key: cord-282504-m3npy0om
authors: Kastritis, Efstathios; Wechalekar, Ashutosh; Schönland, Stefan; Sanchorawala, Vaishali; Merlini, Giampaolo; Palladini, Giovanni; Minnema, Monique; Roussel, Murielle; Jaccard, Arnaud; Hegenbart, Ute; Kumar, Shaji; Cibeira, Maria Teresa; Blade, Joan; Dimopoulos, Meletios A.
title: Challenges in the Management of patients with systemic light chain (AL) amyloidosis during the COVID‐19 pandemic
date: 2020-06-01
journal: Br J Haematol
DOI: 10.1111/bjh.16898
sha: 
doc_id: 282504
cord_uid: m3npy0om

The SARS‐CoV‐2‐associated disease (COVID‐19) is primarily manifested as a respiratory tract infection but may affect and cause complications from multiple organ systems (cardiovascular, gastrointestinal, kidneys, hematopoietic and immune systems) while no proven specific therapy exists. The challenges associated with COVID‐19 are even greater for patients with light chain (AL) amyloidosis, a rare multisystemic disease affecting the heart, kidneys, liver, gastrointestinal and nervous system. Patients with AL amyloidosis may need to receive chemotherapy, which probably increases infection risk. Management of COVID‐19 may be particularly challenging in patients with AL amyloidosis who often present with cardiac dysfunction, nephrotic syndrome, neuropathy, low blood pressure and gastrointestinal symptoms. In addition, AL patients may be more susceptible to toxicities of drugs used to manage COVID‐19. Access to health care may be difficult or limited, diagnosis of AL amyloidosis may be delayed with detrimental consequences, treatment administration may need modification. Both patients and treating physicians need to adapt in a new reality.

A pandemic associated with a SARS-CoV2 infection has become major global challenge, causing a health care crisis even in regions with developed health care systems and access to advanced health technologies. A major shift of health care resources has been made towards the management of the pandemic. Mortality is higher among older people, morbidly obese individuals and those with comorbidities, but younger people without major underlying diseases may also develop severe disease (Madjid, et al 2020 , Tang, et al 2020 . Challenges associated with COVID-19 are greater for patients with chronic conditions: they are considered more vulnerable to the infection while still need access to health care for the treatment of their underlying condition, in a situation of restricted resources. In addition, visiting hospitals may increase the risk of infection.

Patients with malignancies were at increased risk, more likely to be diagnosed with COVID-19 and had a higher incidence of severe complications (Liang, et al 2020 , while in some studies recent cancer treatment further increased this risk, but not in others (Robilotti, et al 2020) .

Patients with light chain (AL) amyloidosis have an underlying usually low-grade plasma or B-cell malignancy causing their disease, and they receive chemotherapy (Merlini, et al 2018) , thus, being at higher risk for infections (Kristinsson, et al 2012) , including from SARS-CoV-2, and probably at higher risk for severe COVID-19 (Pietrantonio and Garassino 2020) . AL amyloidosis is a rare and challenging disease and the challenges may be even greater because special situations

This article is protected by copyright. All rights reserved may go unnoticed or unattended amid the pandemic. It is difficult to gather data for the management of the infection, design specific interventions and predict the special challenges in the management of patients with AL, who suffer a multisystemic disease and are facing an infection with multiorgan complications. Finally, there is a perception in the medical community in general about the futility of treatment in advanced amyloidosis, a fallacy that remains persistent in the era of modern treatments, leading to difficulties in decision making for patients who become unwell with COVID-19. The International Society of Amyloidosis (ISA) has issued a short guidance for patients with amyloidosis during the pandemic and called for data collection (2020) . In this review we attempt to describe potential challenges associated with the management of patients with AL amyloidosis during the SARS-CoV2 pandemic.

SARS-CoV-2 invades the host human cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor followed by viral spike protein priming by host cell proteases including TMPRSS2 (Lu, et al 2020) . SARS-CoV-2 primarily affects tissues expressing high levels of ACE2, including the lungs, the heart, the GI and the kidneys (Pan, et al 2020) . COVID-19 is primarily manifested as a respiratory tract infection but affects multiple systems including the cardiovascular, gastrointestinal (GI), kidneys, hematopoietic and immune (Driggin, et al 2020 , Mehta, et al 2020 . In some patients, about 5 to 14 days from the onset of the first symptoms, a surge of clinical manifestations occurs with a pronounced systemic syndrome due to increase of inflammatory mediators and cytokines, characterized as "cytokine storm" (Huang, et al 2020 , Mehta, et al 2020 . This can be associated with microvascular thrombosis of the lung and other vital organs (Ciceri, et al 2020) . Given the spread of the virus in multiple organs and the cytokines which cause a deregulation in tissue homeostasis, this disease may become rapidly fatal.

