Effects of Amyloid Light-chain Amyloidosis on Clinical Characteristics and Prognosis in Multiple Myeloma: A Single-center Retrospective Study

doi:10.21203/rs.3.rs-49285/v1

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Effects of Amyloid Light-chain Amyloidosis on Clinical Characteristics and Prognosis in Multiple Myeloma: A Single-center Retrospective Study

https://doi.org/10.21203/rs.3.rs-49285/v1

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Background

Amyloid light-chain amyloidosis (AL amyloidosis) is commonly associated with multiple myeloma. However, the clinical characteristics and prognosis of multiple myeloma with AL amyloidosis are not particularly clear.

Methods

Patients with multiple myeloma in the Peking University First Hospital registry from 2010 to 2018 were studied. The clinical and laboratory information were collected from first presentation to death or until the last available clinical follow-up. The patients’ survival and outcomes were analyzed, and the relationships between the clinical parameters and survival were also assessed.

Results

Compared with patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP ≧ 1000 pg/ml (P = 0.001), ALP > 187.5 IU/L (P = 0.002) and ALB < 35 g/L (P = 0.001), but lower incidence of HB < 85 g/L (P = 0.031), hypercalcemia > 2.65 mmol/L (P = 0.008), bone destruction more than three (P < 0.001), bone marrow plasma cell ratio ≧ 30% (P < 0.001) and worse D-S stage (P < 0.001). Multiple myeloma was more often complicated by λ-type AL amyloidosis than κ-type AL amyloidosis. However, further comparison found that multiple myeloma with κ-type AL amyloidosis had higher incidence of ALP > 187.5 IU/L (P = 0.001) and renal insufficiency (P = 0.001) along with worse D-S stage (P = 0.003) than multiple myeloma with λ-type AL amyloidosis. Renal biopsies of many patients suggested AL amyloidosis, but their bone marrow biopsies or subcutaneous abdominal fat pad aspirates results were negative. The existence of AL amyloidosis especially the heart involvement was related to shorter long-term survival of multiple myeloma according to univariate analysis. Cox regression model for overall survival detected the presence of AL amyloidosis in multiple myeloma having independent prognostic significance (RR = 4.52, P = 0.049).

Conclusions

Patients with multiple myeloma accompanied by AL amyloidosis have milder target organ damage and lower tumor burden. The incidence of AL amyloidosis in κ-type multiple myeloma is lower but more severe than λ-type multiple myeloma. Renal biopsy can help to identify patients with AL amyloidosis. AL amyloidosis is an independent poor prognostic factor for multiple myeloma is mainly because involvements of important organs especially the heart.

Oncology

multiple myeloma

AL amyloidosis

poor prognostic factor

Multiple myeloma is mainly manifested by abnormal proliferation of bone marrow plasma cells and accompanied by large amounts of M protein secretion or light chain, leading to hypercalcemia, renal injury, anemia and bone destruction¹. Many prognostic factors have been analyzed in multiple myeloma. Some Studies have found that age, albumin, lactate dehydrogenase, percentage of abnormal plasma cell in bone marrow, β2-microglobulin and high-risk cytogenetic abnormalities are significantly associated with the prognosis of multiple myeloma².

AL amyloidosis (ALA) is a rare and poorly prognostic disease that is clearly associated with monoclonal gammopathy of unknown significance, multiple myeloma and Waldenström macroglobulinemia³. The abnormal plasma cells of the above plasma cell diseases secrete a large number of light chains, which deposit in various organs and become amyloid proteins, causing damage to the organs³. The organs usually affected are skin, soft tissue, kidney, liver, heart, gastrointestinal tract and peripheral nerves⁴. The median survival time for AL amyloidosis is two to three years⁵.

Whether and how AL amyloidosis affects the survival time of multiple myeloma is rarely studied and inconclusive. Only three studies have been done, and these studies had conflicting results. These studies are affected by the characteristics of the included population and treatment plans, so different results are obtained. In our study, the population we included basically had clinical manifestations of amyloidosis and organ involvement. We analyzed not only the prognostic impact of AL amyloidosis on multiple myeloma but also the impact of various amyloid organ involvement on the prognosis.

