Differentiation of Multiple Myeloma and MGUS by Cross Validated Differential Proteomic Analysis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3524-3524
Author(s):  
Ross D. Brown ◽  
Larissa Belov ◽  
Cris dos Remedios ◽  
Daniel Sze ◽  
Simon Cooper ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Discriminant Analysis ◽  
Monoclonal Gammopathy ◽  
Prognostic Significance ◽  
Antigen Expression ◽  
Monoclonal Gammopathies ◽  
Specificity And Sensitivity ◽  
Significant Difference ◽  
Consensus Pattern

Abstract The recent development of a standardised proteomic microarray technique, DotScan, has allowed an innovative approach to the investigation of haematological disorders. In this study, mononuclear cells from 49 peripheral blood samples were studied to determine whether the technology could identify a differential consensus pattern of antigen expression for patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). An automated reader simultaneously determined the expression of 82 different cell surface antigens by binding cells to antibodies on microscopic dots on the nitrocellulose-coated region of a microscope slide. The figure illustrates the image from a typical slide. A consensus pattern of antigen expression was analysed in duplicate by cross-validated discriminant analysis and a pilot database of disease groups was accumulated. Cross validated discriminant analysis successfully predicted patients with monoclonal gammopathy (98% success) and a discrete mosaic pattern could differentiate patients with MM who were treated with thalidomide (n=9). As expected, no single antigen could be used to discriminate between multiple myeloma (n=24), MGUS (n=14) and normal controls (n=11). Antigens with the highest ranking for differentiating the monoclonal gammopathies were CD25 (reduced after thalidomide), CD8 and CD57 (high in MM), CD28 (reduced in MM) and CD95 (reduced in MGUS) reinforcing the importance of immunomodulatory mechanisms in both MM and MGUS. Traditional flow cytometry was used to confirm these specific observations but also to demonstrate that the reduced CD28 expression was specific for CD8+ cells and the reduced CD95 expression was on CD8+ CD57+ cells. Three patients with MGUS were misclassified as MM but on review these 3 patients could have been classified as smoldering myeloma. There was no significant difference in the mosaic of 5 long term survivors of MM (> 10 years). This study has demonstrated the potential of using disease-specific databases to compare the mosaic of antigen expression for the diagnosis of monoclonal gammopathies. Long term studies will be required to accurately determine the prognostic significance at diagnosis and the ability of consensus patterns to identify which MGUS patients develop MM. Figure Figure Specificity and sensitivity of proteomic array for monoclonal gammopathies MGUS MM MM Thal Normal Sensitivity % Specificity % MGUS prediction 5 3 2 4 35 100 MM prediction 0 15 0 0 100 91 MM Thal prediction 0 0 9 0 100 95 Normal prediction 0 0 0 11 100 89

scholarly journals Gamapatias Monoclonais de Significado Indeterminado: Critérios de Diagnóstico e Acompanhamento Clínico

2014 ◽  
Vol 27 (5) ◽  
pp. 661
Author(s):  
Joana Parreira ◽  
Paulo Lúcio ◽  
Cristina João ◽  
Ana Macedo ◽  
Ana Bela Sarmento ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Clinical Management ◽  
Monoclonal Gammopathy ◽  
Long Term Care ◽  
Term Care ◽  
Monoclonal Gammopathies ◽  
Undetermined Significance

<p>The Portuguese group of multiple myeloma of the Portuguese Society of Hematology proposes a national protocol for diagnosis and clinical follow-up of monoclonal gammopathies. The proposed protocol aims to standardize clinical management of monoclonal gammopathies. Furthermore, it would also define the major risk factors for progression to Multiple Myeloma that require a precocious close articulation between general practitioners and a Hematology Clinic.</p><p><br /><strong>Keywords: </strong>Monoclonal Gammopathy of Undetermined Significance; Prognosis; Disease Progression; Long-Term Care; Portugal.</p>

scholarly journals Long-term outcome after allogeneic stem cell transplantation in multiple myeloma

2021 ◽  
Author(s):  
Sini Luoma ◽  
Raija Silvennoinen ◽  
Auvo Rauhala ◽  
Riitta Niittyvuopio ◽  
Eeva Martelin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Outcome ◽  
Significant Difference ◽  
Relapse Group