The diagnosis of amyloidosis requires an increased index of clinical suspicion in the setting of multisystemic disease. Given the non-specific nature of most symptoms, the diagnosis is often missed or delayed (Lousada, et al 2015) . Some tests (including imaging, cardiac and renal biomarkers) can increase or set the suspicion of the disease, but the correct diagnosis depends on tests (biopsies, typing, genetic testing) that require expertise, and which may not be widely available (Merlini, et al 2018) . In the context of current pandemic many of the required resources

This article is protected by copyright. All rights reserved (health personnel or imaging facilities) may not be available, be overwhelmed (Emanuel, et al 2020 , Moghadas, et al 2020 or be difficult to get access to, leading to significant delays in establishing correct diagnosis. In addition, there is a real risk that patients with less severe symptoms may defer to seek medical advice/care due to the fear of COVID-19, resulting in additional delays.

Patients with AL amyloidosis have multisystemic involvement, with different degrees of organ dysfunction and the clinical presentation in case of COVID-19 infection may be more severe, while patterns of COVID-19 evolution may differ from other patients. In addition, therapeutic approaches for COVID-19 may be associated with special challenges. Table 1 presents the systems involved in AL amyloidosis and COVID-19, depicting the complexity of a potential infection in AL patients.

Most patients with AL have cardiac dysfunction of various degrees. Patients with COVID-19 and preexisting cardiovascular disease are at increased risk of severe complications and death (Driggin, et al 2020 , Guo, et al 2020 , Shi, et al 2020 . In addition, COVID-19 has been associated with cardiovascular complications (Chen, et al 2020c , Driggin, et al 2020 , Guo, et al 2020 , Shi, et al 2020 . Patients with AL and heart involvement have a limited reserve to cope with COVID-19 associated cytokine storm, due to autonomic nervous system involvement, heart failure with low cardiac output (Stamatelopoulos, et al 2019 , Wechalekar, et al 2013 , low albumin due to nephrotic syndrome which further enhances extravascular leak, all of which reduce the effectiveness of vasoconstrictors (Stamatelopoulos, et al 2019) . Patients with AL have a continuous loss of myocardial cells, as reflected by elevated troponin levels and pathology studies (Brenner, et al 2004) . COVID-19 has also been associated with myocardial injury , including cases of fulminant myocarditis with cardiogenic shock, as well as associated atrial and ventricular arrhythmias (Driggin, et al 2020 , Hu, et al 2020 . Hypoxia and electrolyte abnormalities are common in severe cases and further increase cardiac arrhythmia risk. There is limited data to understand these specific risks in the general COVID-19 infected population, even less in infected patients with AL amyloidosis. Monitoring of troponins may be useful but the rise due to COVID-19 myocarditis, in patients with AL amyloidosis needs to be interpreted in context of baseline levels which may already be increased. Most patients with AL amyloidosis are also receiving diuretics, placing them at increased risk of electrolyte imbalances, which may further trigger arrhythmias. The potential role of monitoring for arrhythmias (e.g. with telemetry) or

This article is protected by copyright. All rights reserved additional pharmacologic therapies or interventions (such as implantable cardioverter defibrillator) is unknown. Given the poor tolerability of standard therapies for heart failure, such as betablockers and ACE inhibitors in patients with AL amyloidosis (Maurer, et al 2017) , the management of arrhythmias during COVID-19 infection may be particularly difficult. The use of ACE inhibitors or angiotensin-receptor blockers is limited in amyloidosis patients due to poor tolerance, but data do not support their discontinuation specifically for COVID-19(Hanff, et al 2020 , Vaduganathan, et al 2020 .

