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BACKGROUND: The optimal timing of vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines after cellular therapy is incompletely understood. The objectives of this study are to determine whether humoral and cellular responses after SARS-CoV-2 vaccination differ if initiated <4 months versus 4-12 months after cellular therapy. METHODS: We conducted a multicenter, prospective, observational study at 30 cancer centers in the United States. SARS-CoV-2 vaccination was administered as part of routine care. We obtained blood prior to and after vaccinations at up to 5 time points and tested for SARS-CoV-2 spike (anti-S) IgG in all participants and neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains, as well as SARS-CoV-2-specific T-cell receptors, in a subgroup. RESULTS: We enrolled 466 allogeneic hematopoietic cell transplantation (HCT) (n = 231), autologous HCT (n = 170), and chimeric antigen receptor T-cell (CAR-T-cell) therapy (n = 65) recipients between April 2021 and June 2022. Humoral and cellular responses did not significantly differ among participants initiating vaccinations <4 months versus 4-12 months after cellular therapy. Anti-S IgG ≥2500â U/mL was correlated with high neutralizing antibody titers and attained by the last time point in 70%, 69%, and 34% of allogeneic HCT, autologous HCT, and CAR-T-cell recipients, respectively. SARS-CoV-2-specific T-cell responses were attained in 57%, 83%, and 58%, respectively. Pre-cellular therapy SARS-CoV-2 infection or vaccination and baseline B-cell count were key predictors of post-cellular therapy immunity. CONCLUSIONS: These data support mRNA SARS-CoV-2 vaccination prior to, and reinitiation 3 to 4 months after, cellular therapies with allogeneic HCT, autologous HCT, and CAR-T-cell therapy.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Transplante de Células-Tronco Hematopoéticas , SARS-CoV-2 , Humanos , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Feminino , COVID-19/prevenção & controle , COVID-19/imunologia , SARS-CoV-2/imunologia , Adulto , Anticorpos Antivirais/sangue , Anticorpos Neutralizantes/sangue , Idoso , Vacinação , Imunoterapia Adotiva/métodos , Imunoglobulina G/sangue , Receptores de Antígenos Quiméricos/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Estados UnidosRESUMO
BACKGROUND: Cytomegalovirus-specific T-cell-mediated immunity (CMV-CMI) protects from CMV infection in allogeneic hematopoietic cell transplantation (allo-HCT), but to date, there is no validated measure of CMV immunity for this population. METHODS: In this prospective, observational, pilot study, CMV T-cell responses were evaluated monthly and at onset of graft-versus-host disease (GVHD) or CMV infection in CMV-seropositive allo-HCT recipients using a commercial flow cytometry assay, the CMV inSIGHT T-Cell Immunity Panel (CMV-TCIP). The primary endpoint was the time to first positive CMV-TCIP, defined as percentage of interferon-γ-producing CD4+ or CD8+ CMV-specific T cells >0.2%. Letermovir was prescribed from day +10 to ≥100. RESULTS: Twenty-eight allo-HCT recipients were enrolled. The median time to first positive CMV-TCIP result was earlier for CD4+ (60 days [interquartile range, IQR 33â148]) than for CD8+ T cells (96 days [IQR 33â155]) and longer for haploidentical and mismatched transplant recipients (77 and 96 days, respectively) than for matched donors (45 and 33 days, respectively). CD4+ and CD8+ CMV-CMI recovery was sustained in 10/10 (100%) and 10/11 (91%) patients, respectively, without GVHD, whereas CD4+ and/or CD8+ CMV-CMI was lost in 4/6 and 2/6 patients, respectively, with GVHD requiring steroids. As a predictor of clinically significant CMV infection in patients with low-level CMV reactivation, the sensitivity and negative predictive value of CMV-TCIP were 90% and 87.5%, respectively, for CD4+ CMV-TCIP and 66.7% and 62.5%, respectively, for CD8+ CMV-TCIP. CONCLUSIONS: There was significant variability in time to CMV-CMI recovery post-HCT, with slower recovery after haploidentical and mismatched HCT. CD4+ CMV-CMI may protect against CS-CMVi, but immunity may be lost with GVHD diagnosis and treatment.
