Original Article
High-Dose Melphalan versus Melphalan plus Dexamethasone for AL Amyloidosis
N Engl J Med 2007; 357:1083-1093September 13, 2007
- Abstract
Background
High-dose chemotherapy followed by autologous hematopoietic stem-cell transplantation has been reported to provide higher response rates and better overall survival than standard chemotherapy in immunoglobulin-light-chain (AL) amyloidosis, but these two strategies have not been compared in a randomized study.
Methods
We conducted a randomized trial comparing high-dose intravenous melphalan followed by autologous hematopoietic stem-cell rescue with standard-dose melphalan plus high-dose dexamethasone in patients with AL amyloidosis. Patients (age range, 18 to 70 years) with newly diagnosed AL amyloidosis were randomly assigned to receive intravenous high-dose melphalan plus autologous stem cells or oral melphalan plus oral high-dose dexamethasone.
Results
Fifty patients were enrolled in each group. The results were analyzed on an intention-to-treat basis, with overall survival as the primary end point. After a median follow-up of 3 years, the estimated median overall survival was 22.2 months in the group assigned to receive high-dose melphalan and 56.9 months in the group assigned to receive melphalan plus high-dose dexamethasone (P=0.04). Among patients with high-risk disease, overall survival was similar in the two groups. Among patients with low-risk disease, there was a nonsignificant difference between the two groups in overall survival at 3 years (58% in the group assigned to receive high-dose melphalan vs. 80% in the group assigned to receive melphalan plus high-dose dexamethasone; P=0.13).
Conclusions
The outcome of treatment of AL amyloidosis with high-dose melphalan plus autologous stem-cell rescue was not superior to the outcome with standard-dose melphalan plus dexamethasone. (ClinicalTrials.gov number, NCT00344526.)
Media in This Article
Figure 1
Randomization, Treatment Assignments, and Receipt of Treatment.Figure 2
Survival According to Hematologic Responses and Treatment Group.Article Activity
- Article
The origin of amyloid in systemic immunoglobulin-light-chain (AL) amyloidosis is a clone of plasma cells in the bone marrow that synthesizes monoclonal immunoglobulin light chains. In tissues, these light chains aggregate into amyloid fibrils. The accumulation of amyloid deposits in vital organs leads to progressive disability and death. Life expectancy depends on the degree of organ involvement and ranges from a few years to less than 6 months for patients with severe cardiomyopathy.1 In the mid-1990s, two randomized trials showed that standard-dose chemotherapy with melphalan and prednisone could prolong survival in patients with AL amyloidosis,1,2 but clinical responses were rare and overall survival was extended by only a few months.
High-dose melphalan with autologous hematopoietic stem-cell rescue was introduced in the early 1990s, and it is increasingly used to treat patients with AL amyloidosis. However, transplant-related mortality is high, ranging between 13% (in referral centers) and 43% (in a French retrospective multicenter study).3-5 The survival benefit of high-dose melphalan has been attributed to a patient-selection bias,6 but a case–control study suggested a survival advantage for high-dose melphalan plus hematopoietic stem-cell rescue as compared with conventional treatment.7 The present study is a randomized comparison of high-dose melphalan plus autologous hematopoietic stem-cell rescue with standard-dose melphalan plus high-dose dexamethasone in patients with AL amyloidosis.
Methods
Patients
Patients between 18 and 70 years of age who had biopsy-proven systemic AL amyloidosis, who had received no more than two previous courses of any chemotherapy regimen, who did not have symptomatic multiple myeloma, and who had an Eastern Cooperative Oncology Group (ECOG) performance-status score of 2 or lower were eligible. The inclusion criteria were a histologic diagnosis of amyloidosis and either immunohistochemical characterization of the amyloid deposits or evidence of a monoclonal immunoglobulin protein in the serum or urine specimen or a monoclonal staining pattern of bone marrow plasma cells. When immunohistochemical characterization was lacking, an effort was made to rule out hereditary amyloidosis by taking into account the patient's family history and the pattern of organ involvement.
The protocol was approved by the local ethics committee, and all of the patients gave their written informed consent. Randomization was based on a balanced randomization list with the use of blocks of variable size, stratified according to age (younger than 65 years or 65 years or older) and according to the affected organ system (cardiac, renal, neurologic, or other).
Treatment
Patients in the group assigned to receive melphalan plus dexamethasone received monthly courses of oral melphalan (10 mg per square meter of body-surface area on days 1 to 4) plus high-dose oral dexamethasone (40 mg per day on days 1 to 4) for up to 18 treatment courses if no severe adverse effects occurred. In January 2002, when 43 patients had been included, the protocol was amended to permit discontinuation of treatment after 12 courses if a complete hematologic remission occurred. The dose of melphalan was adjusted during the first three courses in order to induce mild cytopenia (white-cell count, <3000 per cubic millimeter) at midcourse. Prophylaxis with proton-pump inhibitors and trimethoprim–sulfamethoxazole (one double-strength tablet thrice weekly) was recommended.
In the group assigned to receive high-dose melphalan, autologous hematopoietic stem cells were obtained from the peripheral blood with granulocyte colony-stimulating factor (G-CSF) (5 μg per kilogram of body weight subcutaneously, twice daily). Cytapheresis was performed on day 5, with the use of the procedure described in the Supplementary Appendix, available with the full text of this article at www.nejm.org. The goal was to collect 2×106 CD34+ cells per kilogram. If this goal was not achieved, a second attempt to obtain the cells was permitted. Patients then received melphalan, 200 mg per square meter given intravenously on day 0, and stem cells were infused on day 2. The dose of melphalan was reduced to 140 mg per square meter for patients 65 years of age or older and for those with an ejection fraction below 30%, a calculated creatinine clearance of less than 30 ml per minute, or severe liver disease (prothrombin index, <50%; total bilirubin or alkaline phosphatase level, >5 times the normal level). G-CSF was administered subcutaneously daily from day 7 until neutropenia resolved. Transfusions to maintain the platelet count at more than 50,000 per cubic millimeter were recommended.
Assessment of Organ Involvement, Responses, and Outcome
Organ involvement and the response to therapy were evaluated according to the international consensus guidelines,8 except that bone marrow studies were not required to define a complete response (Table 1Table 1
Criteria for Organ Involvement, Organ Response, and Hematologic (Immunochemical) Response.). Hematologic and clinical responses were analyzed only in patients who received three or more courses of melphalan plus dexamethasone and in patients who survived for more than 3 months after stem-cell transplantation. A clinical response was defined as improvement of an organ known to be involved with amyloid. A complete hematologic response was defined as the complete disappearance of the monoclonal immunoglobulin or light chain in a serum or urine specimen; a partial hematologic response was defined as more than a 50% reduction in these proteins. Light-chain levels in serum were assessed, whenever possible, with the free light-chain assay (Freelite, Binding Site),9 which became available for use in this trial in 2003.Statistical Analysis
The number of patients required for the study was calculated with the use of the log-rank test. The working hypothesis was that high-dose melphalan would improve the survival rate (estimated to be 55.5% in the group assigned to receive melphalan plus dexamethasone) by 25% at 18 months, with a type 1 error rate of 5% and a statistical power of 80%.10 Thus, a minimum of 46 patients per group was required, with a total in both groups of at least 25 deaths. We decided to include a total of 100 patients.
