Extended high cut-off haemodialysis for myeloma cast nephropathy in Auckland, 2008-2012.

Myeloma cast nephropathy contributes to high morbidity and early mortality associated with the development of end-stage renal disease. Treatment with extended high cut-off haemodialysis coupled with novel anti-myeloma therapies enables significant reduction of serum-free light chains and has been shown to improve renal outcomes. In this case series, medical records of 6 patients who received high cut-off haemodialysis for biopsy-proven cast nephropathy were retrospectively reviewed. Patients received a total of 344 hours of high cut-off haemodialysis and concurrent chemotherapy. Only 50% became dialysis independent following treatment. One patient who achieved sustained remission remained dialysis dependent. The added benefit of high cut-off haemodialysis in the light of novel anti-myeloma therapies requires further evaluation.

Increased serum tumor markers (CA125 and CA15.3) in primary plasma cell leukemia: a case report and review of the literature.

73-year-old woman complaining of bone pain and weight loss was suspected to have a malignant disease, and extensive laboratory investigations were carried out. She was diagnosed with multiple myeloma; however, because of the finding of extremely high serum levels of CA125 and CA15.3 and focal liver lesions, a concomitant solid tumor was suspected, which was then excluded with the appropriate tests, including an ultrasound-guided liver biopsy. While being diagnosed, the patient developed a rapidly evolving plasma cell leukemia with a simultaneous increase in CA125 and CA15.3. After treatment with cyclophosphamide and dexamethasone, the peripheral blood plasma cells disappeared and there was a dramatic decrease in the CA125 and CA15.3 tumor markers. High levels of the latter can be observed in patients with aggressive plasma cell dyscrasias, an observation that is crucial in order to avoid unnecessary tests that can result in treatment delay.

Gene expression profiling of plasma cell dyscrasias reveals molecular patterns associated with distinct IGH translocations in multiple myeloma.

Multiple myeloma (MM) is the most common form of plasma cell dyscrasia, characterized by a marked heterogeneity of genetic lesions and clinical course. It may develop from a premalignant condition (monoclonal gammopathy of undetermined significance, MGUS) or progress from intramedullary to extramedullary forms (plasma cell leukemia, PCL). To provide insights into the molecular characterization of plasma cell dyscrasias and to investigate the contribution of specific genetic lesions to the biological and clinical heterogeneity of MM, we analysed the gene expression profiles of plasma cells isolated from seven MGUS, 39 MM and six PCL patients by means of DNA microarrays. MMs resulted highly heterogeneous at transcriptional level, whereas the differential expression of genes mainly involved in DNA metabolism and proliferation distinguished MGUS from PCLs and the majority of MM cases. The clustering of MM patients was mainly driven by the presence of the most recurrent translocations involving the immunoglobulin heavy-chain locus. Distinct gene expression patterns have been found to be associated with different lesions: the overexpression of CCND2 and genes involved in cell adhesion pathways was observed in cases with deregulated MAF and MAFB, whereas genes upregulated in cases with the t(4;14) showed apoptosis-related functions. The peculiar finding in patients with the t(11;14) was the downregulation of the alpha-subunit of the IL-6 receptor. In addition, we identified a set of cancer germline antigens specifically expressed in a subgroup of MM patients characterized by an aggressive clinical evolution, a finding that could have implications for patient classification and immunotherapy.

[Effective measurement of coronary flow velocity reserve (CFVR) with transthoracic Doppler echocardiography (TTDE) for plasma cell leukemia with hyperviscosity syndrome].

A 67-year-old woman was admitted with impaired general performance, suffering from fatigue, chest oppression on exertion, and paresthesia of the finger trips. The laboratory findings showed increased white blood cells with abnormal cells, and serum immunofixation test showed monoclonal IgM kappa paraprotein. On flow cytometric immunophenotyping with CD38 gating, most of the abnormal cells expressed surface CD20, CD138, cytoplasmic IgM, but neither surface CD56 nor surface IgM. Immunohistochemical staining of abnormal cells was positive for surface CD38, surface CD20 and cytoplasmic IgM. The final diagnosis was plasma cell leukemia IgM kappa type. Electrocardiography (ECG) on admission showed ST depression in II, III, aV(F), V4, V5, and V6. Coronary angiography (CAG) is invasive and difficult for patients with renal failure, therefore the patient underwent transthoracic Doppler echocardiography (TTDE), which revealed reduced coronary flow velocity reserve (CFVR). Two courses of VAD therapy were administered, then the condition improved, the serum IgM level decreased, abnormal cells were decreased in peripheral blood and bone marrow aspirates, and the creatinine levels improved. With the return of normal ECG findings and improved CFVR, the abnormal ECG and reduction in CFVR was thought to be associated with the hyperviscosity syndrome in PCL. Noninvasive assessment of CFVR by TTDE is significantly useful for the patients who have renal failure and need chemotherapy.