AbstractThe role of allogeneic hematopoietic stem cell transplantation (allo-SCT) in multiple myeloma is controversial. We analyzed the results of 205 patients transplanted in one center during 2000–2017. Transplantation was performed on 75 patients without a previous autologous SCT (upfront-allo), on 74 as tandem transplant (auto-allo), and on 56 patients after relapse. Median overall survival (OS) was 9.9 years for upfront-allo, 11.2 years for auto-allo, and 3.9 years for the relapse group (p = 0.015). Progression-free survival (PFS) was 2.4, 2.4, and 0.9 years, respectively (p < 0.001). Non-relapse mortality at 5 years was 8% overall, with no significant difference between the groups. Post-relapse survival was 4.1 years for upfront-allo and auto-allo, and 2.6 years for the relapse group (p = 0.066). Survival of high-risk patients was reduced. In multivariate analysis, the auto-allo group had improved OS and chronic graft-versus-host disease was advantageous in terms of PFS, OS, and relapse incidence. Late relapses occurred in all groups. Allo-SCT resulted in long-term survival in a small subgroup of patients. Our results indicate that auto-allo-SCT is feasible and could be considered for younger patients in the upfront setting.

scholarly journals Impact of optimal follow-up of monoclonal gammopathy of undetermined significance on early diagnosis and prevention of myeloma-related complications

Blood ◽  
2010 ◽  
Vol 116 (12) ◽  
pp. 2019-2025 ◽  
Author(s):  
Giada Bianchi ◽  
Robert A. Kyle ◽  
Colin L. Colby ◽  
Dirk R. Larson ◽  
Shaji Kumar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Laboratory Testing ◽  
Monoclonal Gammopathy ◽  
Incidental Finding ◽  
Optimal Frequency ◽  
Future Studies ◽  
Risk Of Progression ◽  
Undetermined Significance

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is associated with a long-term risk of progression to multiple myeloma (MM) or related malignancy. To prevent serious myeloma-related complications, lifelong annual follow-up has been recommended, but its value is unknown. We reviewed all patients from southeastern Minnesota seen at Mayo Clinic between 1973 and 2004 with MGUS who subsequently progressed to MM. Of 116 patients, 69% had optimal follow-up of MGUS. Among these, abnormalities on serial follow-up laboratory testing led to the diagnosis of MM in 16%, whereas MM was diagnosed only after serious MM-related complications in 45%. In the remaining, workup of less serious symptoms (25%), incidental finding during workup of unrelated medical conditions (11%), and unknown (3%) were the mechanisms leading to MM diagnosis. High-risk MGUS patients (≥ 1.5 g/dL and/or non-IgG MGUS) were more likely to be optimally followed (81% vs 64%), and be diagnosed with MM secondary to serial follow-up testing (21% vs 7%). This retrospective study suggests that routine annual follow-up of MGUS may not be required in low-risk MGUS. Future studies are needed to replicate and expand our findings and to determine the optimal frequency of monitoring in higher-risk MGUS patients.

Long-Term Prognostic Significance of Response in Hodgkin Lymphoma Before Autologous Stem Cell Transplantation :Results of the Prospective Multicenter H96 Trial by the GELA/SFGM-TC Study Group

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3070-3070
Author(s):  
David Sibon ◽  
Matthieu Resche-Rigon ◽  
Franck Morschhauser ◽  
Christophe Fermé ◽  
Isabelle Gaillard ◽  
...  
Keyword(s):  
Risk Group ◽  
Prognostic Significance ◽  
Salvage Chemotherapy ◽  
Secondary Malignancy ◽  
Intermediate Risk ◽  
Poor Risk ◽  
The Poor ◽  
Significant Difference