The data were analyzed on an intention-to-treat basis. Descriptive analyses were based on frequencies for qualitative variables and means, standard deviations, and medians for quantitative variables. Comparisons were made with the use of the Student's t-test or the Mann–Whitney U test. Frequencies were compared with the use of the chi-square test or Fisher's exact test.
Survival analyses according to the treatment group and organ involvement were based on the Kaplan–Meier method with the use of the log-rank test and a univariate Cox proportional-hazards regression analysis. A two-sided P value of less than 0.05 was considered to indicate statistical significance. The start date was the date of randomization, and the cutoff date was August 15, 2006.
Subgroup analyses of patients with low-risk and those with high-risk AL amyloidosis were planned on the basis of the Mayo Clinic criteria. Patients with low-risk disease have all the following: an interventricular cardiac septum thickness of less than 15 mm, an ejection fraction of more than 55%, a serum creatinine level of 2 mg per deciliter (177 μmol per liter) or less, and a direct bilirubin value of 2 mg per deciliter (34 μmol per liter) or less.6
A landmark analysis was also performed to study the efficacy of the two strategies independently of early toxic effects. This analysis focused on patients who survived for at least 6 months after randomization and who received their assigned treatment (either high-dose melphalan or three or more courses of melphalan plus high-dose dexamethasone).11
Results
Between January 11, 2000, and January 7, 2005, 100 patients were enrolled in 29 centers (Figure 1Figure 1
Randomization, Treatment Assignments, and Receipt of Treatment.). Two patients who had previously received three cycles of standard-dose chemotherapy were not excluded from the group assigned to receive melphalan plus dexamethasone, since this was considered a minor deviation from the inclusion criteria.Table 2Table 2
Baseline Characteristics of the Patients. shows the baseline characteristics of the 100 patients. The AL amyloidosis type was determined by means of immunohistochemical analysis in 60 patients. All of the other patients had a monoclonal protein in blood or urine specimens and clinical features that were characteristic of AL amyloidosis. The AL type of amyloid was confirmed by means of immunohistochemical analysis in all five patients who had normal serum levels of kappa and lambda free light chains at diagnosis.The characteristics of amyloid disease were well balanced between the two groups of patients (Table 2). A total of 47 patients had cardiac involvement, 69 patients had renal involvement, 22 patients had nerve involvement, and 26 patients had liver involvement. The median number of organs involved was two (range, one to five). Sixteen patients in the group assigned to melphalan plus dexamethasone and 17 patients in the group assigned to high-dose melphalan had only one affected organ.
Treatment
Of the 50 patients in the group assigned to high-dose melphalan, 13 did not receive the planned treatment (Figure 1). Of the patients who did not receive the planned treatment, 1 patient declined treatment, 2 patients had an insufficient stem-cell harvest, and 10 patients died (8 patients died suddenly or had progressive heart failure, 1 had progressive hepatic amyloidosis, and 1 had sepsis). One patient's condition worsened before treatment with G-CSF began, and the patient died 40 days after undergoing randomization. Four patients died during treatment with G-CSF. No deaths occurred during leukapheresis. Five patients died between 11 and 45 days after stem-cell collection.
The median number of stem-cell harvests was two (range, 1 to 3); sufficient numbers of stem cells were collected after one course of G-CSF in 35 patients and after two courses of G-CSF in 2 patients. The median number of harvested CD34+ cells was 4.48×106 per kilogram (range, 0.68 to 11.0).
Of the 37 patients who received stem cells, 10 were given melphalan at a dose of 140 mg per square meter and 27 were given melphalan at a dose of 200 mg per square meter. Of these 37 patients, 9 died within 100 days after receiving high-dose melphalan — 5 from multiorgan failure with acute renal failure, 2 from sepsis, and 2 from cardiac arrhythmia. The transplant-related mortality was 24%. In total, 19 patients died within 130 days after randomization. In 11 patients, the serum creatinine level increased to more than three times the baseline level, and 8 patients required hemodialysis.
In the group assigned to melphalan plus dexamethasone, two patients died early of cardiac arrhythmia — one before receiving any treatment and one on the third day of the first course of treatment. Five other patients died within 130 days after randomization, all from disease progression. Seven patients had toxic effects of grade 3 or more, 16 patients had grade 1 or 2 toxic effects, 10 patients had sepsis, 18 patients had cytopenia, and 1 patient had diabetes mellitus.
The median number of courses of melphalan plus dexamethasone received was 12 (range, 0 to 25). The median time between randomization and initiation of treatment with melphalan plus dexamethasone was 2 days (range, 0 to 41), and the median time between randomization and initiation of treatment with G-CSF was 8 days (range, 0 to 43). The median time between randomization and administration of high-dose melphalan was 36 days (range, 16 to 83).
Hematologic Responses
Forty-three patients in the group assigned to receive melphalan plus dexamethasone received three or more courses of treatment, and 29 patients in the group assigned to receive high-dose melphalan survived for more than 3 months after grafting.
In 65 of these patients (38 in the group assigned to receive melphalan plus dexamethasone and 27 in the group assigned to receive high-dose melphalan), hematologic responses could be evaluated by means of serum and urine electrophoresis, immunofixation, or both methods. The free light-chain assay could also be used to evaluate these responses.
Hematologic responses did not differ significantly between the two treatment groups (Table 3Table 3
Hematologic Response to Chemotherapy by Serum Free Light-Chain Assay, Conventional Techniques, and Both Approaches.). They occurred in 26 patients in the group assigned to receive melphalan plus dexamethasone (68%) and in 18 patients in the group assigned to receive high-dose melphalan (66%); the response rates in the intention-to-treat analysis were 52% and 36%, respectively (P=0.11). Responses were evaluated by means of the free light-chain assay in 37 patients (19 in the group assigned to receive melphalan plus dexamethasone and 18 in the group assigned to receive high-dose melphalan). A complete remission was achieved in 9 patients (47%) in the group assigned to receive melphalan plus dexamethasone and in 11 patients (61%) in the group assigned to receive high-dose melphalan; 5 patients (26%) and 2 patients (11%), respectively, had partial remission, and no response was seen in 5 patients in each group.The median levels of free light chains in serum at the time of best response after treatment were 28 mg per liter (range, 8 to 344) in the group assigned to receive melphalan plus dexamethasone and 26 mg per liter (range, 0.6 to 1140.0) in the group assigned to receive high-dose melphalan. Median pretreatment serum levels of true light chains in patients who underwent evaluation were 239 mg per liter (range, 32 to 1260) in the group assigned to receive melphalan plus dexamethasone and 118 mg per liter (range, 27 to 5460) in the group assigned to receive high-dose melphalan; normal serum values for kappa light chains range from 3.3 to 19.4 mg per deciliter, and normal serum values for lambda light chains range from 5.7 to 26.3 mg per deciliter.
Organ Responses
Organ responses (Table 1) could be assessed in 73 patients. At least one response occurred in 39% of the patients (17 of 44) assigned to receive melphalan plus dexamethasone and in 45% of the patients (13 of 29) assigned to receive high-dose melphalan (P=0.60). In these two groups, renal responses occurred in 11 and 8 patients, hepatic responses occurred in 3 and 5 patients, cardiac responses occurred in 3 and 4 patients, and neurologic responses occurred in 2 patients and 1 patient, respectively.
