Antibodies contained in "M" component of some patients with multiple myeloma are directed to food antigens?

Multiple myeloma is malignant disease that is characterized in most patients, by the presence in the serum of monoclonal gamma globulins, which in agarose gel after electrophoresis appear as protein band of restricted mobility, “M” component.

The aim of this study was to determine are the antibodies contained in M-component directed to some antigen chronically present in the organism, to some of food antigens.

Seventeen patients with secretory plasmacytoma were included in the study: eight of them had IgG(kappa), three had IgG(lambda), and one had biclonal IgG(kappa) and IgA(kappa), while two had IgA(kappa), the other two IgA(lambda) and one IgM(lambda) as paraproteins. M-proteins were detected analyzing patients’ sera by agarose gel electrophoresis in 0.09 M barbital buffer. The each M-protein was confirmed by immunotyping (immunofixation) with corresponding antihuman antibodies directed to heavy or light chains of immunoglobulins. After the patients serum separation on agarose gel by electrophoresis, fresh 0.4% solution of crude gliadin (Sigma) in 1% SDS was put over the slides for immunoprecipitation.

Preliminary results showed the interaction of gliadin with patient's serum proteins present in the protein fraction of the same mobility as it was the mobility of the M-component, in 6 from 17 investigated sera.

These results are the first reporting that in sera of some patients with multiple myeloma antibodies from M-component could be directed to some of gliadin antigens.

As the serum antigliadin immunoreactivity is present in patients with gluten intolerance, celiac disease, it could be of importance to elucidate is the multiple myeloma more severe form of gluten intolerance than celiac disease.     

A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival.

The presenting clinical features of 71 patients with multiple myeloma were correlated with myeloma cell mass (myeloma cells X 10(12)/m2 of body surface area) determined from measurements of monoclonal immunoglobulin (M-component) synthesis and metabolism. Bivariate correlation and multivariate regression analyses showed that myeloma cell mass could be accurately predicted from A) extent of bone lesions, B) hemoglobin level, C) serum calcium level, and D) M-component levels in serum and urine. Analyses of response to chemotherapy and survival indicated significant correlation with measured myeloma cell burden. The results were synthesized to produce a very reliable and useful clinical staging system with three tumor cell mass levels (Table 7). For clinical research purposes, multivariate regression equations were developed to predict optimally the exact myeloma cell mass. Thus, initial staging can be quantitatively related to followup using tumor cell mass changes calculated from changes in M-component production. Use of the clinical staging system sould provide better initial assessment and followup of individual patients, and should lead to improved study design and analysis in large clinical trials of therapy for multiple myeloma.     

Malignant transformation of monoclonal gammopathy of undetermined significance: cumulative incidence and prognostic factors.

The cumulative incidence of malignant transformation was studied in 88 patients with monoclonal gammopathy of undetermined significance (MGUS) that had a complete prospective follow-up. At a median follow-up of 6.75 years, 10 patients developed multiple myeloma (MM) (11.4%) and 2 developed immunocytoma (2.3%). The cumulative incidence of malignant transformation was 9.1, 21.3, 38 and 48.3% at 5, 10, 15 and 20 years, respectively. In univariate analysis on 102 MGUS patients, M-component level, bone marrow plasma cell percentage and kappa light chain correlated significantly with the development of a malignancy (p=0.0289, 0.0265 and 0.0013, respectively). In multivariate analysis, light chain type of M-component and plasma cell percentage had independent prognostic significance. A high-risk (M-component level > 10 g/l and/or plasma cell percentage > 2%) and a low-risk group ( M-component level < 10 g/l and/or plasma cell percentage < 2%) of MGUS patients was identified, which differed significantly in the cumulative incidence of developing a malignancy (p<0.001 for M-component level and p=0.007 for plasma cell percentage). These results imply that high-risk patients should receive a more frequent follow-up, in comparison to low-risk patients.     

