Oligoclonal Bands In Patients Research Articles

Cerebrospinal fluid characteristics of patients presenting for evaluation of pediatric acute-neuropsychiatric syndrome.

This study characterizes cerebral spinal fluid (CSF) indices including total protein, the albumin quotient, IgG index and oligoclonal bands in patients followed at a single center for pediatric acute-neuropsychiatric syndrome (PANS) and other psychiatric/behavioral deteriorations. In a retrospective chart review of 471 consecutive subjects evaluated for PANS at a single center, navigational keyword search of the electronic medical record was used to identify patients who underwent lumbar puncture (LP) as part of the evaluation of a severe or atypical psychiatric deterioration. Psychiatric symptom data was ascertained from parent questionnaires and clinical psychiatric evaluations. Inclusion criteria required that subjects presented with psychiatric deterioration at the time of first clinical visit and had a lumbar puncture completed as part of their evaluation. Subjects were categorized into three subgroups based on diagnosis: PANS (acute-onset of severe obsessive compulsive disorder (OCD) and/or eating restriction plus two other neuropsychiatric symptoms), autoimmune encephalitis (AE), and "other neuropsychiatric deterioration" (subacute onset of severe OCD, eating restriction, behavioral regression, psychosis, etc; not meeting criteria for PANS or AE). 71/471 (15.0 %) of patients underwent LP. At least one CSF abnormality was seen in 29% of patients with PANS, 45% of patients with "other neuropsychiatric deterioration", and 40% of patients who met criteria for autoimmune encephalitis. The most common findings included elevated CSF protein and/or albumin quotient. Elevated IgG index and IgG oligoclonal bands were rare in all three groups. Elevation of CSF protein and albumin quotient were found in pediatric patients undergoing LP for evaluation of severe psychiatric deteriorations (PANS, AE, and other neuropsychiatric deteriorations). Further studies are warranted to investigate blood brain barrier integrity at the onset of the neuropsychiatric deterioration and explore inflammatory mechanisms.

The Effect of Oligoclonal Bands in Patients with Multiple Sclerosis

The Effect of Oligoclonal Bands in Patients with Multiple Sclerosis

The Clinical Significance of Oligoclonal Bands in Patient with Multiple Myeloma

To investigate the clinical value of oligoclonal bands (OB) in patients with multiple myeloma (MM). The laboratory test and clinical data of 624 newly diagnosed MM patients admitted to Blood Diseases Hospital of Chinese Academy of Medical Sciences from January 2013 to December 2019 were retrospectively analyzed, including 30 patients with OB, and the clinical characteristics, treatment effects and survival of OB and non-OB patients were analyzed and compared. OB occurred in 11.8% (22/187) of patients who received autologous stem cell transplantation(ASCT) and only 1.8% (8/437) of patients who did not receive ASCT (P=0.000). The median time to the appearance of oligoclonal bands was 3.2(0.6-10.5) months after transplantation. The M protein types of oligoclonal bands mainly include IgG κ, IgG λ, IgM λ and λ light chains. In the presence of oligoclonal bands, 90% of patients were evaluated as complete remission (CR) and above. There were no statistically significant differences in disease stage, tumor burden, and genetic abnormalities between OB and non-OB patients. Among the all patients, the prognosis of OB patients was significantly better than that of non-OB patients, and OB patients showed deeper disease remission (significantly higher CR rate, MRD negative rate, and longer MRD negative duration). Among patients who underwent ASCT, OB patients showed earlier immune recovery, but the depth of treatment response and survival outcomes were similar between OB and non-OB patients, it was no statistically difference. Although OB patients showed earlier immune reconstitution, this did not translate into better survival, suggesting that the better prognosis of OB patients was mainly related to deeper and durable remission rather than early immune reconstitution. Further analysis in patients who received ASCT and obtained MRD negative indicated that there was no additional survival benefit in patients with OB. The better prognosis of OB patients may be related to the deeper treatment response, but not to the early immune reconstitution. The appearance of OB is only a sign of deep remission and early immune reconstitution in patients, it cannot be translated into survival benefit of MM patients.

