Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation: long-term results in a series of 421 patients.

Previous studies have suggested that, in patients with AL amyloidosis treated with high-dose melphalan and autologous stem-cell transplantation (HDM/SCT), the greatest benefit is seen in those patients achieving a hematologic complete response (CR). We analyzed a series of 421 consecutive patients treated with HDM/SCT at a single referral center and compared outcomes for patients with and without CR. Treatment-related mortality was 11.4% overall (5.6% in the last 5 years). By intention-to-treat analysis, the CR rate was 34% and the median event-free survival (EFS) and overall survival (OS) were 2.6 and 6.3 years, respectively. Eighty-one patients died within the first year after HDM/SCT and were not evaluable for hematologic and organ response. Of 340 evaluable patients, 43% achieved CR and 78% of them experienced an organ response. For CR patients, median EFS and OS were 8.3 and 13.2 years, respectively. Among the 195 patients who did not obtain CR, 52% achieved an organ response, and their median EFS and OS were 2 and 5.9 years, respectively. Thus, treatment of selected AL patients with HDM/SCT resulted in a high organ response rate and long OS, even for those patients who did not achieve CR.

Amyloid deposits in the bone marrow of patients with immunoglobulin light chain amyloidosis do not impact stem cell mobilization or engraftment.

Amyloid deposits are often found in the bone marrow in patients with Immunoglobulin light chain (AL) amyloidosis. We sought to determine whether this affects stem cell collection or engraftment after high-dose melphalan and autologous stem cell transplantation (HDM-SCT). We reviewed data on 361 patients with AL amyloidosis who had Congo red staining of pretreatment bone marrow biopsy specimens and underwent HDM-SCT between July 1994 and December 2011. We analyzed data on stem cell yield, days of stem cell collection, and days to neutrophil and platelet engraftment posttransplantation. Bone marrow amyloid deposits were found in 65% of patients (n = 233). There were no significant differences in median number of stem cells collected and days to neutrophil or platelet engraftment between patients with bone marrow amyloid deposits and those without these deposits. Thus, our data indicate that although amyloid involvement of the bone marrow is common, it does not negatively affect stem cell mobilization or neutrophil and platelet engraftment after HDM-SCT.

Kidney dysfunction during lenalidomide treatment for AL amyloidosis.

BACKGROUND: Lenalidomide is an immunomodulatory agent used to treat plasma cell dyscrasias. We previously observed worsening of kidney function in a high proportion of patients with AL amyloidosis during lenalidomide treatment. The objective of this study is to characterize alterations in kidney function among patients with AL amyloidosis undergoing treatment with lenalidomide. METHODS: This is a secondary analysis of an ongoing clinical trial at a single referral centre. Forty-one patients with AL amyloidosis received lenalidomide with or without dexamethasone in monthly cycles. Kidney dysfunction was defined as ≥ 50% increase in serum creatinine. Severe kidney dysfunction was defined as ≥ 100% increase in serum creatinine. Recovery of renal function was defined as a return of serum creatinine to within 25% of the pre-treatment value or discontinuation of dialysis. RESULTS: Twenty-seven of 41 patients (66%) developed kidney dysfunction during lenalidomide treatment. The kidney dysfunction was severe in 13 of these patients (32%); four of whom required initiation of dialysis (10%). The median time to kidney dysfunction after starting lenalidomide was 44 days (interquartile range 15-108 days). Four of eight patients without underlying renal amyloidosis developed kidney dysfunction. Patients with severe kidney dysfunction were older and had a higher frequency of underlying renal amyloidosis, greater urinary protein excretion, and lower serum albumin. Recovery of renal function occurred in 12 patients (44%). CONCLUSIONS: Among patients with AL amyloidosis, worsening of kidney function occurs frequently during lenalidomide treatment. While a causal role of the drug has not been established, our findings suggest that kidney function should be monitored closely during treatment with this drug.

Short and long-term outcome of treatment with high-dose melphalan and stem cell transplantation for multiple myeloma-associated AL amyloidosis.

High-dose melphalan chemotherapy and autologous peripheral blood stem cell transplantation (HDM/SCT) has been shown to result in a durable hematologic response and prolonged overall survival in systemic amyloid light-chain (AL) amyloidosis as well as multiple myeloma. However, little is known about the myeloma associated with AL amyloidosis (MM/AL). In this retrospective study, we evaluated 87 patients with MM/AL from 1994 to 2007. Sixteen of these patients underwent HDM/SCT at Boston University Medical Center. Three patients (19%) died from treatment-related mortality. The overall median survival for all 87 patients was 22 months by Kaplan-Meier estimates. However, this was improved to 54.5 months for those who received HDM/SCT compared to 21 months for those who did not receive HDM/SCT. A hematologic complete response was achieved by 25% (4/16) of patients at 6 months after HDM/SCT. Hematologic relapses occurred in 60% of patients at a median of 1 year after HDM/SCT. In conclusion, HDM/SCT can prolong overall survival in patients with MM/AL who are eligible to receive it.