Idiotype immunity (natural and vaccine-induced) in early stage multiple myeloma

Idiotypic structures expressed on the myeloma immunoglobulin (Ig) protein (M-component) might be regarded as tumor-specific antigens. Naturally occurring, idiotype-specific type I T-cell immunity has been observed preferentially in patients with early stage myeloma. The idiotypic structures on the clonal myeloma B-cells (B lymphocytes and plasma cells) may serve as targets for active immunization. Vaccination using the autologous monoclonal Ig as a vaccine has conferred resistance to tumor cell challenge in murine myeloma. The autologous myeloma Ig protein was used for immunization in patients with progressive stage I and early stage II multiple myeloma. When the idiotype (emulsified in aluminium phosphate) was used alone for immunization, a weak and transient idiotype-specific T-cell response was observed with no clinical effects. In our second series, the idiotype (in alum) was combined with GM-CSF. In all five patients, a specific T-cell response was induced consisting preferentially of MHC class I restricted (CD8+) T-cells. Ig-specific CD4+ T-cells were also induced. A clinical response ( > 50% reduction of the M-component concentration) was observed in one patient. These results indicate that idiotype-specific T-cell immunity may be induced or enhanced by idiotype Ig vaccination in patients with early stage multiple myeloma, in which the tumor load is relatively low and the immune system is functionally less compromized than in patients with chemotherapy-treated, advanced stages of the disease. The use of GM-CSF seems to be mandatory for the frequency and magnitude of the induced T-cell response. The optimal route, schedule and cytokine combination for idiotype immunization remains to be established.     

Short or Long Survival in Multiple Myeloma. A Simple Method for Determining the Prognosis

Finding prognostic factors in multiple myeloma is a real challenge. Several attempts might be found in the literature for that purpose but the results are not satisfactory. Therefore, in the current retorpective study authors analyzed the potential prognostic value of some laboratory data in 104 patients with multiple myeloma. They found the albumin and M-component ratio being lower than 1 and the initial WBC <4,5 × 10⁹/l correlated strongly with poor prognosis. In addition the low albumin level was not related to albuminuria and that the low WBC was not linked to bone marrow infiltration rate or to antineutrophil antibody formation. On the basis of their experiences authors created an AMWBC score containing A/M and WBC at diagnosis found to be in good correlation to prognosis. Further studies involving more patients are needed to verify the real prognostic value of AMWBC score in multiple myeloma treated with new targeted therapies.     

Bortezomib (Velcade) for progressive myeloma after autologous stem cell transplantation and thalidomide

Twenty-one patients with multiple myeloma, all relapsed after frontline autologous stem cell transplantation and all relapsed again after or resistant to thalidomide (employed as second line treatment) received bortezomib (1.3 mg/m(2) body surface twice weekly for 2 weeks followed by an interval of 10-12 days) without adjunct of steroids as third line therapy. Three patients died of progressive disease during the first 2 cycles with bortezomib. Eighteen patients received at least 2 cycles and were evaluated for response. According to EBMT criteria, two complete (negative immunofixation) and seven partial (reduction of M-component > 50-75%) remissions were achieved (ITT response rate 42.8%). Duration of response lasted from 2 to 14+ months. Grades 3-4 toxicities (thrombocytopenia, leucopenia, peripheral neuropathy and vasculitis) were observed in seven patients, but no patient interrupted the treatment due to side effects. We conclude that bortezomib alone may induce high quality responses as third line salvage therapy with acceptable toxicity in a significant proportion of homogeneously pre-treated myeloma patients with progressive disease after autologous transplantation and thalidomide.     

FND方案治疗难治性、复发性多发性骨髓瘤的初步报告

背景与目的:多发性骨髓瘤(multiplemyeloma,MM)完全缓解率低、复发率高,绝大多数的MM患者经数个联合化疗方案后都会进入难治或复发阶段。本研究旨在观察含氟达拉滨(Fludarabine,Flu)的FND方案(Flu、米托蒽醌、地塞米松)治疗难治和复发性MM的疗效、毒副反应,以期为难治和复发性MM探索出安全有效的治疗方法。方法:将采用VAD方案(长春新碱、吡柔比星、地塞米松)化疗的22例患者作为历史对照组,观察和比较FND组(11例)和VAD组的疗效、达到缓解所需的时间,M蛋白下降50%以上、骨髓涂片中骨髓瘤细胞比例下降80%或占有<5%及血红蛋白上升20g/L的患者例数和时间,化疗后外周血白细胞和血小板的变化,治疗前后血钙、血肌酐、谷丙转氨酶的变化及不良反应。比较FND组治疗前后MM患者血清β2-微球蛋白的变化。结果:FND组的PR率是45.5%(5/11),高于VAD组的22.7%(5/22)(P<0.05),FND组达到PR的中位时间为76天,长于VAD组的68天(P<0.05)。M蛋白下降50%以上、血红蛋白上升20g/L在FND组分别为45.5%(5/11)、54.5%(6/11),均高于VAD组的22.7%(5/11)、18.2%(4/22)(P<0.05)。两组在治疗前后血钙、血肌酐、谷丙转氨酶均无明显变化;FND组治疗后MM患者血清β2-微球蛋白为(1042.8±72.3)μg/L,显著低于治疗前的(2350.2±184.0)μg/L(P<0.05)。FND组白细胞下降最低值为(0.9±0.5)×109/L,明显低于VAD组的白细胞下降的最低值[(2.1±0.6)×109/L](P<0.05);用FND方案治疗MM过程出现发热、咳嗽分别为36.4%(4/11)、45.5%(5/11),高于VAD组(分别为4.5%和9.0%)(P<0.05)。结论:用含Flu的FND方案治疗难治性、复发性多发性骨髓瘤PR率优于VAD组,但FND方案发挥明显疗效的时间较长,对骨髓的抑制较VAD方案显著,无肝肾毒性,是一种有效、安全的治疗难治性、复发性MM的方案。     