Serum and Urine Protein Electrophoresis and Serum-Free Light Chain Assays in the Diagnosis and Monitoring of Monoclonal Gammopathies.

Laboratory methods for diagnosis and monitoring of monoclonal gammopathies have evolved to include serum and urine protein electrophoresis, immunofixation electrophoresis, capillary zone electrophoresis, and immunosubtraction, serum-free light chain assay, mass spectrometry, and newly described QUIET. This review presents a critical appraisal of the test methods and reporting practices for the findings generated by the tests for monoclonal gammopathies. Recommendations for desirable practices to optimize test selection and provide value-added reports are presented. The shortcomings of the serum-free light chain assay are highlighted, and new assays for measuring monoclonal serum free light chains are addressed. The various assays for screening, diagnosis, and monitoring of monoclonal gammopathies should be used in an algorithmic approach to avoid unnecessary testing. Reporting of the test results should be tailored to the clinical context of each individual patient to add value. Caution is urged in the interpretation of results of serum-free light chain assay, kappa/lambda ratio, and myeloma defining conditions. The distortions in serum-free light chain assay and development of oligoclonal bands in patients' status post hematopoietic stem cell transplants is emphasized and the need to note the location of original monoclonal Ig is stressed. The need for developing criteria that consider the differences in the biology of kappa and lambda light chain associated lesions is stressed. A new method of measuring monoclonal serum-free light chains is introduced. Reference is also made to a newly defined entity of light chain predominant intact immunoglobulin monoclonal gammopathy. The utility of urine testing in the diagnosis and monitoring of light chain only lesions is emphasized.

Cerebrospinal fluid oligoclonal bands in Neuroborreliosis are specific for Borrelia burgdorferi.

Cerebrospinal fluid (CSF) oligoclonal bands (OCB) occur in chronic or post-acute phase of inflammatory diseases of the central nervous system. To determine whether CSF OCB in patients with neuroborreliosis (NB) are specific for borrelia burgdorferi senso lato. We performed isoelectric focusing followed by immunoblotting in CSF of 10 NB patients and 11 controls (7 patients with multiple sclerosis, 2 patients with neuromyelitis optica spectrum disease, 1 patient with dementia and 1 patient with monoclonal gammopathy). Immunoblotting was performed using an uncoated as well as a borrelia antigen pre-coated nitrocellulose membrane (NCM). OCB were counted by visual inspection and photometric analysis. OCB were compared between uncoated und pre-coated NCM both in the NB and control group. For validation purposes inter-assay precision was determined by calculating the coefficient of variation (CV). Borrelia-specific OCB were found in the CSF of 9 NB patients and in none of the control subjects resulting in a sensitivity of 90% and a specificity of 100%. Number of NB specific OCB were 11±7 bands by photometric analyses compared to 9±5 bands by visual inspection. Validation experiments revealed an inconsistent inter-assay precision between visual and photometric analyses (NB uncoated: visual 28% versus photometric 14%, control subject uncoated: visual 16% versus photometric 24%). In CSF samples with positive OCB, Borrelia-specific bands were detected in almost all NB patients and in none of the control subjects. Inconsistent inter-assay precision may be explained by a poor comparability of visual and photometric approach.

