Diagnosis and treatment of AL amyloidosis

AL (amyloid light-chain) amyloidosis is a plasma cell disorder in which depositions of amyloid light-chain protein cause progressive organ failure. Virtually all patients with AL amyloidosis have a monoclonal protein in the serum or urine or a monoclonal population of plasma cells in the bone marrow. The most common target organ is the kidney and renal amyloidosis manifests as proteinuria or nephrotic syndrome in 3/4 of the patients. The median survival is one to two years. It is important to recognize that the amyloidosis is a dynamic process, and chemotherapy induced reduction of the activity of the plasma cell clone reduces the supply of the amyloid precursor protein and can result in a major regression of the deposits. Amyloid-related nephrotic syndrome and renal failure are potentially reversible. Conventional-dose melphalan as standard treatment can prolong the median duration of survival about 10 months, but the clinical response rates with improvement of impaired organ function are low with a slow response. Upfront high-dose chemotherapy with autologous peripheral blood stem cell transplantation is much more effective and can result in a major improvement of the patient's clinical condition, but the treatment-related toxicity can be relevant due to impaired organ function. The initial use of a conventional-dose chemotherapy consisting of vincristine, doxorubicin and dexamethasone (VAD) to achieve a remission and subsequent high-dose chemotherapy is the concept of a German trial. The improvement of the condition of the patient by this approach may increase the tolerability of high-dose chemotherapy and reduce transplantation-related problems.     

How to treat patients with systemic amyloid light chain amyloidosis? Comparison of high-dose melphalan, low-dose chemotherapy and no chemotherapy in patients with or without cardiac amyloidosis

Background

High-dose melphalan and autologous stem cell transplantation (HDM) is an effective treatment for systemic amyloid light chain (AL) amyloidosis but the eligibility criteria exclude many patients with this disorder. The aim of this study was to determine appropriate treatment strategies for systemic AL amyloidosis according to each patient??s clinical condition in Japan.

Methods

Historical cohort study. Fifty-three patients with systemic AL amyloidosis (those with malignancies were excluded) were treated in our hospital with HDM (15 patients), melphalan + prednisolone (MP) (17 patients), vincristine + adriamycin + dexamethasone (VAD) (11 patients), or supportive treatment (no chemotherapy, 10 patients). We compared the survival rates among these treatment groups.

Results

Mean survival was significantly longer in the HDM group than in the other three groups (P?P?Conclusions HDM should be considered the treatment of choice in eligible patients with systemic AL amyloidosis even in the presence of cardiac amyloidosis. If HDM is not eligible, indications for VAD therapy should be carefully evaluated in patients with cardiac amyloidosis.     

Hyperkalemia: An adaptive response in chronic renal insufficiency

Immunoglobulin light chain amyloidosis and the kidney. Amyloidosis (AL) is a common cause of nephrotic syndrome in nondiabetic, nonhypertensive adults. All adult patients with nephrotic syndrome should have immunofixation of serum and urine as a screen. The finding of a monoclonal protein, particularly of lambda type, should lead to a subcutaneous fat aspirate or bone marrow biopsy to search for amyloid deposits. When the result of either test is positive, a kidney biopsy is unnecessary. The prognosis of patients who have renal amyloidosis depends on the concentration of serum creatinine at presentation and whether an echocardiographic evaluation demonstrates infiltrative cardiomyopathy. Most therapies are directed against the plasma cell dyscrasia present in all patients with AL and can include melphalan and prednisone, high-dose dexamethasone, and, most recently, peripheral blood stem cell transplantation.     

