Follow-up Of Multiple Myeloma Patients Research Articles

Electrophoresis Testing in the Follow-up of Multiple Myeloma Patients with a Measurable M Protein in Gamma Region: Good Laboratory Practice for the Laboratory Specialist

Electrophoresis Testing in the Follow-up of Multiple Myeloma Patients with a Measurable M Protein in Gamma Region: Good Laboratory Practice for the Laboratory Specialist

Long-Term Follow-Up of Multiple Myeloma Patients Treated with Tandem Autologous Transplantation Following Melphalan and Upon Recovery, Total Marrow Irradiation

Total body irradiation in combination with melphalan for multiple myeloma (MM) has been shown to be prohibitively toxic. To ameliorate toxicity, total marrow irradiation (TMI) has been administered as the sole ablative modality during the second cycle of tandem autologous stem cell transplantation (TASCT) for MM patients on a phase I-II trial. Patients with MM in response or with stable disease and ≤18 months from diagnosis received melphalan 200 mg/m2 and autologous stem cell transplantation (ASCT) (cycle 1) and then, after recovery, TMI and another ASCT (cycle 2), followed by maintenance with an immunomodulatory drug (ImiD) and dexamethasone for up to 12 months. TMI doses were escalated from 1000 cGy to 1800 cGy in 200-cGy increments. Fifty-four patients were to receive TASCT between 2004 and 2011; 8 patients received single ASCT because of patient or physician preference. The median time between melphalan and TMI was 65 days (range, 47 to 125 days). Thirty patients (55.6%) underwent TASCT at the maximum tolerated dose of 1600 cGy. The complete response and very good partial response rates were 48.1% and 22.2%, respectively, following ASCT and maintenance. The median follow-up among survivors was 12.3 years (range, 9.2 to 15.5+ years). Progression-free survival (PFS) and overall survival at 10 years were 20.4% (95% confidence interval [CI], 10.9% to 31.9%) and 38.8% (95% CI, 25.9% to 51.5%), respectively. Secondary neoplasms included (1 each) acute myelogenous leukemia, papillary thyroid and prostate carcinoma, and melanoma, and there was 1 case of ductal carcinoma in situ and 4 cases of nonmelanoma skin cancers. TMI as part of TASCT was well tolerated, and TASCT was associated with a 20.4% PFS plateau. The inclusion of TMI as a conditioning regiment for MM before ASCT warrants further study in the context of modern induction and maintenance therapies.

Immunophenotypic Markers Associated with Minimal Residual Disease Status and Outcome in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation

Multiple Myeloma (MM) is one of the most common hematologic malignancies, with a heterogeneous prognosis. Therefore, the recognition of biomarkers can be useful to understand the differences in patient outcomes. Minimal Residual Disease (MRD) has been considered a very important prognostic factor in MM. In parallel, the prognostic value of immunophenotypic markers expressed in MM Plasma Cells (PCs) has also been described. The aim of this study was to assess the impact of CD27, CD28, CD45, CD56, CD117 and β2-microglobulin expressions on the outcome of 154 MM patients undergoing Autologous Stem Cell Transplantation (ASCT). The relation of each marker studied with the Overall Survival (OS) and Progression-Free Survival (PFS) was assessed, alone and in association with pre-ASCT MRD. Scores of good (GPM) and poor Prognostic Markers (PPM) were established, according to their respective survival curves. The expressions of CD27 and CD45 were associated to longer OS (p=0.013 and p=0.00, respectively) and PFS (p=0.00) as well as the absence of CD28 (OS p=0.026; PFS p=0.001) and CD56 (OS p=0.004; PFS p=0.009), in patients with undetectable MRD. The number of GPM showed an inverse correlation with the level of MRD (p=0.04), while a higher number of PPM was observed in patients with higher levels of MRD (p=0.04), which were also significantly associated with OS and PFS. In conclusion, although pre-ASCT MRD is a powerful prognostic factor in MM, these biomarkers can provide additional prognostic information and be used in the follow-up of MM patients.