Therapies under investigation for COVID-19 have been associated with cardiovascular side effects (Driggin, et al 2020) . Hydroxychloroquine (Gautret, et al 2020 , Perinel, et al 2020 and Kim 2020) with or without azithromycin(Gautret, et al 2020) is used in many centers despite the lack of strong data, but this therapy has been associated with QT prolongation, increasing the risk of drug-induced torsades de pointes and drug induced-sudden cardiac death (Juurlink 2020 , Mehra, et al 2020 . This risk can be further amplified if multiple medications which prolong QTc (i.e. azithromycin, lopinavir/ritonavir) are combined. For the general population which needs to be assessed for the risk of QTc prolongation and further management, there is some guidance (Giudicessi, et al) . Baseline QTc status should be obtained and if exceeding 480 ms, in the absence of any drugs or factors prolonging QTc, may identify individuals at increased risk for QT-related ventricular arrhythmias. Patients with a resting QTc≥500 ms, due to any cause (drugs, electrolyte abnormalities etc) have a greater risk for drug-induced arrhythmias; in such patients every effort should be made to correct electrolyte abnormalities (hypocalcemia, hypokalemia and hypomagnesemia), and re-evaluate non-essential medication causing QTc-prolongation. Closer monitoring should be considered, in the context of availability of such devices, staff and equipment protection and resources. The decision to start anti-COVID-19 therapy should depend on the risk-benefit ratio in each individual patient, but due to lack of data, clinical judgment is critical. Tocilizumab has been used in patients with COVID-19 during cytokine storm phase, with some encouraging results (Luo, et al 2020 . It blocks IL-6 receptor, a key cytokine during this phase of the disease, however, several more cytokines are critical. 

This article is protected by copyright. All rights reserved Patients with renal involvement due to AL amyloidosis lose large amounts of albumin in urine, leading to low osmotic pressure, low intravascular volume, low blood pressure, peripheral edema and effusions, and are at increased risk of thromboembolic complications (Bever, et al 2016 , Kastritis, et al 2017 , Palladini, et al 2014 , Sidana, et al 2019 .

Often, they have hypogammaglobulinemia due to urine loses of gamma-globulins further contributing to immunecompromised status while mounting an immune response may be inadequate. Beyond susceptibility to COVID-19, these patients may be more vulnerable to severe complications. It is more challenging to maintain intravascular volume and vascular tone in case of cytokine storm, and they are at risk for acute renal failure. Acute kidney injury common among patients with severe COVID-19, ranging from 0.5%(Guan, et al 2020) up to 25% (Chen, et al 2020c) . Data from China showed that 43.9% of SARS-CoV-2-infected patients, especially those with AKI, developed proteinuria(Cheng, et al 2020) while SARS-CoV-2 could be detected in the urine of patients with severe COVID-19(Guan, et al 2020). Single cell transcriptomic analysis of normal kidneys indicated that there is co-expression of ACE2 and TMPRSS genes in podocytes and proximal straight tubule cells (Pan, et al 2020) , suggesting that kidney might be a target organ for SARS-CoV-2. Thus, the risk for renal complications in patients with AL increases: a combination of direct viral insult with pre-renal complications due to a compromised circulatory system and pre-existing renal dysfunction may lead rapidly to renal failure and may portend a poorer outlook for renal function recovery. Dosing of many drugs may need adjustments due to renal dysfunction, including antibiotics, anti-coagulation and COVID-19-specific therapy. Chloroquine

This article is protected by copyright. All rights reserved is excreted partly (up to 50%) by the kidneys; some acute effects in patients with severe renal dysfunction have been described (Thorogood, et al 2007) , but in the short term is relatively safe.

About 15% to 25% of hydroxychloroquine is cleared by the kidneys (Tett, et al 1993) , which is not dialyzable (Jallouli, et al 2015) and is bound to plasma proteins (McLachlan, et al 1993) ; in nephrotic patients this may cause an additional challenge to predict efficacy and safety.

Experience with remdesivir in patients with eGFR<30 ml/min is limited. A significant proportion of patients with AL amyloidosis require chronic dialysis, due to ESRD; these patients have significantly worse outcome than patients on dialysis for other indications (Leung, et al 2016) . Renal transplantation is increasingly used for the management of ESRD in patients with should be cautious and closely monitored.

