BACKGROUND: Plasma cell leukemia (PCL) is a rare monoclonal gammopathy, associated with short survival. Because of its very low incidence, only a few cohorts have been reported and thus, information on this disease is scarce. The goal of this study was to better understand the clinical features, prognostic factors, and efficacy of modern treatments in both primary PCL (pPCL) and secondary PCL (sPCL).
METHODS: We performed a retrospective, multicenter study of patients diagnosed with PCL, defined as circulating plasma cells ≥20% of total leukocytes and/or ≥2 × 109/L.
RESULTS: We identified 99 eligible PCL patients, of whom 33 were pPCL and 66 were sPCL. The median progression-free survival (PFS) to frontline treatment and overall survival (OS) were, respectively, 4.8 (95% CI, 0.4-9.2) and 18.3 months (95% CI, 0.0-39.0) for pPCL and 0.8 (95% CI, 0.5-1.1) and 1.2 months (95% CI, 0.9-1.5) for sPCL (both p < 0.001). We observed no improvement in OS over time (2005-2012 vs. 2013-2020, p = 0.629 for pPCL and p = 0.329 for sPCL). Finally, our data suggested that sPCL originates from a high-risk multiple myeloma (MM) population with a short OS (median 30.2 months), early relapse after stem cell transplant (median 11.9 months) and a high proportion of patients with multiple cytogenetic abnormalities (36% with ≥2 abnormalities).
CONCLUSIONS: This study is one of the largest PCL cohorts reported. We are also the first to investigate characteristics of MM before its transformation into sPCL and demonstrate that high-risk biologic features already present at the time of MM diagnosis. Moreover, our data highlights the lack of improvement in PCL survival in recent years and the urgent need for better treatment options.

Monoclonal gammopathy of undetermined significance (MGUS) is a pre-neoplastic condition involving plasma cells or lymphoplasmacytic proliferation-clinical presentations ranging from asymptomatic to symptoms of systematic organ involvement. It is commonly associated with light chain amyloidosis and usually strengthens during diagnosis. It is usually associated with thrombocytopenia in addition to anemia. This case report focuses on a 63-year-old Hispanic female who initially presented without any symptoms but with severe thrombocytosis. The finding of renal amyloidosis boosts the final diagnosis of MGUS. Rarely a patient is initially presented with severe thrombocytosis despite thrombocytopenia, which is commonly associated with plasma cell disorders. The case emphasizes the need for considering plasma cell disorders in patients with abnormal hematologic manifestations. It highlights the importance of timely identification and intervention to prevent irreversible organ damage by providing a detailed analysis of the clinical presentation and diagnostic evaluation.

POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disorder, Skin changes) refers to a rare paraneoplastic entity linked to a plasma cell disorder, characterized by multiple systemic manifestations that must be studied together to establish a timely diagnosis. We report a case of a 60-year-old female who had been initially classified to have Guillain Barré syndrome for one year and seven months, receiving three cycles of immunoglobulin without a positive response. The clinical picture was characterized by painful paresthesias in four limbs and paraparesis, with the patient also developing distal cutaneous hyperpigmentation and multiple adenopathies. Neuroconduction studies revealed chronic sensorimotor axonal polyneuropathy and albumin-cytological dissociation was evidenced in the study of cerebrospinal fluid (CSF). In the subsequent evaluation, Lambda light chains and a lymph node biopsy compatible with Castleman\'s disease were found, and hence it was determined that the patient met the criteria for POEMS syndrome. This case report highlights the importance of incorporating other diagnostic perspectives when encountering patients with polyneuropathy of immunological origin who fail to respond to conventional therapies.

BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare multisystemic clonal plasma cell disorder. Pulmonary involvement is frequently found in patients with POEMS syndrome, manifesting various clinical features. Therefore, to improve diagnostic accuracy and provide treatment strategies, a comprehensive analysis of pulmonary manifestations of POEMS syndrome is needed.
METHODS: This retrospective study included patients with POEMS syndrome at Peking Union Medical College Hospital, a major referral medical center in China, between June 1, 2013, and June 1, 2023. Demographic data, laboratory findings, pulmonary function test results, echocardiograms, and chest imaging data were extracted. Continuous variables were compared using the t-test or Mann-Whitney method. Pearson\'s chi-square test or Fisher\'s exact test was conducted to compare categorical data.
RESULTS: Overall, 282 individuals diagnosed with POEMS syndrome were included in this study, of which 56% were male with an average age of 48.7 years. Respiratory symptoms were found in 40.1% of the patients, with dyspnea as the most common symptom (34.4%). Chest computed tomography and echocardiography findings showed that 56.4% of patients exhibited pleural effusion, 62.8% displayed mediastinal or hilar lymphadenopathy, 46.5% presented pleural thickening, 27.3% demonstrated bone lesions of the ribs or thoracic vertebra, 7.8% showed lung interstitial abnormalities, and 35.5% had pulmonary hypertension. Decreased diffuse capacity and restrictive ventilatory patterns were identified in 85.2% (115 cases) and 47.4% (64 cases) of patients, respectively. Patients with respiratory symptoms exhibited higher declined lung function measures than those having no respiratory symptoms. High-risk patients with poor prognosis showed more pulmonary function abnormalities.
CONCLUSIONS: Abnormalities in pulmonary manifestations constitute the significant features of POEMS syndrome. Several patients with POEMS syndrome presented with respiratory symptoms at the initial evaluation. These findings underscore the importance of early identification and accurate diagnosis of POEMS syndrome by clinicians, particularly in cases involving lung and multisystem.

Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes (POEMS) syndrome is a rare disorder with multiple presentations and a constellation of symptoms. We present a 62 year-old female who presented to the Emergency Department for acute dyspnea. Chest Xray showed sclerotic lesions in the ribs and thoracic spine. Further imaging studies with computed tomography (CT) and positron emission tomography (PET) scans were suggestive of a benign process. Improvement was seen with supportive management. A few months later, patient developed neurological symptoms with reduced exercise tolerance. Mixed demyelinating and axonal polyneuropathy was diagnosed by electromyography. Further work up with bone marrow biopsy and immunochemistry testing revealed lambda and kappa plasma cell disorder, with elevated vascular endothelial growth factor (VEGF). Patient was diagnosed with POEMS and initiated on chemotherapy. POEMS syndrome is commonly missed due to its rarity and varied clinical presentations. VEGF plays a crucial role in the diagnosis. Management requires a multidisciplinary approach.

Immunoglobulin light chain amyloidosis can be either systemic or localized. Although these conditions share a similar name, they are strikingly different. Localized light chain amyloidosis has been challenging to characterize due to its lower incidence and highly heterogeneous clinical presentation. Here, we review the emerging literature, emphasizing recent reports on large cohorts of patients with localized amyloidosis, and provide insights into this condition\'s pathology and natural history. We find that patients with localized amyloidosis have an excellent prognosis with overall survival similar to that of the general population. Furthermore, the risk of progression to systemic disease is low and likely represents initial mischaracterization as localized disease. Therefore, we argue for the incorporation of more sensitive techniques to rule out systemic disease at diagnosis. Despite increasing mechanistic understanding of this condition, much remains to be discovered regarding the cellular clonal evolution and the molecular processes that give rise to localized amyloid formation. While localized surgical resection of symptomatic disease is typically the treatment of choice, the presentation of this disease across the spectrum of plasmacytic B-cell lymphoproliferative disorders, and the frequent lack of an identifiable neoplastic clone, can make therapy selection a challenge in the uncommon situation that systemic chemotherapy is required.

Electron microscopy is the gold standard to characterize centrosomal ultrastructure. However, production of significant morphometrical data is highly limited by acquisition time. We therefore developed a generalizable, semi-automated high-throughput electron tomography strategy to study centrosome aberrations in sparse patient-derived cancer cells at nanoscale. As proof of principle, we present electron tomography data on 455 centrioles of CD138pos plasma cells from one patient with relapsed/refractory multiple myeloma and CD138neg bone marrow mononuclear cells from three healthy donors as a control. Plasma cells from the myeloma patient displayed 122 over-elongated centrioles (48.8%). Particularly mother centrioles also harbored gross structural abnormalities, including fragmentation and disturbed microtubule cylinder formation, while control centrioles were phenotypically unremarkable. These data demonstrate the feasibility of our scalable high-throughput electron tomography strategy to study structural centrosome aberrations in primary tumor cells. Moreover, our electron tomography workflow and data provide a resource for the characterization of cell organelles beyond centrosomes.

