Localized light chain (AL) amyloidosis (amyloidoma) is a rare disease with unclear pathogenesis and undeveloped approaches to therapy. This article presents 3 clinical observations of localized AL amyloidosis with lesions of the respiratory tract, eyes, and soft tissues of the face. Tumor masses consisted of amyloid masses in which single monotypic plasma cells were "embedded". To verify the cell substrate, the method of chromogenic in situ hybridization with probes to immunoglobulin light chains was used. Amyloid typing was performed using FITC-labeled antibodies to kappa and lambda light chains after enzymatic treatment of paraffin sections with pronase. The absence of monoclonal secretion (in two cases) made it difficult to assess the efficacy of the therapy. Taking into account the prevalence and severity of vital organs damage, as well as the recurrent nature of the disease course, systemic combination therapy with targeted drugs was prescribed. Stabilization of the process in all patients was stated during one year of follow-up. Nevertheless, clonreducing therapy in localized AL amyloidosis is not considered as a standard option, its feasibility and efficacy requires further confirmation.

Diagnosing diseases related to monoclonal gammopathy (MG) with clinical significance is challenging. In real-world practice, proving the connection between organ damage and paraprotein or plasma cell dyscrasia is difficult or even impossible. Only an atypical course of the disease and non-compliance with the established criteria may suggest the contribution of plasma cell neoplasia in pathogenesis. Rheumatic diseases associated with monoclonal secretion do not belong to MG with clinical significance. Therefore, in the absence of hematological malignancy, clone reduction therapy is not indicated. We present the first clinical case of a patient with cutaneous necrotizing vasculitis and MG, who received clone reduction therapy with no hematological malignancy. The rationale for the choice of such treatment approach was the atypical course of vasculitis, as well as the unstable effect after methylprednisolone therapy. Therapy with lenalidomide, cyclophosphamide, and dexamethasone was highly effective; the regression of clinical symptoms was associated with a decrease in paraprotein to trace amounts. However, the lack of evidence of the relationship of vasculitis with plasma cell dyscrasia does not support considering the described case as one of the forms of MG with clinical significance. Further observation and resumption of monoclonal secretion, coinciding with the recurrence of vasculitis, may additionally support the relationship between these two conditions. This case was discussed at the Council of Experts with hematologists, rheumatologists, and pathologists.

Background. Research related to the state of blood vessels in systemic AL amyloidosis (AL-A) is mostly done on experimental models. The pathogenetic and clinical significance of vascular dysfunction in patients with AL-A is poorly understood. Aim. To study the levels of endothelial dysfunction markers in patients with AL-A at the onset of the disease and after anti-tumor therapy. Materials and methods. The study group included 30 patients with AL-A. The comparison group consisted of 10 patients with multiple myeloma (MM), and the control group included 10 healthy individuals. Patients with AL-A were divided into 2 groups: the first group included 20 patients who underwent the full planned induction therapy, and the second group included 10 patients whose treatment was stopped due to a significant increase in N-terminal pro-brain natriuretic peptide (NTproBNP) levels. The levels of asymmetric dimethylarginine (ADMA), big endothelin (bET), and E-selectin were measured by enzyme-linked immunosorbent assay in serum before and after completion (or premature cessation) of anti-tumor therapy. Results. Patients with AL-A had significantly higher levels of E-selectin and ADMA in serum compared to patients with MM and healthy individuals. An increase in at least one marker of endothelial dysfunction (E-selectin and ADMA) was observed in 27 (90%) patients with AL-A at disease onset. There were no differences in bET levels. In all patients in the first group, reaching hematologic remission was associated with a decrease in E-selectin and ADMA levels compared to baseline values (p0.001). In 5 (55%) out of 9 patients with hematologic and organ response, ADMA levels decreased to normal values. In all patients of the second group, the increase in NTproBNP was accompanied by a significant increase in ADMA (p=0.005) and E-selectin (p=0.007) levels compared to baseline values. Adverse cardiovascular events were observed in 80% of patients with elevated NTproBNP levels. The increase in cardiac markers during anti-tumor therapy was more common in advanced stages of heart involvement. Stage IIIA AL-A was present in 23% of patients in the first group and 70% in the second group (p=0.003). After discontinuation of therapy, the levels of cardiac markers decreased to baseline values, which ruled out disease progression. Conclusion. A pronounced endothelial dysfunction was observed in 90% of patients with AL-A. Reduction in endothelial dysfunction markers was observed upon achieving hematologic and organ response. Anti-tumor therapy in patients with amyloid cardiomyopathy can cause additional endothelial damage, resulting in increased NTproBNP levels and cardiovascular complications.