Therefore, we performed a retrospective study in a single-center cohort to elucidate the effects of AL amyloidosis on clinical characteristics and prognosis in multiple myeloma patients.

Patients and institutional review board approval

We included 178 patients with multiple myeloma registered from January 1, 2010 to December 31, 2018. Patients with plasma cell diseases such as monoclonal gammopathy of unknown significance and Waldenström macroglobulinemia were excluded. Informed consent was obtained from each individual participant. This study was approved by the institutional review board (IRB) of Peking University First Hospital.

Diagnosis and response criteria, clinical information and follow-up

Multiple myeloma was diagnosed according to the 2014 International Myeloma Working Group criteria⁶. AL amyloidosis was confirmed by the light and polarized microscopy for the presence of Congo red deposits and green birefringence of the biopsies of affected parts, including skin, heart, liver, kidney, gastrointestinal tract, bone marrow, subcutaneous fat and rectal mucosa. The organ involvement for AL amyloidosis was assessed as per the consensus criteria reported in the 10th International Symposium on Amyloid and Amyloidosis⁷. Immunofixation electrophoresis was performed to identify the type of light chain involved. The diagnosis interval of AL amyloidosis and multiple myeloma was no more than 1 month.

In addition, we extracted the following clinical information at the time of diagnosis retrospectively for all patients: lactate dehydrogenase (LDH), hemoglobin (Hb), calcium (Ca), albumin (ALB), alkalinephosphatase (ALP), serum creatinine (Scr), brain natriuretic peptide (BNP).X-ray or Computed Tomography was used to determine bone destruction. Bone puncture was performed to determine the bone marrow plasma cells ratio. Pathological biopsy was used to identify extramedullary lesions. D-S stage of multiple myeloma was then determined based on the above-mentioned information.

We evaluated the response of multiple myeloma using the 2016 International Myeloma Working Group consensus criteria for response⁸. Follow-up time was defined as the time from the diagnosis to the time of death (despite the cause of death), or the last-documented contact with the patient.

Statistical analyses

Chi-square test was used to compare the categorical variables in different groups of patients, including multiple myeloma with and without AL amyloidosis, and AL amyloidosis with different light chain types. Kaplan–Meier survival curves were used to describe overall survival. Cox proportional hazard model for overall survival was adjusted for age, initial therapeutic effect, presence of amyloid deposits, bone marrow plasma cell ratio, ALB, BNP, HB, Scr, LDH and D-S stage. All quoted P values were from two-sided tests. P < 0.05 is considered statistically significant. All analyses were performed using SPSS 20.0 software (SPSS Institute).

1. Clinical characteristics of multiple myeloma with or without AL amyloidosis.

We identified 178 multiple myeloma patients in our registry from January 1, 2010 to December 31, 2018. Twenty patients were lost during follow up. Therefore, 158 patients were included in the subsequent analyses. Among them, forty-nine patients (31%) were diagnosed with AL amyloidosis. Table 1 lists the clinical characteristics of multiple myeloma patients with or without AL amyloidosis at the time of diagnosis. The two groups showed similar gender and age distributions. Compared with the patients with AL amyloidosis, patients without AL amyloidosis showed higher incidence of serious anemia (53.2% VS 34.7%, P = 0.031), more than three bone lesions (59.6% VS 22.4%, P < 0.001) and hypercalcemia (25.6% VS 6.1%, P = 0.008). Accordingly, patients without AL amyloidosis showed higher proportion for D-S stage III (73.4% VS 38.8%, P < 0.001). Patients without AL amyloidosis showed significantly higher tumor burden indicated by the bone narrow plasmas cells ratio ≧ 30% (55.9% VS 14.2%, P < 0.001), while patients with amyloidosis have significantly higher incidence of BNP ≧ 1000 pg/ml (26.5% VS 7.3%, P = 0.001), ALP > 187.5 IU/L (16.3% VS 1.8%, P = 0.002) and ALB < 35 g/L (75.5% VS 46.7%, P = 0.001). No significant difference in the incidence of renal insufficiency was observed (35.8% VS 24.5%, P = 0.16).

