Multiple Myeloma and Retroperitoneal Fibrosis: A Rare Association Report and Literature Review.

Multiple myeloma (MM) is a common hematological malignancy. Autologous hematopoietic stem cell transplantation (auto-HSCT) can significantly improve the prognosis of patients with MM, but a variety of complications may occur after transplantation. Retroperitoneal fibrosis (RPF) is a rare cause of obstructive nephropathy. Because there are no specific symptoms at the time of onset and the course of the disease is often insidious, special laboratory and instrumental examination methods are usually needed to confirm the diagnosis. This article describes the clinical case of a 50-year-old female patient diagnosed with multiple myeloma. She developed postoperative acute kidney injury (AKI) more than 20 days after transplantation and was subsequently diagnosed with retroperitoneal fibrosis. After multidisciplinary collaboration, early transurethral vesicoureteral stent placement was performed, the obstruction was relieved, and her renal function returned to normal. Reports of retroperitoneal fibrosis after multiple myeloma transplantation are relatively rare. This case report advances our understanding of these 2 diseases, and the correlation between MM and RPF warrants further exploration.

Risk assessment and clinical implications of COVID-19 in multiple myeloma patients: A systematic review and meta-analysis.

INTRODUCTION: Patients with multiple myeloma (MM) face heightened infection susceptibility, particularly severe risks from COVID-19. This study, the first systematic review in its domain, seeks to assess the impacts of COVID-19 on MM patients. METHOD: Adhering to PRISMA guidelines and PROSPERO registration (ID: CRD42023407784), this study conducted an exhaustive literature search from January 1, 2020, to April 12, 2024, using specified search terms in major databases (PubMed, EMBASE, and Web of Science). Quality assessment utilized the JBI Critical checklist, while publication bias was assessed using Egger's test and funnel plot. The leave-one-out sensitivity analyses were performed to assess the robustness of the results by excluding one study at a time to identify studies with a high risk of bias or those that significantly influenced the overall effect size. Data synthesis involved fitting a random-effects model and estimating meta-regression coefficients. RESULTS: A total of 14 studies, encompassing a sample size of 3214 yielded pooled estimates indicating a hospitalization rate of 53% (95% CI: 40.81, 65.93) with considerable heterogeneity across studies (I2 = 99%). The ICU admission rate was 17% (95% CI: 11.74, 21.37), also with significant heterogeneity (I2 = 94%). The pooled mortality rate was 22% (95% CI: 15.33, 28.93), showing high heterogeneity (I2 = 97%). The pooled survival rate stood at 78% (95% CI: 71.07, 84.67), again exhibiting substantial heterogeneity (I2 = 97%). Subgroup analysis and meta-regression highlighted that study types, demographic factors, and patient comorbidities significantly contributed to the observed outcome heterogeneity, revealing distinct patterns. Mortality rates increased by 15% for participants with a median age above 67 years. ICU admission rates were positively correlated with obesity, with a 20% increase for groups with at least 19% obesity. Mortality rates rose by 33% for the group of patients with at least 19% obesity, while survival rates decreased by 33% in the same group. CONCLUSION: Our meta-analysis sheds light on diverse COVID-19 outcomes in multiple myeloma. Heterogeneity underscores complexities, and study types, demographics, and co-morbidities significantly influence results, emphasizing the nuanced interplay of factors.

Lambda light chain - restricted non - crystalline proximal tubulopathy with cast nephropathy in multiple myeloma: a case report and literature review.

BACKGROUND: Multiple myeloma (MM) often causes renal tubular damage, such as the light chain cast nephropathy (LCCN) and the light chain proximal tubulopathy (LCPT). The excessive light chains deposited in the proximal and distal tubules usually manifest with different characteristics, leading to a rare coexistence of the two pathological conditions. Here we report a unique case of a patient with multiple myeloma (MM) who presented with acute kidney injury (AKI) due to dual conditions of λ light chain-restricted non-crystalline LCPT and LCCN. This report reviews the clinical presentation and histological findings, comparing them with previously published cases. CASE PRESENTATION: A 49-year-old male patient was admitted with a chief complaint of "fatigue, loss of appetite for 40 days and elevated blood creatinine for 10 days." In serum and urine, the λ light chain level and the ratio of κ to λ free light chain were 1235 mg/dl and 93.25 mg/dl, 0.0022 and 0.0316, respectively. Additionally, serum protein electrophoresis showed an M-spike with monoclonal IgD-λ. Bone marrow puncture revealed 30.5% primitive naive plasma cells, indicative of IgD-λ MM. Light microscopy of kidney biopsy specimen showed periodic acid-Schiff (PAS)-negative cytoplasm in some proximal tubules and PAS-negative casts with a rigid appearance in some distal tubule lumens. On immunofluorescence, these proximal tubular epithelial cells cytoplasm and casts stained exclusively with λ-light chains. Electron microscopy did not reveal any crystalline inclusions. Given the clinical and bone marrow puncture findings, the overall pathological presentation was LCPT with LCCN secondary to IgD-λ MM. After chemotherapy and dialysis, the patient's condition was improved and he was tracked in follow-ups. CONCLUSION: In some tubular renal injuries caused by MM, the morphological changes are subtle and often overlooked. In this paper, we present a rare case of LCPT with LCCN showing λ restriction in patient with MM. Through the clinicopathological analysis of patients, the understanding of the disease can be deepened and the diagnosis rate improved.

