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Dermatomyositis (DM) and polymyositis are idiopathic inflammatory myopathies (IIMs), most associated with solid organ malignancies, and less commonly hematological malignancies. We discuss a case of DM associated with diffuse large B-cell lymphoma, followed by a review of literature on the pathogenesis, clinical course, treatment, and prognosis. Various challenges with the diagnosis and management of underlying lymphoproliferative disorders (LPDs) in patients with IIM are discussed. The case demonstrates the importance of being vigilant of the association between IIM and LPD. Cancer screening in patients with IIM is discussed, including the recently published International Guideline for IIM-Associated Cancer Screening. More research is required to address knowledge gaps in cancer screening in IIM.
Assuntos
Dermatomiosite , Linfoma Difuso de Grandes Células B , Humanos , Dermatomiosite/diagnóstico , Dermatomiosite/complicações , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/complicações , Transtornos Linfoproliferativos/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Detecção Precoce de Câncer , PrognósticoRESUMO
PCAB (prednisone, cyclophosphamide, doxorubicin, carmustine) is a single-day regimen previously used for induction and now in relapsed/refractory multiple myeloma (RRMM). We retrospectively analysed the outcomes of 85 patients from five Australian centres. These included 30 patients (35.3%) who received PCAB with one additional agent (bortezomib most frequently). Median age of the patients was 65 years (37-80), with a median of four (1-8) prior lines of therapy. ORR was 37% (CR 4.9%). Median progression free survival and overall survival were 4.4 months (95% CI 3.5-6.7) and 7.4 months (95% CI 6.4-10.2), respectively. Extramedullary disease (EMD) was associated with shorter survival. Grade 3 or 4 cytopenia and febrile neutropenia occurred in 76.2% and 39.1%, respectively, with six (7.1%) treatment-related mortalities. Median inpatient stay was 3.3 days/28-day cycle (IQR 0.6-13), and for patients who died, a median of 20.2% of days alive were spent inpatient (IQR 6.4-39.1%). Three patients were successfully bridged to CAR T-cell therapy using PCAB, despite being penta-exposed and having EMD. PCAB may be considered as a useful salvage therapy amongst other polychemotherapy regimens in late relapse. Further studies is warranted to investigate and define its role as a bridging therapy to novel therapeutics.
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Drug-induced thrombotic microangiopathy (DITMA) is a life-threatening condition which may be immune or nonimmune mediated. Quinine is the most implicated drug in immune-mediated DITMA. However, the optimal treatment is unclear. Complement inhibition by eculizumab has demonstrated success in many DITMA (e.g., carfilzomib, gemcitabine, and tacrolimus), but there are limited data in DITMA, including quinine-associated cases. A 55-year-old female was diagnosed with quinine-associated thrombotic microangiopathy (TMA), as confirmed by a positive quinine-dependent platelet-associated antibody. This was successfully treated with eculizumab with complete resolution of thrombocytopenia and anemia by 1 and 6 weeks. She required hemodialysis for a month and gained full recovery of renal function. We discuss various challenges with the diagnosis and management of DITMA. We also review published data on the use of eculizumab in various DITMA. Our case demonstrates successful treatment of quinine-induced TMA with eculizumab. We recommend further studies to assess the efficacy of complement inhibition in quinine and other DITMA.
Assuntos
Quinina , Microangiopatias Trombóticas , Feminino , Humanos , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/uso terapêutico , Quinina/efeitos adversos , Diálise Renal , Microangiopatias Trombóticas/tratamento farmacológicoRESUMO
Introduction: Acquired angioedema due to C1 esterase inhibitor deficiency (C1INH-AAE) is most associated with lymphoproliferative disorders (LPDs), particularly low-grade B-cell subtypes. The condition remains under-recognized with long diagnostic delays due to various challenges including a lack of awareness of the condition. Case Presentation: We discuss 4 cases of C1INH-AAE associated with low-grade B-cell LPDs, including various diagnostic and management challenges. As our cases illustrate, constitutional symptoms or overt manifestations of LPD at diagnosis are often absent. Hence, a comprehensive multimodal approach to screening for an underlying B-LPD is important when a diagnosis of acquired angioedema is made. Levels of complement C4, C1q, and C1INH are useful for diagnosing C1INH-AAE and for monitoring disease activity. Changes in these parameters may also indicate relapse of the underlying hematological malignancy. Treating the underlying disorder is important as this commonly leads to clinical improvement with decreased episodes of angioedema and normalization of complement studies. Conclusion: Awareness of C1INH-AAE can lead to an early diagnosis of hematological malignancies. The absence of constitutional symptoms emphasizes the need for a comprehensive multimodal approach to screening for LPD in C1INH-AAE. C4, C1INH level, and function are useful for monitoring disease activity.
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Obinutuzumab is a third-generation anti-CD20 monoclonal antibody widely used in the treatment of B-lymphoproliferative disorders but infrequently associated with severe thrombocytopenia, which can be life-threatening. The pathophysiology is unclear, but platelet clearance can be extremely rapid (usually within 24 h). In a retrospective case series, we have identified four cases among 149 recipients of obinutuzumab-containing chemotherapy regimens between 2015 and 2022 treated for haematological malignancies in Canberra, Australia (frequency 2.7%). We illustrate four cases of obinutuzumab-induced thrombocytopenia with a review of the literature. Research is required to identify the pathophysiology and improve early recognition and management of the condition in the context of multiagent chemotherapy.