BACKGROUND: Cardiac amyloidosis is a serious progressive disease with a high mortality rate. The differential diagnosis of cardiomyopathies due to amyloid light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis is important for selecting the optimal treatment strategy. AIM: The aim of this study was to evaluate the capabilities of cardiac magnetic resonance imaging in the differential diagnosis of cardiomyopathies due to AL and ATTR amyloidosis. MATERIALS AND METHODS: A retrospective analysis of the medical records of 25 patients with a confirmed diagnosis of amyloid cardiomyopathy was performed. Patients were divided into two groups according to the type of amyloidosis, with group 1 including patients with cardiomyopathy due to AL amyloidosis and group 2 including patients with cardiomyopathy due to ATTR amyloidosis. All patients underwent contrast-enhanced cardiac magnetic resonance imaging. Volumetric and linear cardiac parameters, ventricular function, and late gadolinium enhancement patterns were assessed. Standard statistical methods were used, and differences were considered significant at p 0.05. RESULTS: Group 2 showed a more significant thickening of the myocardial walls compared to group 1 (interventricular septum: 18 [17; 18] vs. 14.5 mm [12.8; 16.0], p 0.01, posterior wall of the left ventricle: 14 [13; 17] vs. 10.5 mm [10; 12.3], p 0.01). The indexed mass of the left ventricle myocardium was 110 [92; 125] in group 2 and 85 mm [69.3; 91.8] in group 1 (p 0.01). In group 2, late gadolinium enhancement with a transmural left ventricle pattern was more frequently observed in the basal and mid-lower-lateral segments, whereas in group 1, a subendocardial pattern of late gadolinium enhancement was more frequent in the mid-anterior and lower-lateral segments (p 0.05). In addition, frequency of simultaneous contrast enhancement in the subendocardial layers of the interventricular septum on the left ventricle and right ventricle sides was higher in group 2 (100% of cases vs. 50%, p 0.01). Late gadolinium enhancement of the right ventricle was also more common in group 2 (100 vs. 58%, p 0.05), especially in the interventricular septum and inferior wall area (p 0.05). Semi-quantitative assessment of LGE using the Query Amyloid Late Enhancement (QALE) showed greater contrast enhancement in group 2: 13 [12; 14] vs. 10.5 [1.75; 12], p 0.01), and a score greater than 13 differentiated between cardiomyopathy due to AL amyloidosis and ATTR amyloidosis with a sensitivity of 69% and a specificity of 83%. CONCLUSIONS: Cardiac MRI identifies typical features of cardiomyopathies due to AL amyloidosis and ATTR amyloidosis for their differential diagnosis. Further research is needed to confirm diagnostic accuracy of the patterns identified.