Prognostic factors in Waldenstrom's macroglobulinemia: description of the complications during the evolution-preliminary results on 101 patients

Data on clinical features observed in patients with Waldenstrom's macroglobulinemia (WM) during follow-up remain limited. Therefore, we evaluated 860 follow-up procedures in 101 patients. Median age was 66 years and 5-year overall survival 72%, with a median follow-up of 36 months in surviving patients. Sixteen patients presented at diagnosis with two or three cytopenias lasting for at least 3 months (multiple cytopenias [MC]), and MC improved after treatment in eight patients, 4 to 18 months later. MC was observed during at least 6 consecutive months in 23 other patients, 2 to 73 months (median, 24) after diagnosis. MC occurred off-therapy in 12 patients, and on-therapy in 11. Regression occurred in three of the former patients, and in seven of the latter (6 to 24 months after completion of treatment; median, 7). Finally, the 4-year estimated cause-specific cumulative incidence was 40% in the 101 patients. A second malignancy was observed in 11 patients, histological transformation in three, and rapid rise of M-component in only six patients. In conclusion, the present analysis pointed out a high incidence of long lasting MC during the evolution of WM, and a low frequency of rapid rise of M component.     

Possible multiple myeloma dedifferentiation following thalidomide therapy: a report of four cases

Thalidomide has been shown to be effective in approximately 30% of patients with refractory or advanced multiple myeloma (MM). Here we report on 4 cases of patients treated with thalidomide for refractory MM showing dedifferentiation of the neoplasm. In these cases thalidomide treatment despite reduction of M-component-was followed by disease progression and a very poor clinical outcome which was paralleled by bone marrow plasmacytosis showing marked signs of dedifferentiation, inducing us to speculate on a potential role of thalidomide on dedifferentiation of myeloma cells. In our opinion, a possible dedifferentiation of MM should therefore be taken into account in MM patients treated with thalidomide when clinical course deteriorates despite reduction of M-component.     

Prognostic Factors and Therapeutic Results in Multiple Myeloma

Prognostic factors in 68 consecutive patients with myeloma treatedat the National Cancer Center Hospital from 1962 to 1984 wereanalyzed. Median survival time from onset was 100 months forstage I, 72 months for stage II, and 26 months for stage IIIof the Durie and Salmon's clinical staging system. It was 55months in patients with normal renal function and 18 monthsin those with abnormal renal function. All early deaths occurredin patients with stage III disease. Hemoglobin level, bone lyticlegions and presence of Bence Jones protein were also significantprognostic factors. On the other hand, heavy chain as well aslight chain subtypes of monoclonal immunoglobulin (M-component)and M-component production rate did not influence the survivalof myeloma patients. The analysis of chemotherapeutic responsesand survival curves according to the chemotherapy used in thisstudy (alkylating agent vs Vinca-alkaloid plus alkylating agent)did not disclose any significant difference between the twogroups. The overall response rate was 67%. The survival timefrom the initial chemotherapy of responding patients was significantlylonger than that of nonresponders.     

