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Amyloid : the International Journal of... Mar 2022AL amyloidosis is a systemic amyloidosis and is associated with an underlying plasma cell dyscrasia. High dose intravenous melphalan and autologous stem cell...
AL amyloidosis is a systemic amyloidosis and is associated with an underlying plasma cell dyscrasia. High dose intravenous melphalan and autologous stem cell transplantation was developed for the treatment of AL amyloidosis in the early 1990s and was prompted by its success in multiple myeloma. This application has evolved significantly over the past three decades. These guidelines provide a comprehensive assessment of eligibility criteria, stem cell collection and mobilisation strategies and regimens, risk-adapted melphalan dosing, role for induction and consolidation therapies, specific supportive care management, long-term outcome with respect to survival, haematologic response and relapse and organ responses following stem cell transplantation. These guidelines are developed by the experts in the field on behalf of the stem cell transplant working group of the International Society of Amyloidosis (ISA) and European Haematology Association (EHA).
Topics: Amyloidosis; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Melphalan; Neoplasm Recurrence, Local; Stem Cell Transplantation; Transplantation, Autologous; Treatment Outcome
PubMed: 34783272
DOI: 10.1080/13506129.2021.2002841 -
Oncotarget Apr 2023Systemic Light chain (AL) amyloidosis is a monoclonal plasma cell proliferative disorder characterized by deposition of amyloidogenic monoclonal light chain fragments... (Review)
Review
Systemic Light chain (AL) amyloidosis is a monoclonal plasma cell proliferative disorder characterized by deposition of amyloidogenic monoclonal light chain fragments causing organ dysfunction. It is a fatal disease and if not diagnosed and treated early can lead to organ failure and potentially death. The renal system along with the cardiovascular system are the most common organs involved but other organs such as gut and liver can be involved as well. The initial evaluation of patients requires confirming the diagnosis with tissue biopsy and staining with Congo red followed by confirmatory typing with mass spectrometry of the Congo red positive tissue. Then establishing the extent of the organs involvement by various staging and biomarkers testing. The treatment options and the tolerability of therapy depend on the disease staging, frailty, and co-morbidities. The autologous hematopoietic cell transplantation (HCT) after high dose melphalan therapy is an effective strategy which is usually done after initial bortezomib induction therapy. Unfortunately, most systemic AL amyloidosis patients are not candidate for HCT due to frailty, old age, multi-organ involvement, renal and heart failure at the time of diagnosis. While it is widely accepted that the patients need to be treated until they achieve complete hematologic response, the maintenance therapy after HCT is not well established in AL amyloidosis. In this review, we report the literature on the latest treatment updates of AL amyloidosis and the ongoing clinical trials highlighting the future treatments.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Congo Red; Frailty; Melphalan; Hematopoietic Stem Cell Transplantation; Paraproteinemias
PubMed: 37185672
DOI: 10.18632/oncotarget.28415 -
Blood Cancer Journal May 2021Amyloid light chain (AL) amyloidosis is among the more common and more severe of the amyloidoses usually involving the slow proliferation of a bone-marrow-residing... (Review)
Review
Amyloid light chain (AL) amyloidosis is among the more common and more severe of the amyloidoses usually involving the slow proliferation of a bone-marrow-residing plasma cell (PC) clone and the secretion of unstable immunoglobulin-free light chains (FLC) that infiltrate peripheral tissues and result in detrimental end-organ damage. Disease presentation is rather vague, and the hallmark of treatment is early diagnosis before irreversible end-organ damage. Once diagnosed, treatment decision is transplant-driven whereby ~20% of patients are eligible for autologous stem cell transplantation (ASCT) with or without bortezomib-based induction. In the setting of ASCT-ineligibility, bortezomib plays a central role in upfront treatment with the recent addition of daratumumab to the current emerging standard of care. In general, management of AL amyloidosis is aimed at achieving deep, durable responses with very close monitoring for early detection of relapse/refractory disease. This article provides a comprehensive review of the management of patients with AL amyloidosis including goals of therapy, current treatment guidelines in the setting of both ASCT-eligibility and ineligibility, treatment response monitoring recommendations, toxicity management, and treatment of relapse/refractory disease.
Topics: Animals; Antineoplastic Agents; Bortezomib; Disease Management; Humans; Immunoglobulin Light-chain Amyloidosis; Neoplasm Recurrence, Local; Stem Cell Transplantation; Transplantation, Autologous
PubMed: 34006856
DOI: 10.1038/s41408-021-00486-4 -
American Journal of Hematology Jun 2022Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in...
DISEASE OVERVIEW
Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical smoldering multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS)."
DIAGNOSIS
Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for the diagnosis of AL amyloidosis. Invasive organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy.
PROGNOSIS
N-terminal pro-brain natriuretic peptide (NT-proBNP or BNP), serum troponin T (or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four groups of similar size; median survivals are 73, 35, 15, and 5 months.
THERAPY
All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first-line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a complete response (CR). In patients failing to achieve this depth of response options for consolidation include pomalidomide, stem cell transplantation, venetoclax, and bendamustine.
FUTURE CHALLENGES
Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure. Trials of antibodies to catabolize deposited fibrils are underway.