Background. The problem of hemostasis system pathology in patients with AL amyloidosis (AL-A) is of great practical importance. Currently, there are no recommendations concerning indications and methods of prevention of thrombotic complications.Aim. To study the main parameters of blood coagulation system in patients with AL amyloidosis, to determine the indications for anticoagulant therapy, to evaluate the efficacy and safety of apixaban prophylactic use during antitumor therapy.Materials and methods. A prospective single-center study included 65 patients with newly diagnosed systemic AL amyloidosis. The median age was 58 (34–74) years. Induction therapy according to the program BorCyDex (bortezomib, cyclophosphamide, dexamethasone) was given to 59 (90 %) patients, of which 5 patients received the combination of BorCyDex with a monoclonal antibody to CD38 – daratumumab. The remaining 6 (10 %) patients were treated with melphalan. Patients with laboratory signs of hypercoagulability or thrombotic complications were treated with apixaban in therapeutic or prophylactic dose. Indications for apixaban therapy in therapeutic dose (10 mg/day): atrial fibrillation, arterial thrombosis or pulmonary embolism less than 1 year ago. Indications for apixaban therapy in prophylactic dose (5 mg/day) were considered the presence of one or more factors: hypoalbuminemia less than 20 g/L; increase in D-dimer level more than 500 ng/mL without instrumentally verified arterial or venous thrombosis; increase in D-dimer level more than 500 ng/mL within 3 months after resolved episode of thrombosis; increase in fibrinogen level more than 4 g/L; increase in FVIII activity more than 150 %. When two or more factors were present, an antiplatelet agent (acetylsacylicylic acid) was added to apixaban therapy. The follow-up period was 4–9 months (median 6 months).Results. Before the start of antitumor therapy, thrombotic complications were diagnosed in 15 (23 %), bleeding – in 3 (5 %) patients. Hemostasis study revealed an increase in one or more laboratory parameters reflecting hypercoagulability in 92 % of patients. Increase in fibrinogen level was found in 70 %, D-dimer – in 72 %, FVIII activity – in 92 % of patients. 3 (5 %) patients received a therapeutic dose of apixaban, 58 (89 %) patients ‒ a prophylactic dose. Therapy with apixaban and antiplatelet agent was performed in 10 (15 %) patients. During the follow-up 3 patients developed complications related to hemostasis system disorders: 1 (2 %) patient had thrombosis (ischemic stroke), 2 (3 %) – gastrointestinal bleeding of mild severity. All these patients received a prophylactic dose of apixaban due to the presence of 1 thrombosis risk factor: an increase in FVIII activity of more than 150 %.Conclusion. Clinical signs of hemostasis system pathology were observed in 28 % of AL amyloidosis patients, and laboratory signs of hypercoagulability were detected in 92 %. Our developed indications for thrombosis prophylaxis in AL amyloidosis were effective. The issue of FVIII activity increase as the only indication for anticoagulant therapy in AL amyloidosis patients requires further research.

Aim. To assess the outcomes of induction therapy in patients with newly diagnosed systemic AL Amyloidosis (AL-А). Materials & Methods. The prospective single-center clinical study enrolled 60 patients (32 women and 28 men) with newly diagnosed systemic AL-A stage I/IIIA. The median age was 59 years (range 34–74 years). In 57 patients, BorСyDex (bortezomib, cyclophosphamide, dexamethasone) was used as first-line therapy. RCd regimen (lenalidomide, cyclophosphamide, dexamethasone) was administered to 3 patients. Patients with the lack of efficacy or pronounced toxicity (n = 24) received second-line induction therapy with lenalidomide or melphalan combined with dexamethasone. High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) was administered to 11 (18 %) patients. Results. Hematologic targeted response (complete remission [CR] and very good partial remission [VGPR]) to BorCyDex was achieved in 62 % of patients. As a result of all lines of induction therapy, including auto-HSCT, targeted response increased to 69 %, specifically in 7/51 (14 %) patients with stringent CR (sCR), 8/51 (16 %) patients with CR, and 20/51 (39 %) patients with VGPR. Renal response after BorCyDex was registered in 10/38 (26 %) patients, 6/31 (19 %) patients showed heart response, and in 4/5 (80 %) patients liver response was reported. All therapy lines with auto-HSCT led to organ response (in ≥ 1 organ) in 15/46 (32 %) patients. Clinical response was shown by all patients with achieved sCR, by 67 % of patients with CR, and 47 % with VGPR (p = 0.04). With lower hematologic response rates, no clinical improvement was observed. With follow-up duration of 36 months, the median disease-free survival (without signs of hematologic and clinical progression) was not achieved. The 3-year overall survival was 80 %. Mortality during induction therapy was 10 % (6 patients died, including 2 patients with COVID-19). The planned 6 courses of BorCyDex could be completed only in 13 (23 %) out of 55 patients. During the induction therapy using BorCyDex, 4 patients died. The treatment was discontinued in 7/55 (12 %) patients due to its inefficacy and in 22/55 (39 %) patients because of severe peripheral and autonomic polyneuropathy. Nine (16 %) out of 55 patients with the achieved hematologic response showed excessive NT-proBNP elevation, which was accompanied by cardiovascular complications and provided ground for chemotherapy withdrawal. Conclusion. Low organ recovery rate remains the most challenging issue for AL-A treatment. Hematologic response depth (achieved CR) is a critical factor in achieving clinical effect. The obtained data confirmed high toxicity of BorCyDex regimen in AL-A patients. Despite the advances in AL-А therapy which are associated with the use of proteasome inhibitors, treatment of this disease calls for new and more effective approaches.