Metabolism of a cholesterol-rich microemulsion (LDE) in patients with multiple myeloma and a preliminary clinical study of LDE as a drug vehicle for the treatment of the disease

Purpose: Previously we have shown that cholesterol-rich microemulsions that bind to LDL receptors have the ability to concentrate in acute myeloid leukemia cells and in ovarian and breast carcinomas. Thus, LDE may be used as a vehicle for drugs directed against neoplastic cells. Indeed, we subsequently showed that when carmustine is associated with LDE the toxicity of the drug is significantly reduced in patients with advanced cancers. The aim of the present study was to verify whether LDE may be taken up by multiple myeloma cells and whether patients with multiple myeloma respond to treatment with LDE associated with carmustine.Methods: A total of 131 consecutive volunteer patients with recently diagnosed multiple myeloma classified as clinical stage IIIA had their plasma lipid profile determined. LDE plasma kinetics were performed in 14 of them. Cell uptake of LDE and the cytotoxicity of carmustine associated with the emulsion were evaluated in a multiple myeloma cell line. A pharmacokinetic study of LDE-carmustine was performed in three patients. Finally, an exploratory clinical study of LDE-carmustine (carmustine dose 180 mg/m² body surface every 4 weeks) was performed in seven untreated multiple myeloma patients.Results: LDL cholesterol was lower in the 131 multiple myeloma patients than in healthy controls and the fractional clearance rate (FCR, in units per minute) in the 14 multiple myeloma patients was twice that in 14 paired healthy control subjects. Moreover, entry of LDE into multiple myeloma cells was shown to be mediated by LDL receptors. Taken together, these findings indicate that LDE may target multiple myeloma. The exploratory clinical study showed that gammaglobulin decreased by 10–70% (mean 36%) after three cycles and by 25–75% (mean 44%) after six cycles. Furthermore, there was amelioration of symptoms in all patients. Cholesterol concentrations increased after treatment, suggesting that the treatment resulted in at least partial destruction of neoplastic cells with receptor upregulation. Side effects of the treatment were negligible.Conclusions: Because it targets multiple myeloma and, when associated with an antineoplastic agent, produces therapeutic responses in patients with fewer side effects, LDE has the potential for use as a drug vehicle in the treatment of the disease. Published online: 22 October 2003     

脊柱浆细胞骨髓瘤中骨桥蛋白的表达及其临床意义

目的:探讨脊柱浆细胞骨髓瘤（plasma cell myeloma,PCM）中骨桥蛋白(osteopontin,OPN)的表达及其与临床病理特征和预后的相关性。方法：选取第二军医大学长征医院19982006年间41例脊柱PCM及14例脊柱良性单纯性骨囊肿手术切除标本;应用免疫组织化学链霉菌抗生物素蛋白过氧化物酶连结（SP）法检测OPN的表达。结果：（1）OPN在脊柱PCM中的阳性表达率为82.93%(34/41) ,而良性骨囊肿中OPN表达均呈阴性 (P<0.01);（2）脊柱PCM中OPN蛋白的表达程度在M蛋白分型和临床分型各组之间差异均有统计学意义（P<0.05）,而与患者轻链分型、病理形态学分级、年龄和性别无显著关联（P>0.05）;（3）OPN表达阳性患者整体生存率明显高于阴性组(P<0.01)。结论：OPN表达阴性脊柱PCM患者的预后可能较差。联合检测OPN和M蛋白分型以及临床分型对脊柱PCM预后判断可能有一定的临床意义。     

Tumor necrosis factor-alpha and interferon-gamma in serum of multiple myeloma patients

The levels of TNF-alpha and IFN-gamma were examined in serum from 32 patients with multiple myeloma and 33 healthy controls using sensitive enzyme-linked immunosorbent assays (ELISA). The detection limits for TNF-alpha and IFN-gamma were 80 pg/ml and 200 pg/ml, respectively. All samples were obtained at the time of diagnosis, before treatment. In sera from 8 of the myeloma patients the TNF-alpha concentrations were above the detection limit with a maximum value of 1.0 ng/ml. Overall, the TNF-alpha levels of the myeloma patients did not differ from the levels of the control group. Detectable amounts of IFN-gamma were found in 17 of the patient sera with 10.7 ng/ml as the top value. In contrast, the control group showed significantly lower s-IFN-gamma levels without detectable amounts in any of the samples (p less than 0.01). High IFN-alpha levels in 4 patients coincided with intercurrent infections but were not accompanied by a parallel increase of the TNF-alpha levels. The TNF-alpha and IFN-gamma values were compared with the serum levels of beta 2-microglobulin, calcium and creatinine, the M-component, the erythrocyte sedimentation rate, the degree of plasma cell infiltration of the bone marrow, the degree of skeletal destructions and with patients survival. No significant correlations could be observed between TNF-alpha or IFN-gamma and these variables of myeloma activity. We conclude that detection of serum TNF-alpha and IFN-gamma levels in multiple myeloma appears to be without any clinical value.     