Abstract Abstract 3070 Introduction. The standard treatment for relapsed or refractory Hodgkin lymphoma (HL) is high-dose therapy followed by autologous stem cell transplantation (HDT/ASCT). The prognostic significance of response to initial salvage therapy (i.e. prior to HDT/ASCT) has been shown in many studies. However, the existing results have been based either on retrospective studies or on prospective studies with a relatively short median follow-up, and long-term prospective data are missing. The aim of the present study was to establish the actual prognosis for the different response categories in a prospective cohort of HL patients (pts) treated with HDT/ASCT after long-term follow-up. Methods. The GELA/SFGM-TC H96 trial was a prospective, multicenter, phase II trial evaluating a risk-adapted salvage treatment with single or tandem HDT/ASCT for HL pts who experienced first-line treatment failure (Morschhauser F, J Clin Oncol 2008). Pts were stratified as follows: the poor-risk group included pts with primary refractory disease or at least two risk factors at relapse (time to relapse < 12 months, stage III or IV at relapse, or relapse within previously irradiated sites); the intermediate-risk group included pts with only one risk factor at relapse. Poor-risk and intermediate-risk pts were eligible for tandem and single HDT/ASCT, respectively. The primary end point was to evaluate the freedom from second failure (FF2F) rate in the poor- and intermediate-risk groups. Secondary end points included overall survival (OS) for both groups, FF2F and OS according to the response to salvage chemotherapy. Response was assessed according to 1999 standard guidelines: complete remission (CR), unconfirmed CR (CRu), partial remission (PR), stable disease (SD) or progressive disease (PD). Results. Between 1995 and 2002, 245 pts were enrolled. The pts characteristics at diagnosis and at time of treatment failure/relapse have been previously described (Morschhauser F, J Clin Oncol 2008). The median follow-up is now 9.2 years (yrs). In the poor-risk group (n=150 [77 pts with primary refractory HL and 73 pts with unfavorable relapse]), the 9-yr FF2F and OS were 41% and 50%, respectively, without significant difference between primary refractory HL and unfavorable relapse. In the intermediate-risk group (n=95), the 9-yr FF2F and OS were 61% and 70%, respectively. The response to salvage treatment was assessable for 243 pts. In the poor-risk group, the 9-yr FF2F according to each response category was 67% for CR/CRu (n=39), 45% for PR (n=55), 12% for SD (n=24), and 23% for PD (n=31). The 9-yr OS were 76% for CR/CRu, 60% for PR, 16% for SD, and 26% for PD. Significant differences in FF2F were found between CR/CRu and PR groups (p=0.02), between PR and SD groups (p=0.006), but not between SD and PD groups (p=0.82). For OS, no significant differences were found between CR/CRu and PR groups (p=0.09) and between SD and PD groups (p=0.89), but there was a significant difference between PR and SD groups (p=0.001). In the intermediate-risk group, the 9-yr FF2F was 66% for CR/CRu (n=65) and 60% for PR (n=26) [no SD and 3 PD]. The 9-yr OS was 71% for CR/CRu and 67% for PR. No significant differences in FF2F (p=0.98) and OS (p=0.96) were observed between the CR/CRu and PR groups. In all, 100 pts relapsed after HDT/ASCT (76 in the poor-risk group [primary refractory, n=44; unfavorable relapse, n=32] and 24 in the intermediate-risk group). Half of relapses occurred in the first yr following HDT/ASCT. In the poor-risk group, the cumulative incidence of relapse at 1, 2, 5 and 9-yr was 33%, 43%, 47% and 52%. In the intermediate-risk group, the cumulative incidence of relapse at 1, 2, 5 and 9-yr was 5%, 15%, 23% and 26%. Among relapsing pts, 21 (poor-risk group, n=16) underwent allogeneic transplantation (alloSCT). In all, 101 pts died (poor-risk group, n=76). The cause of death was PD in 78 pts (poor-risk group, n=65) or other cause in 23 pts (secondary malignancy, n=6; non-relapse mortality after alloSCT, n=5; infection, n=4; other, n=5; unknown, n=3). Secondary malignancy occurred in 11 pts (solid tumor, n=7; acute leukemia, n=4), including 2 pts in the poor-risk group (solid tumor only). Secondary cardiac toxicity occurred in 7 pts (2 pts in the poor-risk group). Conclusion. This prospective study emphasized the prognostic impact of response to salvage chemotherapy on the long-term outcome after HDT/ASCT for first relapsed/refractory HL. Disclosures: No relevant conflicts of interest to declare.