Relapses and Salvage Treatment
Hematologic progression after the conclusion of treatment (Table 1) occurred in six patients in each group. The median time from randomization to hematologic progression was 32.5 months (range, 26 to 47) in the group assigned to receive melphalan plus dexamethasone and 32.0 months (range, 15 to 55) in the group assigned to receive high-dose melphalan. Three patients in the former group received second-line treatment with high-dose melphalan for resistant disease, with less than a partial response. Only one of these patients had a hematologic (complete) response. Other patients with disease progression or resistant disease received various other treatments, but none received more than one high-dose regimen.
Overall Survival
At the cutoff date of August 15, 2006, the median follow-up time for the entire cohort was 24 months, and for surviving patients it was 36 months. The median survival for the entire cohort was 48 months. Fifty-one patients died (20 in the group assigned to receive melphalan plus dexamethasone and 31 in the group assigned to receive high-dose melphalan) (P=0.04). At the cutoff date, among the surviving patients in the two groups, 23 of 30 patients assigned to receive melphalan plus dexamethasone and 11 of 19 patients assigned to receive high-dose melphalan did not receive additional chemotherapy; the performance-status score was 2 or more in 3 and 5 patients, respectively, and 3 patients and 1 patient, respectively, required long-term dialysis. Only the two late deaths (due to lung cancer and gastric cancer) in the group assigned to receive melphalan plus dexamethasone were not directly related to amyloidosis or to the treatments received. Overall survival after randomization was strongly related to the rate of hematologic responses (Figure 2AFigure 2
Survival According to Hematologic Responses and Treatment Group.).In the intention-to-treat analysis, the Kaplan–Meier estimate of median overall survival was 56.9 months in the group assigned to receive melphalan plus dexamethasone and 22.2 months in the group assigned to receive high-dose melphalan (P=0.04 by the log-rank test) (Figure 2B). The crude estimated hazard ratio for death in the group assigned to receive melphalan plus dexamethasone was 0.57 (95% confidence interval [CI], 0.32 to 0.99; P=0.05). The hazard ratio did not change after adjustment for the main prognostic factors (performance status, number of organs involved, risk group, presence or absence of renal insufficiency, and presence or absence of cardiac involvement). Exclusion of the two patients who had received three courses of melphalan plus dexamethasone before enrollment did not affect these results.
On the basis of the Mayo Clinic criteria,6 59 patients were at low risk for an adverse outcome of intensive treatment, and 41 were at high risk, mainly because of severe cardiac disease.6 The estimated 3-year overall survival rates were 70% among patients with low-risk disease and 25% among patients with high-risk disease (P<0.001) (Figure 3AFigure 3
Survival According to Risk Group, According to the Treatment Group among Patients with Low-Risk Disease, and According to the Treatment Group in the Landmark Analysis.). Overall survival was similar in the two groups with high-risk disease (P=0.27). In the group with low-risk disease, overall survival at 3 years was 80% in the group assigned to receive melphalan plus dexamethasone and 58% in the group assigned to receive high-dose melphalan (P=0.13) (Figure 3B). Among the 69 patients with renal involvement (proteinuria, defined as >0.5 g of protein per liter), the estimated 3-year overall survival rates were 70% in the group assigned to receive melphalan plus dexamethasone and 37% in the group assigned to receive high-dose melphalan (P=0.02).In a landmark analysis of patients who survived for at least 6 months after randomization and who received their assigned treatment, there were 10 deaths among the 28 patients in the group assigned to receive high-dose melphalan and 8 deaths among the 37 patients in the group assigned to receive melphalan plus dexamethasone (P=0.38) (Figure 3C).
Discussion
This study, which was powered to show a 25% survival advantage with high-dose melphalan as compared with melphalan plus dexamethasone, did not show any superiority of high-dose melphalan over melphalan plus dexamethasone. On the contrary, the median overall survival was significantly longer (56.9 months) in the group assigned to receive melphalan plus dexamethasone than in the group assigned to receive high-dose melphalan (22.2 months) (P=0.04). Moreover, we found no significant difference in response rates between the two treatment groups. In a nonrandomized study with the use of the free light-chain assay, Lachmann et al. also found no difference in responses to high-dose chemotherapy or cytotoxic regimens such as vincristine, doxorubicin, and dexamethasone (VAD) or cyclophosphamide, vincristine, doxorubicin, and methylprednisolone (C-VAMP).12
More than two thirds of patients who received oral melphalan plus dexamethasone had durable hematologic responses. Similar results were reported in 2004 by Palladini et al., who treated 46 patients with melphalan plus dexamethasone and obtained a hematologic response rate of 67% and a clinical response rate of 48%.13 These rates are two to three times better than those obtained with the classic melphalan–prednisone combination mainly used in the case–control study in which intensive treatment was shown to offer better survival.7
One explanation for the relatively poor results with high-dose melphalan in our study is the high mortality rate before and after such intensive treatment. Most patients were treated in the same hospital where amyloidosis was diagnosed, and the median time from diagnosis to randomization was only 48 days for the two groups combined. Treatment in the same center would tend to limit the selection bias that may occur when patients are treated in tertiary referral centers, where patients who die rapidly after diagnosis cannot be treated.14 Because of the time required to collect stem cells and arrange hospitalization for treatment with high-dose melphalan, the delay before initiation of therapy was about 1 month longer in the group assigned to receive high-dose melphalan than in the group assigned to receive melphalan plus dexamethasone. This delay also contributed, along with the toxic effects of the procedure, to the higher number of early deaths in the group assigned to receive high-dose melphalan.
The treatment-related mortality rate after high-dose melphalan was higher in our multicenter study (24%) than in single-center studies of intensive treatment.4,5 However, it was similar to that observed in two other multicenter series: 25% among 114 patients treated in 50 U.S. centers15 and 23% among 92 patients treated in 31 British centers.16 Thus, our results are representative of those obtained with intensive treatment for AL amyloidosis in multicenter trials, even if the treatment-related mortality rate is reduced by strict patient selection.17 The toxic effects of G-CSF in patients with AL amyloidosis should be emphasized, since four of our patients died while receiving G-CSF.18
Our inclusion criteria were not as stringent as those used in large North American centers.4,19 To take into account the possible enrollment of patients with advanced disease, resulting in a disadvantage for the group assigned to receive high-dose melphalan, we stratified the patients according to whether they had low-risk or high-risk disease, using the criteria defined by Dispenzieri et al.6 Patients with high-risk disease in the two treatment groups had similarly poor outcomes, underlining the need for new treatments for these patients. Patients with low-risk disease are usually considered to be good candidates for intensive treatment. Among such patients in our study, survival did not differ significantly between the two groups.
To reduce the influence of early treatment-related deaths on the survival analysis, we performed a landmark analysis that included only patients who survived for more than 6 months after randomization and who received their assigned treatment. This analysis also showed no advantage of high-dose melphalan as compared with melphalan plus dexamethasone (Figure 3C).
In conclusion, this trial shows that high-dose melphalan is not superior to melphalan plus dexamethasone in patients with AL amyloidosis. A trial comparing the two treatments in a tertiary referral center, where the treatment-related mortality rate is likely to be lower, may have different results.
Presented in part at the 47th annual meeting of the American Society of Hematology, Atlanta, December 2005, and the 39th annual meeting of the American Society of Nephrology, San Diego, CA, November 2006.
Supported by Direction de la Recherche Clinique, Centre Hospitalier Universitaire, Limoges, and by grants from the Programme Hospitalier de Recherche Clinique and Limousin Association pour la Recherche en Hématologie Clinique.