Immunoglobulin D myeloma--problems with diagnosing and staging (own experience and literature review)

Immunoglobulin D (IgD) myeloma is a rare disease accounting for about 2% of all myelomas. The distinctive features are the predominant occurrence in males and young patients, short survival time, uncertain appearance of M-component in serum electrophoresis, predominance of lambda light chains, frequent renal impairment, hypercalcemia and amyloidosis. The aim of the present study was to show diagnostic difficulties resulting from a variety of non-specific initial symptoms and laboratory findings as well as to compare the staging system proposed by Durie and Salmon with the new risk grouping by Shimamoto. Case histories of 7 patients were analyzed retrospectively. Five of them were diagnosed as IgD multiple myeloma (IgD MM), 1 as non-secretory IgD myeloma and 1 as solitary bone IgD plasmocytoma that evolved to an IgD MM. All patients were staged according to the Durie and Salmon classification and the new risk grouping by Shimamoto. We report diagnostic problems with IgD myeloma in our patients, with special emphasis on non-specific rheumatoidal and neurological symptoms in 1 case. There was a very good correlation of the Japanese classification with the severity of the disease and the risk of death. In conclusion, the initial symptoms of IgD myeloma can be very misleading. Wide differential diagnosis, including autoimmunological disorders of the connective tissue, is necessary. The new Japanese risk grouping seems to be of greater prognostic significance for IgD myeloma than the Durie and Salmon staging system.     

80岁以上高龄老年多发性骨髓瘤11例临床分析

  目的  探讨80岁以上高龄老年多发性骨髓瘤的临床特点。  方法  对本院2000年12月至2013年12月收治的11例80岁以上多发性骨髓瘤患者的临床资料进行回顾性分析。  结果  11例老年多发性骨髓瘤平均年龄为（83.5±3.4）岁，所有患者至少合并2个以上其他基础性疾病。DS分期Ⅲ期为8例、ISS分期Ⅲ期7例。共10例患者接受了个体化的治疗方案，无效进展3例，CR 1例，PR 3例，MR 4例。中位生存28（2~97）个月，1、2、3年生存率分别为72.7%、54.5%、36.3%。因疾病进展导致死亡的6例，疾病稳定期因肺炎死亡3例、AMI死亡2例。  结论  高龄老年多发性骨髓瘤分期较晚，临床表现不典型。治疗应根据患者情况进行个体化的治疗，感染和心血管并发症较常见且是主要死亡原因。经过个体化治疗及有效的支持治疗，生存期得到明显延长，尤其是Ⅰ~Ⅱ期患者经个体化治疗后生存期可接近5年。      

Appropriateness of applying the response criteria for multiple myeloma to Waldenstrom's macroglobulinemia?

Since the presence of an M-component is an essential disease feature in both multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM), the decrease in the M-protein size applied for response in MM is also a crucial criteria for assessing response in WM. However, WM frequently displays lymphoma-like features that should be included in the response criteria.     

Breast cancer after multiple myeloma treatment

Breast cancer is the most common cancer in women. In addition, it is the second leading cause of death after lung cancer.^1,2 The prevalence of epidemiological studies in previous studies is 22%-26%. The risk of mortality due to breast cancer is around 18%.^3,4Multiple myeloma (MM) is a malignant disease of differentiated plasma cells. It is also the most common hematological neoplasm after lymphoma. Thirty five percent of MM patients are under the age of 65, 28% are between 65 and 74 of age and 37% are over the age of 75.⁵ Pathophysiological mechanisms of MM include abnormal plasma cells (myeloma cells) occupying bone marrow, producing monoclonal immunoglobulin (M protein, M-component, and paraprotein) and increased bone destruction.⁶Breast cancer cases diagnosed concurrently with myeloma have been reported in previous case reports. There is also a patient diagnosed with myeloma following breast cancer chemotherapy. In our case, the patient was first diagnosed with MM. And then autologous bone marrow transplantation was performed following 3 cycles of chemotherapy. This presentation is unique, because in literature there is no breast cancer case after myeloma in literature review.     