Clinically isolated syndrome, oligoclonal bands and multiple sclerosis

AbstractObjectiveClinically isolated syndrome (CIS) is a first demyelinating episode targeting the central nervous system. It can later fulfill the diagnostic criteria for multiple sclerosis (MS) or remain as a single event with no further clinical or paraclinical evidence of disease. Given the difficulty of predicting the long‐term course of the disease at the moment of the first episode, we intended to examine clinical and laboratory features associated with MS conversion, underlining the prognostic value of oligoclonal bands (OCBs) determination.MethodsWe analyzed patients with an episode compatible with CIS (not fulfilling the 2010 McDonald criteria) as the first manifestation of MS (according to the same criteria), observed in our MS clinic (n = 82).ResultsFrom our cohort, 76.8% of patients converted to MS. OCBs were present at baseline in 68.0% of MS patients, but also in 73.7% of stable CIS patients (P = .77). After stratification of the results by treatment, there was also no statistically significant association between the presence of OCBs and conversion to MS. Additionally, positive OCBs did not predict earlier conversion to MS.ConclusionsOur study outlines the high prevalence of positive OCBs in patients with CIS, even in those who, until now, do not fulfill the 2010 diagnostic criteria for MS. This raises questions about the early assumption of MS diagnosis based on OCB status. A very hasty diagnosis could result in chronic treatment initiation and a possibly lifelong stigma in patients who might never develop new lesions or have a second attack.

Impact of Autologous Stem Cell Transplantation on the Incidence and Outcome of Oligoclonal Bands in Patients with Light-Chain Amyloidosis

The emergence of oligoclonal bands (OB) in patients with multiple myeloma achieving a complete remission (CR) after autologous stem cell transplantation (ASCT) and the use of novel agents is a well-recognized event. The presence of OB is associated with favorable outcome. However, the emergence of OB in light-chain (AL) amyloidosis has never been investigated. The aim of the study was to determine the incidence, natural history, and prognostic impact of OB in 50 patients with AL amyloidosis who achieved at least a partial response either after upfront ASCT (20 patients [40%]) or after conventional treatment in patients ineligible for transplantation (30 patients [60%]). OB were observed in 60% of the patients, with IgG-kappa (30.7%) the most frequently detected isotype. This phenomenon was more prevalent in patients achieving CR than those in other response categories (88% versus 32%, P = .0001). The landmark analysis at 1 year after diagnosis demonstrates a significantly longer progression-free survival and an improvement trend in overall survival (P = .04 and P = .06, respectively). This prognostic impact was also observed in patients who achieved CR and in patients with more advanced stage. In summary, this is the first report of OB in patients with AL amyloidosis. Although its biological meaning remains unclear, it could reflect a more robust humoral immune response.

Clinical significance of the number of oligoclonal bands in patients with clinically isolated syndromes

CSF oligoclonal bands (OCBs) in patients with clinically isolated syndromes (CIS) are a risk factor for clinically definite multiple sclerosis (CDMS). We aimed to address the relevance of the number of OCBs in the prognosis of CIS patients. 219 CIS patients were included in the study, and 42% of them developed the disease during follow-up (median: 5.04years). Patients with a high number of CSF OCBs (third quartile, 8–12 OCBs) had 2.5-fold increase in CDMS risk, while no further increase in the HR of disease was observed for patients with more than 12 OCBs. The results did not change after adjustment for additional correlates of CDMS development. This association may be due to the epitope-spreading phenomenon and may reflect the stage of the disease at the time of the examination.

Prognostic Implications of Oligoclonal Bands in Patients with Multiple Myeloma:Its Development per Se did Not Confer the Prologation of Survival