Hepatic response after high-dose melphalan and stem cell transplantation in patients with AL amyloidosis associated liver disease.

High-dose melphalan chemotherapy and autologous peripheral blood stem cell transplantation has been shown to result in durable hematologic response and prolonged overall survival in systemic AL amyloidosis. In this retrospective study, we evaluated clinical and hematologic responses in 69 patients with predominant liver involvement who were treated with high-dose intravenous melphalan and autologous stem cell transplantation from 1998 to 2006. Nine patients (13%) died from treatment-related mortality, similar to patients without hepatic involvement. The overall survival was 81% at one year and 61% at five years, by Kaplan-Meier estimates. A hematologic complete response was achieved by 53% (31/58) of patients at one year. A hepatic response occurred in 57% (33/58) at one year after high-dose intravenous melphalan and autologous stem cell transplantation and 63% (19/30) at two years after high-dose intravenous melphalan and autologous stem cell transplantation. In conclusion, hepatic disease improves in almost 2/3 patients treated with high-dose intravenous melphalan and autologous stem cell transplantation who have a complete or partial hematologic response to treatment.

High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: an 8-year study.

BACKGROUND: AL amyloidosis is a fatal disease resulting from tissue deposition of amyloid fibrils derived from monoclonal immunoglobulin light chains. Treatment with oral chemotherapy is minimally effective. OBJECTIVE: To test survival and organ response in a large sample of patients treated with high-dose intravenous melphalan (100 to 200 mg/m2) and autologous blood stem-cell transplantation. DESIGN: 8-year longitudinal analysis of clinical effectiveness. SETTING: University-affiliated specialty referral clinic. PATIENTS: 701 consecutive new patients with AL amyloidosis. INTERVENTION: High-dose chemotherapy and autologous stem-cell transplantation for patients who met eligibility requirements based on organ involvement and clinical status. MEASUREMENTS: Survival analysis of all patients evaluated and a detailed analysis of treatment outcome in the subgroup that received high-dose melphalan and stem-cell transplantation. RESULTS: Among 701 patients with AL amyloidosis, 394 (56%) were eligible for high-dose melphalan and stem-cell transplantation; 82 did not proceed with treatment because of patient choice or disease progression. Median survival of the 312 patients who initiated treatment was 4.6 years. A complete hematologic response, defined as no evidence of an underlying plasma cell dyscrasia 1 year after treatment, was achieved in 40% of patients and was associated with prolonged survival. Statistically significant improvements occurred in end-organ disease and were greater in patients with a complete hematologic response. Mortality rate within 100 days of treatment with high-dose melphalan and stem-cell transplantation was 13%; patients with cardiomyopathy had the highest mortality rates. CONCLUSIONS: Treatment of selected patients with AL amyloidosis by using high-dose melphalan and stem-cell transplantation resulted in hematologic remission, improved 5-year survival, and reversal of amyloid-related disease in a substantial proportion.

Tolerability and efficacy of thalidomide for the treatment of patients with light chain-associated (AL) amyloidosis.

Thalidomide is an effective therapy for multiple myeloma, although its mechanisms of action remain unclear. Light chain-associated (AL) amyloidosis is a plasma cell disorder related to multiple myeloma, but in AL amyloidosis, fibrillar tissue deposits of clonal immunoglobulin light chains produce organ dysfunction. To test the toxicity and efficacy of thalidomide in AL amyloidosis we initiated a phase I/II trial for patients with AL amyloidosis, most of whom had failed prior therapy with high-dose melphalan and autologous stem cell transplantation. This trial was designed as an individualized 6-month dose-escalation study with reevaluation of bone marrow plasmacytosis and serum and urine monoclonal proteins after 3 and 6 months. Sixteen patients were enrolled in the study with a median age of 62 years (range, 37-70 years). Fourteen patients had renal involvement, 4 had cardiac involvement, 4 had liver involvement, and 2 had predominant soft tissue or lymph node involvement. The median maximum tolerated dose was 300 mg, with fatigue and other central nervous system side effects being the major dose-limiting toxicities. Side effects not frequently reported for other patient populations included exacerbation of peripheral and pulmonary edema and worsening azotemia. In all, 50% of patients experienced grade 3/4 toxicity, and 25% had to discontinue the study drug. No complete hematologic responses were seen, but 25% of patients had a significant reduction in Bence-Jones proteinuria. Thus, while thalidomide has activity in AL amyloidosis, it also has significant toxicity in this patient population.

Health behaviors, readiness to change, and interest in health promotion programs among smokers with lung cancer and their family members: a pilot study.

