RESUMO
The association between Hairy Cell Leukemia (HCL) and non-tuberculous mycobacterial infections (NTMs) is well described, most notably Mycobacterium kansasii. The exact pathophysiology is not known. We report a case of a 31-year-old male with concomitantly diagnosed HCL and disseminated M kansasii infection who presented with rash, pancytopenia, and bulky axillary lymphadenopathy. The M kansasii was initially diagnosed through use of cell-free DNA detection and confirmed by bone marrow and lymph node cultures. Hairy Cell Leukemia was diagnosed with peripheral flow cytometry and confirmed via the same bone marrow sample. His HCL was put into remission with a single course of cladribine and rituximab chemotherapy; however, his M kansasii infection persisted for 6 months despite aggressive antimicrobial and surgical therapy. It was finally controlled using high-dose rifampin in combination with azithromycin and ethambutol. This case highlights the known link between HCL and M kansasii. Furthermore, it hints at potential causes beyond chemotherapy-induced immunocompromise. Notable possibilities include HCL cells acting as sanctuary sites for M kansasii to evade the immune system, and subclinical M kansasii infections causing NLRP3 inflammasome overactivation to trigger the oncogenic transformation to HCL. More research into the pathophysiologic link between HCL and M kansasii infections would allow for more effective prevention, diagnosis, and treatment of these severe atypical infections which are the major cause of morbidity in the cladribine era of HCL treatment.
Assuntos
Leucemia de Células Pilosas , Infecções por Mycobacterium não Tuberculosas , Mycobacterium kansasii , Humanos , Masculino , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/tratamento farmacológico , Adulto , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/complicações , Cladribina/uso terapêutico , Rifampina/uso terapêutico , Azitromicina/uso terapêutico , Rituximab/uso terapêuticoRESUMO
Haemophagocytic lymphohistiocytosis (HLH) is a rare, aggressive, excess immune activation syndrome. Diagnosis can be challenging due to its several clinical mimics including sepsis. There are multiple aetiologies of HLH; in adults, it is most commonly triggered by infection, malignancy, drugs and autoimmune processes. Failure to rapidly diagnose and treat this condition can be fatal. The management of HLH includes identifying and removing the trigger, supportive management and immunosuppression. Identifying the trigger is essential to inform the most appropriate type of immunosuppression. Here, we report a case of likely drug-induced HLH in a patient recently treated for hairy cell leukaemia. The culprit drug was thought to be co-trimoxazole and this case report highlights a very rare complication of this commonly used drug. We discuss our management approach with steroid monotherapy and withdrawal of co-trimoxazole.
Assuntos
Leucemia de Células Pilosas , Linfo-Histiocitose Hemofagocítica , Neoplasias , Sepse , Humanos , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/induzido quimicamente , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Neoplasias/complicações , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Hairy cell leukemia commonly presents with pancytopenia, indolent course, and predisposition as infectious complications. Current first-line therapeutic options are purine analogues, particularly cladribine, with a high percentage of complete responses and durable remissions. However, their use is poorly investigated in patients affected by severe chronic renal insufficiency. CASE PRESENTATION: Here, we describe a case of HCL in a 68-year-old man affected by multiple comorbidities, including severe chronic renal failure. After a course of interferon-α, the patient received therapy with Cladribine every other week, obtaining a complete hematological remission and improvement of renal function. DISCUSSION: With a different soft schedule of cladribine, the patient was treated adequately, obtaining a complete remission. CONCLUSION: Cladribine can be administered with caution, even in patients with renal failure, with good results.