This article is protected by copyright. All rights reserved

Gastrointestinal involvement is common in AL, presenting with diarrhea, constipation or alternating between the two, malabsorption, poor nutritional status and sarcopenia (Sattianayagam, et al 2013) , further increasing susceptibility to infections. Diarrhea, a common symptom of COVID-19 was initially neglected; an incidence rate ranging from 2% to 50% of cases is reported(D'Amico, et al 2020). Importantly, it may precede or present along with the respiratory symptoms. SARS-CoV-2 binds to ACE2 and TMPRSS2 that are expressed in the small intestinal epithelia and viral RNA may shed in feces (Chen, et al 2020a , Chen, et al 2020d to be increased in patients with COVID-19, as they are also increased in patients with AL amyloidosis, especially those with cardiac involvement.

This article is protected by copyright. All rights reserved

The therapeutic approach to a patient with AL amyloidosis is individualized based on risk assessment (Merlini, et Cytotoxic and/or immunomodulatory therapy in a patient with AL amyloidosis who has been infected with SARS-CoV-2 should be discontinued until recovery.

AL amyloidosis is a deadly disease; delays in the diagnosis and initiation of therapy may be detrimental. There is no "asymptomatic" AL amyloidosis and most patients are diagnosed due to symptoms and complications. Therapy should start upon confirmation of the diagnosis in almost all cases; very few will be asymptomatic and be diagnosed as part of monitoring for prior MGUS.

Despite the pandemic, indications to start therapy should not change, especially in patients with heart involvement who are at increased risk of amyloidosis-related death, and which in most cases

This article is protected by copyright. All rights reserved exceeds the risk of acquiring COVID-19. It is not possible to define the optimal balance between the need for treatment for AL and the potential risk of infection. There is significant geographic variation in the severity of the pandemic and in some areas the risk of acquiring the infection is low, so that there may be no need for modifications of therapy.

In patients in good clinical status, without cardiac amyloidosis and with stable organ function, for example with isolated renal involvement, one must balance the risks of delayed therapy vs risk of infection, in the each phase of the pandemic. Patients with preserved organ function (low-grade proteinuria and preserved eGFR, low cardiac biomarkers) have the best chances to achieve a remission, improve organ function and avoid complications such as dialysis. However, a short delay for 4-6 weeks, until the pandemic is under control in the area and local health care system adjusts, may be without significant consequences. Patients in relapse are often more "stable" than newly diagnosed ones. In those with slow increase and relatively low levels of circulating FLCs, without heart involvement, the indications to start therapy are anyway unclear ( A common question that arises is whether the treatment should change to a regimen or schedule that reduces hospital visits. Many experts suggested that oral therapies may be used instead of intravenous (IV) or subcutaneous (SC) therapies given in the hospital, or change to regimens that require less frequent visits or even delaying or skipping doses (Banna, et al 2020 , Hanna, et al 2020 , Pietrantonio and Garassino 2020 . These strategies are expected to reduce the exposure of vulnerable patients to hospital environment and other "risk" contacts, while they save resources.

However, these strategies cannot be applied to all cancer patients and a potential risk/benefit assessment should be performed before deciding to change therapy or skip doses/visits. For patients with acute diseases, in which full therapy may be life-saving the treatment should probably not change. This is the case of newly diagnosed AL amyloidosis: a rapid disease control is required in most patients with the most effective and safe therapy and for some patients optimal anti-AL therapy should start even in the midst of the outbreak, for example for patients with cardiac involvement. Treatments for AL amyloidosis have not been developed in the context of multiple randomized studies, thus, we have limited data to propose one therapy over the other or assess the importance of full vs reduced dosing of critical drugs such as bortezomib or For selected patients who have achieved a satisfactory hematologic response (for example CR or VGPR or even PR with organ response), the treating physician may discuss to complete therapy earlier or continue with a less intensive schedule (for example reduce weekly to bi-weekly bortezomib). Steroid dose can be reduced or discontinued in patients on long term lenalidomide, supported by data in myeloma (Larocca, et al 2018) . If HDM/ASCT is planned, delaying or deferring the transplant may be a safer approach (Terpos, et al 2020) . HDM/ASCT requires hospitalization, may require intensive care for management of complications in some patients,

This article is protected by copyright. All rights reserved blood and platelet transfusions and causes severe immunosuppression. In addition, there is no randomized data to support superiority of transplant over modern conventional-dose therapies in patients with AL amyloidosis; deferring transplant may also be an option (Manwani, et al 2018 , Trachtenberg, et al 2019 .

Enrollment in clinical trials has been affected by the pandemics, some have temporarily hold enrolment or modified visit schedule to essential ones, without compromising patient safety and data integrity. However, clinical trials are critical for the development of new therapies for AL amyloidosis and patients should be encouraged to participate.