2. Clinical characteristics of multiple myeloma with different light chain types of AL amyloidosis.

We observed more patients with multiple myeloma had λ-type AL amyloidosis (N = 35, 71.5%) than κ-type AL amyloidosis (N = 14, 28.5%).We then further compared the clinical characteristics of multiple myeloma patients with different light chain types of AL amyloidosis (Table 2). Although there was no significant difference (P > 0.05) in the incidence of serious anemia, more than three bone lesions, hypercalcemia, LDH ≧ 240 IU/L or bone marrow plasma cells ≧ 30% between the two groups, patients with κ-type AL amyloidosis showed a higher proportion of D-S stage III (71.5% VS 25.8%, P = 0.003).There is no difference in the incidence of ALB < 35 g/L between the two groups, but κ-type AL amyloidosis patients had significantly higher incidence of renal insufficiency (57.1% VS 11.4%, P = 0.001). Patients with κ-type AL amyloidosis had a higher incidence of ALP > 187.5 IU/L (42.8% VS 5.7%, P = 0.001). No statistically significant difference was observed for BNP ≧ 1000 pg/ml between two groups (42.8% VS 20%, P = 0.102).

3. Pathological biopsy of AL amyloidosis.

AL amyloidosis was confirmed from pathological biopsies at ≥ one body part. Bone narrow biopsy was performed in all 49 patients with AL amyloidosis, and 17 patients (34.6%) were positive. Six of nine patients (66.6%) were positive for the subcutaneous abdominal fat pad aspirates biopsy. All the 28 patients with renal biopsy were positive, including 21 patients with negative bone narrow biopsies and 2 patients with negative subcutaneous abdominal fat pad aspirates. Histologic confirmation of AL amyloidosis at other sites were obtained for the six patients that were undetermined from the bone marrow, subcutaneous abdominal fat and the renal biopsies, including two tongue biopsies, one liver biopsy, one myocardial biopsy, one nerve biopsy and one gastrointestinal tract biopsy.

4.Organ involvement, death rate and causes of death in patients with amyloidosis.

Organs involvement among the 49 patients with multiple myeloma and AL amyloidosis are as follows: kidney (36, 73.4%), heart (26, 53%), liver (13, 26.5%), skin (8, 16.3%) gastrointestinal tract (6, 12.2%), soft tissue (4, 8.2%), nerve (4, 8.2%), and pulmonary (1, 2%). Thirty-four patients (69.4%) had one or two organs involved and 15 (30.6%) patients had ≥ 3 organs involved. Ten of 13 patients with liver involvement also had heart involvement. Five of 6 patients with gastrointestinal tract involvement also had heart involvement. Regarding the death rate, 31 of the 49 (63.3%) patients died during study period, including 19/34 patients (55.8%) with one or two organs involvement and 12/15 patients (80%) with ≥ 3 organs involvement died. Specifically, 19/26 (73%) patients with heart involvement died. All 13 patients with liver involvement died, six of which died of cardiovascular disease. Twenty four of the 36 patients (66.7%) with kidney involvement died. Five of six patients (83.3%) with gastrointestinal tract involvement died, three of which died of cardiovascular disease. Causes of death are showed in Table 4. Twelve patients did not have clear causes of death, among the remaining 19 patients, 13 died of cardiovascular disease, making it the leading cause of death. Other causes include renal failure (2), digestive tract hemorrhage (2), disease progression of multiple myeloma (1) and infection (1).

5. Survival of all patients with multiple myeloma and patients complicated by AL amyloidosis.

The Median follow-up time was 57 months (41.0-72.9 months) .Eighty five of the 158 patients (53.8%) died during the follow-up. The overall median survival time for patients was 50.9 months (range, 1–105 months). The survival rates at 1, 2, 3, 5 years were 72.2%, 52.5%, 35.5%, 18.4%, respectively. We divided the patients by the clinical characteristics to study the factors affecting patients’ survival. Survival time was significantly shorter in patients with age ≧ 65 years old, ALB < 35 g/L, LDH ≧ 240 IU/L, BNP ≧ 1000 pg/ml, initial therapeutic effect worse than VGPR, and the presence of AL amyloidosis (Table 4). Cox regression adjusting for covariates was performed to evaluate the hazard ratio of each clinical character in multiple myeloma having prognostic significance: AL amyloidosis (HR = 4.52, P = 0.049), age ≧ 65 (HR = 1.827, P = 0.009), LDH ≧ 240 IU/L (HR = 2.26, P = 0.006) and initial therapeutic effect worse than VGPR (HR = 4.03, p < 0.001). However, BNP ≧ 1000 pg/ml and ALB < 35 g/L have no statistical significance in the COX regression model.