New advances in renal amyloidosis

Renal amyloidosis is a rare and intractable disease that accounts for 0.2% of the original kidney diseases of dialysis patients in Japan. However, the number of patients with renal amyloidosis seems to be increasing in recent years. There have been some new concepts focusing on the mechanism of amyloidogenesis, such as molecular chaperones, seeding mechanism, and genetic polymorphisms of precursor protein. Clinical and histological features of renal amyloidosis vary according to the type. Significantly higher levels of urinary protein excretion are seen in the AL type, whereas microscopic haematuria is more prominent in the AA type. Histologically, amyloid deposition of AL type has stronger predilection for GBM than mesangium, and spicule formation is more frequently observed. In contrast, AA type has a higher affinity to TBM and interstitial area. For the histological diagnosis of renal amyloidosis, plural staining methods including Congo-red, Daylon and thioflavin-T stains are available. Combinations of these staining methods are necessary for establishing the precise diagnosis. The more recent and intensive treatments for renal amyloidosis are expected to improve patient outcome. For AL amyloidosis, high-dose melphalan plus high-dose dexamethasone or VAD, in conjunction with bone marrow stem cells transplantation, have shown a definitive effect on reducing urinary protein excretion. The biological agent, tumor necrosis factor (TNFα) blocker, improves the renal function in AA-type renal amyloidosis, as well as suppresses the inflammatory reactions in patients with rheumatoid arthritis. Clinical advances have been made in various aspects of renal amyloidosis.     

Successful treatment of nephrotic syndrome due to systemic AL amyloidosis after autologous stem cell transplantation: renal response is an important therapeutic end point

Primary systemic (AL) amyloidosis involves vital organs from the early phase of illness, resulting in poor prognosis. Today, high-dose melphalan followed by autologous peripheral blood stem cell transplantation is an effective treatment for systemic AL amyloidosis. We report a patient with nephrotic syndrome due to systemic AL amyloidosis, who was successfully treated with autologous peripheral blood stem cell transplantation. At follow-up 36 months from ASCT, the patient showed a significant improvement in the signs of peripheral neuropathy and reduction in proteinuria without further organ involvement. Due to poor prognosis with conventional therapy, autologous stem cell transplantation should be considered for treatment in patients with systemic AL amyloidosis, and favorable outcome is ensured with achievement of renal response after ASCT.     

AL amyloidosis with IgD-lambda monoclonal gammopathy and lambda-type Bence-Jones protein: successful treatment by autologous stem cell transplantation

A 45-year-old Japanese woman had been diagnosed with monoclonal gammopathy of undetermined significance (MGUS) featuring urinary Bence-Jones protein of the lambda type (BJP-lambda) for 11 years. She then developed eyelid purpura, dyspnea, and flank pain. Abdominal CT scans revealed renal infarction. Biopsy of the kidney, heart, jejunum, and skin demonstrated amyloid deposits in the vessel walls, but not in the glomeruli. She was diagnosed as having AL amyloidosis with IgD-lambda monoclonal gammopathy and BJP-lambda. Autologous stem cell transplantation (SCT) was done after chemotherapy with vincristine, daunorubicin, dexamethasone (VAD), and high-dose melphalan (HDM). This reduced the IgD level from 156 to 0.1 mg/dL, along with the disappearance of BJP, despite cerebral infarction during chemotherapy. We recommend SCT for patients with IgD-associated AL amyloidosis.     

Current treatment of AL amyloidosis

Systemic AL amyloidosis is a rare complication of monoclonal gammopathies. Renal manifestations are frequent, mostly characterized by heavy proteinuria, with nephrotic syndrome and renal failure in more than half of the patients at diagnosis. Without treatment, median survival does not exceed 12 months. Amyloid heart disease and diffusion of amyloid deposits are associated with reduced survival. Treatment of systemic AL amyloidosis has been profoundly modified with the introduction of international criteria for the definition of organ involvement and hematologic response, and with the use of sensitive tests for the measurement of serum-free light chain levels. Melphalan plus dexamethasone is now established as the gold standard for first line treatment of systemic AL, with similar efficacy and reduced treatment-related mortality compared to high-dose therapy. Modern chemotherapy regimens, based on the use of novel agents such as bortezomib and lenalidomide, might further improve patient survival.     