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Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Infecções por Citomegalovirus , Citomegalovirus , Citometria de Fluxo , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante Homólogo , Humanos , Projetos Piloto , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/prevenção & controle , Pessoa de Meia-Idade , Masculino , Citomegalovirus/imunologia , Estudos Prospectivos , Feminino , Citometria de Fluxo/métodos , Adulto , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD4-Positivos/imunologia , Transplante Homólogo/efeitos adversos , Idoso , Imunidade Celular , Antivirais/uso terapêuticoRESUMO
The use of CD19 chimeric antigen receptor T-cell (CAR-T) therapy for relapsed/refractory solid organ transplantation (SOT)-related post-transplant lymphoproliferative disorder (PTLD) is not well studied. We conducted a multicentre, retrospective analysis of adults with relapsed/refractory SOT-associated PTLD. Among 22 relapsed/refractory SOT-PTLD patients, the pathology was monomorphic B cell. Prior SOTs included 14 kidney (64%), three liver (14%), two heart (9%), one intestinal (5%), one lung (5%), and one pancreas after kidney transplant (5%). The median time from SOT to PTLD diagnosis was 107 months. Pre-CAR-T bridging therapy was used in 55% of patients, and immunosuppression was stopped completely before CAR-T infusion in 64%. Eighteen (82%) patients experienced cytokine release syndrome: one (5%) each grade (G) 3 and G4. The immune effector cell-associated neurotoxicity syndrome was observed in 16 (73%) patients: six (27%) G3 and two (9%) G4. The overall response rate was 64% (55% complete response). Three patients (14%) experienced allograft rejection after CAR-T. The two-year progression-free survival and overall survival rates were 35% and 58%, respectively. Additionally, the achievement of CR post-CAR-T was strongly associated with survival. Collectively, the safety and efficacy of CD19 CAR-T therapy in relapsed/refractory SOT-related PTLD appeared similar to pivotal CAR-T data, including approximately one-third of patients achieving sustained remission.
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Transtornos Linfoproliferativos , Transplante de Órgãos , Receptores de Antígenos Quiméricos , Adulto , Humanos , Estudos Retrospectivos , Imunoterapia Adotiva/efeitos adversos , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/terapia , Antígenos CD19 , Transplante de Órgãos/efeitos adversos , Terapia Baseada em Transplante de Células e TecidosRESUMO
Clinical trials of novel salvage therapies have encouraging outcomes for relapsed/refractory transplant-eligible classic Hodgkin lymphoma (R/R cHL) but comparison with conventional chemotherapy is lacking. Herein, we report the final analysis of a multicenter retrospective cohort of R/R cHL assessing outcomes by type of salvage therapy before autologous stem cell transplant (ASCT). R/R cHL patients who underwent ASCT at 14 institutions across the United States were included. Outcomes were compared among patients receiving conventional chemotherapy, brentuximab vedotin (BV) + chemotherapy, BV alone, and a checkpoint inhibitor (CPI)-based regimens before ASCT. Study endpoints included event-free survival (EFS), progression-free survival (PFS), and overall survival (OS). All endpoints are defined from relapse. Of 936 patients, 728 received conventional chemotherapy, 73 received BV + chemotherapy, 70 received BV alone, and 65 received CPI-based regimens prior to ASCT. When adjusted for time to relapse, pre-ASCT response and use of BV maintenance, patients receiving CPI-based regimens had superior 2-year EFS compared to conventional chemotherapy, BV + chemotherapy, and BV alone (79.7, 49.6, 62.3, and 36.9%, respectively, p < .0001). Among 649 patients transplanted after 1 line of salvage therapy, CPI-based regimens were associated with superior 2-year PFS compared to conventional chemotherapy (98% vs. 68.8%, hazard ratio: 0.1, 95% confidence interval: 0.03-0.5, p < .0001). OS did not differ by pre-ASCT salvage regimen. In this large multicenter retrospective study, CPI-based regimens improved EFS and PFS compared to other salvage regimens independent of pre-ASCT response. These data support earlier sequencing of CPI-based regimens in R/R cHL in the pre-ASCT setting.
