Presenting signs and symptoms in multiple myeloma: High percentages of stage III among patients without apparent myeloma-associated symptoms

We studied the medical histories of 127 patients diagnosed with multiple myeloma included in a population-based registry of 945 patients with a paraprotein or multiple myeloma in the region of the Comprehensive Cancer Center West (CCCW). We defined patients not immediately diagnosed or delayed diagnosis as those patients in whom myeloma was not included in the initial differential diagnosis. We found that 37% belonged to this category. These patients more often had symptoms not associated with multiple myeloma. Since a surprising 51% of patients with delayed diagnosis turned out to have stage-Ill myeloma, the physician should be alert to the presence of this disease, despite the fact that co-morbidity may mask its presence.     

Novel use of the Friedewald formula to tackle anomalous HDL-C results in two cases of paraproteinaemia

OBJECTIVES: We report here two cases of paraproteinaemia with one falsely low and the other dubiously high HDL-cholesterol (HDL-C) results. The spurious results seemed to be related to the nature (IgG or IgM) as well as the concentration of the paraproteins. DESIGN AND METHODS: We have been using an alternative approach to estimate the HDL-C concentration by incorporating into it the LDL-cholesterol (LDL-C) value obtained by direct measurements and by back-calculation based on the time-honored Friedewald equation in these atypical specimens as an interim measure, pending optimization of the Roche direct HDL-C plus assay currently in use in our laboratory. RESULTS: This approach is convenient and does not require sophisticated instrumentation. What we are suggesting is to tackle this analytical problems on HDL-C assay due to paraprotein interference by back-calculating the HDL-C values from the measured LDL-C and triglyceride values using the Friedewald formula and is to be regarded as an alternative way to circumvent the interference issue without the need for more elaborative laboratory procedures. We do not intend to advocate screening every single HDL-C value obtained by the direct method for possible analytical errors using this approach. CONCLUSIONS: The back-calculation for HDL-C based on the Friedewald formula is conceived by the authors as an alternative and relatively simple way to estimate the HDL-C value in the presence of paraprotein interference, in particular when there is a minus HDL-C value or when the result is dubiously high. By the same token, when the measured HDL-C and the calculated HDL-C do not match further investigations would be warranted to safeguard the validity of the reported result. It is also, to the best of our knowledge, the first time extra bands due to the IgM and IgG paraproteins were demonstrated in the lipoprotein electrophoresis plate.     

Monoclonal cryoglobulin of IgG (λ) type interacting with transferrin

Summary We report on a 49 year old patient with myeloma who suffered from serious disturbance of the blood circulation in both legs and who had a fatal outcome. Histologically ubiquitous thrombosis of the small arteries and veins of the skin and muscles was found. The formation of these thrombi is probably caused by the intravascular precipitation of a fragment of a monoclonal cryoglobulin of the IgG () type. The peculiarity of this cryoglobulin was its occurrence in vitro in a complex with transferrin and fibrinogen. The interaction between transferrin and paraprotein was verified by chromatography of the serum of this patient on DEAE Sephadex A-50 ion exchanger. The spontaneous precipitation of the cryoglobulin in EDTA plasma was observed immediately after the venipuncture even if the sample was kept at 37°C whereas in the serum a faint precipitate formed only after a period of 48 h storage at 4°C. This precipitate would have been overlooked under routine conditions. It seems that in vitro the interaction between transferrin and paraprotein fragment initiates the formation of the complex which then is completed by fibrinogen in the presence of EDTA.Supported by Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg (We 445)     

Paraproteins in rheumatoid arthritis and related disorders

Summary There is evidence that the prevalence of monoclonal parparoteinaemia is slightly increased in patients with rheumatoid arthritis. The possibility that this may be a marker of the development of later malignancy in such patients is explored. Mortality rates in rheumatoid arthritis are increased although the development of lymphoreticular malignancy contributes only a small percentage of this increase. However, it does seem likely that patients with longstanding severe rheumatoid arthritis are more at risk of developing myeloma or lymphoma if they have a monoclonal paraprotein band in their serum. IgA paraprotein seems to carry a higher risk than IgG whilst other factors such as urinary free light chains and the presence of secondary Sj?gren's syndrome are of less prognostic significance. Similarly a monoclonal para-protein may identify patients with primary Sj?gren's syndrome who have a particular risk of later lymphoma whilst this risk does not appear to extend to patients with systemic lupus erythematosus. Patients with an overlap syndrome do not appear to be at greater risk than those with “pure disease”. The association of other rheumatological disease and paraproteinaemia is briefly discussed.     