No potential conflict of interest relevant to this article was reported.
We thank Fabienne Auroy, Abdeslam Bentaleb, Sandrine Naturel, and Valérie Pradel in Limoges and Claire Aguilar and Maria Basile in Paris for their excellent data monitoring and Benoît Marin from the Department of Clinical Research and Biostatistic in Limoges for his contribution to the statistical analysis.
Source Information
From Centre Hospitalier Universitaire, Université et Centre National de la Recherche Scientifique, UMR 6101, Limoges (A.J., F.Q., M.C.); Centre Hospitalier Universitaire, Nantes (P.M.); Hôpital Pitié–Salpêtrière, Assistance Publique–Hôpitaux de Paris and Université Paris VI, Paris (V.L., J.-C.P.); Centre Hospitalier Universitaire, Lille (X.L.); Centre Hospitalier Universitaire, Tours (L.B.); Hôpital Necker, Assistance Publique–Hôpitaux de Paris, Université Paris V, and Centre National de la Recherche Scientifique UM 814, Paris (O.H.); Centre Hospitalier Universitaire Hôpital Purpan, Toulouse (C.R.); Hôpital Saint-Louis, Assistance Publique–Hôpitaux de Paris, Paris (B.A., J.-P.F.); Centre Hospitalier Universitaire, Strasbourg (B.L.); Centre Hospitalier Universitaire, Amiens (B.R.); Centre Henri Becquerel, Rouen (F.J.); Centre Hospitalier Universitaire, Poitiers (F.B.); Centre Hospitalier Universitaire, Rennes (B.G.); Institut de Cancérologie de la Loire, Saint Priest en Jarez (J.J.); and INSERM Unité 702, Université Paris VI, and Hôpital Tenon, Assistance Publique–Hôpitaux de Paris, Paris (P.R.) — all in France.
Address reprint requests to Dr. Jaccard at the Department of Hematology, Centre Hospitalier Universitaire, Limoges, 87000 Limoges, France, or at arnaud.jaccard@chu-limoges.fr.
Other investigators in the MAG and IFM Intergroup are listed in the Appendix.
Appendix
In addition to the authors, the following investigators were members of the MAG and IFM Intergroup: J. Ducroix, V. Salle, Hôpital Sud, Amiens; S. Francois, M. Hunault, N. Ifrah, Centre Hospitalier Universitaire, Angers; B. Corront, F. Ducret, Centre Hospitalier, Annecy; D. Deconinck, J. Fontan, L. Voillat, Centre Hospitalier Universitaire, Besançon; N. Arzouk, A. Durrbach, Hôpital Bicêtre, Le Kremlin-Bicêtre; L. Moulonguet Doleris, Hôpital Ambroise-Paré, Boulogne; M. Escoffre, Centre Hospitalier Universitaire, Brest; X. Levaltier, M. Macro, Centre Hospitalier Universitaire, Caen; F. Dreyfus, P. Ravaud, Hôpital Cochin, Paris; M. Divine, Hôpital Henri-Mondor, Créteil; S. Courby, R. Gressin, J.J. Sotto, Centre Hospitalier Universitaire, Grenoble; F. Bauters, V. Coiteux, E. Hachulla, Centre Hospitalier Universitaire, Lille; B. Christian, V. Dorvaux, Centre Hospitalier Régional, Metz; C. Hulin, P. Lederlin, Centre Hospitalier Universitaire, Nancy; R. Delarue, A. Buzin, Hôpital Necker, Paris; A. Ayache, A. Thierry, Centre Hospitalier Universitaire, Poitiers; B. Kolb, J.L. Pennafore, Centre Hospitalier Universitaire, Reims; T. Lamy de La Chapelle, P. Le Prise, C. Cazalets, C. Dauriac, Centre Hospitalier Universitaire, Rennes; A. Stamatoullas-Bastard, H. Tilly, Centre Henri Becquerel, Rouen; Z. Amoura, J. Gabarre, J.P. Vernant, N. Dhedin, L. Sutton, Hôpital Pitié–Salpêtrière, Paris; P. Coppo, A. Najman, Hôpital Saint-Antoine, Paris; M. Malphettes, B. Arnulf, J.C. Brouet, Hôpital Saint-Louis, Paris; H. Ruellan, J. Sibilia, R.M. Javier, B. Goichot, Centre Hospitalier Universitaire, Strasbourg; M. Attal, F. Huget, A. Huynh, G. Laurent, Centre Hospitalier Universitaire, Toulouse; J.P. Lamagnere, P. Colombat, Centre Hospitalier Universitaire, Tours; and H. Jardel, Centre Hospitalier, Vannes.
- References
References
1
Kyle RA ,Gertz MA ,Greipp PR , et al. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone, and colchicine. N Engl J Med 1997;336:1202-1207
Full Text | Web of Science | Medline2
Skinner M ,Anderson JJ ,Simms R , et al. Treatment of 100 patients with primary amyloidosis: a randomized trial of melphalan, prednisone, and colchicine versus colchicine only. Am J Med 1996;100:290-298
CrossRef | Web of Science | Medline3
Skinner M ,Sanchorawala V ,Seldin DC , et al. High-dose melphalan and autologous stem cell transplantation in patients with AL amyloidosis: an 8-year study. Ann Intern Med 2004;140:85-93
Web of Science | Medline4
Comenzo RL ,Gertz MA . Autologous stem cell transplantation for primary systemic amyloidosis. Blood 2002;99:4276-4282
CrossRef | Web of Science | Medline5
Moreau P ,Leblond V ,Bourquelot P , et al. Prognostic factors for survival and response after high-dose therapy and autologous stem cell transplantation in systemic AL amyloidosis: a report on 21 patients. Br J Haematol 1998;101:766-769
CrossRef | Web of Science | Medline6
Dispenzieri A ,Lacy MQ ,Kyle RA , et al. Eligibility for hematopoietic stem-cell transplantation for primary systemic amyloidosis is a favorable prognostic factor for survival. J Clin Oncol 2001;19:3350-3356
Web of Science | Medline7
Dispenzieri A ,Kyle RA ,Lacy MQ , et al. Superior survival in primary systemic amyloidosis patients undergoing peripheral blood stem cell transplantation: a case-control study. Blood 2004;103:3960-3963
CrossRef | Web of Science | Medline8
Gertz MA ,Comenzo R ,Falk RH , et al. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18-22 April 2004. Am J Hematol 2005;79:319-328
CrossRef | Web of Science | Medline9
Katzmann JA ,Clark RJ ,Abraham RS , et al. Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem 2002;48:1437-1444
Web of Science | Medline10
Freedman LS . Tables of the number of patients required in clinical trials using the logrank test. Stat Med 1982;1:121-129
CrossRef | Medline11
Buyse M, Piedbois P. On the relationship between response to treatment and survival time. Stat Med 1996;15:2797-812.
12
Lachmann HJ ,Gallimore R ,Gillmore JD , et al. Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy. Br J Haematol 2003;122:78-84
CrossRef | Web of Science | Medline13
Palladini G ,Perfetti V ,Obici L , et al. Association of melphalan and high-dose dexamethasone is effective and well tolerated in patients with AL (primary) amyloidosis who are ineligible for stem cell transplantation. Blood 2004;103:2936-2938
CrossRef | Web of Science | Medline14
Gertz MA. Amyloidosis: recognition, prognosis, and conventional therapy. In: Hematology 1999. New Orleans: American Society of Hematology, 1999:339-47.