Assuntos
Antineoplásicos , Leucemia de Células Pilosas , Masculino , Humanos , Idoso , Cladribina/uso terapêutico , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/tratamento farmacológico , Antineoplásicos/uso terapêutico , Interferon-alfa/uso terapêutico , Indução de RemissãoRESUMO
BACKGROUND: Hairy cell leukemia (HCL) is a rare indolent lymphoproliferative disease with an accumulation of mature B lymphocytes with fine reticular chromatin and cytoplasm with typical hairy-like cytoplasmic projections. Rarely, hairy cell leukemia manifests as a lung infiltration. The differential diagnosis between infection and malignant involvement with hairy cell leukemia is often challenging in such situations. METHODS AND RESULTS: We present a 53-year-old female with an uncommon pulmonary involvement with hairy cell leukemia. In addition, we discuss the complicated differential diagnosis of pulmonary disease in patients with hairy cell leukemia and the treatment approach to these patients. CONCLUSION: This case report describes the successful therapy management of a patient with pulmonary involvement by hairy cell leukemia. Therapy with interferon-alfa and cladribine resulted in long-term remission of the underlying disease.
Assuntos
Antineoplásicos , Leucemia de Células Pilosas , Feminino , Humanos , Pessoa de Meia-Idade , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/tratamento farmacológico , Antineoplásicos/uso terapêutico , Cladribina/uso terapêutico , PulmãoRESUMO
Multiple primary malignant tumors are characterized by independent occurrence and development of two or more malignant neoplasms in the same patient. We present an extremely rare case of synchronous double primary malignancies, hairy cell leukemia and hepatocellular carcinoma with lethal outcome. Diagnosis of hepatocellular carcinoma was difficult due to the presence of lymphoproliferative disease, which complicated the visualization of the process using ultrasonography. Carcinomatous emboli of hepatocellular carcinoma in small pulmonary arteries without the formation of metastatic foci have led to clinical manifestations typical of pulmonary embolism, pulmonary hypertension and severe respiratory failure. In lymphoproliferative diseases it is necessary to take into account the possibility of the development of another malignant neoplasm, which can be "buried" by tumor infiltration.
Assuntos
Carcinoma Hepatocelular , Leucemia de Células Pilosas , Neoplasias Hepáticas , Neoplasias Primárias Múltiplas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/patologia , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/patologiaRESUMO
Hairy cell leukaemia (HCL) is a rare B cell malignancy that is associated with the BRAF V600E mutation and has good treatment response to purine analogues. Its presentation synchronously with other malignancies has been rarely reported. Here, we present a patient with HCL with hepatic involvement who was also found to have pancreatic adenocarcinoma concomitantly at the time of diagnosis. Treating these rare cases simultaneously is a challenge clinically. Throughout this case study, we provide our approach on how oncological care teams provided care for this complicated and rare disease state.
Assuntos
Adenocarcinoma , Leucemia de Células Pilosas , Neoplasias Pancreáticas , Humanos , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/tratamento farmacológico , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias PancreáticasRESUMO
The detailed clinical course of coronavirus disease 2019 (COVID-19) in patients with hairy cell leukemia (HCL) is rarely reported. We report the first case of HCL diagnosed with prolonged pancytopenia after COVID-19 infection in Japan. We describe the case of a 56-year-old man who was diagnosed with COVID-19. Computed tomography revealed ground-glass opacities in the bilateral lung lobes as well as splenomegaly. Remdesivir and dexamethasone were administered for the treatment of COVID-19. Since the pancytopenia persisted, bone marrow examination was performed, and he was diagnosed with HCL. Although pancytopenia can occur with COVID-19 alone, clinicians should be alerted regarding the presence of hematologic malignancies in patients in whom pancytopenia persists after COVID-19 treatment or in those with splenomegaly. Further, the condition of all previously reported patients with COVID-19 associated with HCL was severe enough to require mechanical ventilation. This is the first case in which the disease was not severe. The interleukin-6 (IL-6) level was lower in this case than in previous cases, suggesting that racial differences in IL-6 production may have contributed to COVID-19 severity.
Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Coronavirus , Leucemia de Células Pilosas , Pancitopenia , COVID-19/complicações , Humanos , Interleucina-6 , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/patologia , Masculino , Pessoa de Meia-Idade , Pancitopenia/complicações , Esplenomegalia/complicações , Esplenomegalia/patologiaRESUMO
Hairy cell leukaemia (HCL) is a rare B cell malignancy with an indolent course leading to pancytopaenia due to bone marrow infiltration. It has been proposed that HCL patients are at risk of developing a secondary malignancy, with a marked likelihood of the development of other hematologic malignancies including Hodgkin lymphoma and high-grade non-Hodgkin lymphomas. Here, we present the case of two patients who developed diffuse large B cell lymphoma after a long course of hairy cell leukaemia. In the case of the female patient, we report on the occurrence of a third malignant disease, which is very uncommon. With our case descriptions we contribute to the very small number of similar cases reported.
Assuntos
Leucemia de Células Pilosas , Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Linfócitos B/patologia , Medula Óssea/patologia , Feminino , Humanos , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/patologia , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/patologiaRESUMO
Venovenous (VV) extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS) is initiated in patients with high mortality as a potential lifesaving intervention. Hematologic malignancy (HM) is considered a relative exclusion criterion by the Extracorporeal Life Support Organization (ELSO). This case examines the relative contraindication and presents a successful outcome. A healthy 59-year-old male presented with respiratory distress. On arrival his SpO2 on room air was 82%, chest x-ray revealed a lobar infiltrate, complete blood count demonstrated severe leukopenia, and a peripheral blood smear demonstrated cytoplasmic inclusions concerning for hairy cells. He was intubated and decision was made to initiate VV-ECMO during hospital day (HD) 1. Cytometry later confirmed a diagnosis of hairy cell leukemia (HCL). A diagnosis of Legionella was confirmed on HD 5. Initial hospitalization was complicated by progression to complete bilateral lung involvement, pulmonary hemorrhage, recurrent tachyarrhythmias, hemodynamic instability, and acute renal failure. Respiratory status stabilized and eventually began to improve. On HD 27, he was decannulated and later discharged to rehabilitation. Four months later he received inpatient chemotherapy and is currently in full remission. This is a successful outcome in a patient with severe ARDS requiring VV-ECMO in the setting of newly diagnosed HCL. The 10-year survival for treated HCL is near 100%. Due to favorable prognosis, HCL should not be considered a relative contraindication to VV-ECMO. While HM remains a relative exclusion criterion by the ELSO, it is important to analyze each patient individually and make decisions based on evolving bodies of evidence.
Assuntos
Oxigenação por Membrana Extracorpórea , Legionella , Leucemia de Células Pilosas , Pneumonia , Síndrome do Desconforto Respiratório , Humanos , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/diagnóstico , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapiaAssuntos
Antineoplásicos/uso terapêutico , Toxinas Bacterianas/uso terapêutico , Exotoxinas/uso terapêutico , Leucemia de Células Pilosas/tratamento farmacológico , Antineoplásicos/metabolismo , Toxinas Bacterianas/metabolismo , Cladribina/uso terapêutico , Exotoxinas/metabolismo , Humanos , Quimioterapia de Indução/métodos , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/metabolismo , Pentostatina/uso terapêutico , Recidiva , Retratamento/métodos , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismoRESUMO
INTRODUCTION: Infectious complications represent a major cause of morbidity and mortality in hairy cell leukemia (HCL) patients. Due to the immunosuppressive nature of the disease, these patients are frequently affected by opportunistic infections and rare pathogens. Furthermore, cytotoxic chemotherapy might lead to poor or even fatal outcomes in the setting of an active infection. CASE PRESENTATION: We report the case of a 62-year-old HCL patient who presented with recurrent fever episodes, pancytopenia, and mediastinal lymphadenopathy. A treatment decision against purine analogs and for rituximab mono was made as lymph node tissue revealed disseminated Mycobacterium kansasii infection. Together with specific antimycobacterial treatment, rituximab mono led to complete hematologic remission after 6 months without aggravating the accompanying infection. CONCLUSION: Here, we demonstrate successful treatment of HCL with rituximab in a patient with concomitant disseminated M. kansasii infection.