组蛋白去乙酰化酶抑制剂LBH589对多发性骨髓瘤复发、难治患者骨髓单个核细胞的抑制作用

目的 探讨单用LBH589或联合硼替佐米及地塞米松对多发性骨髓瘤复发、难治患者骨髓单个核细胞的作用.方法 采用四甲基偶氮唑蓝(MTT)法,检测LBH589(15、25、50)nmol/L及50 nmol/L分别联合硼替佐米(15、25)nmol/L及地塞米松(5、10)μmol/L对MM复发、难治患者骨髓单个核细胞作用24,48 h后的细胞增殖影响;采用流式细胞术测定LBH589对MM复发、难治患者骨髓单个核细胞细胞周期及细胞凋亡的影响;用Westernblot测定LBH589(15、25、50 nmol/L)对复发、难治患者骨髓单个核细胞作用24 h后组蛋白H4乙酰化的变化程度.结果 单用LBH589或联合硼替佐米及地塞米松均能够使复发、难治患者骨髓单个核细胞增殖受到抑制,且与药物剂量和时间变化呈正比例.药物作用于MM复发、难治患者骨髓单个核细胞48 h后,G0/G1期细胞逐渐增加,G2/M期及S期细胞则逐渐降低,细胞在G0/G1期发生阻滞,可观察到细胞凋亡现象,且凋亡程度与药物剂量变化呈正比例,三药联合作用均较单药作用更加显著(P均<0.01);Westernblot测定显示,不同浓度LBH589对MM复发、难治患者骨髓单个核细胞作用24 h后组蛋白H4乙酰化的程度上调,且与药物剂量变化呈正比例.结论 LBH589能够使MM复发、难治患者骨髓单个核细胞增殖受到抑制,阻滞细胞周期,促进细胞凋亡,且三药联合对MM复发、难治患者骨髓单个核细胞有加强抗瘤细胞作用.     

Consolidation therapy of multiple myeloma with thalidomide-dexamethasone after intensive chemotherapy.

BACKGROUND: After myeloablative therapy for multiple myeloma, progression-free survival is shorter for disease in partial remission rather than complete remission. In an attempt to induce more frequent complete remission, we assessed thalidomide-dexamethasone in patients with stable partial remission after intensive therapy. PATIENTS AND METHODS: Twenty-one patients with multiple myeloma were identified with disease in stable partial remission after prior intensive therapy. Thalidomide-dexamethasone was given within 15 months after intensive therapy provided myeloma protein production had been reduced by >75% to a constant level for at least 4 months. Thalidomide was begun at a dose of 100 mg each evening, with increments of 50 mg every 7 days to a maximum of 300 mg. Dexamethasone was given concurrently in a dose of 20 mg/m(2) each morning for 4 days on days 1-4, 9-12 and 17-20, with resumption on day 35. The combination was continued for at least 3 months and patients with marked reduction of myeloma were maintained on thalidomide alone until disease progression. RESULTS: Marked further reduction of myeloma by at least 90% occurred in 12 patients (57%), including four (19%) with disease converted to complete remission. Disease has progressed in six of 21 patients, whose median total remission was 22 months. Common side effects of constipation, fatigue, paresthesias and dry skin were mild, dose-related and reversible. CONCLUSIONS: The combination of thalidomide-dexamethasone reduced tumor mass markedly in 57% of patients with stable, residual disease after myeloablative therapy. Such an effect may produce longer disease-free survival and/or preserve tumor sensitivity to later retreatment with previously effective drugs.     

Plasmacytoma. Treatment results and conversion to myeloma.

Forty-six cases of solitary plasmacytoma were reviewed for response to radiation and progression to multiple myeloma. Cases were classified as solitary plasmacytomas of bone (SPB) (32 cases) or extramedullary plasmacytomas (EP) (14 cases). There was an overall 93% response rate of the tumor to radiation therapy: 62% had a complete response after radiation therapy, whereas 31% had a partial response. Conversion to multiple myeloma was influenced by the type of plasmacytoma; 53% of the patients with SPB converting to myeloma versus 36% of the patients with EP. Time from diagnosis to conversion for patients with SPB showed no evidence of plateau, with conversion continuing to occur even after 17 years. The median survival time for patients after conversion to myeloma was 14.5 months and was not affected by time to conversion. Serum protein level, presence of monoclonal gammopathy, and size of primary lesion were of some prognostic significance in predicting conversion to myeloma. Adjuvant chemotherapy did not affect the incidence of conversion but did appear to delay conversion to myeloma. Seven patients in whom multiple sequential solitary plasmacytomas developed formed a distinct subset, with a median time to a second plasmacytoma of 63 months. In three of these patients, conversion to myeloma occurred subsequently. This study supports the idea of EP having a lower incidence of conversion to myeloma and a different natural history from SPB, with SPB likely to be multiple myeloma in evolution.