Given that patients with amyloidosis had significantly shorter survival time than patients without amyloidosis (32.2 vs. 58.3 months, P < 0.001, Table 4 and Fig. 1A), we further analyzed the impact of the type and number of organ involvement on the survival of all the patients with multiple myeloma. The results showed that survival time was significantly shorter with heart involvement (Fig. 1B; median survival time of 25.9 vs. 55.7 months, P < 0.001), kidney involvement (Fig. 1C; 32.1 vs. 56.4 months, P = 0.001), liver involvement (Fig. 1D; 18.2 vs. 54.6 months, P < 0.001),gastrointestinal tract involvement (Fig. 1E; 18.1 vs. 52 months, P = 0.032) and ≥ 3 organs involvement (Fig. 1F; median survival time of 28.1 vs. 33.9 months, P = 0.001).

AL amyloidosis is a common complication of multiple myeloma. The incidence of AL amyloidosis increased significantly with the use of subcutaneous abdominal fat pad aspirates, ranging from 28–38% compared with previously reported rate of 3–7%⁹. Despite the increased detection rate of this complication, the difference of the clinical characteristics between patients with and without AL amyloidosis remains unclear. A previous study was not able to identify significant clinical differences between the two groups because most patients in this study had clinically occult AL amyloidosis⁹. However, most patients in our study had symptomatic AL amyloidosis involving the kidney, heart and liver, consistent with the higher level of BNP, ALP and ALB. Moreover, bone marrow plasma cells ratios of our multiple myeloma patients with AL amyloidosis were significantly lower than patients with multiple myeloma alone, which explained why they had milder multiple myeloma-related target organ damage and lower D-S stage.

Prior studies had shown the predominance of λ light chain isotype in patients with primary systemic amyloidosis, a finding that had been attributed to the greater “amyloidogenicity” of the λ chains¹⁰. The amyloidogenicity predominance of λ light chain was observed in patients with multiple myeloma complicated by symptomatic AL amyloidosis rather than occult AL amyloidosis^{9, 11}. In our study, we also observed more patients of λ-type multiple myeloma with AL amyloidosis than κ-type multiple myeloma. λ-type multiple myeloma may be a high risk factor for AL amyloidosis during the disease course, which may due to the broken balance of the light chain removal and deposition speed rather than the higher ability of the λ light chain to cause AL amyloidosis⁹. A retrospective study of 231 Chinese patients with systemic AL amyloidosis found higher incidence of liver involvement and severe renal impairment in κ-type amyloidosis than in λ-type amyloidosis¹².In our patients with multiple myeloma accompanied by amyloidosis, the D-S stages of κ-type multiple myeloma were more advanced than those of λ-type multiple myeloma. Moreover, κ-type AL amyloidosis had higher incidence of ALP > 187.5 IU/L and Scr ≧ 176.8umol/L than λ-type AL amyloidosis, suggesting liver involvement and renal insufficiency. Therefore, the incidence of AL amyloidosis in κ-type multiple myeloma is lower but more severe than λ-type multiple myeloma.

Clinically, subcutaneous fat aspiration biopsy, biopsy of bone marrow and gastrointestinal mucosa or rectal are recommended for the diagnosis of AL amyloidosis¹³. However, biopsy of clinically affected organs has higher positive rate. In our study, many patients with renal biopsies suggesting AL amyloidosis had negative results of bone marrow biopsies or subcutaneous abdominal fat pad aspirates. It suggests that it is unreliable to use bone marrow biopsy or subcutaneous abdominal fat pad aspirates as a screening test for AL amyloidosis in patients with multiple myeloma. Renal biopsy identified patients with AL amyloidosis that otherwise would be missed by biopsies at other sites. Therefore, promoting renal biopsy is important for the diagnosis of AL amyloidosis in multiple myeloma.