MALDI-TOF Mass Spectrometry in Serum for the Follow-up of Newly Diagnosed Multiple Myeloma Patients Treated with Daratumumab-Based Combination Therapy

MALDI-TOF Mass Spectrometry in Serum for the Follow-up of Newly Diagnosed Multiple Myeloma Patients Treated with Daratumumab-Based Combination Therapy

Comparison of MALDI-TOF Mass Spectrometry Analysis of Peripheral Blood and Bone Marrow Based Flow Cytometry for Tracking Measurable Residual Disease (MRD) in Patients with Multiple Myeloma

Comparison of MALDI-TOF Mass Spectrometry Analysis of Peripheral Blood and Bone Marrow Based Flow Cytometry for Tracking Measurable Residual Disease (MRD) in Patients with Multiple Myeloma

Leveraging RSF and PET images for prognosis of multiple myeloma at diagnosis.

Multiple myeloma (MM) is a bone marrow cancer that accounts for 10% of all hematological malignancies. It has been reported that FDG PET imaging provides prognostic information for both baseline and therapeutic follow-up of MM patients using visual analysis. In this study, we aim to develop a computer-assisted method based on PET quantitative image features to assist diagnoses and treatment decisions for MM patients. Our proposed model relies on a two-stage method with Random Survival Forest (RFS) and variable importance (VIMP) for both feature selection and prediction. The targeted variable for prediction is the progression-free survival (PFS). We consider texture-based (radiomics), conventional (e.g., SUVmax) and clinical biomarkers. We evaluate PFS predictions in terms of C-index and final prognosis separation in two risk groups, from a database of 66 patients who were part of the prospective multi-centric french IMAJEM study. Our method (VIMP+RSF) provides better results (1-C-index of 0.36) than conventional methods such as Lasso-Cox and gradient-boosting Cox (0.48 and 0.56, respectively). We experimentally proved the interest of using selection (0.61 for RSF without selection) and showed that VIMP selection is more stable and gives better results than minimal depth and variable hunting (0.47 and 0.43). The approach gives better prognosis group separation (a p value of 0.05 against 0.11 to 0.4 for others). Our results confirm the predictive value of radiomics for MM patients, in particular, they demonstrate that quantitative/heterogeneity image-based features reduce the error of the predicted progression. To our knowledge, this is the first work using RFS on PET images for the progression prediction of MM patients. Moreover, we provide an analysis of the feature selection process, which points toward the identification of clinically relevant biomarkers.

CD14+CD16+ monocytes rather than CD14+CD51/61+ monocytes are a potential cytological marker of circulating osteoclast precursors in multiple myeloma. A preliminary study

Osteolytic bone destruction is a major clinical problem in multiple myeloma patients. Osteoclasts can differentiate in vitro from bone marrow-resident monocyte progenitors, such as common monocyte progenitors, as well as circulating monocytes. Various types of monocytes, including osteoclast precursors, appear to circulate systemically. We investigated the possibility of demonstrating, by in vitro differentiation and flow cytometry, a circulating osteoclast precursor population in multiple myeloma (MM) patients by studying the distribution of CD14(+/++) CD11b(+) CD51/61(+) and CD14(+/++) CD16(+/-) populations. Under short-term in vitro osteoclastic differentiation conditions, almost all CD14 monocytes acquired CD51/61 and CD16 expression. Flow cytometry studies failed to demonstrate a statistically significant increase in circulating CD14(+/++) CD11b(+) CD51/61(+) populations in 20 MM patients with osteolytic lesions. However, the minor circulating CD14(+/++) CD16(+) fraction was significantly increased in MM patients compared with healthy volunteers (109.3±63.1/mm(3) vs. 65.3±34.9/mm(3) ; P=0.005), but with no correlation with markers of tumour burden. The CD14(+/++) CD16(+) to CD14(+/++) CD16(-) ratio was higher in MM patients. The circulating CD14(+/++) CD11b(+) CD51/61(+) fraction was not correlated with bone lesions in MM patients. However, CD14(+/++) CD16(+) monocytes may be a candidate marker. A larger study must be conducted to confirm these promising results for the diagnosis and follow-up of MM patients.