Hospital visits should be reduced to those necessary, thus, depending on specific local conditions and standards, local laboratories may be used to follow blood and urine parameters, as in other hematologic malignancies (Willan, et al 2020 has been an option that many patients accept. Simple measures like home measurement of weight, pulse rate and blood pressure can allow for meaningful discussion for management of heart failure in these patients. Telemedicine may be helpful, but one needs to take into consideration certain limitations of the distant physician-patient contact; in a rare and complex disease such as AL amyloidosis direct assessment from specialized experienced physicians may be critical.

There is no vaccine or drug to use as prophylaxis for COVID-19. The most effective prophylactic measure is social distancing, isolation of those at risk for severe complications, and strict hygiene rules to reduce the virus transmission rate. There are no specific measures that patients with AL amyloidosis should follow to prevent COVID-19. Vaccination against influenza and Pneumococcus should be continued, since these two diseases are common and may be lethal.

There is no data to support screening for COVID-19 in patients with malignancies, including with

This article is protected by copyright. All rights reserved AL amyloidosis. Local guidelines should be followed; however, the threshold to test a patient with AL in case of suspicion of COVID-19 should be low, due to the potential risk of rapid clinical deterioration in those with multisystemic amyloidotic involvement. PCR testing is the current standard for the diagnosis of acute infection . It is expected that valid serological tests will become available, that will detect specific antibodies to SARS-CoV-2 allowing to detect past or relatively recent infection; however, there is no data regarding the immune status against the virus based on these tests. If a vaccine becomes available, patients with AL amyloidosis should be considered for vaccination, as with other standard vaccines, taking into account its safety and efficacy. Whether patients on daratumumab, bortezomib or rituximab will mount an immune response to the virus, or develop an adequate immune response to vaccination, is unknown and should be prospectively studied. 

Most health care systems have made major adjustments to routine patient care to allow for high influx of patients presenting with COVID-19 infection. The access to monitored beds and intensive care units may be limited. The outcomes of patients with significant multiorgan damage on ICUs is poor. In the current climate, where every ICU bed has become a precious resource, the best utilization for patients with multiorgan AL amyloidosis and severe COVID-19 infection

This article is protected by copyright. All rights reserved remain unknown. In each case, the care must be individualized -a renal AL patient with good potential long term outcome should be a good case for full care. Early discussion about resuscitation status with the patient and family with realistic assessments of outcomes is important to avoid difficult decisions when patients are admitted with COVID-19 and may not have access to supportive family.

COVID-19 is an ongoing pandemic with data changing continuously, and new information acquired with a speed never seen before. Still, prospective data are scarce. For patients with a rare disease such as AL amyloidosis, is even more difficult to collect information on a large scale and make informed decisions. Ongoing data collection, observations and single case reports are all critical since it is expected that the end of the pandemic is not close. At this date more than 600 clinical trial are registered in clinicaltrials.gov for COVID-19. Since there is limited data for this disease, we urge to enroll patients in clinical trials. The ISA drives an initiative to collect data of amyloidosis patients with COVID-19; ASH is also gathering data for patients with hematologic diseases and COVID-19, including patients with AL amyloidosis.

Given the multisystemic involvement, the use of chemoimmunotherapy and the age of most of our patients, it is essential to consider patients with AL amyloidosis as an extremely vulnerable population, with limited reserves to fight COVID-19. As we accumulate data, we will be able to provide better care to our patients, perhaps with more specific and safe therapies for the infection. All patients with systemic AL amyloidosis should be informed of their vulnerability and encouraged to adhere to measures to prevent infection. We should assure our patients with AL amyloidosis that we will continue our efforts to provide optimal care, even during this period of shortages and limited health care resources. 

This article is protected by copyright. All rights reserved Therapy for AL amyloidosis should start upon confirmation of the diagnosis with few exceptions.

Indications to start therapy should not change, especially in patients with heart involvement For low risk patients, a short delay, until local control of the outbreak, may be reasonable

In relapsing patients, with slow increase and relatively low levels of FLCs, without heart involvement, could probably wait and avoid frequent hospital visits.