Aim. To analyze the frequency and nature of hemorrhagic and thrombotic complications in patients with systemic AL-amyloidosis and compare with laboratory changes in the hemostasis system. Materials and methods. The prospective study included 40 patients with newly diagnosed AL-amyloidosis. To detect amyloid, all patients underwent bone marrow trephine biopsy and duodenal biopsy, and 28 (70%) patients underwent biopsy of the affected organ. Before the start of therapy, all patients were determined the platelet count, activated partial thromboplastin time, thrombin time, fibrinogen concentration, time of XIIa-dependent fibrinolysis, antithrombin III, D-dimer, activity of blood coagulation factors VIII, X and vWF. The statistical part of the study was carried out using the IBM SPSS Statistics 2017 system software (SPSS, Chicago, IL, USA). Results. In 20 (50%) patients, hemorrhages on the skin and mucous membranes were diagnosed as vascular purpura. Before the start of therapy, 7 (17.5%) patients had thrombosis, including leg vein thrombosis (5 patients), ischemic stroke (2 patients). There was a direct correlation between thrombotic complications and cutaneous hemorrhagic syndrome (p=0.007). In 15 (75%) cases, cutaneous hemorrhagic syndrome was accompanied by hypercoagulable shifts in the hemostasis system. Of the 20 patients with cutaneous hemorrhagic syndrome, 19 (95%) patients had kidney damage, including 15 patients with nephrotic syndrome. Hematoma type of bleeding, as well as heavy bleeding was not observed, including after a biopsy of the internal organs. According to the totality of hemostasis indicators, hypercoagulation syndrome was more often observed (in 23; 56% of patients). Hypocoagulation was diagnosed only in 2 (5%) patients with liver damage, 16 (39%) patients had normocoagulation. Conclusion. Cutaneous hemorrhagic syndrome is the most common clinical manifestation of disorders in the hemostasis system in patients with AL-amyloidosis. The relationship of hemorrhages on the skin with nephrotic syndrome has been established, which may indicate a single pathogenetic mechanism. Cutaneous hemorrhagic syndrome is associated with hypercoagulable shifts in hemostasis and a high risk of thrombotic complications.

Paraprotein is a laboratory biomarker of plasma cell tumors and other lymphoproliferative diseases. Its determination is necessary for diagnosing, monitoring and assessment of therapy effectiveness. The lecture presents the main methods of qualitative and quantative analysis of monoclonal proteins: gel electrophoresis, capillary electrophoresis, immunofixation and nephelometry features, possibilities and limitations are reviewed. The main sources of errors and artifacts during these studies are considered. Also the difficulties in the diagnosis and interpretation of the results of serum and urine tests are highlighted.

Neutrophilic leukocytosis is not specific for multiple myeloma (MM) and is a reason for the exclusion of myeloproliferative neoplasm.A clinical case of MM patient with neutrophilic hyperleukocytosis (75 х 109/L), liver and spleen enlargement at the disease onset is presented. Examination did not reveal t(9;22), BCR/ABL gene and JAK2V617F mutation. To exclude the combination of MM with chronic neutrophilic leukemia, a study of the clinically significant part of the CSFR3R gene was performed. The absence of a CSFR3R gene mutation made it possible to exclude chronic neutrophilic leukemia and start MM treatment. After the 1st therapy course with bortezomib, cyclophosphamide and dexamethasone, blood counts returned to normal, liver and spleen size decreased. After 6 therapy courses, complete hematological remission was achieved. An attempt to mobilize peripheral blood stem cells with cyclophosphamide was unsuccessful. The effectiveness of antimyeloma therapy proved the correctness of the diagnosis and the chosen treatment tactics.Neutrophilic leukocytosis in MM is explained by the ability of plasma cells to synthesize granulocyte colony-stimulating factor in some cases. In the presence of a plasma cell tumor, the analysis of the CSFR3R gene may be of decisive importance in the differential diagnosis of reactive neutrophilic leukocytosis due to MM and the combination of MM with chronic neutrophilic leukemia.