Association Of Stringed Response and Immunoparesis Normalization After Bortezomib-Based Therapy Is Related To Better Outcomes In Multiple Myeloma

BackgroundProteasoma inhibitors have proven to be one of the major advances on multiple myeloma (MM) therapy. Their principal effect in growth inhibition of MM cells is achieved not only through the inhibition of proteasomes but also by preventing the adhesion of myeloma cells to stromal cells, induction of cytokines by the microenvironment, decrease angiogenic activity and a direct apoptotic effect on MM cells. Actually it is part of the first-line standard of care therapy for patients with MM. On the other hand, multiple strategies have been developed for trying to predict response or improve the assessment of response and follow-up of MM patients. Currently, the International Myeloma Working Group (IMWG) criteria of response include immunophenotype and immunoparesis analysis. The HevyLiteTMand FreeLiteTM assays (The Binding Site Ltd. Birminghan. UK) permit a separate quantification of the amount of kappa- and lambda-bound to a given immunoglobulin (HLC) and the free light chains kappa or lambda amount quantification (FLC), both being excellent tools for immunoparesis assessment. AimsTo analyze the usefulness of immunoparesis analysis by HevyLiteTM and FreeliteTM in patients who receive bortezomib-based therapy in our institution. Patients and MethodsA retrospective chart review was performed including the patients diagnosed with secretor IgA or IgG MM who received therapy with bortezomib either at relapse or as first-line therapy. General clinical characteristics, therapy schedules, number of cycles, response to therapy according IMWG criteria and relapse were recorded. For the analysis, only patients with at least 4 cycles of bortezomib based regimen and HLC and/or FLC analysis performed between 4-12 weeks after complete therapy were included. Period of study: June 2004 to April 2013. ResultsAt the end of study a total of 67 MM patients had received bortezomib-based therapy, 63 of them completed 4 or more cycles and were included in the analysis. Male/Female ratio: 31/32, mean age: 66.9 years old (46-81), therapeutic schedules were: bortezomib-prednisone: 3 (4.7%), bortezomib-dexametasone: 33 (51.6%), bortezomib-melfalan-prednisone: 18 (28.1%), bortezomib-dexametasone-lenalidomide: 8 (12.5%) and bortezomib-talidomide-dexametasone: 1 (1.6%). 55% of patients received at least 6 cycles of therapy. Immunoglobulin Myeloma subtype: IgAL: 13 (20.4%) patients, IgAK: 10 (15.6%) patients, IgGK: 32 (50.8%) patients and IgGL: 8 (14.1%) patients. A total of 46 (73%) patients showed an abnormal HLC ratio at diagnosis and 48 (76,2%) had immunoparesis before therapy; a total of 47 (74.6%) registered an abnormal FLC ratio at diagnosis. The response to therapy was: 15 (23.8%) of cases achieved a stringent complete response (SR), 3 (4.8%) a very good partial response (VGPR), 36 (57.1%) obtained a partial response (PR) and 9 (14.3%) patients had not-response/progressive-disease. At the time of post-therapy evaluation, 26 (37%) of patients had normalized FLC-ratio, 15 (23.8%) maintain the SR, 1 (1,6%) patient in VGPR and 5 (11.1%) in PR and 1 (1.6%) of non-responder patients. Normalization of HLC-ratio was only observed in patients with SR and VGPR: 13 (20.6%). Regarding the immunoparesis analysis, only 15 (23.8%) of patients with immunoparesis recovered the immune restitution (IR) at the end of therapy, of which 8 (11.7%) were SR patients, 2 VGPR and 5 PR patients. At the end of the study 47(71.4%) patients relapsed, 5 (11.11%) are on maintenance therapy and 11(17.4%) after a median follow-up of 29 months (9-94) without therapy not-relapsed; the association of SR with IR was related to a less tendency to relapse and need of therapy, 7/8 patients who achieved this status are not-relapsed. ConclusionIn our cohort, patients who achieved a SR with a normalization of immunoparesis shows a clear tendency to less incidence of relapse; probably reflecting a better response with not only an undetectable monoclonal protein but also the recovery of the immune function. Even in small cohorts, the immunoparesis recovery analysis through HLC quantifications seems to be an useful tool to determine a new level of response. More investigations on this field are warranted.This work has been partially supported by a grant from Fundación para el Estudio de la Hematología y hemoterapia en Aragón (FEHHA) Disclosures:No relevant conflicts of interest to declare.