BACKGROUND: The diagnosis of lung cancer presents an opportunity to motivate individuals to adopt health-promoting behavior. Little attention has been given to using this opportunity to also motivate relatives to change their health behaviors. OBJECTIVES: The objectives of this study were to describe health behaviors and readiness to change lifestyle, identify interest in health promotion programs, and examine concordance of health behaviors among smokers with lung cancer and their family members. METHODS: Cross-sectional data were collected once from 37 lung cancer patient-family member dyads. Standardized questionnaires were used to collect data. Descriptive statistics and percent agreement were used for analyses. RESULTS: Lung cancer patients and their family members had high rates of continued smoking (43% vs 30%), low intake of fruits and vegetables (92% vs 95%), and high rates of physical inactivity (84% vs 84%). Patients and family members indicated readiness to change behaviors within the next 6 months ranging from 63% for physical activity, 73% for diet, and 88% to quit smoking for patients and 81% for physical activity, 58% for diet, and 91% to quit smoking for family members. Interest in participating in a multiple behavioral risk reduction program was high for patients and family members. CONCLUSIONS: The majority of patients and their family members have multiple behavioral risk factors placing them at risk for poor health outcomes. IMPLICATIONS FOR PRACTICE: Oncology nurses are in a unique position to provide leadership in assessing health behaviors and implementing evidence-based interventions to enhance outcomes for patient-family member dyads with lung cancer.

Long-term outcome of patients with AL amyloidosis treated with high-dose melphalan and stem-cell transplantation.

Long-term survival and outcome were determined for 80 patients with immunoglobulin light chain (AL) amyloidosis treated with high-dose melphalan and stem cell transplantation (HDM/SCT) more than 10 years ago. Seventeen (21%) patients died within the first year of treatment, of treatment-related complications (14%) or progressive disease (8%). Of the 63 surviving evaluable patients at one year, 32 (51%) achieved a complete hematologic response (CR). For all 80 patients, the median survival was 57 months (4.75 yrs). The median survival exceeds 10 years for patients achieving a CR after HDM/SCT, compared with 50 months for those not achieving a CR (P < .001). In conclusion, HDM/SCT leads to durable remissions and prolonged survival, particularly for those patients who achieve a hematologic CR.

Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial.

In immunoglobulin light chain (AL) amyloidosis, amyloid fibril deposits derived from immunoglobulin light chains produced by a clonal plasma cell dyscrasia accumulate in tissues and damage vital organs. Treatment regimens used in multiple myeloma can be effective in AL amyloidosis; however, patients with this disease often tolerate these regimens poorly because of multisystem organ dysfunction. Thalidomide and lenalidomide have both been shown to be effective in myeloma. In this report, we describe results of a phase 2 trial of the use of lenalidomide, as a single agent and in combination with dexamethasone, for the treatment of AL amyloidosis. Thirty-four patients with AL amyloidosis, most with prior therapies, were enrolled in the trial. The initial dose of lenalidomide used (25 mg/d) was poorly tolerated; however, a reduced dose of 15 mg/d was generally well tolerated. Of 24 evaluable patients, 7 (29%) achieved a hematologic complete response and 9 (38%) achieved a partial hematologic response, for an overall hematologic response rate of 67%. Hematologic responses were also associated with clinical responses. Fatigue and myelosuppression were the most common treatment-related adverse events (35%), while thromboembolic complications (9%) were the most serious. Findings from this trial indicate that lenalidomide can be effective in treating AL amyloidosis.

Low-dose continuous oral melphalan for the treatment of primary systemic (AL) amyloidosis.

Median survival of patients with AL amyloidosis with clinically significant cardiac involvement is 5 months when treated with cyclic melphalan and prednisone. We investigated a regimen of continuous oral melphalan as a single agent for patients with cardiac amyloidosis who were unable to tolerate prednisone or more aggressive chemotherapy. Thirty patients with amyloid cardiomyopathy were treated with continuous oral melphalan. Seven of 13 patients, evaluable after 3-4 months of treatment, achieved a partial haematological response and three achieved a complete haematological response; six patients have survived for > 1 year. This regimen appeared to be effective in inducing haematological responses in patients who received total doses of melphalan > 300 mg.

Improvement in quality of life of patients with AL amyloidosis treated with high-dose melphalan and autologous stem cell transplantation.

Treatment of AL amyloidosis patients with high-dose melphalan chemotherapy followed by autologous peripheral blood stem cell transplantation (HDM/SCT) can produce hematologic complete responses (CRs) and improvement in organ function. To determine whether these responses are accompanied by improvement in quality of life (QOL), we employed the Medical Outcomes Study (MOS) 36-item Short Form General Health Survey (SF-36) questionnaire for 544 patients evaluated between 1994 and 2002. At baseline, the scores were significantly lower on all 8 SF-36 scales compared with age-matched population norms: the composite physical component summary (PCS) for the AL patients was 34.5 versus the population norm of 46.8, and the mental component summary (MCS) was 45.0 versus the norm of 51.5. All SF-36 scores improved at 1 year, with the MCS reaching the population norm. The PCS, though improved, was still lower than normal but was greater in the subgroup of patients who achieved a hematologic CR; the PCS normalized at 2 years in these patients. Thus, treatment of AL amyloidosis patients with HDM/SCT produces measurable and sustained improvements in quality of life, particularly in those patients who achieve hematologic CR.