Effective Treatment with Venetoclax and Hypomethylating Agents for the Coexistence of Multiple Myeloma and Acute Myeloid Leukemia: A Case Report and Literature Review.

OBJECTIVE: Multiple myeloma (MM) and Acute myeloid leukemia (AML) are distinct hematologic malignancies originating from different cell lineages. Their coexistence is extremely rare, and current treatment approaches are even more so. Therefore, exploring the clinical features of their coexistence and the promising treatment strategy is worthwhile. CASE REPORT: We described three cases involving the coexistence of MM and DNMT3A-mutant AML, two of which presented simultaneous occurrences, while Case 3 had secondary AML about 70 months after the MM. DISCUSSION: All cases exhibited DNMT3A mutations, which characterized by one missense mutation and two frameshift mutations; all were likely loss of function mutations. Among them, two patients were treated with Venetoclax-based regimens and achieved favorable effects. The patients were alive for 62,38 and 103 months. CONCLUSIONS: Clonal hematopoiesis of DNMT3A may have a crucial role in the coexistence of MM and AML and Venetoclax-based regimens reveal favorable treatment responses. However, drug resistance still needs to be considered, and further research is required to elucidate the underlying mechanisms and treatment strategies.

Efficacy of daratumumab on multiple myeloma patients with renal insufficiency: a systematic review and meta-analysis.

BACKGROUND: Renal insufficiency (RI) is a key factor affecting the prognosis of multiple myeloma (MM) patients. Because the benefit of daratumumab for treating MM patients with RI remains unclear, our objective was to evaluate the efficacy of daratumumab on MM patients with RI. METHODS: We conducted a systematic search of the PubMed, EMBASE, and Cochrane Library databases as of October 24, 2023. Two independent reviewers screened the article titles, abstracts, and full text to identify the randomized controlled trials (RCTs) meeting the inclusion and exclusion criteria. Meta-analyses were performed using RevMan version 5.4. Outcomes of interest were progression-free survival (PFS), overall survival (OS), complete response or better (≥CR), and minimal residual disease (MRD) negativity, all calculated as hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: A total of 10 RCTs with 5003 patients were included. Add-on daratumumab improved PFS and OS among newly diagnosed MM (NDMM) patients with RI (HR 0.48 [95% CI: 0.36, 0.64, I2 = 65%] and HR 0.63 [95% CI: 0.48, 0.82, I2 = 0%]) as well as relapsed/refractory MM (RRMM)-RI patients, compared with the control group (HR 0.46 [95% CI: 0.37, 0.58, I2 = 0%] and HR 0.68 [95% CI: 0.51, 0.92, I2 = 0%]). In terms of the renal status, the efficacy of add-on daratumumab for MMRI patients was similar to that for MM patients with normal renal function. A prolonged PFS benefit for add-on daratumumab treatment versus the control was evident across all RRMM-RI subgroups, and the benefits tended to increase with the follow-up time. CONCLUSIONS: Our results indicate that MM patients with RI could benefit from a daratumumab-added regimen regardless of MM status. Additional high-quality RCTs are still warranted to confirm our findings.

Modest survival benefits of autologous stem cell transplantation in multiple myeloma with renal impairment: a critical appraisal of the pre-antibody era.

The benefit of high-dose melphalan followed by autologous hematopoietic stem cell transplantation (HDM-ASCT) for multiple myeloma (MM) patients with renal insufficiency (RI) is debated. A systematic review and meta-analysis were conducted to assess the safety and efficacy of HDM-ASCT in MM patients with RIs, and the findings were compared with real-world data. The study included 26 articles, 13 of which were pooled for meta-analysis. We compared three different types of MM patients with RI against MM patients with normal renal function (NRF). These patients were: MM patients with RI at the time of transplantation; MM patients with RI at the time of diagnosis; MM patients with RI at diagnosis but with NRF at transplantation. The meta-analysis indicated that MM patients with RIs conditioned with melphalan ≤ 140 mg/m2 followed by ASCT had transplant-related mortality rates comparable to those without RIs. The complete response rates post-ASCT were similar between MM patients with RIs and those with NRF. Although progression-free survival (PFS) was statistically similar between the groups, MM patients with RIs had significantly poorer overall survival (OS) than those with NRF. The real-world data supported these findings. With a reduced dose of melphalan, ASCT is safe and effective for MM patients with RI. MM patients with RI have similar complete response rates and PFS after ASCT compared to MM patients with NRF. The lower OS in MM patients with RI indicates the need for further research to improve OS in these patients.