AL amyloidosis with temporal artery involvement simulates giant-cell arteritis

Light-chain (AL) amyloidosis may present with features suggesting vasculitis, including giant-cell arteritis (GCA). We describe a case of an 80-year-old man, who initially presented with bilateral jaw claudication, bi-temporal headache and arthralgia, however a temporal-artery biopsy then revealed AL amyloidosis. A diagnosis of AL amyloidosis complicating multiple myelome simulates GCA and polymyalgia rheumatica was established. The patient was successfully treated with melphalan and dexamethasone: the free kappa light chains decreased, the patient's jaw claudication and headache disappeared. Then we discuss similarities between GCA and AL amyloidosis and potential confusion in diagnosis. We suggest that, in patients with clinical features of GCA without any temporal-artery typical findings, specimens are stained with Congo red, which then results in a different diagnosis and treatment.     

Incidence and outcome of acute renal failure complicating autologous stem cell transplantation for AL amyloidosis

BACKGROUND: High-dose intravenous melphalan and autologous peripheral blood stem cell transplantation (HDM/SCT) is an effective treatment for AL amyloidosis but is associated with significant toxicity, including the development of acute renal failure (ARF). The incidence and outcome of ARF as a complication of such treatment is not known. METHODS: All AL amyloidosis patients treated with HDM/SCT at a single institution between July 1, 1994 and May 31, 2000 were included in the analysis unless they were dialysis-dependent prior to treatment. Baseline data were collected prospectively. Treatment-related data were obtained from a prospectively maintained database and medical record review. ARF was defined as either a >/=1 mg/dL increase in serum creatinine or a doubling of serum creatinine to >/=1.5 mg/dL for at least 2 days. Recovery of renal function was defined as a return of serum creatinine to less than or within 0.5 mg/dL of the pretreatment value or the ability to discontinue dialysis initiated as a result of ARF. RESULTS: ARF occurred in 37 of 173 patients (21%). Initiation of dialysis was required in nine patients (5%). Forty-six percent of patients with ARF, including four of nine who required dialysis, had recovery of renal function. Baseline clinical variables that were independent predictors of transplant-associated ARF included creatinine clearance, proteinuria, and cardiac amyloidosis. Treatment-related variables associated with ARF included melphalan dose and bacteremia. ARF was associated with reduced survival at 90 days but did not have an impact on overall survival at a median follow-up of 2.9 years. CONCLUSION: ARF is a frequent but often reversible complication of HDM/SCT for AL amyloidosis. Specific clinical and treatment-related factors are associated with the development of this complication.     

High-dose intravenous melphalan with autologous stem cell transplantation in AL amyloidosis-associated end-stage renal disease

BACKGROUND: The development of end-stage renal disease (ESRD) is common among patients with amyloid light-chain AL amyloidosis-associated renal disease and survival of these patients is poor. High-dose intravenous melphalan and autologous stem cell transplantation induce remission of the plasma cell dyscrasia in a significant proportion of patients with AL amyloidosis. The efficacy and tolerability of such treatment for patients with AL amyloidosis-associated ESRD are unknown. METHODS: Between June 1994 and June 2000, 15 patients with AL amyloidosis-associated ESRD were treated with intravenous melphalan (70 to 200 mg/m2) and autologous peripheral blood stem cell transplantation. Clinical and laboratory data were prospectively collected prior to treatment, during the peritransplant period, and at 3 months, 12 months, and annually thereafter. Treatment outcomes and toxicities were compared with 180 non-ESRD patients treated during the study period. RESULTS: Eight of 15 patients (53%) had a hematologic complete response following treatment. Two patients (13%) died during the peritransplant period. Transfusion requirements were greater and there was a trend toward increased severity of mucositis in the ESRD patients compared with the non-ESRD patients. Median survival for the ESRD patients with a hematologic complete response was 4.5 years. Five patients with hematologic complete response have either undergone or are awaiting renal transplantation. CONCLUSION: High-dose intravenous melphalan with stem cell transplantation is an effective treatment in selected patients with AL amyloidosis-associated ESRD. Although the toxicity profile is greater in ESRD patients, the treatment offers the possibility of successful renal transplantation if hematologic remission is achieved. This treatment should be considered for patients with AL amyloidosis-associated ESRD.     