There are a few studies to explore the prognostic impact of AL amyloidosis in patients with multiple myeloma. Early studies found poor prognosis in patients with multiple myeloma accompanied by AL amyloidosis, with a median survival time of 1.1 years VS 2.9 years in patients without AL amyloidosis^{14, 11}. Some researchers found that AL amyloidosis in patients with multiple myeloma was an independent adverse prognostic factor, regardless the presence of amyloid organ involvement at the time of diagnosis¹⁴. However, one study found that neither occult amyloidosis (median survival time 59 months) nor symptomatic amyloidosis (median survival time 38 months) affected the prognosis of multiple myeloma⁹. This result may be caused by the intensive treatment of autologous stem cell transplantation with high-dose melphalan pretreatment in these patients which eliminated the adverse prognostic effect of AL amyloidosis on multiple myeloma. In another study, from among 4319 patients with a diagnosis of MM with at least 6 months of follow-up, 47 selected patients were diagnosed with AL amyloidosis. Although the overall survival time of selected patients was 68.5 months, the survival time after AL amyloidosis diagnosis was only 9.1 months¹¹. In our study, the median survival time was 58.3 months in patients without amyloidosis and 32.2 months in patients with amyloidosis. Further, cox regression identified AL amyloidosis as an independent significant risk factor for poor prognosis in multiple myeloma after adjustment of other risk factors. Patients with AL amyloidosis have 4.52 folds of hazard than patients without amyloidosis.

The prognosis of patient with amyloidosis is largely determined by the number of organs involved and the severity of the involvement¹⁵. Among patients with primary systemic amyloidosis, amyloidosis involving the heart is the worst adverse prognostic factor¹⁶. The median survival time of patients without heart failure caused by cardiac amyloidosis was 30 months, while congestive heart failure caused by cardiac amyloid deposition reduced the survival time to 4–8 months¹⁶. In a retrospective study, multiple myeloma patients with cardiac amyloidosis had a much shorter overall survival time than patients without cardiac amyloidosis (4.3months VS 13months)¹¹. Same in our study, cardiovascular disease is the main cause of death for all multiple myeloma patients complicated by AL amyloidosis. We noticed shorter survival time in patients with liver involvement and gastrointestinal tract involvement than those with heart involvement. This may be caused by multi-organ involvement, as most patients with liver or gastrointestinal tract involvement in this study also had cardiac amyloidosis. Our study showed that patients with multiple myeloma accompanied by AL amyloidosis often died of the cardiovascular disease, renal failure and gastrointestinal tract hemorrhage caused by AL amyloidosis rather than disease progression of multiple myeloma. We also found multiple organs involvement lead to a shorter median survival time. Therefore, multi-organ involvement especially the heart may be the main reason for AL amyloidosis to be an independent poor prognostic factor for multiple myeloma. We found that patients with amyloidosis had the same degree of hematological remission but shorter survival time than patients without amyloidosis, suggesting that the therapeutically achieving hematological remission does not improve the prognosis. Given that organ involvement is the main cause of death in multiple myeloma patients with AL amyloidosis, organ remission as the goal of treatment may lead to better prognosis for these patients.

Patients with multiple myeloma accompanied by AL amyloidosis have milder multiple myeloma-related target organ damage and lower tumor burden than those with multiple myeloma alone. The incidence of AL amyloidosis in κ-type multiple myeloma is lower but more serious than λ-type multiple myeloma. Renal biopsy can help to identify multiple myeloma patients with AL amyloidosis that would have been missed by biopsies at other sites. AL amyloidosis is an independent poor prognostic factor for multiple myeloma mainly because AL amyloidosis involves important organs especially the heart. Organ remission as treatment goal for these patients may improve the prognosis.

AL amyloidosis

amyloid light-chain amyloidosis; BNP:brain natriuretic peptide; ALP:alkaline phosphatase; ALB:albumin; Hb:Hemoglobin; LDH:lactate dehydrogenase; Ca:calcium; Scr:Serum creatinine; OS:overall survival; HR:Hazard Ratio; D-S stage:Durie Salmon stage; PD:progressive disease; SD:stable disease; PR:partial response; VGPR:very good partial remission; CR:complete remission; sCR:stringent complete remission.

Ethics approval and consent to participate

The Ethics Committee of Peking University First Hospital provided ethical approval (NO. 2017[1304]), and informed consent for collecting details was obtained from each patient.