The predictive power of serum κ/λ ratios for discrimination between monoclonal gammopathy of undetermined significance and multiple myeloma

2005 ◽  
Vol 43 (1) ◽  
Author(s):  
Enrique Bergón ◽  
Elena Miravalles ◽  
Elena Bergón ◽  
Isabel Miranda ◽  
Marta Bergón
Keyword(s):  
Multiple Myeloma ◽  
Predictive Value ◽  
Monoclonal Gammopathy ◽  
Predictive Power ◽  
Protein Detection ◽  
M Protein ◽  
Likelihood Ratios ◽  
Geographic Population ◽  
Significant Difference ◽  
Undetermined Significance

AbstractThe predictive power of serum κ/λ ratios on initial presentation of immunoglobulin G (IgG) or IgA monoclonal component was studied to differentiate between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patients. The retrospective study involved 145 patients clinically diagnosed with monoclonal gammopathy of undetermined significance or multiple myeloma, who had serum M-protein IgG <35g/L or IgA <20g/L at M-protein detection. Serum light chains κ and λ were measured by fixed-time nephelometry. Test performance indices, predictive values and likelihood ratios were calculated according to the Weissler recommendation. MM patients were considered as diseased and MGUS patients as non-diseased in order to estimate the performance characteristics of serum κ/λ ratios. There was a statistically significant difference in κ/λ ratios distribution between both groups of patients, in both M-protein κ-type (Mann-Whitney U=168, p<0.001) and in M-protein λ-type (Mann-Whitney U=143, p<0.001). Negative likelihood ratios at threshold levels of 0.6 and 4.2 were 2.17- and 3.32-fold greater, respectively, than positive likelihood ratios, so that the predictive power of a serum κ/λ ratio within these limits is better in ruling out (negative predictive power) than ruling in disease (positive predictive power). The post-test characteristics of a serum κ/λ ratio interval between 0.6 and 4.2 in discriminating MGUS from MM in our geographic population were: sensitivity 0.96 (0.93–0.99 95%CI); specificity 0.70 (0.63–0.77); positive predictive value 0.68 (0.64–0.73); negative predictive value 0.96 (0.94–0.99); likelihood ratios (+)LR 3.23 (2.68–4.04); and (−)LR 17.16 (11.00–63.00). Thus, serum M-protein with a κ/λ ratio between 0.6 and 4.2 increases the posterior probability of MGUS from 0.60 to 0.96 in asymptomatic patients, for whom only monitoring may be suggested when the serum κ/λ ratio is within these limits.

Importance of Achieving a Complete Response in Multiple Myeloma, and the Impact of Novel Agents

2010 ◽  
Vol 28 (15) ◽  
pp. 2612-2624 ◽  
Author(s):  
Asher A. Chanan-Khan ◽  
Sergio Giralt
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Prognostic Significance ◽  
Complete Response ◽  
Maximal Response ◽  
Prognostic Impact ◽  
Long Term Outcomes ◽  
First Line ◽  
The Impact

The goal of treatment for multiple myeloma (MM) is to improve patients' long-term outcomes. One important factor that has been associated with prolonged progression-free and overall survival is the quality of response to treatment, particularly achievement of a complete response (CR). There is extensive evidence from clinical studies in the transplant setting in first-line MM demonstrating that CR or maximal response post-transplant is significantly associated with prolonged progression-free and overall survival, with some studies demonstrating a similar association with postinduction response. Supportive evidence is also available from studies in the nontransplant and relapsed settings. With the introduction of bortezomib, thalidomide, and lenalidomide, higher rates of CR are being achieved in both first-line and relapsed MM compared with previous chemotherapeutic approaches, thereby potentially improving long-term outcomes. While standard CR by established response criteria has been shown to have differential prognostic impact compared with lesser responses, increasingly sensitive analytic techniques are now being explored to define more stringent degrees of CR or elimination of minimal residual disease (MRD), including multiparameter flow cytometry and polymerase chain reaction. Demonstrating eradication of MRD by these techniques has already been shown to predict for improved outcomes. Here, we review the prognostic significance of achieving CR in MM and highlight the importance of CR as an increasingly realizable goal at all stages of treatment. We discuss clinical management issues and provide recommendations relevant to practicing oncologists, such as the routine use of sensitive techniques for assessment of disease status to inform evidence-based decisions on optimal patient management.