Background: Background: Hemorrhages on the skin and mucosa are seen in 30-40% of patients with systemic AL amyloidosis (AL-A). The pathogenesis and clinical significance of this syndrome are poorly understood. Aims: Aims: To analyze the relationship of cutaneous and mucous hemorrhagic syndrome in AL-A patients with the hemostatic system parameters and the leading clinical syndromes. Methods: Methods: A prospective study included 49 patients with newly diagnosed systemic AL-A. 18 (37%) patients were diagnosed with stage I, 16 (33%) with stage II, and 6 (12%) and 9 (18%) with stage III and stage IV, respectively (Mayo 2004/Europian). Activated partial thromboplastin time, thrombin time, fibrinogen concentration, XIIa-dependent fibrinolysis time, antithrombin III (ATIII), D-dimer, factors VIII (FVIII), X (FX) and Von Willebrand factor (VWF) activity were determined before therapy. Patients with cutaneous hemorrhagic syndrome were included in the Group № 1, and those without cutaneous hemorrhages in the Group № 2. Results: Results: Cutaneous and mucosal hemorrhagic syndrome was observed in 23 (47%) patients. Hypercoagulable syndrome (increase of fibrinogen, D-dimer, FVIII, VWF, and decrease of ATIII) was registered in 18 (78%) patients, significantly more frequently than in Group № 2 patients (11 patients - 42%; p=0,01). Eight (35%) patients with skin hemorrhages developed venous and arterial thrombosis before treatment, which were absent in the control group (p=0.002).

Myeloma cast nephropathy (MCN) is morphologically confirmed in 87–94% of patients with dialysis-dependent acute kidney injury (AKI) at multiple myeloma onset. However, kidney biopsy is necessary to detect paraprotein-related nephropathy. Recent studies have shown that kidney biopsy allows not only to establish the nature of damage, but also to determine severity and potential reversibility of pathological process. Clinically this can be helpful in choosing the optimal treatment program of MCN.

Objective of the study: analysis of AL-amyloidosis (AL-A) diagnostics in real clinical practice and to determine the main approaches for the earlier detection of this disease.Materials and methods. A retrospective analysis of medical records of 34 patients with newly diagnosed AL-A.Results. The median time from first symptoms appearance to the diagnosis was more than 2 years. Most often, the pathological process in AL-A involves the kidneys, heart and gastrointestinal tract; moreover, at the time of diagnosis, most patients already have an injury of 2 or more organs. In half of the patients, a biopsy of the damaging organ was performed to verify the diagnosis; according to our data, histological examination of “easily accessible” locus not less informative. Symptoms characteristic of amyloidosis, such as periorbital purpura or macroglossia, are observed in a small part of patients and refer to late manifestations of the disease.Conclusion. The versatility of AL-A manifestations leads to a late diagnosis, which affects overall survival. The main signs were highlighted that should alert doctors in relation to this pathology.