抗人IgK和Igλ链单克隆抗体的制备及临床初步应用

用初乳和血清IgA免疫Balb/c小鼠的脾细胞与SP_2/O和NS-1瘤细胞融合,以ELISA双抗原夹心法检测获得5株杂交瘤细胞。其中3株(1D1、5C3、11A7)分泌抗人游离和结合型λ轻链;2株(4G12、14A6)分泌抗人游离和结合型K轻链。4G12与结合型K链反应比游离K链好。这些细胞株在长达1年的培养中仍能稳定分泌特异性单克隆抗体,经液氮冻存10个月后杂交瘤细胞仍保持原有的特性。用固相抗原竞争ELISA试验表明,两个抗K链McAb是针对不同的抗原位点,而3株抗λ链则针对相同的抗原位点。用于检测副蛋白和本周氏蛋白具有很好的特异性和敏感性。把McAb4G12-HRP和1D1-HRP混合,用于检测-EB病毒早期抗原(EA)和壳抗原(VCA)抗体被证明是满意的,同时试用于抗核抗体的检测也获得了初步的结果。     

52-jährige Patientin mit rezidivierendem Schock unklarer Genese, Hämokonzentration und Hypalbuminämie

Zusammenfassung Das systemische Kapillarlecksyndrom ist eine seltene Erkrankung unklarer Ätiologie mit hoher Letalität. Es wurde erstmals 1960 von Clarkson et al. beschrieben. Klinisch ist es gekennzeichnet durch Attacken mit schwerem hypovolämischem Schock, Hämokonzentration und Hypalbuminämie, bedingt durch ein plötzlich auftretendes Kapillarleck mit Austritt von Flüssigkeit und Makromolekülen ins Interstitium. Ein monoklonales Paraprotein kann in zumeist geringer Konzentration im Serum nachgewiesen werden, ohne dass ein Plasmozytom vorliegt.Wir beschreiben den Verlauf einer Patientin, die trotz prophylaktischer Behandlung entsprechend den Erfahrungen aus der Literatur an einer schweren Attacke nach einem Krankheitsverlauf von nur 25 Monaten verstarb. Aus unserer Sicht ist der Einsatz zytostatisch wirksamer Medikamente unabhängig von der Manifestation eines Plasmozytoms bei schwer beeinflussbaren Verläufen zu erwägen.     

应用高效毛细管电泳筛检和鉴定血清中M蛋白

目的:应用毛细管区带电泳法(CZE)和毛细管区带电泳-免疫削减法(IS-CZE)对M蛋白进行筛检和鉴定。方法:运用CZE和琼脂糖凝胶电泳(AGE)分别对532例血清进行M蛋白的筛检;用IS-CZE和免疫固定电泳(IFE)对M蛋白阳性的64例标本进行免疫分型。结果:与AGE相比较,CZE筛检M蛋白的阳性率为96.9%;与IFE相比较,IS-CZE分型的符合率为89.1%;自包被固相抗体能满足试验要求。结论:毛细管区带电泳可高效、快速完成M蛋白的筛检和鉴定,适合临床推广。     

Necrobiotic xanthogranuloma successfully treated with autologous stem cell transplantation

Paraproteinemia can be complicated by necrobiotic xanthogranuloma. Therapeutic options for this progressive disease are limited, and there is no agreement on a single best strategy. We report the case of a patient with a massive periorbital infiltration narrowing the palpebral fissure and blinding the patient. Conventional myeloma therapy had only limited benefit in our patient. However, he was successfully treated with high-dose chemotherapy followed by autologous stem cell transplantation, rendering the patient free of symptoms. This is the first report of autologous stem cell transplantation in a patient with necrobiotic xanthogranuloma.     

Use of Serum Protein Electrophoresis to Monitor Patients with Post-transplant Lymphoproliferative Disorder

Post-transplant lymphoproliferative disorder (PTLD) is a potentially life-threatening complication of solid organ transplantation. Reduction in immunosuppression is usually the first line of therapy and is often curative. While undergoing treatment, imaging studies including MRI and CT scans are commonly used to follow the disease course. Laboratory studies such as lactate dehydrogenase and Epstein-Barr virus PCR can also be used to monitoring disease status. We report here a case of PTLD developing 48 months post renal transplant. A monoclonal protein (M protein) was demonstrated at diagnosis with a corresponding antibody expressed on the malignant lymphocytes. The patient was followed with serial serum protein electrophoreses (SPEP) to monitor his response to therapy. The amount of M protein paralleled the disease course, decreasing as the clinical symptoms improved. This case illustrates the utility of using SPEP to monitor patients with PTLD.