Long-Term Outcomes of Autologous Transplantation in Multiple Myeloma: Prognostic Significance of Complete Response.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3126-3126
Author(s):  
Marta Krejci ◽  
Roman Hajek ◽  
Zdenek Adam ◽  
Ludek Pour ◽  
Lenka Zahradova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Complete Response ◽  
Advisory Committees ◽  
Term Survival ◽  
Free Survival ◽  
Different Response

Abstract Abstract 3126 Background: Autologous stem cell transplantation (ASCT) after high-dose melphalan 200mg/m2 has got an important role in the treatment of symptomatic multiple myeloma (MM). The prognostic significance of achieving complete response (CR) after ASCT was cause of great debate for a long time. Some studies have shown the strong prognostic significance of achieving CR in MM, but other studies have failed to correlation between strength of the response and outcome. Aim: In this report we describe the long-term outcome of cohort 232 MM patients (pts) after ASCT with aim to establish the actual prognosis for the different response categories and to analyse other factors that might predict for long-term survival. Methods: We evaluated 232 pts with newly diagnosed symptomatic MM who received ASCT as a part of the first-line treatment between 1995 and 2005, median follow-up from ASCT was 131 months (range 61–195). Results: Following ASCT, overall response rate was 90% (202/232), 23% (52/232) of pts were in complete remission (CR), very good partial response (VGPR) was achieved in 45% of pts (100/232), partial response (PR) in 22% of pts (50/232), minimal response (MR) or stable disease (SD) in 10% of pts (22/232). Median progression-free survival (PFS) and overall survival (OS) from ASCT were 30.8 and 71.9 months, respectively. Progression-free survival at 12 years after ASCT in different response categories was 41% for pts with CR, 11% for pts with VGPR and 10% for pts with PR. Overall survival at 12 years after ASCT was 51% for pts with CR, 22% for pts with VGPR and 20% for pts with PR. The achievement of CR after ASCT was independent factor for long-term survival, significance differences in OS and PFS were found between CR and non-CR groups (P under 0.001 and P under 0.001, respectively). On multivariate analysis, the other factors associated with significantly better OS were ISS stage under III (P = 0.002), no presence of renal impairment (P = 0.008), age under 60 years (P = 0.001), no presence of deletion 1q21 (P = 0.029) and lenalidomide treatment in the post-transplant relapse (P = 0.002). Conclusion: The achievement of complete response after ASCT in multiple myeloma is the most important prognostic factor, even after long-term follow-up. The relapse rate is low in patients who remained in CR after 12 years from ASCT. A long-term complete remission should be a goal of treatment. Disclosures: Hajek: Merck: 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; Janssen Cilag: Honoraria.

The Role of PET/TC in the Full Range of Monoclonal Gammopathies

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3365-3365
Author(s):  
Rafael Ríos Tamayo ◽  
Juan Sáinz Pérez ◽  
Jose Manuel Puerta Puerta ◽  
Rosario Leyva Ferrer ◽  
Youssef Moatassim de la Torre ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Monoclonal Gammopathy ◽  
Focal Lesion ◽  
Consecutive Series ◽  
Monoclonal Gammopathies ◽  
Extramedullary Disease ◽  
Pet Ct ◽  
Uncertain Significance