Successful treatment of primary AL amyloidosis by VAD therapy, high-dose melphalan, and autologous peripheral stem cell transplantation

We report a 58-year-old Japanese man with primary systemic AL amyloidosis who achieved disappearance of proteinuria including Bence-Jones protein (λ-type) after two courses of VAD therapy (vincristine, doxorubicin, and dexamethasone) and subsequent high-dose melphalan, followed by autologous peripheral blood stem cell transplantation. Because this patient did not have any apparent amyloidosis-related heart or liver damage and met all of the eligibility criteria for this therapy, this treatment was performed. Both proteinuria and M-protein disappeared completely, and he is doing well clinically at 19 months after treatment. However, amyloid deposits were still found in the kidneys, including the glomeruli and tubulointerstitium, when renal biopsy was done at 8 months after treatment. In the future, we may reach a time when clinical remission corresponds to histological remission.     

Renal involvement in systemic amyloidosis: an Italian collaborative study on survival and renal outcome.

BACKGROUND: Few data are available from large population-based studies on survival and renal outcome of patients with renal involvement and different types of systemic amyloidosis. METHODS: Two hundred and ninety of over 373 patients affected from systemic amyloidosis with renal involvement diagnosed in Italy between January 1995 and December 2000 were followed from diagnosis to death or until the last available clinical control. Eighty-three patients were excluded from analysis either because the amyloid type remained undetermined or they were lost at follow-up. Clinical and laboratory information was collected according to the different types of amyloidosis using a specific form which included renal function with 24 h proteinuria at diagnosis and at the end of follow-up, the type and the date of onset of dialysis and the kind of treatment they underwent. RESULTS: The median time of follow-up was 24 months in primary (AL) amyloidosis (range: 1-88 months), 16 months in AL with associated multiple myeloma (MM + AL: range 1-76 months), 30 months in reactive (AA) amyloidosis (range: 1-99 months) and 52 months in patients with familial forms (AF: range 14-82 months). Patients with AL showed a significantly shorter survival than AA. Despite no significant differences of renal outcome or survival on dialysis being observed between the two groups, a lower renal survival with a higher number of patients who progressed to end-stage renal disease (ESRD) was observed in patients with AA. Overall survival was markedly improved in patients with AL who underwent a specific therapy (conventional chemotherapy or autologous stem cell transplantation (ASCT)) even in the absence of a positive kidney response. Multivariate analysis showed cardiac involvement and specific therapy to significantly influence survival in AL whereas age, serum creatinine (sCr) and heart involvement significantly affected survival in AA. In both groups, sCr and heart involvement were the most relevant predictors for renal outcome, together with urinary protein excretion, in patients with AA. CONCLUSIONS: Our results show a worse survival in AL due to the higher prevalence of heart involvement in this group and emphasize that a specific therapy significantly prolongs survival and slows the progression of renal disease in patients with AL. We suggest that a late nephrological referral is likely the cause of the higher sCr found at presentation in patients with AA and probably accounts for the lower renal survival observed in the short term in these patients. At the time being, renal transplantation and ASCT are still rare therapeutic options for renal patients affected from systemic amyloidosis.     

Cardiac transplantation using extended-donor criteria organs for systemic amyloidosis complicated by heart failure

