in patients with CLL do not cause “passenger effect” CLL infiltration. Therefore, LPI usually represents a specific pathologic process. We conclude that bronchoscopy with transbronchial biopsy is an effective tool for guiding treatment decisions for symptomatic patients with CLL with pulmonary infiltrates. Moreover, LPI by CLL is not a bystander effect secondary to acute inflammation, but instead represents a distinct pathologic process in a subset of patients.

Leukemic infiltration of the lung following allogeneic hematopoietic stem cell transplantation

Pulmonary leukemic infiltration (PLI) is more common than generally recognized, but accurate antemortem diagnosis with pathological proof is rarely achieved. We describe herein the clinical courses of two patients with PLI following hematopoietic stem cell transplantation (HSCT). One case is a male patient with acute biphenotypic leukemia, and the other is a female patient with myelodysplastic syndrome. In both cases, hyperleukocytosis did not proceed to PLI. Moreover, the former case presented PLI as the initial manifestation of relapsed leukemia and the latter was accompanied with the fungal pneumonia. High-resolution computed tomography (HRCT) of the chest at onset of PLI showed diffuse small nodular lesions along peribronchovascular bundle, and diagnosis of leukemic infiltration was made based on pathological findings obtained from transbronchial lung biopsy. Biopsy specimens further revealed leukemic infiltration along the lymphatic surrounding the peribronchial or perivascluar regions, which corresponded well with HRCT findings. Thus, radiological and pathological corroborating assessment was important to reach the correct diagnosis.

Asistencia pulmonar extracorpórea sin bomba: una alternativa en el tratamiento del síndrome de distrés respiratorio agudo grave persistente

A 34-year old woman who developed persistent and severe acute respiratory distress syndrome with underlying myelomonocytic leukemia (M4FAB) is described. After ruling out the most common causes of pulmonary infiltration in this type of patient and one week of broad spectrum antibiotics and steroids therapy, we proposed leukemic pulmonary infiltration as etiological diagnosis. Despite using a protective ventilatory strategy, recruitment maneuvers, prone position and high frequency oscillatory ventilation, her gas exchange became worse. Under this condition we used a Pumpless-Extracorporeal life assist (PELA) and begun chemotherapy. The method, arterial blood gases, hemodynamic parameters and ventilatory mechanics before and after its use are described. The patient remained on P-ELA for nine days; one week later she was extubated and ten days after she was discharged from the Intensive Care Unit the patient left the hospital in good health condition.

Acute Respiratory Distress Syndrome Caused by Leukemic Infiltration of the Lung

Respiratory distress syndrome resulting from leukemic pulmonary infiltrates is seldom diagnosed antemortem. Two 60- and 80-year-old women presented with general malaise, progressive shortness of breath, and hyperleukocytosis, which progressed to acute respiratory distress syndrome (ARDS) after admission. Acute leukemia with pulmonary infection was initially diagnosed, but subsequent examinations including open lung biopsy revealed leukemic pulmonary infiltrates without infection. In one case, the clinical condition and chest radiography improved initially after combination therapy with chemotherapy for leukemia and aggressive pulmonary support. However, new pulmonary infiltration on chest radiography and hypoxemia recurred, which was consistent with acute lysis pneumopathy. Despite aggressive treatment, both patients died due to rapidly deteriorating condition. Leukemic pulmonary involvement should be considered in acute leukemia patients with non-infectious diffusive lung infiltration, especially in acute leukemia with a high blast count.