Abstract Positron emission tomography (PET) with 18fluorine-fluoro-deoxyglucose (FDG) integrated with computed tomography (PET/CT) is a functional imaging technique helping us to assess bone marrow infiltration as well as unsuspected disease sites involving the bones and/or extramedullary sites. PET/TC has proved to be an independent prognostic factor for overall survival (OS) in symptomatic multiple myeloma (MM)(Zamagni,2011). However, its role in other monoclonal gammopathies (MG) is still a matter of debate. We have prospectively analyzed the contribution of baseline PET/TC in a unselected consecutive series of 158 patients with MG, including 88 MM, 7 MM smoldering (MMS), 11 Waldenstršm's macroglobulinemia (WM), 3 WM smoldering (WMS), 3 solitary bone plasmacytoma (SBP) and 46 monoclonal gammopathy of uncertain significance (MGUS). Patients with only palliative care were excluded. The pattern of bone marrow uptake on PET/TC was described as negative (NEG), diffuse involvement (DI) or focal lesions (FLs). Patients with more than 3 FLs as well as the presence of extramedullary disease (EMD) were analyzed separately. Overall survival (OS) was estimated by the Kaplan-Meier method. The main characteristics of PET/TC findings according to the type of MG are shown in Table 1. PET/TC was positive in 70 (79,5 %) of MM and 8 (72,7%) of WM. PET/TC was NEG in 100 % of MMS, WMS and SBP (except for the primary lesion). In MGUS, the findings reflect the clinical heterogeneity of this group: 19,6 % had bone disease (all but one case of probable inflammatory etiology), 17,4 % positive lymphadenopathy, 15,2 % lung disease (infection, fibrosis, pulmonary nodules), 6,5 % splenomegaly, 6,5 % liver disease, 6,5 % positive uptake in adrenal gland and other organs such as thyroid, stomach, colon or skin were affected less frequently. Median age of MM patients was 62 years (12-91), 51 men and 37 women (42%), the distribution according ISS was I (36,5 %), II (28,2 %) and III (35,3%). Among PET-positive MM, 39 (55,7 %) had >3 FLs, 17 (24,3 %) 3 or less FLs and 14 (24,3 %) DI. Median OS was 40 months, not reached (NR) and 85,7 months, respectively (p=ns). Mean bone marrow plasma cells in the >3 FLs group vs 3 or less FLs was 25 vs 12 (p=0,028). EMD was present in 13 (18,6 %) of PET-positive MM. Response with PET/CT was available in 32 patients: 18 achieved CR, 8 PR and 8 progressed. OS was NR for CR and PR vs 40 months (p <0,0001). In WM, patients with NEG or FL had NR OS vs 26 months in those with DI (p=0,16). PET/CT is positive in the majority of MM and WM patients, helping to separate patients with true indolent disease. At baseline, PET/TC is a useful tool to improve prognostic assessment in patients with MG. MM with >3 FLs or EMD at baseline had a trend towards lower OS. Negative serial PET/CT in MM is associated with favorable prognosis. Table SEQ Tabla \* ARABIC 1. Characteristics of main PET/TC findings according to the type of MG Type MM MMS WM WMS SBP MGUS n 88 7 11 3 3 46 Positive n /% 70/79,5 0 8/72,7 0 0 9/19,6 ->3 FLs 39/55,7 0 0 0 0 0 -3 or < FLs 17/24,3 0 1/12,5 0 0 1/2,2 -DI 14/20 0 5/62,5 0 0 1/2,2 -EMD 13/18,6 0 0 0 0 0 -Adenopathy 2/2,9 2/28,6 2/25 0 0 8/17,4 -Spleen 3/4,3 0 1/12,5 0 0 3/6,5 MG: Monoclonal gammopathy; MM: Multiple myeloma symptomatic; MMS: Smoldering myeloma; WM: Waldenstršm's macroglobulinemia; WMS: Smoldering Waldenstršm's macroglobulinemia; SBP: Solitary bone plasmocytoma; MGUS: Monoclonal gammopathy of uncertain significance; FL: Focal lesion; DI: Diffuse involvement; EMD: Extramedullary disease. Disclosures No relevant conflicts of interest to declare.

Immunophenotyping to Detect Minimal Residual Disease in Adult Acute Lymphoblastic Leukemia - Feasibility and Prognostic Significance.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4489-4489
Author(s):  
Jerzy Holowiecki ◽  
Sebastian Giebel ◽  
Krystyna Jagoda ◽  
Malgorzata Krawczyk-Kulis ◽  
Beata Stella-Holowiecka ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Antigen Expression ◽  
Term Outcome ◽  
Long Term Outcome ◽  
B Lineage ◽  
Minimal Residual

Abstract Although well documented for pediatric patients, the prognostic value of minimal residual disease (MRD) detected with the use of immunophenotyping has not been established for adults with acute lymphoblastic leukemia (ALL) so far. With the use of standard “quadrans” analysis based on evaluation of the number of blasts bearing atypicial antigen combinations, the method may be applied to the majority of T-derived and only approximately half of B-lineage ALL. In this study we tested the feasibility and prognostic significance of a new “empty spaces” method taking into account the individual antigen expression pattern for each blast cell tested. The “forbidden” gates were established with the use of triple staining by comparison with the pattern obtained for healthy volunteer bone marrow donors. At least two antigen combinations were tested for each patient. MRD was evaluated after induction and after consolidation therapy. Only patients who achieved complete remission after a single course of induction were analysed with regard to the impact of MRD on long-term outcome. Thirty adult ALL patients (B-lineage n=24, T-lineage n=6) were included in the study. For all cases it was possible to determine unique antigen expression pattern and to monitor MRD with the use of immunophenotyping at the level of 1/1000 cells. MRD was detected in 8/30 patients after induction and in 7/28 patients after consolidation tharapy (two patients relapsed during consolidation). For 11/30 patients the MRD resulted positive at least once. At 20 months the relapse rate equaled 53% for patients with MRD detected after induction or consolidation and 28% for those with MRD always negative (p=0.08). The difference was more pronounced for patients with B-lineage ALL (67% vs. 26%, p=0.02). A single MRD evaluation after induction therapy had no significant prognostic value for the risk of relapse whereas there was a trend for higher relapse rate in B-lineage ALL patients with positive MRD after completion of consolidation therapy compared to those MRD-negative at that time-point (75% vs. 32%, p=0.06). Results of the study prove the feasibility of immunophenotypic MRD evaluation in ALL. “Empty spaces” in addition to the standard “quadrans” analysis allows monitoring of the vast majority of patients regardless the immune subtype. Even with a small number of cases we were able to demonstrate its prognostic value for long-term outcome of adults with ALL.