Bortezomib-induced neuropathy in multiple myeloma manifesting as foot drop due to peroneal nerve palsy.

We present the case of a man in his 50s with multiple myeloma who developed foot drop after receiving bortezomib-dexamethasone combination chemotherapy. Diagnostic evaluations, including haematological parameters, nerve conduction studies and imaging, were performed to confirm the diagnosis and assess the extent of neuropathy. He was managed conservatively with analgesics and vitamin supplements, and bortezomib was temporarily withheld. The neuropathy gradually improved, and bortezomib was successfully reintroduced without recurrence of foot drop. Bortezomib-induced foot drop is a rare complication of bortezomib-based therapy in patients with multiple myeloma. Early recognition and intervention are crucial to minimise impact on quality of life. This case report emphasises the safe reintroduction of bortezomib post-neuropathy resolution, emphasising the importance of early recognition and multidisciplinary management.

Recurrent Cutaneous Manifestation in Multiple Myeloma.

Cutaneous involvement is an uncommonly encountered manifestation in multiple myeloma (MM), more commonly observed in patients with aggressive subtypes, and often resistant to conventional therapies. Due to its infrequency, reported clinical characteristics have been diverse and relatively non-specific. Particularly uncommon is lower extremity involvement. In this case report, we present a unique case of a patient with refractory immunoglobulin G lambda MM, who subsequently developed recurrence in the lower leg, while being on systemic therapy. Initially, the lesion resembled squamous cell carcinoma, posing a diagnostic challenge. Through meticulous histopathological and immunohistochemical evaluation, cutaneous involvement by MM was confirmed. This case highlights the importance of maintaining a high clinical suspicion for cutaneous involvement in patients with MM who present with new skin lesions, as early diagnosis is crucial for appropriate management.

Multisite distribution of fibrillary inclusions in a patient with light chain proximal tubulopathy: A case report.

RATIONALE: Light chain proximal tubulopathy (LCPT) is a rare form of renal impairment associated with multiple myeloma (MM). LCPT is caused by inclusions formed of free light chains that are typically crystalline, but can also be noncrystalline structures. PATIENT CONCERNS: A 62-year-old man was hospitalized for the investigation of abnormal urine test results lasting for 1 year and kidney-function abnormalities persisting for more than 1 month. DIAGNOSES: Noncrystalline LCPT and MM. INTERVENTIONS: The patient was treated with the lenalidomide, bortezomib, and dexamethasone and pomalidomide, bortezomib, and dexamethasone chemotherapy regimens. OUTCOMES: Complete remission of MM was achieved, and the patient's renal function returned to normal. LESSONS: This case report highlights the importance of renal pathology in the diagnosis of patients with unexplained chronic kidney disease and proteinuria.

[Aortic Valve Replacement Using Minimally Invasive Cardiac Surgery Procedure in a Patient with Multiple Myeloma:Report of a Case].

Multiple myeloma (MM) is a disease with a poor prognosis, and there are few reports of cardiac surgery complicated by this disease, which can lead to various perioperative complications such as bleeding tendency due to coagulation defects, changes in blood viscosity, immunocompromise, and bone marrow insufficiency when undergoing cardiac surgery. In recent years, with the spread of minimally invasive cardiac surgery (MICS), avoidance of sternotomy has become an option. We present a case of a 70-year-old man who underwent aortic valve replacement using MICS procedure for aortic regurgitation complicated with MM.

Extramedullary plasmacytoma with associated multiple myeloma as a presentation of the posterior mediastinal mass: a rare clinical encounter.

A plasmacytoma is a single, isolated tumour of abnormal plasma cells. It can develop within the bone, known as solitary plasmacytoma of bone, or outside the bone, referred to as extraosseous (extramedullary) plasmacytoma, without spreading to other parts of the body. Plasmacytoma, an uncommon presentation in the posterior mediastinum, usually arises as solitary or multiple lesions in bone or soft tissues. The standard treatment involves definitive radiotherapy, potentially curative for extramedullary cases. The prognosis varies, being more favourable without concurrent multiple myeloma and worsening with high-risk cytogenetics. The case involves a male in his early 80s with an extensive medical history presenting with difficulty swallowing and dyspnoea. The diagnosis revealed a rare posterior mediastinal plasmacytoma associated with multiple myeloma, emphasising the importance of prompt diagnosis and treatment.