Assuntos
Leucemia de Células Pilosas , Infecções por Mycobacterium não Tuberculosas , Infecções Oportunistas , Rituximab/uso terapêutico , Humanos , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/tratamento farmacológico , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium kansasii , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/tratamento farmacológicoRESUMO
Standard treatment options in classic HCL (cHCL) result in high response rates and near normal life expectancy. However, the disease itself and the recommended standard treatment are associated with profound and prolonged immunosuppression, increasing susceptibility to infections and the risk for a severe course of COVID-19. The Hairy Cell Leukemia Foundation (HCLF) has recently convened experts and discussed different clinical strategies for the management of these patients. The new recommendations adapt the 2017 consensus for the diagnosis and management with cHCL to the current COVID-19 pandemic. They underline the option of active surveillance in patients with low but stable blood counts, consider the use of targeted and non-immunosuppressive agents as first-line treatment for cHCL, and give recommendations on preventive measures against COVID-19.
Assuntos
COVID-19/complicações , Leucemia de Células Pilosas/terapia , COVID-19/epidemiologia , COVID-19/patologia , COVID-19/virologia , Consenso , Humanos , Leucemia de Células Pilosas/complicações , Pandemias , Guias de Prática Clínica como Assunto , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de DoençaRESUMO
Standard therapy in hairy cell leukemia (HCL) is often impossible at the time of deep neutropenia/agranulocytosis with or without infectious complications; it is thus a complex therapeutic problem. Vemurafenib has been used to treat resistant HCL since 2012. Because vemurafenib does not have a myelotoxic effect, we thought that it could be used to treat HCL associated with deep neutropenia/agranulocytosis with or without the development of infectious complications as a preliminary stage before treatment with cladribine. We conducted a retrospective analysis of treatment with vemurafenib followed by a standard course of cladribine provided to 22 patients with deep neutropenia/agranulocytosis with or without infectious complications at diagnosis. Vemurafenib was provided to 22 patients with HCL. The response to therapy was evaluated by complete blood cell count (absolute neutrophil count [ANC], hemoglobin concentration, platelet count, absence of hairy cells), spleen size (assessed by ultrasound), and reduce infectious complications. After that, a standard course of cladribine was provided. Among the 22 patients, the male/female sex ratio was 2:1, and median (range) age was 52 (24-78) years. There were 7 patients with severe infectious manifestations admitted to the intensive care unit, including 1 patient during extracorporeal membrane oxygenation. The median (range) ANC at diagnosis was 0.3 (0.04-0.7) × 109/L. Vemurafenib was provided at a dosage of 240 mg 1 or 2 times a day. In 20 patients, vemurafenib was provided for 3 months or more. In 1 case, the effect was not obtained during 1 month of treatment, and the patient died from severe infectious complications during prolonged agranulocytosis. In 21 patients treated with vemurafenib, an increase of ANC was observed and the infectious complications resolved, thus allowing the application of cladribine therapy. After a standard course (0.1 mg/kg per day for 7 days) of cladribine chemotherapy, 18 patients (90%) experienced complete clinical remission and 2 patients (10%) experienced partial remission with residual splenomegaly. In 1 patient, vemurafenib therapy was still ongoing 2 months after initiating therapy. In cases of proven BRAFV600E mutation, vemurafenib can be successfully used as an effective preliminary therapy in patients with deep neutropenia/agranulocytosis with or without infectious complications before standard therapy with purine analogs.