Omitting bortezomib for MDex is not recommended, since a randomized study showed that BMDex is associated with faster and deeper responses and longer survival than MDex

Using SC bortezomib instead of IV reduces toxicity and in-hospital time and may be delivered in outpatient setting

Oral instead of IV cyclophosphamide has similar pharmacokinetics and efficacy Prophylactic growth factors might be considered in selected patients receiving potentially myelotoxic therapy.

Daratumumab should be given at lower volumes (500 ml) and in shorter time (90 min) after the first few infusions, provided that no major infusion-related reactions occurred.

Daratumumab discontinuation may be considered in patients in complete response or after 2 years of therapy.

Cannot substitute bortezomib with ixazomib, at least in previously untreated patients or those with severe cardiac involvement.

In patients with relapsed disease, ixazomib-based therapy is reasonable

This article is protected by copyright. All rights reserved

There is no data to support any dose modifications of any of the oral anti-plasma cell drugs (IMiDs, ixazomib, alkylating agents)

In selected patients, who have achieved a satisfactory hematologic response and/or organ response, earlier completion of therapy or a less intensive schedule may be reasonable Steroid dose can be reduced or discontinued in patients on long term lenalidomide.

If HDM/ASCT is planned, delaying or deferring the transplant may be a safer approach.

Hospital visits for follow up evaluation should be reduced to those necessary, depending on local conditions and standards. Using local laboratories may be feasible in some areas Specialized testing can be usually postponed for stable patients in hematologic remission and reserved for those in which a major treatment decision needs to be made.

Home measurement of weight, pulse rate and blood pressure should be encouraged and can be helpful to manage heart failure in many patients.

Telemedicine may be helpful, but has major limitations in a rare and complex disease such as AL amyloidosis Accepted Article

Bortezomib therapy-related lung disease in a patient with light chain amyloidosis: A case report

How we treat patients with lung cancer during the SARS-CoV-2 pandemic: primum non nocere

Ninety-minute daratumumab infusion is safe in multiple myeloma

Human amyloidogenic light chains directly impair cardiomyocyte function through an increase in cellular oxidant stress

2020) Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection. bioRxiv

SARS-CoV-2-Positive Sputum and Feces After Conversion of Pharyngeal Samples in Patients With COVID-19

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Cyclophosphamide-bortezomib-dexamethasone (CyBorD) produces rapid and complete hematologic response in patients with AL amyloidosis

Projecting hospital utilization during the COVID-19 outbreaks in the United States

A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis

Daratumumab Plus CyBorD for Patients With Newly Diagnosed AL Amyloidosis: Safety Run-in Results of ANDROMEDA

When should treatment of AL amyloidosis start at relapse? Early, to prevent organ progression

Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis

Towards Optimization of Hydroxychloroquine Dosing in Intensive Care Unit COVID-19 Patients

Caring for Patients With Cancer During the COVID-19 Outbreak in Italy

Clinical features, laboratory characteristics and outcomes of patients with renal versus cardiac light chain amyloidosis

Reactive Vasodilation Predicts Mortality in Primary Systemic Light-Chain Amyloidosis

Plasma pharmacokinetics of cyclophosphamide and its cytotoxic metabolites after intravenous versus oral administration in a randomized, crossover trial

Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

Hematological findings and complications of COVID-19

Insights from pharmacokinetic and pharmacodynamic studies of hydroxychloroquine

The risk of antimalarials in patients with renal failure

Delayed autologous stem cell transplantation following cardiac transplantation experience in patients with cardiac amyloidosis

Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19

Detection of SARS-CoV-2 in Different Types of Clinical Specimens

Accepted Article This article is protected by copyright. All rights reserved

Systemic amyloidosis

A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis

Encouraging impact of doxycycline on early mortality in cardiac light chain (AL) amyloidosis

2020) Care of haematology patients in a COVID-19 epidemic

Use of Hydroxychloroquine and Chloroquine During the COVID-19 Pandemic: What Every Clinician Should Know

SARS-CoV-2 Transmission in Patients With Cancer at a Tertiary Care Hospital in Wuhan, China

Lenalidomide-associated pneumonitis in patients with plasma cell dyscrasias

Rapid response to high-dose steroids of severe bortezomib-related pulmonary complication in multiple myeloma

Liver injury in COVID-19: management and challenges

Clinical characteristics of COVID-19-infected cancer patients: A retrospective case study in three hospitals within Wuhan

First case of COVID-19 in a patient with multiple myeloma successfully treated with tocilizumab

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan