OBJECTIVETo evaluate the efficacy and feasibility of bortezomib plus dexamethasone (BD) in patients with primary systemic (AL) amyloidosis.

METHODSEleven AL amyloidosis patients, including four relapsed or progressed after previous therapies and 7 newly diagnosed were treated with BD. Ten patients had two or more organs involved. Precursor protein analysis showed that 1 was κ light chain, 9 λ light chain; 5 patients with positive immunofixation including 1 IgG κ, 3 IgG λ and 1 IgA λ. BD was administered according to standard two-week schedule.

RESULTSEight patients were evaluable, the median number of treatment cycles was 3 (range 1 - 6). Median follow-up duration was 6 months. At least one affected organ response was observed in six patients and median time to organ response was 2 months. Three patients progressed and two of them died. Toxicities were mainly diarrhea, thrombocytopenia, peripheral neuropathy, fatigue and herpes zoster, and 7 evaluable patients who had toxicities were adjusted dosage and 2 of them interrupted therapy. Epilepsia, paralytic ileus, acute cardiac dysfunction, and postural hypotention were occurred in 3 inevaluble patients.

CONCLUSIONBortezomib plus dexamethasone is effective in AL amyloidosis. Adverse events are common, and in some patients are severe.

Amyloidosis ; drug therapy ; Boronic Acids ; therapeutic use ; Bortezomib ; Dexamethasone ; administration & dosage ; Humans ; Multiple Myeloma ; drug therapy

Objective: To evaluate the response of oral melphalan plus high-dose dexamethasone (MDex) for patients with primary light chain amyloidosis (pAL). Methods: Clinical data, hematological and organ responses, and survival of 76 patients with pAL who had received MDex from January 2009 to July 2017 were retrospectively analyzed. Results: Of 76 patients (47 males and 29 females with the median age of 56 [range, 20-74] years old), 19.70% patients were defined as Mayo 2004 stage 3, involvement of more than or two organs was presented in 65 (85.53%) patients. Among 60 response evaluable patients, overall hematological response was 48.33% with complete response of 20.00% and very good partial response of 20.00%, respectively. The median time to the hematological response was 5 (range, 1-15) months. 36.67% patients achieved organ response. After the median follow up of 23(range, 1-113) months for surviving patients, median progression-free survival (PFS) and overall survival (OS) were 34 and 43 months, respectively. In a three months landmark analysis, the median rates of PFS and OS were 46 and 65 months, respectively. The median OS rates of patients with Mayo 2004 stage 3 and non Mayo 2004 stage 3 were 5 and 65 months (P=0.001), respectively. Conclusions: MDex was an effective treatment for patients with early stage pAL, but was not suitable for those with severe cardiac involvement.
Adult ; Aged ; Amyloidosis/drug therapy* ; Dexamethasone/administration & dosage* ; Drug Combinations ; Female ; Humans ; Immunoglobulin Light-chain Amyloidosis ; Male ; Melphalan/administration & dosage* ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo analyze the efficacy and side effects of the combination regimen containing bortezomib, cyclophosphamide and dexamethasone(BCD) in the treatment of primary systemic amyloidosis (PSA).

METHODSThe clinical manifestation, efficacy and side effects of 22 PSA patients after treatment were retrospectively analyzed.

RESULTSOf the 22 PSA patients, 9 were newly diagnosed cases and 13 relapsed cases, 20(90.9%) had symptomatic cardiac involvement and 20 (90.9%) had 2 or more organs involved. The median free light chain were 140 mg/L. There were no specific abnormality was found by G-banding and FISH. RQ-PCR-MAGE C1/CT7/ABL had high positive incidence in amyloidosis and can be observed ahead of the flow cytometry and morphology examination. Hematological response occurred in 88.9% in newly diagnosed patients, with 55.6% organ response, 2 patients occured sudden death during BCD interval. For relapsed patients, the hematological response was 46.2%, with 30.7% organ response. Ten of the 22 PSA patients developed peripheral neurophathy, 1 liver dysfunction, 1 severe infection after intra-tracheal stent.

CONCLUSIONSBCD produces rapid and high hematological responses in the PSA patients especially in newly diagnosed patients. It is well tolerated with few side effects. MAGE C1/CT7 might be helpful in the early detection of the clonal plasma cell.