15
Vesole DH ,Perz WS ,Reece DE ,Akasheh M ,Horowitz MM ,Bredeson C . High-dose therapy with autologous hematopoietic stem cell transplantation (HSCT) for patients with primary systemic amyloidosis (AL): results from the Autologous Blood and Marrow Transplant Registry (ABMTR). Blood 2003;102:118a-118a
CrossRef | Web of Science16
Goodman HJ ,Gilmore JD ,Lachmann HJ ,Wechalekar AD ,Bradwell AR ,Hawkins PN . Outcome of autologous stem cell transplantation for AL amyloidosis in the UK. Br J Haematol 2006;134:417-425
CrossRef | Web of Science | Medline17
Gertz MA ,Blood E ,Vesole DH ,Abonour R ,Lazarus HM ,Greipp PR . A multicenter phase 2 trial of stem cell transplantation for immunoglobulin light-chain amyloidosis (E4A97): an Eastern Cooperative Oncology Group Study. Bone Marrow Transplant 2004;34:149-154
CrossRef | Web of Science | Medline18
Gertz MA ,Lacy MQ ,Bjornsson J ,Litzow MR . Fatal pulmonary toxicity related to the administration of granulocyte colony-stimulating factor in amyloidosis: a report and review of growth factor-induced pulmonary toxicity. J Hematother Stem Cell Res 2000;9:635-643
CrossRef | Medline19
Gertz MA ,Lacy MQ ,Dispenzieri A , et al. Stem cell transplantation for the management of primary systemic amyloidosis. Am J Med 2002;113:549-555
CrossRef | Web of Science | Medline
- Citing Articles (92)
Citing Articles
1
Morie A. Gertz. (2012) Immunoglobulin light chain amyloidosis: 2012 update on diagnosis, prognosis, and treatment. American Journal of Hematology 87:2, 183-189
CrossRef2
S. W. Dubrey, R. L. Comenzo. (2012) Amyloid diseases of the heart: current and future therapies. QJM
CrossRef3
Frank Bridoux, Sébastien Delbes, Christophe Sirac, François Pourreau, Matthieu Puyade, Estelle Desport, Arnaud Jaccard, Jean-Paul Fermand, Guy Touchard. (2012) Atteintes rénales des dysglobulinémies : avancées diagnostiques et thérapeutiques. La Presse Médicale
CrossRef4
Hans K. Meier-Ewert, Vaishali Sanchorawala, John L. Berk, Frederick L. Ruberg. (2011) Cardiac Amyloidosis: Evolving Approach to Diagnosis and Management. Current Treatment Options in Cardiovascular Medicine 13:6, 528-542
CrossRef5
Prashant Kapoor, Thenappan Thenappan, Ekta Singh, Shaji Kumar, Philip R. Greipp. (2011) Cardiac Amyloidosis: A Practical Approach to Diagnosis and Management. The American Journal of Medicine 124:11, 1006-1015
CrossRef6
Ping Zhou, James Hoffman, Heather Landau, Hani Hassoun, Lakshmanan Iyer, Raymond L. Comenzo. (2011) Clonal Plasma Cell Pathophysiology and Clinical Features of Disease Are Linked to Clonal Plasma Cell Expression of Cyclin D1 in Systemic Light-Chain Amyloidosis. Clinical Lymphoma Myeloma and Leukemia
CrossRef7
M. T. Cibeira, V. Sanchorawala, D. C. Seldin, K. Quillen, J. L. Berk, L. M. Dember, A. Segal, F. Ruberg, H. Meier-Ewert, N. T. Andrea, J. M. Sloan, K. T. Finn, G. Doros, J. Blade, M. Skinner. (2011) Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation: long-term results in a series of 421 patients. Blood 118:16, 4346-4352
CrossRef8
A. D. Wechalekar. (2011) ASCT for AL: all's well that ends well. Blood 118:16, 4298-4299
CrossRef9
Cabot, Richard C.Harris, Nancy Lee, Shepard, Jo-Anne O., Rosenberg, Eric S., Cort, Alice M., Ebeling, Sally H.Peters, Christine C., Raje, Noopur S., Steele, David J.R., Lawrimore, Tara M., Johri, Amer M., Sohani, Aliyah R., . (2011) Case 29-2011. New England Journal of Medicine 365:12, 1129-1138
Full Text10
M A Gertz. (2011) How to manage primary amyloidosis. Leukemia
CrossRef11
Junichi Hoshino, Yoshifumi Ubara, Naoki Sawa, Keiichi Sumida, Rikako Hiramatsu, Eiko Hasegawa, Tatsuya Suwabe, Noriko Hayami, Masayuki Yamanouchi, Fumi Takemoto, Shuichi Taniguchi, Kenmei Takaichi. (2011) 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. Clinical and Experimental Nephrology 15:4, 486-492
CrossRef12
D. E. Reece, U. Hegenbart, V. Sanchorawala, G. Merlini, G. Palladini, J. Blade, J.-P. Fermand, H. Hassoun, L. Heffner, R. A. Vescio, K. Liu, C. Enny, D.-L. Esseltine, H. van de Velde, A. Cakana, R. L. Comenzo. (2011) Efficacy and safety of once-weekly and twice-weekly bortezomib in patients with relapsed systemic AL amyloidosis: results of a phase 1/2 study. Blood 118:4, 865-873
CrossRef13
S O Schönland, P Dreger, T de Witte, U Hegenbart. (2011) Current status of hematopoietic cell transplantation in the treatment of systemic amyloid light-chain amyloidosis. Bone Marrow Transplantation
CrossRef14
David C. Seldin, John L. Berk, Flora Sam, Vaishali Sanchorawala. (2011) Amyloidotic Cardiomyopathy: Multidisciplinary Approach to Diagnosis and Treatment. Heart Failure Clinics 7:3, 385-393
CrossRef15
M A Gertz, M Q Lacy, A Dispenzieri, S K Kumar, F K Buadi, D Dingli, N Leung, W J Hogan, S R Hayman. (2011) Trends in day 100 and 2-year survival after auto-SCT for AL amyloidosis: outcomes before and after 2006. Bone Marrow Transplantation 46:7, 970-975
CrossRef16
A. Dispenzieri. (2011) Ushering in a new era for POEMS. Blood 117:24, 6405-6406
CrossRef17
J. Li, W. Zhang, L. Jiao, M.-H. Duan, H.-Z. Guan, W.-G. Zhu, Z. Tian, D.-B. Zhou. (2011) Combination of melphalan and dexamethasone for patients with newly diagnosed POEMS syndrome. Blood 117:24, 6445-6449
CrossRef18
R. Ryšavá, J. Straub, B. Vacková, J. Kořen, M. Trněný, Z. Potyšová, I. Špička. (2011) Results of autologous stem cell transplantation for AL amyloidosis in one Czech center. Amyloid 18:Suppl. 1, 139-141
CrossRef19
S. M. S. Herrmann, M. A. Gertz, M. D. Stegall, A. Dispenzieri, F. C. Cosio, S. Kumar, M. Q. Lacy, P. G. Dean, M. Prieto, S. R. Zeldenrust, F. K. Buadi, S. J. Russell, S. L. Nyberg, S. R. Hayman, D. Dingli, F. C. Fervenza, N. Leung. (2011) Long-term outcomes of patients with light chain amyloidosis (AL) after renal transplantation with or without stem cell transplantation. Nephrology Dialysis Transplantation 26:6, 2032-2036
CrossRef20
J. Rojas-Rivera, A. Barat, J. Egido. (2011) Glomerulopatías secundarias a enfermedades sistémicas. Medicine - Programa de Formación Médica Continuada Acreditado 10:82, 5560-5580
CrossRef21
(2011) Abstracts. Amyloid 18:Suppl. 1, 6-238
CrossRef22
A. Penot, J. Abraham, H. Debarri, E. Desport, C. Aguilar, D. Lavergne, F. Auroy, X. Leleu, A. Goldstein, B. Kolb, F. Bridoux, J. P. Fermand, V. Leblond, A. Jaccard. (2011) Effectiveness of second-line treatment in AL amyloidosis patient's refractory to M-Dex. Amyloid 18:Suppl. 1, 145-147
CrossRef23
F. Bridoux, P. Ronco, J. Gillmore, J.-P. Fermand. (2011) Renal transplantation in light chain amyloidosis: coming out of the cupboard. Nephrology Dialysis Transplantation 26:6, 1766-1768
CrossRef24
Efstathios Kastritis, Meletios Athanasios Dimopoulos. 2011. Primary Systemic Amyloidosis (AL). , 355-366.