Background: Multiple myeloma (MM) is characterised by the production of monoclonal immunoglobulin (Ig) and clonal proliferation of neoplastic plasma cells in bone marrow. The emergence of oligoclonal bands (OB) in serum and/or urine immunofixation electrophoresis (IFE) that is different to that observed at diagnosis has been reported with varying frequency in patients with stem cell transplantation (SCT) or favourable response to chemotherapy, although its prognostic relevance remains unclear. Here, we retrospectively analysed clinical records and results serial serum and/or urine IFE to determine the frequency, clinical characteristics and prognostic impact of OB that developed after treatment. We also analysed the effects of OB on the results of free light chain (FLC) assay that may affect the stringent CR (sCR) criteria proposed by the IMWG.Patients: We retrospectively reviewed 180 patients with MM admitted to the Department of Hematology/Oncology at Kameda Medical Center, Kamogawa, Japan, from January 2006 to May 2014.Seventeen patients were excluded from the analysis due to lack of appropriate follow-up data.Method: An OB was defined as the presence of a serum and/or urine IFE monoclonal spike that was different from the original myeloma protein in heavy and/or light chains, as well as a different IFE migration pattern. IFE was performed at least every three months after obtaining very good partial response (VGPR) and then until the disease progression or relapse was confirmed. Overall survival (OS) and progression free survival (PFS) were analyzed in 173 MM patients by the Kaplan–Meier method, and differences between the curves were calculated by two-sided log-rank test. Free light chain (FLC) and minimal residual disease measurement by multicolour flowcytometory (MFC) were performed to evaluate the response to treatment.Results: Myeloma response more than VGPR and CR were achieved in 87 (53.3%) and 54 (33.1%) patients, respectively. None of the patients with less than PR developed OB, and OB developed in 36.3% (12/33) and 51.9% (28/54) of the patients with VGPR and CR, respectively. Among the 30 patients who received SCT, 18 patients (60.0%) developed OB, whereas only 12 of 133 patients who did not receive SCT developed OB. The emergence of OB was significantly higher in patients receiving SCT (P < 0.001). The median PFS of the patients with and without OB were 79.4 months and 19.2 months (P = 0.028), respectively, and those of OS did not reached and 41.1 months (P < 0.001), respectively (Figure 1). However, if patient response was limited to CR, median PFS and OS of patients with and without OB were not significantly different between the two groups (79.4 months vs. 80.1months, respectively, P = 0.646; and not reached and not reached, respectively, P = 0.776; Figure 2). OB was observed in 60% of patients after SCT, and in 36.6% of patients more than VGPR without SCT (P<0.001). In the patients who received SCT, the presence of OB was not associated with either PFS or OS (20.0 months vs 44.7 months, P=0.543 and not reached vs not reached, P= 0.739, respectively; Figure3). We also analyzed the association between residual myeloma cells assessed by the MFC in the patients who achieved CR according to the development of OB. Although the patients with OB showed slightly lower levels of residual myeloma cells than those without OB (2.49 x10-4vs 4.15 x10-4), there was no significant difference between the two groups (P= 0.054). As the presence of OB may result in an abnormal serum FLC kappa/lambda ratio, we examined the association of FLC kappa/lambda ratio and development of OB in 28 patients who achieved CR. Abnormal FLC kappa/lambda ratio was observed in 10 (35.7%) and 4 (15.3%) patients with and without OB, respectively, among those with CR (P = 0.118). Conversely, OB was detected in 10 of the 14 patients with an abnormal FLC ratio (71.4%) versus 18 of 40 (45.0%) with a normal serum FLC ratio (P = 0.164) among those with CR.Conclusions: In conclusion, we showed that the emergence of OB occurred exclusively in patients with favourable myeloma responses (more than VGPR) and was associated with prolonged survival. Patients with OB appeared to have fewer residual myeloma cells compared to those without OB. However, its development did not confer an additional survival benefit among the patients who achieved CR. In addition, it is possible that the emergence of OB affects the sCR response criteria proposed by the IMWG. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Oligoclonal bands in patients with multiple myeloma: its emergence per se could not be translated to improved survival.

The emergence of oligoclonal bands (OB) has been reported in patients with multiple myeloma (MM) after stem cell transplantation (SCT) or successful chemotherapy. However, their clinical relevance remains unclear. We reviewed the clinical records of MM patients from January 2006 to May 2014. Treatment response was evaluated by International Working Group (IMWG) criteria. Serum immunofixation tests were performed at least every 3 months if the patient achieved more than very good partial response (VGPR). Free light chain (FLC) and minimal residual disease measurement by multicolor flow cytometry (MFC) were performed to evaluate the response to treatment. Among the 163 patients included in the study, 40 developed OB. Detection rates of OB in patients with complete response (CR), VGPR and partial response (PR) or less were 51.8, 36.3 and 0%, respectively. Patients with OB showed better progression-free survival (PFS) and overall survival (OS) rates than those without OB (P = 0.028 and P < 0.001, respectively). However, if the patients were limited to ≥VGPR or CR, development of OB did not affect PFS (P = 0.621 and P = 0.646, respectively) or OS (P = 0.189 and P = 0.766, respectively). OB was observed in 60% of patients after SCT, and in 36.6% of patients with more than VGPR without SCT (P < 0.001). Patients with OB tended to have less minimal residual disease than those without OB (P = 0.054) and its presence may affect the stringent CR criteria. In conclusion, the emergence of OB was seen exclusively in patients with favorable responses, but its emergence per se could not be translated to improved survival.