BACKGROUND: Systemic amyloidosis complicated by heart failure is associated with high cardiovascular morbidity and mortality. Heart transplantation for patients with systemic amyloidosis is controversial due to recurrence of disease in the transplanted organ or progression of disease in other organs. METHODS: All patients with systemic amyloidosis and heart failure referred for heart transplant evaluation from 1997 to 2004 were included in this retrospective cohort analysis. An interdisciplinary protocol for cardiac transplantation using extended-donor criteria organs, followed in 6 months by either high-dose chemotherapy and stem cell transplantation for patients with primary (AL) or by orthotopic liver transplantation for familial (ATTR) amyloidosis, was developed. Survival of the transplanted amyloid cohort was compared to survival of those amyloid patients not transplanted and to patients transplanted for other indications. RESULTS: A total of 25 patients with systemic amyloidosis and heart failure were included in the study; 12 patients received heart transplants. Amyloid heart transplant recipients were more likely female (58% vs. 8%, P=0.02) and had lower serum creatinine (1.3+/-0.5 vs. 2.0+/-0.7 mg/dL, P=0.01) than nontransplanted amyloid patients. Survival at 1-year after heart transplant evaluation was higher among transplanted patients (75% vs. 23%) compared to patients not transplanted (P=0.001). Short-term survival posttransplant did not differ between transplanted amyloid patients and contemporaneous standard and extended-donor criteria heart transplant patients (P=0.65). CONCLUSIONS: Cardiac transplantation for amyloid patients with extended-donor criteria organs followed by either stem cell or liver transplantation is associated with improved survival compared to patients not transplanted. Short- to intermediate-term survival is similar to patients receiving heart transplantation for other indications. This clinical management strategy provides cardiac amyloid patients a novel therapeutic option.     

No regression of renal AL amyloid in monoclonal gammopathy after successful autologous blood stem cell transplantation and significant clinical improvement.

BACKGROUND: High-dose chemotherapy followed by autologous blood stem cell transplantation induces remission of plasma cell dyscrasia in patients with AL amyloidosis. The impact of this treatment on the glomerular amyloid mass is still unknown. METHODS: In the present study, the quantity of the renal amyloid mass before and more than 3 years after high-dose melphalan treatment and autologous blood stem cell transplantation was assessed in two patients. At the time of the second renal biopsy, both patients were in complete remission without detectable serum and urinary monoclonal IgA-lambda and a normal percentage of plasma cells in the bone marrow. RESULTS: In both patients with biopsy-proven AL amyloidosis, urinary protein excretion decreased from 7 g/24 h to <2 g/24 h more than 3 years after autologous blood stem cell transplantation. In contrast, glomerular amyloid deposits persisted, as shown in the second biopsy. CONCLUSION: Despite complete remission of the plasma cell dyscrasia and improvement of glomerular permeability, the amount of glomerular amyloid mass did not regress.     

Kidney and liver involvement in monoclonal light chain disorders

Monoclonal light chains (LCs) are responsible for a wide spectrum of renal and hepatic diseases, that above all include amyloid light-chain (AL) amyloidosis and light chain deposition disease (LCDD). Amyloid deposits stain for Congo red on light microscopy and have fibrillar aspect on electron microscopy, whereas deposits in LCDD are positive using monotypic LCs on immunofluorescence and have a granular aspect on electron microscopy. Sometimes fibrillar and granular deposits are observed in the same organ or in different organs of the same patient. Kidney and liver involvement is a frequent finding, both in primary amyloidosis (AL amyloidosis) or in LCDD. Renal manifestations include proteinuria, nephrotic syndrome, and progressive renal failure. End-stage renal disease requiring dialysis is observed in about 20% of patients with AL amyloidosis and in 70% of patients with LCDD. The mean survival time is about 12 to 18 months in AL amyloidosis and 34 months in LCDD. The most important prognostic factor is severe cardiac involvement, which reduces the mean survival to only 6 months. Hepatic manifestations include hepatomegaly, portal hypertension, ascites, intrahepatic cholostatic jaundice, and hepatic insufficiency. The mean survival of patients with liver damage is 14 months, but it is reduced to 5 months in patients with cholostatic jaundice. Contemporary kidney and liver involvement is usually observed on histologic examination, less frequently as clinical manifestation. No specific treatment exists for AL amyloidosis and LCDD, and the prognosis remains severe. The aim of treatment is to suppress proliferation of the abnormal clone of plasma cells and remove tissue deposits. The regimens, including melphalan-prednisone (MP) or vincristine-doxorubicin-dexamethasone (VAD), are used both in AL amyloidosis or in LCDD with some effectiveness. New approaches, especially the use of 4'-iodo-4'deoxydoxorubicin, could achieve better results. Dialysis seems to not worsen the outcome in both diseases because survival of patients on dialysis is not different from that of patients not reaching uremia. Also, kidney and liver transplantation is effective, though amyloidosis or LCDD may occur in transplanted organs. The most interesting therapeutic approach is autologous-blood stem-cell transplantation, which may produce a complete remission of the plasma-cell dyscrasia and a substantial improvement of clinical manifestations related to LC deposits.     