Abstract Introduction: Myeloma cast nephropathy (MCN) is a main cause of acute kidney injury (AKI) at multiple myeloma (MM) onset. Wherein 5-9% of newly diagnosed MM patients are dialysis dependent. The introduction of novel agents has provided the achievement of rapid and deep hematologic response in most patients. However, the renal response in patients on dialysis is only 38-62.5%. The predictors of AKI reversibility in patients with MCN remain not enough studied. Aim: to determine clinical, morphological and immunohistochemical predictors of reversibility dialysis dependent AKI in patients with MCN. Materials and methods: 36 patients aged 38 to 74 years (median age=57 years) with newly diagnosed MM and dialysis dependent AKI stage 3 (AKIN, 2012) due to MCN were enrolled into the study from January 2006 till November 2019. The diagnosis of MM, hematologic and renal response were established according to the 2016 IMWG criteria. MCN was determined by renal biopsy performed prior to induction therapy. The assessment degree of acute tubular injury, tubular atrophy and interstitial fibrosis (IF/TA) were semi-quantitatively evaluated. The number of sclerotic glomerular were calculated manually. The median number of casts was defined by all casts in a section divided by number of fields observed (х100). Additionally, square of interstitial fibrosis, interstitial inflammation, expression of Immunohistochemical markers (E-cadherin, α-smooth muscle actin (α-SMA), vimentin) were measured by computerized quantitatively image analysis using the digital module Leica (Germany). The time from diagnosis of AKI to start of induction therapy did not exceed 3 months. Bortezomib based first line treatment regimen was used in 25 (69%) of patients; 9 (25%) patients received chemotherapeutic agents only, 2 (6%) dead before a start of induction therapy. Statistical software package SAS 9.4 was applied for calculations. Overall survival according to renal response was compared by using Kaplan-Meier curves. Also frequency, logistic, discriminant and ROC analysis were used. All estimates are shown with a 95%CI. Results: Hematologic partial response or better occurred in 19 (53%) of patients, median of 32 (13-129) days. Renal response - in 14 (39%). In 3 (8%) cases renal function improved after correction of dehydration before start of antimyeloma therapy, in the remaining 11 (30%) patients only when hematologic response was achieved (p = 0.001). The frequency of renal response was depending on start of antimyeloma therapy before and after 4 weeks from diagnosis of AKI and was 83% and 17%, respectively (p <0.05). In patients with renal response there was not a single fatal outcome; without renal response 3-year OS was 68% ± 13%. Patients with hematologic response were divided into two groups (Tab.). The main pathological findings associated with renal response were less frequent mild to severe IF/TA in patients with and without renal response (moderate 45% vs 75%, respectively, p=0.008), less area of interstitial fibrosis (24.9% vs 44.7%, respectively, p=0.001), percentage of proximal tubules with save epithelial phenotype and less area of expression E-cadherin at interstitium (15.9% vs 7.1%, respectively, p=0.006). The median number of casts per field was the same (6.4 and 6.3, p=0.64) as well as the percentage of tubule lumen obstruction by casts (13.6% and 15.1%, p=0.81). Statistically significant correlation between the expression area of E-cadherin and interstitial fibrosis was not found (Rs= -0.335, p= 0.065). Therefore, a combination of these factors can be used to predict renal response in the onset of AKI due to MCN (area under the ROC curve is 0.84). The prognostic model and logical rule allow to define groups of renal outcomes (Fig.). If expression area of E-cadherin is less than 10% and / or area of interstitial fibrosis is more than 40% of the interstitium, a renal response is unlikely (OR = 24.5) and will not be achieved in almost 90% of cases, despite hematological response. Discussion. Reversibility of dialysis dependent AKI due to MCN rely on the achievement of hematological response and the time from diagnosis of AKI to start of antimyeloma therapy. There are predictors of renal response of these patients determined by the severity of morphological changes: degree of IFTA, quantitative area of interstitial fibrosis and E-cadherin expression. Disclosures No relevant conflicts of interest to declare.

AIM:Reveal morphological and immunohistochemical predictors of reversibility of dialysis-dependent acute kidney injury (AKI) in patients with myeloma cast nephropathy (MCN) based on the study of kidney biopsy.MATERIALS AND METHODS:Renal pathological findings were studied in 36 patients with MCN and dialysis-dependent stage 3 AKI (AKIN, 2012). The study of biopsy samples was performed by a semi-quantitative and quantitative analysis using computer morphometry. The expression of E-cadherin, vimentin and-smooth muscle actin was determined immunohistochemically in the tubular cells and interstitium. Induction therapy for 26 patients was carried out to bortezomib-based programs; in 10 patients other schemes were used. A comparative analysis of morphological changes in nephrobiopathy depending on the renal response was performed in patients with achieved hematologic remission.RESULTS:Improved renal function was observed only in patients with hematologic response to therapy. There were no differences in the number of sclerotic glomeruli, protein casts, the area of inflammatory interstitial infiltration, and the degree of acute tubular damage in patients with and without renal response. In patients with renal response compared with patients without improving renal function, the area of interstitial fibrosis was less (24.9% and 45.9%, respectively;p=0.001), and the area of E-cadherin expression was larger (15.9% and 7.1%, respectively;p=0.006). Interstitial fibrosis of 40% or more and/or the area of expression of E-cadherin less than 10% of the area of tubulo-interstitium have an unfavorable prognostic value in achieving a renal response in MCN.CONCLUSION:If the interstitial fibrosis area is 40% or more and the expression area of E-cadherin is less than 10%, the probability of the absence of a renal response is 93.3% (OR=24.5) even when a hematological response to induction therapy is achieved. The number of protein casts, the prevalence of acute tubular damage and inflammatory interstitial infiltration have not prognostic value.