Consent for publication

Not applicable.

Availability of data and materials

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Funding

This work was supported by Beijing Municipal Science Technology Commission (No. Z191100006619026).

Authors’ contributions

JHX and MJW designed this project, collected details, performed statistical analysis and wrote the paper; XNC designed this project and supervised this project; MY, YS, ZYS, HHL provided clinical data. All authors read and approved the final manuscript.

Acknowledgments

Not applicable.

Landgren O, Rajkumar SV. New Developments in Diagnosis, Prognosis, and Assessment of Response in Multiple Myeloma. Clin Cancer Res. 2016;22:5428–33.
Levin A, Hari P, Dhakal B. Novel biomarkers in multiple myeloma. Translational Research. 2018;201:49–59.
Ryšavá R. AL amyloidosis: advances in diagnostics and treatment. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association -. European Renal Association. 2018;34:1–7.
Desport E, Bridoux F, Sirac C, et al. AL Amyloidosis Orphanet journal of rare diseases. 2012;7:54.
Vela-Ojeda J, García-Ruiz Esparza MA, Padilla-González Y, et al. Multiple myeloma-associated amyloidosis is an independent high-risk prognostic factor. Ann Hematol. 2009;88:59–66.
Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. The Lancet Oncology. 2014;15:e538-e48.
Grateau G, Solomon A, Sezer O, et al. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from th 10th International Symposium on Amyloid an Amyloidosis, Tours, France, 18–22 April 2004. Clinica Chimica Acta International Journal of Clinical Chemistry. 2005;356:1–8.
Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. The Lancet Oncology. 2016;17:e328-e46.
Desikan KR, Dhodapkar MV, Hough A, et al. Incidence and Impact of Light Chain Associated (AL) Amyloidosis on the Prognosis of Patients with Multiple Myeloma Treated with Autologous Transplantation. Leuk Lymphoma. 1997;27:315–9.
Solomon A, Weiss DT, Kattine AA. Nephrotoxic potential of Bence Jones proteins. N Engl J Med. 1991;324:1845–51.
Madan S, Dispenzieri A, Lacy MQ, et al. Clinical Features and Treatment Response of Light Chain (AL) Amyloidosis Diagnosed in Patients With Previous Diagnosis of Multiple Myeloma. Mayo Clinic Proceedings. 2010;85:232-8.
Huang X, Wang Q, Jiang S, et al. The clinical features and outcomes of systemic AL amyloidosis: a cohort of 231 Chinese patients. Clinical Kidney Journal. 2014;8:120–6.
Rijswijk MHV. Diagnostic accuracy of subcutaneous abdominal fat tissue aspiration for detecting systemic amyloidosis and its utility in clinical practice. Arthritis Rheumatology. 2014;54:2015–21.
Vela-Ojeda J, Esparza GR, Padilla-González Y, et al. Multiple myeloma-associated amyloidosis is an independent high-risk prognostic factor. Ann Hematol. 2009;88:59–66.
Kastritis E, Dimopoulos MA. Prognosis and risk assessment in AL amyloidosis – There and back again. Br J Haematol. 2017;177:343–5.
Gertz M. Amyloidosis: prognosis and treatment. Semin Arthritis Rheum. 1994;24:124–38.

Table 1: Clinical characteristics of multiple myeloma with or without AL amyloidosis
	*Amyloidosis^pos N=49	†Amyloidosis^neg N=109	P
Age≧65 （%）	14（28.5）	31（28.4）	0.987
Sex=Male （%）	34（69.4）	79（72.5）	0.691
Serious anemia Hb<85g/L（%）	17（34.7）	58（53.2）	0.031
Bone destruction >three lesions （%）	11（22.4）	65（59.6）	<0.001
Hypercalcemia >2.65mmol/L （%）	3（6.1）	28（25.6）	0.008
Renal insufficiency Scr≧176.8umol/L（%）	12（24.5）	39（35.8）	0.16
Extramedullary disease （%）	2（4.1）	18（16.5）	0.055
Alkaline phosphatase>187.5IU/L(%)	8（16.3）	2（1.8）	0.002
Serum albumin<35g/L (%)	37（75.5）	51（46.7）	0.001
Lactate dehydrogenase≧240IU/L (%)	13（26.5）	15（13.7）	0.052
Brain natriuretic peptide≧1000pg/ml（%）	13（26.5）	8（7.3）	0.001
Bone marrow plasma cells≧30% (%)	7（14.2）	61（55.9）	<0.001
Affected light chain types=lamda （%）	35（71.4）	52（47.7）	0.006
D-S staging
I+II （%）	30（61.2）	29（26.6）
III （%）	19（38.8）	80（73.4）	<0.001
*Amyloidosispos=multiple myeloma with Amyloidosis
†Amyloidosisneg =multiple myeloma without Amyloidosis