Outcomes of Heart Transplantation in Cardiac Amyloidosis Patients: A Single Center Experience

BackgroundIndications for heart transplantation are expanding to include amyloid light chain (AL) and transthyretin-related (TTR) amyloidosis. Previously, AL amyloid had been a contraindication to heart transplantation given inferior outcomes. These patients typically have biventricular failure requiring mechanical circulatory support (MCS). We report the outcomes of patients with end-stage cardiac amyloidosis who underwent cardiac transplantation, including some who were bridged to transplantation with a durable biventricular MCSMethodsThe records for patients with cardiac amyloidosis who underwent cardiac transplant between 2010 and 2018 were reviewed. Primary endpoint was post-transplant 1-year survival. Secondary endpoints included 1-year freedom from cardiac allograft vasculopathy (as defined by stenosis ≥ 30% by angiography), nonfatal major adverse cardiac events (myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), and any rejection.ResultsA total of 46 patients received heart transplantation with a diagnosis of either AL or TTR amyloidosis. Of these, 7 patients were bridged to transplantation with a durable biventricular MCS device (6 AL, 1 TTR) and 39 patients were transplanted without MCS bridging. The MCS group consisted of 5 total artificial hearts and 2 biventricular assist devices. The 1-year survival was 91% for the entire cohort, 83% for those with AL amyloidosis, 94% for those with TTR amyloidosis, and 86% for those who received MCS bridging.ConclusionsCardiac transplantation can be safely performed in selected amyloidosis patients with reasonable short-term outcomes. Those bridged to transplantation with biventricular MCS appear to have short-term outcomes similar to those transplanted without MCS. Larger numbers and longer observation are required to confirm these findings.     

Orthotopic heart transplant rejection in association with immunomodulatory therapy for AL amyloidosis: A case series and review of the literature

Although end‐organ damage caused by AL amyloidosis historically portends a poor prognosis, advances in therapy in combination with solid organ transplantation can lead to significant improvements in survival. Immunomodulatory agents (IMiDs), such as lenalidomide and pomalidomide, are an effective class of drugs in the treatment of AL amyloidosis. However, there is growing concern that these agents may precipitate acute transplant rejection via upregulation of interleukin‐2 and inhibition of immune tolerance. This case series describes three patients who underwent orthotopic heart transplantation for AL amyloidosis and later had progression of their underlying plasma cell dyscrasia, leading to treatment with IMiD therapy. Two patients subsequently developed acute allograft rejection, including the first reported case of pomalidomide‐associated allograft rejection. The third patient tolerated long‐term therapy without signs of rejection: the first reported case of IMiD tolerability after heart transplant. These cases, together with a review of the literature, demonstrate variable outcomes and elucidate the potential risk of organ rejection associated with the use of IMiDs. When treatment with IMiDs is necessary, close surveillance and modification of immunosuppression may mitigate risks of rejection and complications.     

Cardiac transplantation for amyloid heart disease: the United Kingdom experience.