The identity of oligoclonal bands in patients with multiple sclerosis

evidence for B cell antigen presentation during EAE and MS, we chose to explore the role of antigen presentation by myelin antigen-specific B cells. We hypothesized that antigen presentation by cognate antigen-specific B cells during EAE is sufficient to support CD4mediated neuroinflammation. We induced active EAE using MOG protein or peptide immunization and induced passive EAE using encephalitogenic CD4 T cell lines in mice expressing MHCII by DCs alone and those in which B cells are deficient in MHCII expression. Further, we examined mice expressing MHCII by B cells alone with or without an increase in precursor frequency for MOG-specific B cell receptors. We found that maximal disease in protein-induced active EAE models is dependent upon B cell antigen presentation. Further, increasing the precursor frequency of MOG-specific B cells, but not the addition of soluble MOG-specific antibody, is sufficient to facilitate passive EAE in mice expressing MHCII by B cells alone. This is the first direct demonstration in vivo that B cells can serve as the sole APC and coordinate CD4 T cell autoreactivity to myelin antigens during EAE. These data support a model in which expansion of antigen-specific B cells during CNS autoimmunity amplifies cognate interactions between B and CD4 T cells and independently drives neuro-inflammation at later stages of disease.

Natural history and prognostic impact of oligoclonal humoral response in patients with multiple myeloma after autologous stem cell transplantation: long-term results from a single institution

The emergence of an oligoclonal humoral response, resulting in the appearance of a different serum M-protein to that observed at diagnosis is a well-recognized event after autologous stem cell transplantation in multiple myeloma in complete response, and it has been considered to be a benign phenomenon. The aim of the present study was to investigate the incidence, biological characteristics and prognostic value of the oligoclonal bands in patients with myeloma who underwent autologous transplantation at our institution in the last 18 years. We proceed with a retrospective systematic review of all serum and urine immunofixation studies performed in the 211 patients with multiple myeloma who underwent melphalan-based autologous transplantation. Oligoclonal bands were observed in 34% of the patients, with a significantly higher prevalence with the use of novel agents versus conventional chemotherapy in induction (63% vs. 22%; P=0.0001). The incidence of oligoclonal bands was most frequent in non-IgG isotype, particularly in light chain only myeloma. The oligoclonal phenomenon was almost exclusive to patients in complete remission compared to other degrees of response (87% vs. 13%; P=0.0001), and lasted for a median of 1.35 years, persisting during follow up in all patients except in those who relapsed. In prognostic terms, the presence of oligoclonality resulted in a significantly longer progression-free and overall survival. Patients with oligoclonal humoral response lasting for more than one year after transplantation had a significantly longer clinical progression-free and overall survival than those with shorter duration (P=0.008 and P=0.0001, respectively), likely reflecting the importance of a robust humoral immune response.

Characterization and Prognostic Impact of Oligoclonal Humoral Response in Patients with Multiple Myeloma After Autologous Stem-Cell Transplantation: Long-Term Results From a Single Institution