Table 2: Clinical characteristics of multiple myeloma patients with different light chain types AL amyloidosis.
	Lamda N=35	Kappa N=14	P
Age≧65 （%）	11（31.4）	3（21.4）	0.72
Sex=Male （%）	26（74.2）	8（57.1）	0.24
Serious anemia HB<85g/L（%）	10（28.5）	7（50）	0.155
Bone destruction >three lesions（%）	6（17.1）	5（35.7）	0.159
Hypercalcemia>2.65mmol/L （%）	1（2.9）	2（14.2）	0.396
Renal insufficiency Scr≧176.8umol/L （%）	4（11.4）	8（57.1）	0.001
Lactate dehydrogenase≧240IU/L (%)	7（20）	6（42.8）	0.102
Bone marrow plasma cells≧30% (%)	4（11.4）	3（21.4）	0.651
Serum albumin<35g/L (%)	26（74.2）	11（78.5）	1
Alkaline phosphatase>187.5IU/L(%)	2（5.7）	6（42.8）	0.001
Brain natriuretic peptide≧1000pg/ml（%）	7（20)	6（42.8）	0.102
D-S stage
I+II n（%）	26（74.2）	4（28.5）	0.003
III n（%）	9（25.8）	10（71.5）

Table 3: Causes of death in all patients with multiple myeloma accompanied by AL amyloidosis
	Number of deaths	^*Proportion
Cardiovascular disease	13	68.42%
Gastrointestinal bleeding	2	10.53%
Renal failure	2	10.53%
Disease progression of multiple myeloma	1	5.26%
Infection	1	5.26%
Unknown causes of death	12
Deaths	31
*Proportion: proportion of known causes of death.

Table 4:Survival analysis of 158 patients with multiple myeloma
	Univariate		Multivariate
Variable	OS median	P-value	OS HR (95% CI)	P-value
	months (95% CI)
Age		0.042	1.827（1.160-2.878）	0.009
≧65 years old	40.1(28.2-52.0)
<65 years old	54.9(46.5-63.4)
Initial therapeutic effect		<0.001	4.03（2.427-6.71）	<0.001
PD+SD+PR	31.7(24.3-39.1)
VGPR+CR+sCR	74.0(64.1-84.0)
AL Amyloidosis		<0.001	4.52（2.965-7.633）	0.049
Without amyloidosis	58.3(49.9-66.7)
With amyloidosis	32.3(21.9-42.6)
LDH		0.034	2.260 (1.263-4.042)	0.006
≧240IU/L	37.6(22.6-52.6)
<240IU/L	53.7(46.0-61.4)
ALB		0.002
<35g/L	41.1(32.3-49.8)
≧35g/L	63.2(52.6-73.8)
BNP		0.009
≧1000pg/ml	35.0(18.6-51.3)
<1000pg/ml	53.1(45.5-60.6)
Anemia		0.533
Hb≧85g/L	53.0(43.0-63.0)
Hb<85g/L	49.0(39.2-58.9)
Renal injury		0.211
Scr≧176.8umol/L	41.9(31.3-52.5)
Scr<176.8umol/L	53.7(45.3-62.2)
Plasma cell ratio		0.148
≧30%	54.1(44.0-64.2)
<30%	46.4(37.6-55.3)
D-S stage		0.462
I+II	50.5(40.1-60.8)
III	49.1(40.7-57.6)

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Effects of Amyloid Light-chain Amyloidosis on Clinical Characteristics and Prognosis in Multiple Myeloma: A Single-center Retrospective Study

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