Clinical Application of18F-FDG-PET/CT in Multiple Myeloma

Multiple myeloma (MM) is a plasma cell malignancy and is characterized by the presence of lytic bone disease causing severe bone pain, pathological fractures and spinal cord compression. Up to 80% of myeloma patients develop osteolytic lesions during the course of their disease. Appropriate use of imaging techniques is essential in the identification and characterization of the skeletal complications resulting from MM and in determination of the extent of intramedullary bone disease. Despite many weaknesses, conventional radiography still remains the standard for the staging procedure of newly diagnosed and relapsed myeloma patients. Magnetic resonance imaging (MRI) is recommended for MM patients with normal conventional radiography and for all patients with an apparently solitary plasmacytoma of bone. Urgent MRI is the diagnostic procedure of choice to assess suspected cord compression. Although Positron emission tomography/CT (PET/CT) is a useful method to assess the patient's response to the treatment and diagnose the extent of bone involvement and extramedullary disease in the patient, PET/CT is not recommended for routine use in myeloma patients. However, further studies are needed before the recommendation of using PET/CT as a standard tool in both diagnosis and follow-up of MM patients. (Korean J Med 2012;82:686-688)

A076 Long-Term Follow-up of Multiple Myeloma Patients Treated by VELCADE

A076 Long-Term Follow-up of Multiple Myeloma Patients Treated by VELCADE

Long-Term Follow-up of Multiple Myeloma Patients Treated by Bortezomib (Velcade®): A Study on Efficacy, Tolerance, Survival and Time to Progression