Abstract 3948 Background:Multiple myeloma (MM) is characterized by the production of a monoclonal immunoglobulin of constant isotype and light chain restriction due to the clonal proliferation of neoplastic plasma cells. The optimal treatment in patients younger than 65 years includes induction therapy followed by high- dose therapy/autologous stem-cell transplantation (ASCT). On the other hand, the emergence of oligoclonal bands is a benign phenomenon frequently associated with complete remission (CR) after ASCT. The aim of the present study was to investigate the incidence, biological characteristics, duration and prognostic value of the oligoclonal bands in patients with MM who underwent ASCT at our institution in the last 18 years. Methods:Two-hundred and eleven patients underwent melphalan-based ASCT at our institution from March 31st, 1994, to December 27th, 2011. Of these, 199 patients (109M/90F; median age 55 years, range 25 to 70) who achieved at the least a partial response (PR) after ASCT are the basis of this study. Initial baseline demographics, clinical and laboratory data, and information concerning treatment and follow up were collected. No patient was lost to follow-up. The median follow-up for alive patients was 4.7 years (range 4 months to 18 years). A retrospective systematic review of all serum and urine immunofixation (IFE) studies was carried out. An oligoclonal humoral response was defined as the presence of a serum and/or urine IFE monoclonal spike different from the original myeloma protein either in heavy and/or light chains, as well as at IFE migration pattern. Response, relapse, and progression were defined according to European Blood and Marrow Transplantation (EBMT) criteria. Results:Median PFS was 87 out of the 199 patients (43.7%) achieved CR. The median progression-free survival (PFS) and overall survival (OS) after ASCT were 3.2 and 6.6 years, respectively. Oligoclonal bands were observed in 34% of the patients, but with different prevalence according to the use of novel agents vs. conventional chemotherapy (63% vs. 22%; p=0.0001) in induction. This phenomena was almost exclusive of patients in CR compared to other degrees of response (92% vs. 8%; p=0.0001). Five patients with IgA and five with Bence Jones MM were the only ones being in PR and having a very transient coexistence of the original M-protein with IgG oligoclonal bands in serum. The median number of different isotypes accounting for oligoclonal humoral response was 2 (range 1 to 6) and this phenomena lasted for a median of 1.35 years. Serum bands were more frequent (75.4%) than those in urine and the main involved serum heavy-chain was IgG (73%), with almost the same distribution kappa/lambda. Kappa light-chain was the predominant isotype in urine (60%).In the overall series, all the oligoclonal bands disappeared before serological and clinical progression, except in two settings. First, patients (n=6) who progressed with extramedullary disease with soft-tissue plasmacytomas without significant bone marrow or serological involvement, had persistent oligoclonal bands for several months. Second, patients with Bence Jones MM (n=6), showing urine M-protein progression at the time of relapse had also a transient persistence of serum oligoclonal bands.The presence of oligoclonal bands after ASCT resulted in a significantly longer PFS (p=0.004). This translated in a significantly longer OS in patients with this humoral oligoclonal response (median OS not reached vs. 5.58 years; p=0.003) (Figure 1). An oligoclonal humoral response stable more than one year after ASCT was associated with a significantly longer clinical PFS and OS than those with shorter duration (p=0.008 and p=0.0001, respectively). Of note, the estimated survival of patients with oligoclonal bands lasting for more than one year at 10 years is 70% (Figure 2). In contrast, the PFS ad OS of patients with oligoclonal bands lasting for less than one year were similar to those who never developed this phenomena. Conclusions:The emergence of oligoclonal bands after ASCT is a prognostic factor and it is usually observed in patients in CR. They reflect a robust humoral immune response and consequently an immune system reconstitution. Duration of this humoral response is also associated with a significant survival prolongation. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Clinical Significance of Oligoclonal Bands in Patients with Multiple Myeloma after Autologous Stem Cell Transplantation

Clinical Significance of Oligoclonal Bands in Patients with Multiple Myeloma after Autologous Stem Cell Transplantation

Serum free light chains and oligoclonal bands in patients with multiple myeloma and autologous stem cell transplantation