Clinical and Biological Features of Biclonal Gammopathies. Review of 203 Cases

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5151-5151
Author(s):  
Olivier Decaux ◽  
Helene Leroy ◽  
Jean-Christophe Ianotto ◽  
Annie Ruelland ◽  
Lucienne Guenet ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Malignant Transformation ◽  
Monoclonal Gammopathy ◽  
Systemic Disease ◽  
Light Chains ◽  
Lymphoproliferative Diseases ◽  
Monoclonal Gammopathies ◽  
Biclonal Gammopathy ◽  
Monoclonal Component

Abstract Introduction: Biclonal gammopathies represent about 5% of clonal gammopathies. We describe the clinical and laboratory features of biclonal gammopathies identified in a French university hospital. Methods: Patients were selected by immunofixation registry of Biochemistry laboratory. Results: From 1987 to 2008, 203 biclonal gammapathies were identified. Patients were 113 men and 90 women. Median age was 72.0 years (35–95). Seventy eight patients (38.3%) had IgG and IgM components, 64 (31,9%) had two IgG, 24 (11,8%) had IgG and IgA, 23 (11,3%) had two IgM, 8 (3,9%) had IgM and IgA, 5 (2,4%) had two IgA, one (0.5%) had Ig G and IgD (0,5%). Of the 406 light chains, 260 (63,8%) were kappa, 146 (36.2%) were lambda. Eighty nine patients (44.1%) had two kappa light chains, 82 (40,2%) had both kappa and lambda and 32 (15,7%) had two lambda chains. Median gammaglobulin concentration was 13.3 g/L (3–59.9). The most frequent diagnosis was biclonal gammopathy of undeterminated significance (BGUS) in 123 patients (60.6%). Others patients could be divided into 3 groups. Forty seven patients (23.1%) had lymphoproliferative diseases, including Waldenström’s macroglobulinemia (21 cases), non Hodgkin lymphoma (20), chronic lymphocytic leukaemia (6). Eighteen (8.87%) had multiple myeloma. For the last 15 patients (7.4%), biclonal gammopathy was associated with a non lymphoid hemopathy or with systemic disease. Biclonal gammopathy was identified in 12 patients already known to have a monoclonal gammopathy (7 monoclonal gammopathy of undetermined significance-MGUS, 3 myeloma and 2 Waldenström’s macroglobulinemia). In 3 cases, the finding of the second monoclonal component was concurrent to the diagnosis of a MGUS malignant transformation to myeloma (2 cases) or Waldenström’s macroglobulinemia (1 case). Median follow-up was 23 months (12 to 252 months) for the 123 patients with BGUS. In 4 cases (3.2%) a malignant transformation was observed. Three patients developed a multiple myeloma (time to transformation was 2 years for one and 4 years for the 2 others) and one patient Waldenström’s macroglobulinemia (6 years). Conclusions: As for monoclonal gammopathies, BGUS represent the most frequent diagnosis. However, in contrast to monoclonal gammopathies, biclonal gammopathies are more frequently associated with lymphoproliferative diseases than with multiple myeloma. The apparition of a second monoclonal component during follow up of MGUS could be associated with malignant transformation and should lead to new evaluation. The risk of transformation of BGUS seems similar to MGUS but further studies are necessary to compare the evolution of MGUS and BGUS.

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