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Leucemia Linfocítica Crônica de Células B , Trombocitopenia , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Estudos Retrospectivos , Anticorpos Monoclonais Humanizados/efeitos adversos , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológicoRESUMO
Acquired hypogammaglobulinemia or secondary immunodeficiency (SID) occurs commonly in hematological malignancies with increasing incidence and complexity in the era of modern therapies. Despite current practice of immunoglobulin replacement (IgRT) in SID, the evidence is lacking, especially for newer treatments. We discuss the current evidence for IgRT in various disease groups including issues, such as actual or ideal body weight (IBW)-based dosing, length of treatment, antibiotic prophylaxis, and vaccination. Incidence of SID with newer treatment is lacking. While there is a trend toward decreased respiratory infections and hospitalizations with IgRT, this is not consistent across all disease course or treatment groups. Dosing and indications for cessation of IgRT are also inadequately characterized. Further randomized controlled trials (RCTs) and observational studies are required to assess the optimal indications, timing, and duration of IgRT to improve the efficacy, safety, and cost-effectiveness. Assessment of alternative and adjunctive therapies, such as vaccination and antibiotic prophylaxis could also improve the outcomes and costs.
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Neoplasias Hematológicas , Síndromes de Imunodeficiência , Humanos , Imunoglobulinas , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/terapia , Vacinação/efeitos adversos , Neoplasias Hematológicas/complicações , AntibioticoprofilaxiaRESUMO
G-CSF only mobilisation has been shown to enhance immune reconstitution early post-transplant, but its impact on survival remains uncertain. We undertook a retrospective review of 12 transplant centres to examine overall survival (OS) and time to next treatment (TTNT) following melphalan autograft according to mobilisation method (G-CSF only vs. G-CSF and cyclophosphamide [CY]) in myeloma patients uniformly treated with bortezomib, cyclophosphamide and dexamethasone induction. Six centres had a policy to use G-CSF alone and six to use G-CSF + CY. Patients failing G-CSF only mobilisation were excluded. 601 patients were included: 328: G-CSF + CY, 273: G-CSF only. Mobilisation arms were comparable in terms of age, Revised International Staging System (R-ISS) groups and post-transplant maintenance therapy. G-CSF + CY mobilisation generated higher median CD34 + yields (8.6 vs. 5.5 × 106/kg, p < 0.001). G-CSF only mobilisation was associated with a significantly higher lymphocyte count at day 15 post-infusion (p < 0.001). G-CSF only mobilisation was associated with significantly improved OS (aHR = 0.60, 95%CI 0.39-0.92, p = 0.018) and TTNT (aHR = 0.77, 95%CI 0.60-0.97, p = 0.027), when adjusting for R-ISS, disease-response pre-transplant, age and post-transplant maintenance therapy. This survival benefit may reflect selection bias in excluding patients with unsuccessful G-CSF only mobilisation or may be due to enhanced autograft immune cell content and improved early immune reconstitution.
Assuntos
Reconstituição Imune , Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Autoenxertos , Bortezomib/uso terapêutico , Ciclofosfamida/uso terapêutico , Dexametasona/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas , Humanos , Melfalan/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Estudos RetrospectivosRESUMO
BACKGROUND: Chronic right ventricular pacing may contribute to deterioration in left ventricular ejection fraction (LVEF). The aim of the study was to identify the prevalence of pacing-induced cardiomyopathy (PICM) in patients with chronic right ventricular pacing. METHODS: Patients attending a pacemaker clinic were retrospectively identified as having had transthoracic echocardiographic LVEF measurement during the 12 months prior to device implantation. Those with cardioverter-defibrillators or biventricular devices were excluded. The remaining patients were invited back for a repeat echocardiogram. Three (3) different definitions of PICM were employed: 1) follow-up LVEF of ≤40% if baseline LVEF was ≥50%, or an absolute reduction in LVEF ≥5% if baseline LVEF was <50%; 2) follow-up LVEF of ≤40% if baseline LVEF was ≥50%, or an absolute reduction in LVEF ≥10% if baseline LVEF was ≤50%; 3) absolute reduction in LVEF ≥10% irrespective of baseline LVEF. Alternate causes of cardiomyopathy were excluded following a chart review. RESULTS: The study cohort of 118 included 67 males (mean age 77.8±10.5years) and 51 females (mean age 76.8±11.2years). The mean time between baseline and follow-up echocardiograms was 3.5+1.4years (range 1.5-6.4 years). The prevalence of PICM ranged from 5.9 to 39.0% depending on PICM definition. Multivariate analysis found that PICM was significantly associated with ventricular pacing burden (p=0.013). CONCLUSIONS: The prevalence of pacing induced cardiomyopathy is dependent on current accepted clinical definitions. A clear definition of PICM is required for a better understanding of the clinical implications of right ventricular pacing.