CrossRef25
M. Matsuda, T. Gono, H. Morita, N. Katoh, M. Kodaira, S. Ikeda. (2011) Peripheral nerve involvement in primary systemic AL amyloidosis: a clinical and electrophysiological study. European Journal of Neurology 18:4, 604-610
CrossRef26
M. Pavic, C. Camus, F. Pasquet, L. Karkowski, E. Galoo, A. Nibaud, P. Debourdeau. (2011) Gravité de l’amylose AL de localisation digestive. La Revue de Médecine Interne 32:4, e52-e54
CrossRef27
R. Specter, V. Sanchorawala, D. C. Seldin, A. Shelton, S. Fennessey, K. T. Finn, J. B. Zeldis, L. M. Dember. (2011) Kidney dysfunction during lenalidomide treatment for AL amyloidosis. Nephrology Dialysis Transplantation 26:3, 881-886
CrossRef28
Giovanni Palladini, Giampaolo Merlini. (2011) Transplantation vs. conventional-dose therapy for amyloidosis. Current Opinion in Oncology 23:2, 214-220
CrossRef29
Morie A. Gertz. (2011) Immunoglobulin light chain amyloidosis: 2011 update on diagnosis, risk-stratification, and management. American Journal of Hematology 86:2, 180-186
CrossRef30
W. Lamm, W. Willenbacher, A. Lang, N. Zojer, E. Müldür, H. Ludwig, B. Schauer-Stalzer, C. C. Zielinski, J. Drach. (2011) Efficacy of the combination of bortezomib and dexamethasone in systemic AL amyloidosis. Annals of Hematology 90:2, 201-206
CrossRef31
Zachary Simmons. 2011. Treatment and Management of Autoimmune Neuropathies. , 215-235.
CrossRef32
Michael Rosenzweig, Heather Landau. (2011) Light chain (AL) amyloidosis: update on diagnosis and management. Journal of Hematology & Oncology 4:1, 47
CrossRef33
FE Davies, KC Anderson. 2011. Abnormalities in immunoglobulin synthesizing cells. , 451-469.
CrossRef34
Efstathios Kastritis, Meletios A. Dimopoulos. (2010) High dose melphalan in primary systemic amyloidosis: status quo?. Leukemia & Lymphoma 51:12, 2149-2151
CrossRef35
Morie A. Gertz, Martha Q. Lacy, Angela Dispenzieri, Suzanne R. Hayman, Shaji K. Kumar, David Dingli, Stephen M. Ansell, Dennis A. Gastineau, David J. Inwards, Patrick B. Johnston, Mark R. Litzow, Ivana N. M. Micallef, Luis F. Porrata, Nelson Leung, William J. Hogan, Francis K. Buadi. (2010) Autologous stem cell transplant for immunoglobulin light chain amyloidosis: a status report. Leukemia & Lymphoma 51:12, 2181-2187
CrossRef36
A. D. Cohen, R. L. Comenzo. (2010) Systemic Light-Chain Amyloidosis: Advances in Diagnosis, Prognosis, and Therapy. Hematology 2010:1, 287-294
CrossRef37
Vaishali Sanchorawala, David C. Seldin, John L. Berk, J. Mark Sloan, Gheorghe Doros, Martha Skinner. (2010) Oral Cyclic Melphalan and Dexamethasone for Patients With AL Amyloidosis. Clinical Lymphoma, Myeloma & Leukemia 10:6, 469-472
CrossRef38
Pierre Ronco, Emmanuelle Plaisier, Pierre Aucouturier. (2010) Ig-Related Renal Disease in Lymphoplasmacytic Disorders: An Update. Seminars in Nephrology 30:6, 557-569
CrossRef39
Simon DJ Gibbs, Philip N Hawkins. 2010. Amyloidosis. , 599-613.
CrossRef40
Chanhyok Sakurai-Chin, Yoshifumi Ubara, Tatsuya Suwabe, Junichi Hoshino, Tomoki Yonaha, Eiko Hasegawa, Keiichi Sumida, Rikako Hiramatsu, Masayuki Yamanouchi, Noriko Hayami, Junji Yamauchi, Naoyuki Tominaga, Naoki Sawa, Fumi Takemoto, Kazuhiro Masuoka, Kenmei Takaichi, Kenichi Oohashi. (2010) AL amyloidosis with IgD-lambda monoclonal gammopathy and lambda-type Bence-Jones protein: successful treatment by autologous stem cell transplantation. Clinical and Experimental Nephrology 14:5, 506-510
CrossRef41
E. C. Heher, N. B. Goes, T. R. Spitzer, N. S. Raje, B. D. Humphreys, K. C. Anderson, P. G. Richardson. (2010) Kidney disease associated with plasma cell dyscrasias. Blood 116:9, 1397-1404
CrossRef42
S. Dietrich, S. O. Schonland, A. Benner, T. Bochtler, A. V. Kristen, J. Beimler, E. Hund, M. Zorn, H. Goldschmidt, A. D. Ho, U. Hegenbart. (2010) Treatment with intravenous melphalan and dexamethasone is not able to overcome the poor prognosis of patients with newly diagnosed systemic light chain amyloidosis and severe cardiac involvement. Blood 116:4, 522-528
CrossRef43
M. A. Gertz. (2010) I don't know how to treat amyloidosis. Blood 116:4, 507-508
CrossRef44
Angela Dispenzieri, Shaji Kumar. 2010. Current Therapies for Light-Chain Amyloidosis. , 775-793.
CrossRef45
D. J. Chen, H. Jiang, H. Yang, Q. He, H. P. Wang, J. H. Chen. (2010) Unusual cause of proteinuria and re-renal failure after kidney transplantation: de novo localized AL amyloidosis in renal allograft. International Urology and Nephrology 42:2, 507-511
CrossRef46
Jun Koyama, Rodney H. Falk. (2010) Prognostic Significance of Strain Doppler Imaging in Light-Chain Amyloidosis. JACC: Cardiovascular Imaging 3:4, 333-342
CrossRef47
Tom Pettersson, Yrjö T. Konttinen. (2010) Amyloidosis—Recent Developments. Seminars in Arthritis and Rheumatism 39:5, 356-368
CrossRef48
R. P. E. Sarkany, S. M. Breathnach, A. A. M. Morris, K. Weismann, P. D. Flynn. 2010. Metabolic and Nutritional Disorders. , 1-103.