BACKGROUND: Heart transplantation (TX) for cardiac amyloidosis is uncommon because of concern about progression of amyloid in other organs and the possibility of amyloid deposition in the donor heart. METHODS: Records of all 24 patients with amyloid heart disease who have undergone TX in the United Kingdom were examined. Seventeen patients had AL amyloidosis (AL) and 7 had non-AL forms of amyloidosis (non-AL). RESULTS: Survival of the 10 patients with AL who underwent TX but had no additional chemotherapy was 50%, 50%, and 20% at 1, 2, and 5 years, respectively; amyloid recurred in the grafts of these patients after a median of 11 months, and extra-cardiac amyloid deposition contributed to mortality in 70% of these patients. Survival of 7 patients with AL who also had chemotherapy was 71%, 71%, and 36% respectively and 2 patients remain alive. Survival of the 7 patients with non-AL was 86%, 86%, and 64% at 1, 2, and 5 years, respectively; 5 patients remain alive. One patient from this group had recurrence of amyloid in the graft at 60 months. Five-year survival for all 24 amyloid patients was 38%, compared to patients undergoing TX in the UK for other indications (n = 4,058) for whom it was 67% (p = 0.013). CONCLUSION: Regardless of the use of adjunctive chemotherapy, the 5-year survival after TX for cardiac AL amyloidosis was less than that after TX for other indications, and progression of the systemic disease contributed substantially to the increased mortality. In contrast, the 5-year survival after TX for non-AL amyloid, combined as necessary with liver or kidney TX, was similar to that after TX in general.     

Treatment options for severe cardiac amyloidosis: heart transplantation combined with chemotherapy and stem cell transplantation for patients with AL-amyloidosis and heart and liver transplantation for patients with ATTR-amyloidosis.

OBJECTIVE: Cardiac amyloidosis (CA) is associated with a poor prognosis and a survival rate of less than 30% 2 years after clinical manifestation. Considered as a semi-malignant disease, CA is often a contraindication for HTx; however, depending on the type of CA, there are excellent treatment regimes that can be combined with HTx. In AL-amyloidosis, chemotherapy and stem cell transplantation are necessary and in TTR-amyloidosis, where the liver is the source of the pathologic protein, liver transplantation is recommended after HTx. METHODS AND RESULTS: More than 60 patients with AL-amyloidosis and more than 25 patients with ATTR-amyloidosis have been investigated at our centre. Eighteen patients showed signs of end-stage heart failure. Four patients died within 1 month after listing for HTx. Seven patients with AL (mean age 41.8 years) and five patients with ATTR-amyloidosis (mean age 42.6 years) were successfully transplanted with an actual survival rate of 91.6%. One patient died 8 months after HTx due to infection. Five AL patients received chemotherapy and SCT and one ATTR patient was liver transplanted. Three AL patients showed complete remission of amyloidosis. CONCLUSIONS: Cardiac amyloidosis is a potentially curative disease after HTx when combined with either chemotherapy and SCT or LiverTx depending on the type of the amyloidosis. Due to the natural course of the disease, urgent HTx after cardiac manifestation is mandatory. With this approach, excellent survival rates and even remission of the underlying disease is possible.     

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

This study sought to retrospectively investigate the outcomes of patients with light‐chain amyloidosis (AL) with advanced cardiac involvement who were treated with a strategy of heart transplantation (HT) followed by delayed autologous stem cell transplantation (ASCT) at 1‐year posttransplant. Patients with AL amyloidosis with substantial cardiac involvement have traditionally had very poor survival (eg, several months). A few select centers have reported their outcomes for HT followed by a strategy of early ASCT (ie, 6 months) for CA. The outcomes of patients undergoing a delayed strategy have not been reported. All patients with AL amyloidosis at a single institution undergoing evaluation for HT from 2004‐2018 were included. Retrospective analyses were performed. Sixteen patients underwent HT (including two combined heart‐kidney transplant) for AL amyloidosis. ASCT was performed in a total of nine patients to date at a median 13.5 months (12.8‐32.9 months) post‐HT. Survival was 87.5% at 1 year and 76.6% at 5 years, comparable to institutional outcomes for nonamyloid HT recipients. In addition to these 16 patients, two patients underwent combined heart‐lung transplantation. A strategy of delayed ASCT 1‐year post‐HT for patients with AL amyloidosis is feasible, safe, and associated with comparable outcomes to those undergoing an earlier ASCT strategy.