Assuntos
Infecções/tratamento farmacológico , Leucemia de Células Pilosas/tratamento farmacológico , Neutropenia/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Adulto , Idoso , Feminino , Humanos , Infecções/genética , Infecções/imunologia , Infecções/mortalidade , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/genética , Leucemia de Células Pilosas/mortalidade , Masculino , Pessoa de Meia-Idade , Neutropenia/genética , Neutropenia/imunologia , Neutropenia/mortalidade , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Vemurafenib/farmacologia , Vemurafenib/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: Polycythemia vera (PV) is one of the Philadelphia-negative myeloproliferative neoplasms (MPN), characterized by a pan-myelosis with an erythroid-predominant proliferation mainly driven by somatic JAK2V617F gain-of-function mutation. Hairy cell leukemia (HCL) is a rare B-cell lineage lymphoproliferative disease (LPD) with a typic immunophenotypic profile. BRAFV600E, leading to constitutive activation of the RAF/MEK/ERK signalling pathway and increased cell proliferation, is identified as the driver mutation in almost all cases. Although the risk of developing an LPD is significantly increased in patients with MPN compared with the general population, few cases of co-occurring PV and HCL are reported to date. BRAF is one of the most frequently mutated oncogenes in human cancer and some point mutations were identified in multiple neoplasms in addition to HCL, including follicular and papillary thyroid adenoma and carcinoma. CASE PRESENTATION: Here we report a molecular diagnostic challenge in a woman with a concomitant diagnosis of JAK2V617F PV, BRAFV600E HCL, and HRASQ61K thyroid follicular adenoma. CONCLUSION: In the age of molecular and precision medicine, this case underlines the importance of integrating molecular results with clinical, radiologic, cytologic, and histopathologic investigations.
Assuntos
Leucemia de Células Pilosas/patologia , Mutação , Policitemia Vera/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias da Glândula Tireoide/patologia , Feminino , Humanos , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/genética , Pessoa de Meia-Idade , Policitemia Vera/complicações , Policitemia Vera/tratamento farmacológico , Policitemia Vera/genética , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genéticaAssuntos
Leucemia de Células Pilosas/complicações , Osteólise/etiologia , Adulto , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Humanos , Leucemia de Células Pilosas/diagnóstico por imagem , Leucemia de Células Pilosas/patologia , Masculino , Osteólise/diagnóstico por imagem , Osteólise/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia ComputadorizadaRESUMO
An 83-year-old man was diagnosed with hairy cell leukemia (HCL). He was treated with cladribine and achieved partial remission. However, pancytopenia due to HCL bone marrow involvement progressed slowly. Nine years later, he developed rectal cancer. Prior to the surgery, endoscopy-assisted submucosal ink injection was performed to identify the area of lower intestinal lesions. The following day, he developed septic peritonitis with shock status, perhaps due to his neutropenia and ink injection procedures. Surgical resection of the cancer was presumed unfeasible; therefore, radiation was performed. Several months later, bone marrow examination revealed HCL infiltration with reticulin fibrosis. Chemotherapy regimens with purine nucleoside analogs, which are the standard treatments for HCL, might accentuate the progression of his rectal cancer and enhance the development of severe infections. Therefore, interferon (IFN) -α was administered as an alternative therapy. Three months later, pancytopenia resolved, and bone marrow examination revealed a remarkable improvement in HCL infiltration and marrow fibrosis. With IFN-α therapy, the patient successfully underwent surgical resection of the rectal cancer. Using INF-α, a prompt recovery from pancytopenia might be expected even in a patient with advanced HCL, who requires surgical treatment for a concomitant cancer.
Assuntos
Antineoplásicos , Leucemia de Células Pilosas , Neoplasias Retais , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Medula Óssea , Cladribina/uso terapêutico , Humanos , Interferon-alfa/uso terapêutico , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/tratamento farmacológico , Masculino , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/cirurgiaRESUMO
Skin lesions have been reported in about 10-12% of hairy cell leukemia (HCL) patients. Most are etiologically related to autoimmune or infectious processes, although secondary cutaneous neoplasms and drug-induced lesions are also reported. However, leukemia cutis with the direct infiltration of the skin by leukemic cells is extremely rare in HCL patients. This paper reviews the epidemiology, pathogenesis, clinical symptoms, diagnosis, and approach to treating skin lesions in HCL. A literature review of the MEDLINE database for articles in English concerning hairy cell leukemia, skin lesions, leukemia cutis, adverse events, infectious, cutaneous, drug reactions, neutrophilic dermatoses, secondary neoplasms, and vasculitis was conducted via PubMed. Publications from January 1980 to September 2020 were scrutinized. Additional relevant publications were obtained by reviewing the references from the chosen articles.