AIM:To assess the safety and efficacy of autologous haematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients with dialysis-dependent renal failure.MATERIALS AND METHODS:During a period from May 2010 to December 2016 fourteen MM patients with dialysis-dependent renal failure aged 48 to 65 years underwent auto-HSCT. After the induction therapy complete response, very good partial response, partial response were documented in 64, 29, 7% of patients, respectively. In no case was a renal response achieved. Haematopoietic stem cell mobilization in most patients (13/14) was performed according to the scheme: G-CSF 10 g/kg. Melphalan in 3 dosages was used as pre-transplant conditioning: 100, 140 and 200 mg/m2; 13 patients underwent a single and in one case underwent a tandem auto-HSCT against the background of hemodialysis. Evaluation of the antitumor and renal response was assessed on the 100th day after auto-HSCT. Subsequently, against the background of programmed hemodialysis and in the setting of high-dosed melphalan (100200 mg/m2), 13 patients underwent a single and one patient underwent a tandem auto-HSCT. At +100 days after auto-HSCT, an antitumor response and renal response were assessed.RESULTS:The period of agranulocytosis after auto-HSCT was from 5 to 12 days (median 8,5) and was accompanied by infectious complications, cardiac and neurological dysfunctions. At +100 days after auto-HSCT, the complete response was confirmed in 71% patients and very good partial response was confirmed in 29% patients. The minimal renal response was registered in 2 patients (14%), hemodialysis was stopped. The transplant-related mortality was absent. After a median follow-up of 53 months 5-year progression-free survival was 59%, and overall survival was 93%.CONCLUSION:Carrying out auto-HSCT in patients with dialysis-dependent renal failure contributed to the achievement of a minimal renal response in 14% of cases, which allowed these patients to stop hemodialysis. Patients whose conditioning regimen was performed using melphalan at a dose of 200 mg/m2showed more frequent complications in the early post-transplant period compared to patients who received a lower dose of melphalan (100140 mg/m2). Auto-HSCT in MM patients with dialysis-dependent renal failure is a feasible and effective treatment method, which in some cases contributes to independence from hemodialysis.

Introduction: According to the recent International Kidney and Monoclonal Gammopathy Research Group Consensus report, the spectrum of monoclonal gammopathies of renal significance merges more than 12 conditions; and combinations of various patterns of monoclonal gammopathies of renal significance–associated kidney damage have already been described. We present a case of a previously unreported combination of C3 glomerulopathy and light-chain proximal tubulopathy. Case description: A 53-year-old Caucasian man presented with general weakness. Three years prior, a check-up revealed proteinuria and microhematuria, later accompanied by arterial hypertension, elevated serum creatinine, and a low serum C3 levels. On admission, his creatinine was 1.5 mg/dL; his protein excretion was 1900 mg/24 h with microhematuria at 150 hpf. His serum C3 was 79 mg/dL with a normal C4 level. Serum protein electrophoresis revealed an M-spike, immunochemistry confirmed monoclonal immunoglobulin G kappa secretion of 920 mg/dL, and traces of Bence–Jones protein kappa in his urine. A kidney biopsy showed mesangial hypercellularity with diffuse fine granular C3 mesangial expression and tubular atrophy with diffuse coarse granular kappa light-chain tubular epithelial cytoplasmic expression. Computed tomography did not reveal any destructive lesions. A bone marrow smear showed 5% plasma cells, and bone marrow cell flow cytometry demonstrated 87.4% of plasma cells with an aberrant phenotype. The patient was diagnosed with an monoclonal gammopathy of renal significance and administered bortezomib–cyclophosphamide–dexamethasone. After four courses, his monoclonal immunoglobulin G kappa secretion halved, but his serum creatinine and proteinuria remained almost unchanged. Chemotherapy was switched to lenalidomide–dexamethasone, and after five courses his immunoglobulin G kappa secretion decreased to traces, Bence–Jones protein was not observed and his urinalysis, serum creatinine, and C3 levels were detected as normal. Conclusion: The combination of kidney damage patterns, one of which was directly and the other indirectly associated with monoclonal gammopathy, complements the monoclonal gammopathies of renal significance spectrum. Chemotherapy led to a very good partial response and kidney function recovery.