Adult ; Aged ; Amyloidosis ; drug therapy ; Boronic Acids ; therapeutic use ; Bortezomib ; Cyclophosphamide ; therapeutic use ; Dexamethasone ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Immunoglobulin Light-chain Amyloidosis ; Male ; Middle Aged ; Pyrazines ; therapeutic use ; Retrospective Studies ; Treatment Outcome

Behcet's Disease (BD) is a chronic inflammatory disorder characterized by vasculitis of unknown cause, involving multiple organs. In the past years, renal involvement has not been regarded as a feature of BD. However, renal lesions in BD, although uncommon, have increasingly been recognized in recent years. Five categories of renal lesions associated with BD have been identified, including glomerulonephritis, amyloidosis, renal vascular involvement, interstitial nephritis, and other problems, such as complications of drug therapy or abnormalities of the genitourinary tract. On the other hand, regional differences in the disease expression of BD are well appreciated. Renal lesions accompanied by BD have rarely been reported in Korea, although it have been described occasionally in the Middle Eastern countries. Hereby, we described a 46-year-old female patient who had BD with persistent hematuria and proteinuria, whose renal biopsy specimens were consistent with thin glomerular basement membrane disease. Interestingly, some portions of her glomerular capillary walls were filled with fuchsinophilic fibrin-like materials.
Amyloidosis ; Basement Membrane ; Biopsy ; Capillaries ; Drug Therapy ; Female ; Glomerular Basement Membrane* ; Glomerulonephritis ; Hand ; Hematuria ; Humans ; Korea ; Middle Aged ; Nephritis, Interstitial ; Proteinuria ; Vasculitis

Primary systemic amyloidosis is associated with plasma cell dyscrasia, such as multiple myeloma. The amyloid fibrils in the disease are composed of amyloid light (AL) protein that is derived from immunoglobulin L chain. Cutaneous manifestations are presented in about 20~40% of patients with mainly petechia, purpura on flexural area of the body and waxy, translucent papulonodules. We report a case of primary systemic amyloidosis associated with multiple myeloma occurring in a 76-year old woman who had suffered from ecchymotic purpura on periorbital and flexural area with hemorrhagic bulla for one year. She also had macroglossia with grouped papulonodules on her tongue, and peripheral neuropathy. The final diagnosis was confirmed by positive PAS, Congo-red stain and specific serum/urine electrophoresis. She had been treated with several cycles of chemotherapy; however, she expired from various complications of the disease, such as congestive heart failure, renal failure, and secondary bacterial infection.
Aged ; Amyloid ; Amyloidosis* ; Bacterial Infections ; Diagnosis ; Drug Therapy ; Electrophoresis ; Female ; Heart Failure ; Humans ; Immunoglobulins ; Macroglossia ; Multiple Myeloma* ; Paraproteinemias ; Peripheral Nervous System Diseases ; Purpura ; Renal Insufficiency ; Tongue

We reported on a 60-year-old man presenting lymphedema of both lower extremities and scrotum for 3 years with unknown cause. We took a computed tomography scan of the lower extremities as a follow-up. There were diffuse subcutaneous edema in both lower extremities and multiple enlarged lymph nodes along the para-aortic and bilateral inguinal areas. For further evaluation, biopsy of an enlarged inguinal lymph node was taken, yielding a diagnosis of primary amyloidosis. A treatment of chemotherapy for amyloidosis was recommended for him. To our knowledge, this is the first report of lymphedema presenting with primary amyloidosis in Asia. This case suggests that primary amyloidosis could be one of the differential diagnoses in patients with lymphedema in the lower extremities.
Amyloidosis* ; Asia ; Biopsy ; Diagnosis ; Diagnosis, Differential ; Drug Therapy ; Edema ; Follow-Up Studies ; Humans ; Lower Extremity ; Lymph Nodes ; Lymphedema* ; Middle Aged ; Scrotum

We report a case of 74 year old man presented with generalized lymphadenopathy with hepatosplenomegaly. Lymph node biopsy revealed angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) and most areas of lymph node were replaced with large atypical lymphocytes which were revealed to be T cells by immunohistochemistry. All together, the patient was diagnosed as AILD-like T cell lymphoma with bone marrow involvement. The patient presented monoclonal gammopathy (IgG lambda) without any evidence of plasma cell dyscrasia or secondary amyloidosis. After three cycles of combination chemotherapy including cyclophosphamide, prednisone, vincristine and doxorubicin, the patient achieved partial remission with decreased level of serum and urine monoclonal protein.
Aged ; Amyloidosis ; Biopsy ; Bone Marrow ; Cyclophosphamide ; Doxorubicin ; Drug Therapy, Combination ; Humans ; Immunoblastic Lymphadenopathy ; Immunohistochemistry ; Lymph Nodes ; Lymphatic Diseases ; Lymphocytes ; Lymphoma, T-Cell* ; Paraproteinemias* ; Prednisone ; T-Lymphocytes ; Vincristine