Topics: Amyloidosis; Bortezomib; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Prognosis
PubMed: 35429180
DOI: 10.1002/ajh.26569 -
Mayo Clinic Proceedings Jun 2021Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder leading to progressive and life-threatening organ failure. The heart and the kidneys are the... (Review)
Review
Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder leading to progressive and life-threatening organ failure. The heart and the kidneys are the most commonly involved organs, but almost any organ can be involved. Because of the nonspecific presentation, diagnosis delay is common, and many patients are diagnosed with advanced organ failure. In the era of effective therapies and improved outcomes for patients with AL amyloidosis, the importance of early recognition is further enhanced as the ability to reverse organ dysfunction is limited in those with a profound organ failure. As AL amyloidosis is an uncommon disorder and given patients' frailty and high early death rate, management of this complex condition is challenging. The treatment of AL amyloidosis is based on various anti-plasma cell therapies. These therapies are borrowed and customized from the treatment of multiple myeloma, a more common disorder. However, a growing number of phase 2/3 studies dedicated to the AL amyloidosis population are being performed, making treatment decisions more evidence-based. Supportive care is an integral part of management of AL amyloidosis because of the inherent organ dysfunction, limiting the delivery of effective therapy. This extensive review brings an updated summary on the management of AL amyloidosis, sectioned into the 3 pillars for survival improvement: early disease recognition, anti-plasma cell therapy, and supportive care.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Multiple Myeloma; Risk Assessment
PubMed: 34088417
DOI: 10.1016/j.mayocp.2021.03.012 -
Hematology/oncology Clinics of North... Dec 2020
Topics: History, 19th Century; History, 20th Century; History, 21st Century; Humans; Immunoglobulin Light-chain Amyloidosis
PubMed: 33099437
DOI: 10.1016/j.hoc.2020.08.008 -
Amyloid : the International Journal of... Mar 2023This guideline has been developed jointly by the European Society of Haematology and International Society of Amyloidosis recommending non-transplant chemotherapy... (Review)
Review
BACKGROUND
This guideline has been developed jointly by the European Society of Haematology and International Society of Amyloidosis recommending non-transplant chemotherapy treatment for patients with AL amyloidosis.
METHODS
A review of literature and grading of evidence as well as expert recommendations by the ESH and ISA guideline committees.
RESULTS AND CONCLUSIONS
The recommendations of this committee suggest that treatment follows the clinical presentation which determines treatment tolerance tempered by potential side effects to select and modify use of drugs in AL amyloidosis. All patients with AL amyloidosis should be considered for clinical trials where available. Daratumumab-VCD is recommended from most untreated patients (VCD or VMDex if daratumumab is unavailable). At relapse, the two guiding principles are the depth and duration of initial response, use of a class of agents not previously exposed as well as the limitation imposed by patients' fitness/frailty and end organ damage. Targeted agents like venetoclax need urgent prospective evaluation. Future prospective trials should include advanced stage patients to allow for evidence-based treatment decisions. Therapies targeting amyloid fibrils or those reducing the proteotoxicity of amyloidogenic light chains/oligomers are urgently needed.
Topics: Humans; Amyloid; Amyloidosis; Drug-Related Side Effects and Adverse Reactions; Immunoglobulin Light-chain Amyloidosis; Neoplasm Recurrence, Local
PubMed: 35838162
DOI: 10.1080/13506129.2022.2093635 -
Hematology/oncology Clinics of North... Dec 2020Please add expansion for AL. Hematologic disease control combined with solid organ transplantation can result in long-term survival in selected patients with light chain... (Review)
Review
Please add expansion for AL. Hematologic disease control combined with solid organ transplantation can result in long-term survival in selected patients with light chain (AL) amyloidosis and limited other organ involvement. Restoration of critical cardiac function with organ transplantation can render patients eligible for effective disease-directed therapies, including high-dose therapy and autologous stem cell transplantation. Access to directed-donor organs, exchange programs for renal transplantation, and extended-donor organs for cardiac transplantation improves the availability of organs for patients with AL amyloidosis. Disease recurrence in the graft and progression in other organs remain concerns but often can be managed with a variety of effective plasma cell-directed therapies.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Organ Transplantation; Transplantation Conditioning; Transplantation, Autologous
PubMed: 33099431
DOI: 10.1016/j.hoc.2020.08.006 -
Innere Medizin (Heidelberg, Germany) Sep 2023Light chain amyloidosis (AL) is a rare protein deposition disease. It is caused by a clonal plasma cell or B‑cell disease in the bone marrow. With the exception of... (Review)
Review
Light chain amyloidosis (AL) is a rare protein deposition disease. It is caused by a clonal plasma cell or B‑cell disease in the bone marrow. With the exception of the central nervous system, all organs can be affected by amyloid deposits. Cardiac involvement is the most frequent organ manifestation that leads to significantly increased mortality when it is diagnosed at an advanced stage. The causal treatment of AL amyloidosis is reduction of amyloidogenic light chains by chemotherapy. Early diagnosis of the disease is essential to reduce early mortality, to effectively treat patients and to prevent further deterioration of organ function. New treatment approaches for AL amyloidosis are aimed at inhibiting amyloid formation or degradation of amyloid in organs.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Amyloid
PubMed: 37540260
DOI: 10.1007/s00108-023-01568-0 -
Journal of Cutaneous Medicine and... 2022
Topics: Amyloidosis, Familial; Humans; Immunoglobulin Light-chain Amyloidosis; Skin Diseases, Genetic
PubMed: 34878924
DOI: 10.1177/12034754211064314