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Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin , Humanos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Intervalo Livre de Progressão , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Brentuximab Vedotin/uso terapêutico , Transplante de Células-Tronco , Transplante Autólogo , Terapia de SalvaçãoRESUMO
Ruxolitinib is an oral JAK1/2 inhibitor that is approved for use in patients with intermediate and high-risk myelofibrosis (MF) based on its proven spleen and symptom burden reduction. Its impact on hematopoietic stem cell transplantation (HSCT) outcomes is largely unknown, however. A significant number of patients proceeding to HSCT have been treated with ruxolitinib, and the specifics of its peritransplantation use vary widely in the published literature. Here we review the currently published data and experience to guide management of patients with MF on ruxolitinib proceeding to HSCT.
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Transplante de Células-Tronco Hematopoéticas , Mielofibrose Primária , Humanos , Nitrilas , Mielofibrose Primária/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , PirimidinasRESUMO
Dasatinib is a dual Src/Abl tyrosine kinase inhibitor approved for frontline and second line treatment of chronic phase chronic myelogenous leukemia. Pulmonary arterial hypertension is defined by an increase in mean pulmonary arterial pressure >25 mmHg at rest. Dasatinib-induced pulmonary hypertension has been reported in less than 1% of patients on chronic dasatinib treatment for chronic myelogenous leukemia. The pulmonary arterial hypertension from dasatinib may be categorized as either group 1 (drug-induced) or group 5 based on various mechanisms that may be involved including the pathogenesis of the disease process of chronic myelogenous leukemia. There have been reports of dasatinib-induced pulmonary arterial hypertension being reversible. We report a case of pulmonary arterial hypertension in a 46-year-old female patient with chronic phase chronic myelogenous leukemia on dasatinib treatment for over 10 years. She had significant improvement in symptoms after discontinuation of dasatinib and initiation of vasodilators. Several clinical questions arise once patients experience significant adverse effects as discussed in our case.
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Antineoplásicos/efeitos adversos , Dasatinibe/efeitos adversos , Hipertensão Pulmonar/induzido quimicamente , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Autoimmune hypophysitis is an immune-related adverse event of immune checkpoint inhibitors. In this article, we present the case of a 58-year-old female patient who presented to the emergency room with gradually worsening nonspecific symptoms of headache, nausea, vomiting and decreased oral intake of one week duration. The patient had been diagnosed with relapsed extensive stage small cell lung cancer. She was being treated with a combination of ipilimumab and nivolumab after progression on chemotherapy. Gadolinium-enhanced magnetic resonance imaging of head revealed pituitary enlargement up to 1.5 cm and pituitary stalk enlargement up to 4 mm consistent with hypophysitis. The patient was treated with corticosteroids resulting in rapid resolution of her symptoms. The objective of our report is to highlight this rare but important adverse event associated with checkpoint inhibitors, and discuss its clinical features, diagnostic work-up and treatment.
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Antineoplásicos Imunológicos/efeitos adversos , Hipofisite Autoimune/induzido quimicamente , Hipofisite Autoimune/diagnóstico por imagem , Imunoterapia/efeitos adversos , Feminino , Humanos , Ipilimumab/efeitos adversos , Pessoa de Meia-Idade , Nivolumabe/efeitos adversosRESUMO
Rasburicase is indicated for the prevention and treatment of tumor lysis syndrome which can be a potentially life-threatening emergency. The drug has oxidizing potential and as an adverse effect, it can convert the ferrous form of iron in erythrocytes to its ferric form resulting in the formation of methemoglobin which makes the heme component incapable of carrying oxygen. Patients with glucose-6-phosphate dehydrogenase enzyme deficiency are at high risk of methemoglobinemia from oxidizing agents. Symptoms of methemoglobinemia range from none to life-threatening hypoxemia, cyanosis and respiratory compromise. Treatment is indicated at levels above 20% and at lower levels if the patient is significantly anemic. We present a case of a 60-year-old male with diffuse large B cell lymphoma at high risk of tumor lysis syndrome. Rasburicase was administered to prevent renal failure and further rise in uric acid. Twenty-four hours later, a bedside pulse oximetry showed an oxygen saturation ranging from 60 to 65% with minimal cyanosis. Co-oximetry revealed a methemoglobin level of 9.8%. Methylene blue was administered and the methemoglobin level decreased to 2.6%. However, the patient developed hemolysis several hours later, likely secondary to rasburicase and methylene blue, requiring transfusion support. We discuss this potentially fatal and initially asymptomatic adverse effect of rasburicase along with diagnostic and treatment considerations, and review the cases described in the current literature.
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Supressores da Gota/efeitos adversos , Metemoglobinemia/induzido quimicamente , Metemoglobinemia/diagnóstico , Urato Oxidase/efeitos adversos , Humanos , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Metemoglobinemia/sangue , Pessoa de Meia-Idade , Proteínas Recombinantes/efeitos adversos , Síndrome de Lise Tumoral/tratamento farmacológicoRESUMO
Background: The optimal timing of vaccination with SARS-CoV-2 vaccines after cellular therapy is incompletely understood. Objective: To describe humoral and cellular responses after SARS-CoV-2 vaccination initiated <4 months versus 4-12 months after cellular therapy. Design: Multicenter prospective observational study. Setting: 34 centers in the United States. Participants: 466 allogeneic hematopoietic cell transplant (HCT; n=231), autologous HCT (n=170), or chimeric antigen receptor T cell (CAR-T cell) therapy (n=65) recipients enrolled between April 2021 and June 2022. Interventions: SARS-CoV-2 vaccination as part of routine care. Measurements: We obtained blood prior to and after vaccinations at up to five time points and tested for SARS-CoV-2 spike (anti-S) IgG in all participants and neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains, as well as SARS-CoV-2-specific T cell receptors (TCRs), in a subgroup. Results: Anti-S IgG and neutralizing antibody responses increased with vaccination in HCT recipients irrespective of vaccine initiation timing but were unchanged in CAR-T cell recipients initiating vaccines within 4 months. Anti-S IgG ≥2,500 U/mL was correlated with high neutralizing antibody titers and attained by the last time point in 70%, 69%, and 34% of allogeneic HCT, autologous HCT, and CAR-T cell recipients, respectively. SARS-CoV-2-specific T cell responses were attained in 57%, 83%, and 58%, respectively. Humoral and cellular responses did not significantly differ among participants initiating vaccinations <4 months vs 4-12 months after cellular therapy. Pre-cellular therapy SARS-CoV-2 infection or vaccination were key predictors of post-cellular therapy anti-S IgG levels. Limitations: The majority of participants were adults and received mRNA vaccines. Conclusions: These data support starting mRNA SARS-CoV-2 vaccination three to four months after allogeneic HCT, autologous HCT, and CAR-T cell therapy. Funding: National Marrow Donor Program, Leukemia and Lymphoma Society, Multiple Myeloma Research Foundation, Novartis, LabCorp, American Society for Transplantation and Cellular Therapy, Adaptive Biotechnologies, and the National Institutes of Health.
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In the pre-novel agent era, the median postprogression overall survival (PPS) of patients with classic Hodgkin lymphoma (cHL) who progress after autologous stem cell transplant (ASCT) was 2 to 3 years. Recently, checkpoint inhibitors (CPI) and brentuximab vedotin (BV) have improved the depth and durability of response in this population. Here, we report the estimate of PPS in patients with relapsed cHL after ASCT in the era of CPI and BV. In this multicenter retrospective study of 15 participating institutions, adult patients with relapsed cHL after ASCT were included. Study objective was postprogression overall survival (PPS), defined as the time from posttransplant progression to death or last follow-up. Of 1158 patients who underwent ASCT, 367 had progressive disease. Median age was 34 years (range, 27-46) and 192 were male. Median PPS was 114.57 months (95% confidence interval [CI], 91-not achieved) or 9.5 years. In multivariate analysis, increasing age, progression within 6 months, and pre-ASCT positive positron emission tomography scan were associated with inferior PPS. When adjusted for these features, patients who received CPI, but not BV, as first treatment for post-ASCT progression had significantly higher PPS than the no CPI/no BV group (hazard ratio, 3.5; 95% CI, 1.6-7.8; P = .001). Receipt of allogeneic SCT (Allo-SCT) did not improve PPS. In the era of novel agents, progressive cHL after ASCT had long survival that compares favorably with previous reports. Patients who receive CPI as first treatment for progression had higher PPS. Receipt to Allo-SCT was not associated with PPS in this population.