Leukoencephalopathy in the setting of multiple myeloma (MM) is a rare demyelinating condition, with few reported cases in literature. Daratumumab is a CD38 targeted monoclonal antibody that has been widely used for the management of MM. In the absence of central nervous system (CNS) disease, many medication-induced leukoencephalopathy cases reported with MM, including daratumumab-induced, are associated with progressive multifocal leukoencephalopathy (PML) and John Cunningham (JC) virus. Currently, there are no reported cases of daratumumab-induced leukoencephalopathy among patients without CNS involvement or PML. We discuss 2 patients who developed leukoencephalopathy while receiving daratumumab-based therapy without evidence of PML or CNS disease. Both patients had baseline MRIs without significant white matter changes before daratumumab-based therapy. Patients began experiencing neurological deficits about 6 to 8 months after daratumumab-based therapy initiation. One patient passed away before being assessed for improvement of symptoms with daratumumab cessation. The second patient had some stabilization of symptoms after cessation; however, the leukoencephalopathy remained irreversible. As the class of anti-CD38 monoclonal antibodies expands in MM therapy, we highlight a potential treatment complication and the importance of detecting leukoencephalopathy early among patients receiving anti-CD38 therapy. We recommend vigilant monitoring of any new or worsening neurological symptoms to avoid serious complications of irreversible leukoencephalopathy.

The TEMPI syndrome is a novel and rare disease with five distinct clinical features: Telangiectasis, Erythrocytosis, Monoclonal gammopathy, Perinephric fluids collection, and Intrapulmonary shunting. Here, we report three cases of TEMPI syndrome and their treatment response. The three patients were presented to our department with polycythemia, abdominal distension, and dyspnea. On admission, all patients manifested telangiectasis, erythrocytosis, monoclonal gammopathy, and intrapulmonary shunting. Patient 1 and 2 manifested perinephric fluids collection. In addition, all patients had skin pigmentation, patient 1 and 2 had polyserosal effusion, two symptoms that had not been associated with TEMPI syndrome before. The three patients showed various response to plasma cell-directed therapy. We demonstrated their treatment response by measuring erythropoietin, hemoglobin, and M protein levels throughout therapy. This report suggested that TEMPI syndrome is a rare yet treatable disease. The diagnosis and treatment of it remain challenging.

Historically, kidney transplantation has been considered inappropriate for most patients with AL amyloidosis-associated kidney failure because of concerns about recurrent disease in the allograft and poor long-term survival. With improvements in rates and durability of hematologic responses and survival that have accompanied treatment advances, a greater proportion of patients with AL amyloidosis may be suitable for kidney transplantation. However, there are no widely accepted criteria for kidney transplant eligibility for this patient population.
We administered surveys electronically to transplant nephrologists and amyloidosis experts at a geographically diverse set of academic medical centers in the United States. Questions were designed to elucidate views about suitability and timing of kidney transplantation for patients with AL amyloidosis-associated kidney failure.
The survey was completed by 20 (65%) of invited amyloidosis experts and 20 (29%) of invited transplant physicians. Respondents indicated that, for patients with AL amyloidosis, most transplant nephrologists have limited experience with both determining eligibility for and providing care after kidney transplantation. Most transplant nephrologists and amyloidosis experts viewed anticipated patient survival as the most important determinant of suitability for kidney transplantation. Compared with transplant program respondents, amyloidosis program respondents reported a higher degree of confidence in determining suitability for kidney transplantation, were comfortable proceeding with kidney transplantation earlier after patients attained a hematologic response, and were less concerned about extrarenal amyloid involvement as a barrier to kidney transplantation. In both groups, most respondents indicated that there is a lack of consensus between amyloidosis and kidney transplant physicians about criteria for determining suitability for kidney transplantation.
Views about criteria for kidney transplantation for patients with AL amyloidosis-associated kidney failure differed between amyloidosis and transplant nephrology program respondents, with amyloidosis specialists generally favoring a less-restrictive approach to transplant eligibility. The findings suggest a need for consensus building across specialties.