CrossRef49
P Ljungman, M Bregni, M Brune, J Cornelissen, T de Witte, G Dini, H Einsele, H B Gaspar, A Gratwohl, J Passweg, C Peters, V Rocha, R Saccardi, H Schouten, A Sureda, A Tichelli, A Velardi, D Niederwieser. (2010) Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe 2009. Bone Marrow Transplantation 45:2, 219-234
CrossRef50
Rodney H. Falk, Simon W. Dubrey. (2010) Amyloid Heart Disease. Progress in Cardiovascular Diseases 52:4, 347-361
CrossRef51
KAZUEI OGAWA, KAZUHIKO IKEDA, MIKI FURUKAWA, KAYO HARADA-SHIRADO, YUMIKO MASHIMO, HIROSHI TAKAHASHI, HAYATO MATSUMOTO, SATOSHI KIMURA, AKIKO SHICHISHIMA-NAKAMURA, HIROSHI OHKAWARA, YUKO HASHIMOTO, KOICHI ASAHI, HIDEYOSHI NOJI, HITOSHI OHTO, YASUCHIKA TAKEISHI. (2010) A LONG-TERM REMISSION OF RENAL AMYLOIDOSIS WITH NEPHROTIC SYNDROME AFTER AUTOLOGOUS PERIPHERAL BLOOD STEM-CELL TRANSPLANTATION. FUKUSHIMA JOURNAL OF MEDICAL SCIENCE 56:2, 151-156
CrossRef52
Ambuj Kumar, Rahul Mhaskar. (2010) Response: Re: High-Dose Chemotherapy with Autotransplantation in AL Amyloidosis: A Flawed Meta-analysis. Biology of Blood and Marrow Transplantation 16:1, 140-141
CrossRef53
Jayesh Mehta, Angela Dispenzieri, Morie A. Gertz. (2010) High-Dose Chemotherapy with Autotransplantation in AL Amyloidosis: A Flawed Meta-analysis. Biology of Blood and Marrow Transplantation 16:1, 138-140
CrossRef54
Prayman Sattianayagam, Philip Hawkins, Julian Gillmore. (2009) Amyloid and the GI tract. Expert Review of Gastroenterology & Hepatology 3:6, 615-630
CrossRef55
R. L. Comenzo. (2009) How I treat amyloidosis. Blood 114:15, 3147-3157
CrossRef56
A. V. Kristen, F.-U. Sack, S. O. Schonland, U. Hegenbart, B. M. Helmke, A. Koch, P. A. Schnabel, C. Rocken, S. Hardt, A. Remppis, H. Goldschmidt, M. Karck, A. D. Ho, H. A. Katus, T. J. Dengler. (2009) Staged heart transplantation and chemotherapy as a treatment option in patients with severe cardiac light-chain amyloidosis. European Journal of Heart Failure 11:10, 1014-1020
CrossRef57
Osamu Yamazaki, Yoshifumi Ubara, Tatsuya Suwabe, Shohei Nakanishi, Junichi Hoshino, Naoki Sawa, Noriko Hayami, Masayuki Yamanouchi, Fumi Takemoto, Takaichi Kenmei, Kazuhiro Masuoka, Kenichi Oohashi. (2009) Successful treatment of primary AL amyloidosis by VAD therapy, high-dose melphalan, and autologous peripheral stem cell transplantation. Clinical and Experimental Nephrology 13:5, 522-525
CrossRef58
P. Ronco, P. Aucouturier. (2009) Renal involvement in AL amyloidosis: the facts, the promise and the hope. Nephrology Dialysis Transplantation 24:10, 2967-2969
CrossRef59
Félicie Costantino, Damien Loeuille, Hervé Dintinger, Patrice Péré, Isabelle Chary-Valckenaere. (2009) Fixed digital contractures revealing light-chain amyloidosis. Joint Bone Spine 76:5, 553-555
CrossRef60
D. E. Reece, V. Sanchorawala, U. Hegenbart, G. Merlini, G. Palladini, J.-P. Fermand, R. A. Vescio, X. Liu, Y. A. Elsayed, A. Cakana, R. L. Comenzo, . (2009) Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis: results of a phase 1 dose-escalation study. Blood 114:8, 1489-1497
CrossRef61
M. Gertz. (2009) Finishing off fibrils. Blood 114:8, 1456-1457
CrossRef62
Rahul Mhaskar, Ambuj Kumar, Madhusmita Behera, Mohamed A. Kharfan-Dabaja, Benjamin Djulbegovic. (2009) Role of High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation in Primary Systemic Amyloidosis: A Systematic Review. Biology of Blood and Marrow Transplantation 15:8, 893-902
CrossRef63
Félicie Costantino, Damien Loeuille, Hervé Dintinger, Patrice Péré, Isabelle Chary-Valckenaere. (2009) Fixed digital contractures revealing light-chain amyloidosis. Joint Bone Spine 76:4, 404-408
CrossRef64
Valérie Frossard, Nicolas Ketterer, Anne Rosselet, Pascal Meier, Anne Cairoli, Michel A. Duchosal, Tibor Kovacsovics. (2009) Early intensification and autologous stem cell transplantation in patients with systemic AL amyloidosis: a single-centre experience. Annals of Hematology 88:7, 681-685
CrossRef65
E. Roig, L. Almenar, F. González-Vílchez, G. Rábago, J. Delgado, M. Gómez-Bueno, M. G. Crespo-Leiro, J. M. Arizón, L. de la Fuente, N. Manito, . (2009) Outcomes of Heart Transplantation for Cardiac Amyloidosis: Subanalysis of the Spanish Registry for Heart Transplantation. American Journal of Transplantation 9:6, 1414-1419
CrossRef66
S.O. Schönland, T. Bochtler, A.V. Kristen, A.D. Ho, U. Hegenbart. (2009) Aktuelle Diagnostik und Therapie der Leichtkettenamyloidose. Der Pathologe 30:3, 205-211
CrossRef67
Giovanni Palladini, Paola Russo, Francesca Lavatelli, Mario Nuvolone, Riccardo Albertini, Tiziana Bosoni, Vittorio Perfetti, Laura Obici, Stefano Perlini, Remigio Moratti, Giampaolo Merlini. (2009) Treatment of patients with advanced cardiac AL amyloidosis with oral melphalan, dexamethasone, and thalidomide. Annals of Hematology 88:4, 347-350
CrossRef68
Ingrid I van Gameren, Edo Vellenga, Bouke PC Hazenberg. (2009) Novel treatments for systemic amyloidosis. International Journal of Clinical Rheumatology 4:2, 171-188
CrossRef69
Eliot C. Heher, Thomas R. Spitzer, Nelson B. Goes. (2009) Light Chains: Heavy Burden in Kidney Transplantation. Transplantation 87:7, 947-952
CrossRef70
Morie A. Gertz, Steven R. Zeldenrust. (2009) Treatment of immunoglobulin light chain amyloidosis. Current Hematologic Malignancy Reports 4:2, 91-98
CrossRef71