Biclonal primary plasma cell leukemia.

Authors present a multiparameter pathological study in a case of rapid biclonal primary plasma cell leukemia. The immunohistochemical data revealed aberrant phenotypes (monocyte, epithelial and T-cell) probably in connection with microenvironmental influences. Biclonality can be attributed to class switching during malignant transformation. Static image cytometry showed aneuploidy. The blasts of this process are active immunoregulatory cells.

[Plasma cell leukemia with amyloid deposition and osteogenetic change at the site of an extramedullary plasmacytoma].

A 49-year-old man was admitted with swelling in the left lower extremity, and a mass in the left lower abdomen. Laboratory findings showed an increased WBC of 15,000/microliter with 41% plasma cells, and immunoglobulin (Ig) A of 2,557mg/dl with a monoclonal component. A roentgenogram and computed tomograph of the abdomen revealed that a 5 x 10 cm mass with calcification located in the iliopsoas muscle. Plasma cell leukemia with extramedullary plasmacytoma was diagnosed, and the patient was treated with high-dose dexamethasone (40 mg/day for 4 days), resulting in a good response with the disappearance of plasma cells in peripheral blood and a marked decrease in serum Ig A. However, the patient's condition deteriorated in spite of various treatments, and he died of heart failure 5 months after admission. With informed consent from relatives, a necropsy was performed and infiltration of plasma cells in the mass in the iliopsoas muscle was noted. We reported this case because plasma cell leukemia with amyloid deposition and osteogenesis at the site of extramedullary plasmacytoma is very rare.

Plasma cell leukemia: concepts and management.

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell dyscrasia. Patients with PCL have a very poor prognosis with median survival measured in months. PCL can present de novo or following a prodrome of plasma cell myeloma. Patients with PCL tend to present with aggressive clinical features, such as extramedullary disease, bone marrow failure, advanced stage disease and expression of distinct immunophenotypic markers, such as lack of CD56 and presence of CD20. Historically, the treatment of PCL has primarily been palliative, with only a small minority of patients achieving a durable remission. The impact of newer agents, such as bortezomib and lenalidomide, in conjunction with autologous and allogeneic stem cell transplantation is uncertain, but emerging data suggest that use of these modalities may help improve the poor prognosis of patients with PCL.

Peripheral blood dendritic cell subsets from patients with monoclonal gammopathies show an abnormal distribution and are functionally impaired.

Objectives. The information currently available about dendritic cells (DCs) in patients with different types of monoclonal gammopathy (MG) is limited and frequently controversial. In the present study, we analyzed the ex vivo distribution as well as the phenotypic and functional characteristics of peripheral blood (PB) DCs from different types of MG. Methods. For this purpose, 61 untreated patients in total with MG were analyzed-MG of undetermined significance (MGUS), 29 cases; multiple myeloma (MM), 28 cases; and plasma cell leukemia (PCL), 4 cases-in comparison with a group of 10 healthy controls. Results. Our results show an absolute overall higher number of all subsets of PB DCs in PCL, together with lower numbers of myeloid DCs in MM patients. From a phenotypic point of view, PB DC subsets from all types of MG expressed significantly higher levels of HLA molecules and altered patterns of expression of the CD2, CD11c, CD16, CD22, CD62L, and CD86 molecules, in association with altered patterns of secretion of inflammatory cytokines. Conclusion. In summary, we show the existence of significant abnormalities in the distribution, phenotype, and pattern of secretion of inflammatory cytokines by different subsets of PB DCs from patients with MGs, which could reflect a potentially altered homing of DCs, together with a greater in vivo activation and lower responsiveness of PB DCs, which are already detectable in MGUS patients.

Plasma cell leukemia presenting with diplopia due to unilateral abducens paralysis and complex chromosomal abnormalities.