Prognosis of concurrent renal impairment at diagnosis of multiple myeloma: a systematic review.

BACKGROUND: Multiple myeloma is a malignant tumour of the blood in which abnormal proliferation of plasma cells leads to bone destruction, renal impairment, anaemia, and hypercalcaemia. Renal impairment caused by multiple myeloma is a common and serious condition; however, the prognosis of multiple myeloma at the time of diagnosis remains unclear. METHOD: We conducted searches for literature in PubMed, Web of Science, Cochrane, Embase, CNKI, Wanfang, and VIP databases up to 30 April 2023. Progression-free survival and overall survival with and without renal impairment at the time of multiple myeloma diagnosis were compared, and prognostic indicators were analysed. RESULTS: Six studies were finally included. Among patients with multiple myeloma, 319 had renal impairment, and 1166 had no renal impairment. Compared to the control group, no significant difference was observed in overall or progression-free survival in patients with multiple myeloma complicated with renal impairment. CONCLUSION: The limited low-quality evidence available does not support an association between prognosis and multiple myeloma complicated by kidney injury.

Coexistence of double seropositivity for MPO antibody and anti-GBM antibody in ANCA-associated vasculitis concurrent with multiple myeloma: A case report.

RATIONALE: Immune-mediated vasculitis with 2 or more autoantibodies, for example, anti-proteinase-3, combined with anti-myeloperoxidase (MPO) or anti-glomerular basement membrane (GBM) antibodies, is extremely unusual. Furthermore, the coexistence of autoimmune vasculitis and hematological malignancies is uncommon. Herein, we describe a case of double-seropositive anti-neutrophil cytoplasmic antibody (ANCA) vasculitis with multiple myeloma. PATIENT CONCERNS: A 79-year-old Asian man presented with persistent leg edema and kidney dysfunction. His kidney function rapidly decreased, and serologic test results showed higher titers of the anti-MPO antibody (54.7 IU/mL) and anti-GBM antibodies (>200 IU/mL). Additionally, the clinical features showed the possibility of monoclonal gammopathy with anemia and hyperglobulinemia. We performed kidney and bone marrow biopsy. Serum protein electrophoresis and immunofixation revealed no significant differences, but the results of the bone marrow smear were compatible with those of myeloma with 15% plasmacytosis. However, kidney biopsy showed diffuse crescentic glomerulonephritis without deposition of the immune complex or kappa/lambda chain. DIAGNOSES AND INTERVENTIONS: Finally, the patient was diagnosed with double-seropositive ANCA-associated glomerulonephritis and multiple myeloma. Given the patient's performance status, we initiated low-dose steroid pulse therapy, followed by conservative management. OUTCOMES: While the pulmonary lesions showed improvement, the kidney function did not regain its previous state, prompting the initiation of kidney replacement therapy by hemodialysis. There has been a decrease in the levels of anti-GBM and anti-MPO antibodies since the initial diagnosis. LESSONS: This case elucidates the complex interplay between ANCA-associated glomerulonephritis and hematologic malignancy and emphasizes the need for a nuanced treatment strategy considering its multifaceted clinical presentation.

Renal impairment in monoclonal gammopathies and multiple myeloma.

The incidence of monoclonal gammopathy (MG) increases with age. In individuals over 80 years of age, we can diagnose the presence of monoclonal immunoglobulin (MIg) in up to 10 % of cases. Not only malignant diseases such as multiple myeloma (MM), but also benign forms such as MGUS (monoclonal gammopathy of undetermined significance) can lead to renal involvement. The light chains of immunoglobulins (LC) are the most damaging to the kidneys, as they are freely filtered into the urine due to their molecular weight. Detection of MIg relies mainly on a combination of immunofixation electrophoresis of serum (IELFO) and urine and determination of free light chains (FLC) of kappa and lambda and their ratio (κ/λ) in serum. The combination of these tests will detect the presence of MIg with 99 % sensitivity. Renal damage in MG may be caused by direct deposition of MIg in the glomeruli (e.g. AL amyloidosis, LC deposition disease) or tubules (in the distal tubule as a myeloma kidney or in the proximal tubule as Fanconi syndrome or proximal tubulopathy). Typical urinary findings in these diseases are moderate or severe proteinuria or nephrotic syndrome. Acute kidney injury (AKI) can be expected especially when serum FLC is >500 mg/l. Renal biopsy is crucial to establish an accurate diagnosis and thus initiate the correct treatment. Treatment of these types of renal damage involves the same treatment regimens used in the treatment of MM, including proteasome inhibitors or daratumumab.