To establish stringent complete remission (SCR) in patients with multiple myeloma (MM), it is currently recommended to obtain a normal serum free light chains (sFLC) ratio. The appearance of serum oligoclonal bands (OB) after autologous stem cell transplantation (ASCT) is considered a favorable prognostic factor. The objective of this study was to examine sFLC for assessing SCR in patients with MM, and ASCT with OB. We also examined how capillary electrophoresis (CE) compares with agarose gel electrophoresis (Aga) in identifying oligoclonal bands. Out of 238 patients studied in our institution between April 1992 and December 2008 a serum protein electrophoresis (SPE) was performed by means of CE and sFLC determination on 37 patients with MM in complete remission (CR), ASCT and OB presence were assigned by conventional Aga electrophoresis and IF. Statistically significant differences (SSD) were found when comparing CE vs. Aga, regarding BO visualization in SPE, favoring the latter. In connection with sFLC, the group of patients with an abnormal ratio presented elevated values in the γ-globulin zone of the SPE, whereas the group of patients with a normal ratio of sFLC presented with normal values resulting in SSD between the groups. It is essential to perform immunofixation to certify the presence of OB, especially if CE is used as it is difficult to distinguish them using this method. A normal sFLC was observed in most of the patients with OB and normal values of the SPE γ-globulin zone. The above-mentioned information might demonstrate a limitation of sFLC test in SCR evaluation for patients with MM, ASCT and CR if OB has been detected.

Oligoclonal Bands In Patients with Multiple Myeloma In Complete Remission After Induction Chemotherapy: Strong Association with the Use of Novel Agents

AbstractAbstract 2945 Background:The emergence of oligoclonal bands is a well recognized event after autologous stem cell transplantation in multiple myeloma (MM). These atypical serum immunofixation (IFE) patterns are associated with good prognosis, likely due to a durable immune reconstitution. They can appear with novel immunomodulatory drugs such as lenalidomide, but its prevalence with other induction treatments has not been reported. Aims:To determine the prevalence of serum and/or urine immunoglobulin oligoclonality in patients with MM in CR after primary therapy with cytotoxic agents or with new induction chemotherapy regimens incorporating novel drugs up-front. Methods:Thirty-three patients (15M/18F; median age at diagnosis 59 years, range 25 to 89) with MM in CR after different induction regimens were studied. Initial baseline demographics, clinical and laboratory data, treatment and follow-up were collected. An oligoclonal band was defined as the presence of a serum and/or urine IFE monoclonal spike different either in heavy and/or light chain component from the original myeloma protein. Results:The initial clinical and laboratory findings as well as the induction treatments are shown in the table 1. Eighteen patients (54.5%) received induction with conventional chemotherapy and 15 (45.5%) with novel agents. In the latter group, the induction regimen was based on combinations of glucocorticoids with lenalidomide (26.7%), thalidomide (26.7%), bortezomib (33.3%) or bortezomib plus lenalidomide (13.3%). In the overall series, 11 out of the 33 patients (33.3%) developed an oligoclonal band. These abnormal bands observed in the IFE pattern lasted from 2.2 to 55.7 months (median 11.5 months).Four patients (36.4%) had a fluctuating oligoclonal pattern during their follow-up while the remaining showed a single oligoclonal immunoglobulin. The most frequent isotype seen in oligoclonal bands was IgG-κ (72.7%), as it was previously described after ASCT. In the group treated with cytotoxic agents, the prevalence of oligoclonal bands was observed in 2 patients (11.1%), both of them had been treated with cyclophosphamide and dexamethasone. In contrast, induction with novel drugs resulted in 9 out of 15 patients (60%) developing oligoclonal bands in serum and/or urine (chi-square test 2-sided, p=0.003). Interestingly, five patients with oligoclonal humoral response have already relapsed (45.5%). In four of them, relapse was coincident with the disappearance of the previous oligoclonality, while in the remaining case the disappearance of the oligoclonality preceded relapse in six months. Conclusions:This is the first report showing a significantly different frequency of oligoclonal bands in patients with MM in CR after conventional cytotoxic therapy versus induction incorporating novel agents. This difference is likely due to a greater antimyeloma effect, a strongest immune reconstitution resulting from the effect of novel drugs, or both. With the progressive use of these drugs, the CR rate and consequently the proportion of patients who develop an oligoclonal immune response with oligoclonal bands will likely increase. However, the mechanism associated with the emergence of the oligoclonal bands as well as its prognostic impact is still unknown and deserve further investigation.Table 1Patient characteristicsVariableTotal group (n=33)Cytotoxic drugs group (n=18)Novel drugs group (n=15)Median age, y (range)59ü(25–89)57.9ü(25–89)61.4ü(47–79)Male/female, n15/188/107/8Heavy-chain component (%)IgG27.316.740IgA27.327.826.7Only light chains30.338.920IgD12.116.76.7IgM306.7Light-chain (%)κ48.55066.7λ51.55033.3 Disclosures:Cibeira:Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Rosiñol:Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Blade:Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Emergence of oligoclonal bands in patients with multiple myeloma in complete remission after induction chemotherapy: association with the use of novel agents