Assuntos
Doença de Hodgkin , Imunoconjugados , Adulto , Feminino , Humanos , Masculino , Brentuximab Vedotin , Doença de Hodgkin/terapia , Estudos Retrospectivos , Transplante de Células-Tronco , Pessoa de Meia-IdadeRESUMO
While umbilical cord blood is increasingly utilized as a stem cell source, immune complications associated with the procedure have been recognized. These complications result from significant immune system dysregulation and defective reconstitution following transplant causing an imbalance between T-cell subsets, aberrant B cells, and abnormal antibody production. This may occur up to 12 months after transplant coinciding with thymic regeneration in adults. The aim of our review is to describe the incidence, pathophysiology, clinical features, and prognosis of autoimmune cytopenias following umbilical cord blood transplant. Furthermore, we review the treatment strategies reported in the existing literature, describe the authors' experience with the complication, and highlight novel treatment options being studied. The knowledge of the occurrence and timing of autoimmune complications of umbilical cord blood transplantation is essential for detection and treatment of the disease. Emerging therapeutic options include interleukin-2 (IL-2), which is also being studied for the treatment of acute and chronic graft-versus-host disease. IL-2 has favorable effects on growth, differentiation, and function of regulatory T cells. Monoclonal antibody treatments, such as daratumumab, are also on the forefront and more experience with them will guide further treatment strategies.
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Anemia/etiologia , Doenças Autoimunes/etiologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Neutropenia/etiologia , Púrpura Trombocitopênica Idiopática/etiologia , Anemia/imunologia , Anemia/patologia , Anemia/terapia , Animais , Anticorpos Monoclonais/uso terapêutico , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Doenças Autoimunes/terapia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Linfócitos B/patologia , Humanos , Interleucina-2/uso terapêutico , Neutropenia/imunologia , Neutropenia/patologia , Neutropenia/terapia , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Idiopática/patologia , Púrpura Trombocitopênica Idiopática/terapia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/patologiaRESUMO
Morbidly adherent placenta is a rare clinical condition resulting from abnormally invasive implantation of the placenta into the uterine substance and potentially into the surrounding organs (percreta). We report a case of invasive placentation extending through the uterine wall into the bladder and causing primary and recurrent secondary postpartum hemorrhage. It is emphasized that to avoid catastrophic complications, efforts to reach an early antenatal diagnosis should be made through various imaging modalities available in patients with a history of lower segment caesarean section.
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Placenta Acreta/diagnóstico , Adulto , Feminino , Humanos , Hemorragia Pós-Parto/etiologia , GravidezRESUMO
Thoracostomy tubes are indicated for management of air or fluid in the pleural cavity. Pigtail catheters have emerged as an effective and less morbid alternative to traditional large bore chest tubes for evacuation of pleural air or fluid. However, they do not come without complications which commonly include pneumothorax and hemothorax. Rare complications in the literature such as left ventricular penetration, subclavian artery laceration and cerebral air embolism have been reported. We report a case of a 72-year-old male who presented with dyspnea and was found to have a right-sided pleural effusion requiring thoracentesis and subsequent pigtail catheter placement because of re-accumulation of the fluid. After accidental dislodgement of the catheter, it was replaced and the following day a chest X-ray (CXR) demonstrated diffuse subcutaneous emphysema. Computed tomography (CT) scan of the chest demonstrated the pigtail catheter tracking through the right middle and lower lobes reaching the posterior pleural space. We discuss the implications of this occurrence and recommended management based on our experience.
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Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder that can be familial in etiology or a result of infections, malignancy, and autoimmune or inflammatory disorders. Disseminated intravascular coagulation (DIC) is common in patients admitted to intensive care units and can confound and delay the diagnosis of HLH. We present a case of a 69-year-old female who presented with dyspnea and malaise. Her condition declined rapidly with laboratory parameters consistent with DIC. In addition, she had a ferritin of 32,522 ng/mL, low haptoglobin, and elevated LDH, and bone marrow biopsy showed hemophagocytic lymphohistiocytes. She was started on HLH-directed therapy, and later, a diagnosis of ALK-negative anaplastic large cell lymphoma was made on an excisional inguinal lymph node biopsy specimen. Our case emphasizes the importance of prompt recognition, diagnosis, and treatment of HLH while workup for a primary disorder is still being pursued.