Giovanni Palladini, Paola Russo, Tiziana Bosoni, Gabriele Sarais, Francesca Lavatelli, Andrea Foli, Letizia Zenone Bragotti, Vittorio Perfetti, Laura Obici, Franco Bergesio, Riccardo Albertini, Remigio Moratti, Giampaolo Merlini. (2009) AL Amyloidosis Associated with IgM Monoclonal Protein: A Distinct Clinical Entity. Clinical Lymphoma, Myeloma & Leukemia 9:1, 80-83
CrossRef72
David Goldberg, Ilan Weisberg, David Diuguid, Paul Gaglio, Bachir Alobeid, Scott Fink, Jai Radhakrishnan. (2009) Worth a Second Look. The American Journal of Medicine 122:1, 24-26
CrossRef73
C. Foguem, B. Kantelip, E. Deconinck, C. Hafsaoui, N. Méaux-Ruault, H. Gil, N. Magy-Bertrand, J.-L. Dupond. (2009) Maladie de Randall, simulant une maladie de Gougerot-Sjögren, traitée avec succès par chimiothérapie et autogreffe de moelle osseuse. La Revue de Médecine Interne 30:1, 49-52
CrossRef74
V. Audard, M. Matignon, L. Weiss, P. Remy, A. Pardon, C. Haioun, K. Belhadj, L. Salomon, M. L. Hillon, D. Sahali, E. Vermes, P. Lang, P. Grimbert. (2009) Successful Long-Term Outcome of the First Combined Heart and Kidney Transplant in a Patient with Systemic AL Amyloidosis. American Journal of Transplantation 9:1, 236-240
CrossRef75
Hiroyuki Hata, Kazuhiko Nishi, Wataru Oshihara, Jiro Arai, Kazuyuki Shimizu, Tetsuro Kawakita, Miki Nakamura, Hiroaki Mitsuya. (2009) Adsorption of Bence–Jones protein to polymethylmethacrylate membrane in primary amyloidosis. Amyloid 16:2, 108-110
CrossRef76
Ashutosh D Wechalekar, Mark Offer, Julian D Gillmore, Philip N Hawkins, Helen J Lachmann. (2008) Cardiac amyloidosis, a monoclonal gammopathy and a potentially misleading mutation. Nature Clinical Practice Cardiovascular Medicine 6:2, 128-133
CrossRef77
A. Solomon, S. D. Macy, C. Wooliver, D. T. Weiss, P. Westermark. (2008) Splenic plasma cells can serve as a source of amyloidogenic light chains. Blood 113:7, 1501-1503
CrossRef78
PAULA MOYER. (2008) Two Patients with Sporadic Late-Onset Nemaline Myopathy Respond to Stem Cell Therapy. Neurology Today 8:18, 18,24
CrossRef79
Martha Q. Lacy, Angela Dispenzieri, Suzanne R. Hayman, Shaji Kumar, Robert A. Kyle, S. Vincent Rajkumar, Brooks S. Edwards, Richard J. Rodeheffer, Robert P. Frantz, Sudhir S. Kushwaha, Alfredo L. Clavell, Joseph A. Dearani, Thoralf M. Sundt, Richard C. Daly, Christopher G.A. McGregor, Dennis A. Gastineau, Mark R. Litzow, Morie A. Gertz. (2008) Autologous Stem Cell Transplant after Heart Transplant for Light Chain (AL) Amyloid Cardiomyopathy. The Journal of Heart and Lung Transplantation 27:8, 823-829
CrossRef80
D. Peest, M. Haubitz. (2008) Klinik und Therapie der AL-Amyloidose. Der Nephrologe 3:4, 291-296
CrossRef81
André Tichelli, Smita Bhatia, Gérard Socié. (2008) Cardiac and cardiovascular consequences after haematopoietic stem cell transplantation. British Journal of Haematology 142:1, 11-26
CrossRef82
Asha Rajashekar, Mark A. Perazella, Susan Crowley. (2008) Systemic Diseases with Renal Manifestations. Primary Care: Clinics in Office Practice 35:2, 297-328
CrossRef83
Jeannine Silberman, Sagar Lonial. (2008) Review of peripheral neuropathy in plasma cell disorders. Hematological Oncology 26:2, 55-65
CrossRef84
S. K. L. LAM, G. S. NGIAN, R. TRAVERS, K. K. T. LIM. (2008) Amyloidosis: a rheumatological perspective on diagnosis, further investigation and treatment. International Journal of Rheumatic Diseases 11:1, 55-60
CrossRef85
Benjamin Terrier, Arnaud Jaccard, Jean-Luc Harousseau, Richard Delarue, Olivier Tournilhac, Mathilde Hunault-Berger, Mohamed Hamidou, Jacques Dantal, Marc Bernard, Bernard Grosbois, Pierre Morel, Valérie Coiteux, Olivier Gisserot, Philippe Rodon, Arnaud Hot, Caroline Elie, Véronique Leblond, Jean-Paul Fermand, Fadi Fakhouri. (2008) The Clinical Spectrum of IgM-Related Amyloidosis. Medicine 87:2, 99-109
CrossRef86
(2008) High-Dose Melphalan versus Melphalan plus Dexamethasone for AL Amyloidosis. New England Journal of Medicine 358:1, 91-93
Full Text87
B.H. Thiers. (2008) High-Dose Melphalan versus Melphalan plus Dexamethasone for AL Amyloidosis. Yearbook of Dermatology and Dermatologic Surgery 2008, 393-394
CrossRef88
Keiichi Onji, Shoichi Takahashi, Takayasu Kuwabara, Yuki Kimura, Takahiro Azakami, Yoshio Katamura, Fukiko Mitsui, Tomokazu Kawaoka, Hiromi Saneto, Michio Imamura, Yoshiiku Kawakami, Hiroshi Aikata, Hiroto Ishihara, Koji Arihiro, Kazuaki Chayama. (2008) Successful treatment of primary hepatic amyloidosis with melphalan plus dexamethasone: a case report. Kanzo 49:12, 581-588
CrossRef89
Yasukazu Kawai, Ippei Sakamaki, Eiju Negoro, Nozomi Ootsuki, Kouji Morinaga, Keiichi Kinoshita, Naoko Hosono, Shinji Kishi, Takahiro Yamauchi, Yoshimasa Urasaki, Akira Yoshida, Hiromichi Iwasaki, Hiroshi Tsutani, Takanori Ueda. (2008) HIGH-DOSE MELPHALAN WITH AUTOLOGOUS STEM CELL TRANSPLANTATION FOR THE TREATMENT OF AMYLOID LIGHT-CHAIN AMYLOIDOSIS. Japanese Journal of Transfusion and Cell Therapy 54:4, 497-502
CrossRef90
Angela Dispenzieri, Giampaolo Merlini, Raymond L. Comenzo. (2008) Amyloidosis: 2008 BMT Tandem Meetings (February 13-17, San Diego). Biology of Blood and Marrow Transplantation 14:1, 6-11
CrossRef91
Meletios Dimopoulos, Efstathios Kastritis. (2008) High dose therapy for light chain amyloidosis: Can we reduce treatment related mortality further?. Leukemia & Lymphoma 49:1, 4-5
CrossRef92
Joline L.T. Chen, Laura M. Dember. 2008. Amyloidosis and Other Fibrillary and Monoclonal Immunoglobulin-Associated Kidney Diseases. , 257-271.
CrossRef
- Letters