The emergence of oligoclonal bands is associated with a favorable outcome after autologous stem cell transplantation in multiple myeloma. The aim of this study was to determine the prevalence of immunoglobulin oligoclonality in 33 patients with multiple myeloma in complete remission achieved with primary therapy with either cytotoxic agents (n = 18, 54.5%) or new induction regimens incorporating novel drugs (n = 15, 45.4%). Eleven patients (33.3%) developed oligoclonal bands. In the group treated with novel agents, this oligoclonal immune response was observed in 60% (9 of 15) of the patients versus only 11.1% (2 of 18) of those given cytotoxic therapy (P = 0.003). This is the first report showing a different frequency of oligoclonal humoral response in patients in complete remission achieved after conventional cytotoxic therapy versus induction incorporating novel agents. This difference could be due to a higher antitumor effect associated with the use of novel drugs, a stronger immune reconstitution, or both.

Abnormal serum free light chain ratio in patients with multiple myeloma in complete remission has strong association with the presence of oligoclonal bands: implications for stringent complete remission definition

AbstractThe prevalence of an abnormal serum free light chain (FLC) ratio in 34 patients with multiple myeloma in complete response (CR) after hematopoietic stem cell transplantation was studied. Fourteen of 34 patients (41.2%) showed an abnormal FLC ratio. The frequency of abnormal FLC ratio in patients with or without oligoclonal bands was 72.7% versus 26%, respectively (P = .023). The median value of FLC ratio was 2.55 (95% confidence interval, 1.89-3.20) in patients with oligoclonal bands versus 0.87 (95% confidence interval, 0.70-1.04) for those with no oligoclonal bands (P = .011). This is the first report showing that the presence of oligoclonal bands in patients with multiple myeloma in CR frequently results in an abnormal FLC ratio. Because an oligoclonal immune response is associated with a good outcome, our results question the current definition of stringent CR and support that the prognostic impact of oligoclonal bands should be also assessed on multivariate analysis.

Multimodal evoked responses compared to CSF occurrence of oligoclonal bands in patients with multiple sclerosis

Multimodal evoked responses compared to CSF occurrence of oligoclonal bands in patients with multiple sclerosis

Agarose isoelectric focusing of unconcentrated CSF and radioimmunofixation for detection of oligoclonal bands in patients with multiple sclerosis and other neurological diseases

Agarose isoelectric focusing (AIEF) of concentrated CSF was compared with AIEF of unconcentrated CSF and subsequent immunofixation with radiolabeled antihuman IgG Fc fragment antiserum and autoradiography for the demonstration of oligoclonal bands in CSF from 287 neurological patients. Oligoclonal bands were demonstrated by AIEF in 98% of 43 patients with multiple sclerosis, 72% of 18 patients with infectious CNS diseases, and 23% of 226 patients with other neurological diseases. The corresponding figures obtained with AIEF of unconcentrated CSF and radioimmunofixation were 98%, 67%, and 21%, respectively. In 15 of the patients, oligoclonal bands were demonstrated in CSF and serum by both techniques. They are both useful alternatives for the demonstration of oligoclonal bands in CSF, and the method for unconcentrated CSF can be safely applied when only small CSF volumes are available. The oligoclonal IgG pattern obtained by AIEF was not influenced by concentration of CSF by ultrafiltration and subsequent dilution to the original IgG concentration, nor by storage for 6 months.