Objective: The study investigated the efficacy and safety of daratumumab in the treatment of cardiac light chain (AL) amyloidosis. Methods: We retrospectively analyzed the clinical characteristics, hematologic response, organ response, long-term survival, and adverse events of 20 patients with newly diagnosed or relapsed/refractory cardiac AL amyloidosis treated with daratumumab in Peking Union Medical College Hospitalo from January 2017 to March 2021. Results: The overall median age of 20 patients was 62 (range, 45-73) yeas, with a male to female ratio of 2.3:1. Nine patients were newly diagnosed, while 11 patients had relapsed or refractory disease. Based on Mayo 2004 cardiac AL staging system, stages Ⅱ and Ⅲ diseases were present in 20 patients respectively. Four patients died during the first cycle of daratumumab, and the remaining 16 patients completed a median of 3 (range, 1-10) cycles of treatment. Overall hematologic response rates were 80% each at 1, 3, and 6 months after treatment initiation, and 45% , 60% , and 60% of the patients achieved at least a very good partial response at 1, 3, and 6 months respectively. The median duration to hematologic response was 13 (range, 6-28) days. At 3, 6, and 12 months, 20% , 30% , and 40% of the patients respectively achieved a cardiac response, and the median days to response was 91 (range, 30-216) days. As of the last follow-up, 9 (45% ) patients died. The 1-month mortality rate of all the patients and stage IIIb patients was 25% and 40% , respectively. The 1-year overall survival rate was 48.4% . Lymphocytopenia was the most common hematological adverse event (above grade 3) . Non-hematological adverse events were mainly infusion-related reactions and infections. Conclusion: Daratumumab could induce deep and rapid hematologic response in newly diagnosed and previously treated cardiac AL amyloidosis patients. However, daratumumab was not effective in preventing the high and early mortality rate in stage Ⅲb patients.
Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Female ; Humans ; Immunoglobulin Light-chain Amyloidosis/drug therapy* ; Male ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo investigate the treatment of primary amyloidosis with high-dose melphalan and autologous hematopoietic stem cell transplantation to further examine the survival, hematologic response, and improvement of amyloid-related organ dysfunction.

METHODSRetrospective analysis of 20 patients with primary amyloidosis treated with autologous hematopoietic stem cell transplantation. The status of major organ function before transplantation, mobilization programs and conditioning regimen as possible risk factors for survival were also investigated.

RESULTSOf 20 cases, 11 out of 15 evaluable cases achieved hematologic response, among them, 6 got complete remission (CR, 40%) and 5 partial remission (PR, 33%). The median onset time was 3.0 months (1.5 - 4.0 months) and 4 months (3 - 5 months), respectively after transplantation. The overall hematologic response was 73%. The 11 hematologic responders also had kidney responses. The median time to achieve kidney response was 3 months (2 - 6 months). The 3-year overall survival of the cohort of cases was 71.4%. The major causes of death were heart failure, renal dysfunction and gastrointestinal bleeding. G-CSF alone could obtain satisfactory mobilization results and most of patients well tolerated to the conditioning regimen of melphalan doses from 140 mg/m(2) to 200 mg/m(2).

CONCLUSIONTreatment of primary amyloidosis with high-dose melphalan followed by autologous peripheral blood stem cell transplantation produced high efficacy. The cardiovascular system involvement, renal dysfunction and the abnormality of coagulation function before transplantation may be the risk factors for survival.

Adult ; Aged ; Amyloidosis ; drug therapy ; mortality ; surgery ; Cardiovascular System ; physiopathology ; Female ; Gastrointestinal Hemorrhage ; physiopathology ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunoglobulin Light-chain Amyloidosis ; Kidney ; physiopathology ; Male ; Melphalan ; therapeutic use ; Middle Aged ; Retrospective Studies ; Risk Factors ; Survival Rate ; Transplantation, Autologous ; Treatment Outcome

Amyloidosis is an abnormal extracellular deposit of amyloid in various organs of the body. Amyloid goiter, defined by a clinically detectable thyroid enlargement due to amyloid deposition, is a rare cause of hyperthyroidism. We report the case of amyloid goiter mimicking Graves' disease in a 62-year-old woman. Graves' disease was diagnosed by diffuse goiter, hyperthyroidism, and positive TSH receptor antibody. Total thyroidectomy was planned due to progression of Graves' disease and respiratory distress. At surgery thyroid gland was very friable and fragmented like cobblestones when grasped with forceps. A diagnosis of amyloid goiter was established by the presence of diffuse amyloid deposits in the parafollicular areas. After systemic evaluation for amyloidosis, coexisting both multiple myeloma and systemic amyloidosis involving kidney and heart were detected. She underwent palliative chemotherapy but disease progressed. Amyloid goiter might be suspected in patient with thyroid enlargement and concomitant systemic disease such as renal or heart failure.
Amyloid* ; Amyloidosis ; Diagnosis ; Drug Therapy ; Female ; Goiter* ; Graves Disease* ; Hand Strength ; Heart ; Heart Failure ; Humans ; Hyperthyroidism ; Kidney ; Middle Aged ; Multiple Myeloma ; Plaque, Amyloid ; Receptors, Thyrotropin ; Surgical Instruments ; Thyroid Gland ; Thyroidectomy