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Sarcomatoid carcinoma (SC) of the lung is a rare and aggressive biphasic lung tumor with a 5-year survival of 20%. Early detection and treatment is the only way to improve outcomes in patients with SC of the lung. We present a case of primary SC identified early based on high suspicion. A 56-year-old female with a history of chronic obstructive pulmonary disease (COPD) presented with hemoptysis and exertional dyspnea. Chest X-ray revealed right upper lobe (RUL) opacity and patient was started on antibiotics for pneumonia. Due to the persistence of hemoptysis, a computed tomography scan was performed which showed RUL bronchiectasis with scattered nodular opacities suggestive of an infectious process. The patient underwent bronchoscopy which revealed a pedunculated mass in the RUL biopsy of which was consistent with poorly differentiated SC. Positron-emission tomography scan revealed Flourdeoxyglucose-avid right peri-hilar mass and another nodule in the RUL. The patient was not a surgical candidate because of severe COPD and was started on chemoradiation therapy. SC of the lung can have various presentations and is usually detected at a later stage and hence, difficult to treat. Our case highlights the importance of critical thinking and prompt diagnostic evaluation in high-risk patients with localized bronchiectasis even without an obvious lung mass on imaging.
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Empirical evidence has long suggested that oncogenic driver mutations in non-small-cell lung cancer are mutually independent. However, recent studies reported in pertinent literature reveal that concomitant epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangement can occur in a subset of patients with NSCLC. In order to shed further light on this issue, we report a case of adenocarcinoma of lung harboring both EGFR mutation in exon 21 (L861Q) and ALK rearrangement. This allows us to speculate on likely molecular mechanisms underlying this uncommon phenomenon, while also offering some practical guidelines on the therapeutic options that could benefit patients diagnosed with this dual-positive tumor.
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Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Receptores ErbB/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Mutação/genética , Receptores Proteína Tirosina Quinases/genética , Adenocarcinoma de Pulmão , Idoso , Quinase do Linfoma Anaplásico , Humanos , MasculinoRESUMO
Primary bronchus-associated lymphoid tissue (BALT) lymphoma comprises 5% of non-Hodgkin's lymphoma (NHL) and usually has an indolent course. Synchronous primary lung cancers with BALT lymphoma are seldom seen in patients with adenocarcinoma of the lung. Synchronous squamous cell carcinoma (SCC) and BALT lymphoma is an extremely rare occurrence. We report an unusual case of stage 4 BALT lymphoma requiring treatment that revealed an underlying ipsilateral mass causing a diagnostic dilemma. An 84-year-old female with a history of systemic lupus erythematosus, deep vein thrombosis, and thrombotic microangiopathy presented to the hospital with cough and dyspnea on exertion. A chest X-ray revealed right hemi-thorax opacification and computed tomography (CT) of the chest showed a large right effusion and a soft tissue density extending into the proximal right bronchus. She required repeated thoracentesis until the pleural fluid analysis showed the presence of small lymphocytes and bronchial washings revealed an abnormal B cell population consistent with extranodal marginal zone lymphoma. The patient received four cycles of bendamustine and rituximab resulting in near-complete resolution of the effusion. Four months from diagnosis, imaging showed an increase in the size of the soft tissue density with pathologic fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET). A CT-guided biopsy was consistent with squamous cell lung cancer (SCLC) and radiotherapy was started for clinical stage 2 disease since the patient was not a surgical candidate. BALT lymphoma is a low-grade malignancy classified as extranodal marginal zone lymphoma with a five-year survival rate of over 80%. Several cases of synchronous lung adenocarcinoma and BALT lymphoma have been described. However, our case is among the rare few cases of synchronous occurrence of SCLC with BALT lymphoma. This report highlights the challenges associated with establishing an accurate and timely diagnosis.
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Treatment of lung cancer has been revolutionized with development of drugs that target key driver mutations and immune checkpoints. Until recently, it was believed that these driver mutations are mutually exclusive. However, few reports have emerged citing the presence of both mutations either synchronously or metachronously. We describe a case report of lung adenocarcinoma harboring two driver mutations in the same tumor cells as well as exhibiting high PDL1 expression. We further discuss the possible association of these driver mutations with PDL1 expression.