Involvement of cranial nerves is rare in plasma cell leukemia (PCL). Here, we report a case of PCL presenting with unilateral abducens paralysis. Cranial magnetic resonance imaging (MRI) disclosed a mass in the sphenoid sinus. Although the patient showed an initial response to chemotherapy, he died of disease progression 5 months later. Cytogenetic analysis showed translocation of chromosomes 11 and 14, t(11;14) (q13;q32), with additional complex abnormalities. This case implies an association between clinical manifestations and chromosomal abnormalities.

Aggressive course of primary plasma cell leukemia with unusual morphological and cytogenetic features.

A case of aggressive plasma cell leukemia with unusual morphological and cytogenetic features is reported. A 65-year-old man was admitted to hospital due to anemia, thrombocytopenia, and renal insufficiency. Bone marrow examination and peripheral blood smear revealed a large number of pleomorphic cells with convoluted and multilobulated nuclei. Immunohistochemistry of the bone marrow biopsy was negative for anti-keratin antibodies CAM.5.2 and AE1/AE3, but positive for EMA. The immunophenotypic features of these cells were suggestive of plasma cell origin with positivity for CD38, CD56, CD9, and CD44 and a weak positivity for CD71 and CD45 (40% of the cells), while all other markers of hematopoietic origin were negative. Furthermore, a serum protein electrophoresis showed a monoclonal component type IgG-kappa of 70 g/l. The cytogenetic analysis demonstrated a hypotetraploid clone with multiple numerical and structural abnormalities. Although some of the aberrations found are associated with plasma cell malignancies--e.g., structural rearrangement of chromosome 1, del(6q), and monosomy 13--the karyotypic complexity in the present case is unusual. The course of the disease was very aggressive, and the patient died 3 days after admission.

Blast cell and granulocyte production in human leukemia: pathophysiological concepts based on computer simulation using discrete modeling techniques.

The granulocyte production of two patients suffering from leukemia was studied extensively by means of the tritiated thymidine method of cellular kinetics. The data obtained (1-h labeling index, pattern of cell labeling, labeling intensity, as well as other conventional parameters of bone marrow and blood) were used to develop a computer model (GPSS-language) to fit the observations. From these models, it was concluded that patients with leukemia may have an abnormal granulopoiesis, characterized by a high degree of inefficiency (premature cell death, skipping of divisions with undisturbed maturation). However, the underlying mechanisms may be quite different. While it cannot be excluded that in acute myelocytic leukemia there is a stem and/or progenitor cell pool that is highly ineffective but still capable of feeding some cells into the granulocytic pathway, it is nevertheless possible, as shown in plasma cell leukemia, that the ineffective granulopoiesis may be the result of direct or indirect interaction between the "leukemic" and the "normal" cell clone.

Plasma cell leukemia and hyperviscosity syndrome.

A 56-year-old man had dyspnea, weight loss, hemoptysis, and a generalized bleeding diathesis. Physical examination disclosed hepatosplenomegaly, congestive heart failure, and multiple sites of bleeding. Severe anemia, thrombocytopenia, rouleaux formation, and a leukocytosis with circulating immature plasma cells were observed, along with azotemia, hyperuricemia, and marked elevation of total proteins with a monoclonal IgG kappa spike. The finding of increased serum viscosity confirmed the clinical impression of the hyperviscosity syndrome. Emergency plasma exchange produced marked improvement in the clinical manifestations of hyperviscosity syndrome. Systemic chemotherapy resulted in a partial remission of the disease, but the patient ultimately died of complications of treatment. In this review, we discuss the diagnosis and management of the hyperviscosity syndrome.

IgE plasma cell leukemia successfully treated with combination VAD (vincristine, doxorubicin, dexamethasone) and MP (melphalan, prednisolone) followed by interferon-alpha.

A 69-year-old woman with IgE/kappa plasma cell leukemia (PCL) was treated with a sequential combination of VAD (vincristine, doxorubicin, dexamethasone) and MP (melphalan, prednisolone) followed by interferon-alpha (IFN alpha). A complete remission was achieved for 14 months. Maintenance therapy with IFN alpha has continued for an additional 10 months. IgE PCL is extremely rare. The biological characteristics of the myeloma cells, including surface marker, adhesion molecule, karyotype, DNA analysis, and the response to various cytokines, are presented.

High-output cardiac failure as a presenting symptom of plasma cell leukemia.

A patient presented with high-output cardiac failure and was found to have plasma-cell leukemia. No cause for the cardiac failure was found, and there was no response to treatment with diuretics and thiamine. Chemotherapy for the leukemia resulted in resolution of the cardiac failure, suggesting that the latter was caused by the leukemia--a hitherto unreported association.