We conducted a retrospective single institution analysis to evaluate the immediate and long-term efficacy, tolerance, survival and time to progression of MM patients (pts) who received VELCADE (Vel.) as induction and in those who relapsed or were refractory after standard therapies. A total of 92 pts were included, 62 (67%) males and 30 (33%) females. Median age at treatment was 60 years [35–79]. At diagnosis, there were 48 (52%) IgG, 24 (26%) IgA, 2 (2%) IgD, 15 (16%) light chains and 3 (4%) plasma cell leukaemias, 11pts (12%) were in stage I A, 12 (13%) stage IIA and 69 (75%) stage III (51 A and 18B). The median level of β2 microglobulin was 3.28 mg/l (1.12–24). Among 42 evaluated del(13), 19 (45%) were + in which there was two t(4;14)+. We defined 3 groups: group1:16 (17%) pts who received Vel. as induction, group2:58 (63%) pts who received Vel. as 2nd line n=41 or 3rd line n=17, group 3:18 (12%) pts who received Vel. as ≥ 4th line. Prior to Vel.(groups 2 and 3), 53 (70%) pts had received an autologous hematopoietic stem cell transplantation (HSCT), 13 (14%) allogeneic HSCT and 35 (46%) thalidomide (Thal.) (median dose of 200mg/day, median duration of 4 months). The median interval between diagnosis and Vel. initiation was 28.3 months (0.2–125); 28 pts had an interval less than 12 months (16 in 1st line), 27 pts between 12 and 36 months and 37 pts with more than 36 months. The median number of Vel. cycles in group 1, 2 and 3 were 4[2–9], 5[2–12] and 5[3–12] respectively with a standard dose of 1.3 mg/m2 decreased to 1.0 mg/m2 in case of toxicity (<3 cycles: n=18, 4–6: n=52; 7–8: n=14; >8: n=8). Fifty-two (57%) pts received an association of dexamethasone (40mg/day). There were 6 Vel. discontinuation (<3 Vel.cycles) and 25 (27%) dose reduction due to neuropathy [3cycles n=2 (17%), 4–6 cycles n=12 (23%), 7–8 cycles, n=7 (50%) and ≥9 n=4 (50%)]. Peripheral neuropathy occurred in 61 pts (66%) [32 (52%)gr1, 18 (30%)gr2, 9 (15%)gr3 and 4 (3%)gr4], in which, 25 (41%) had previously received Thal. [12 (48%)gr1, 8 (32%)gr2, 5 (20%)gr3]. The most other common toxicities were, fatigue n=35 (38%), constipation n=18(20%), diarrhea n= 11(12%), nausea n=14(15%) and vomiting n=7(8%). The overall response rate was observed in 67 (73%) pts [13 (14%)CR, 22 (24%)VGPR and 32 (35%)PR]. With a median follow-up of 23.4 months, the median overall survival (OS) for the whole population and for group 1 and 2 was not reached, and was 17 months for group 3. The probability of OS at 3 years for the whole population was 61%[50–73.5] (Figure 1) and were: 80%[62–100], 66%[54–81] and 45%[25–82.5] for groups 1, 2 and 3 respectively (Figure 2). The probability of OS at 5 years for the whole population from MM diagnosis was 72.5%[63–84]. The median time to progression (TTP) was 25.5 months for the whole population; it was not reached for group 1, were 25.5 and 13 months for group 2 and 3 respectively. The probability of progression-free survival (PFS) at 2 years was 51%[40–64,5] for the whole population and 66%[45–96], 52%[39–70] and 29%[12–71] for group 1, 2 and 3 respectively. We showed no significant difference in term of OS (p=0,166) and PFS (p=0.495) between the patients with del(13) [51% (31–83) and 42(23–78)] and without del(13) [83%(68,5–99,6) and 58%(40–85,5)]. Finally we observed a better PFS at 2 years for pts receiving lenalidomide after Vel. versus those who did not, 64%[42–96] and 48%[36–63] respectively. The multivariate analysis (studying: age, sex, stage, beta2M, del(13), previous lines, allogeneic HSCT, Thal., and interval diag-Vel.) showed only a significant impact of thalidomide HR=3.06 (1.37–6.85) (p=0,006), and a trend for interval diag-Vel. In conclusion, this analysis showed a very good percentage of long-term OS with a median not reached for Vel. naïve or 2nd, 3rd Vel line MM pts. Moreover, we showed a significant negative impact of previous Thal. treatment and no impact of del(13). [Display omitted] [Display omitted]

Technetium‐99m sestamibi scintigraphy is sensitive and specific for the staging and the follow‐up of patients with multiple myeloma: a multicentre study on 397 scans

We evaluated the additional benefit of Technetium(99)-sestamibi (99mTc-MIBI) scanning in comparison with standard X-ray techniques for multiple myeloma patients either at diagnosis or during follow-up. Between February 2001 and January 2005, 397 whole body scans were acquired. On 229 scans performed at diagnosis, 146 (64%) were positive and 81 cases have discordant X-ray results. The sensitivity of 99mTc-MIBI and X-ray were 77% and 45% respectively. As a result of 99mTc-MIBI, 40% of asymptomatic myeloma patients were up-staged. The positivity of 99mTc-MIBI correlated significantly with all of the most relevant clinical and biological parameters. Multivariate analysis selected only high reactive C protein (P = 0.0005), bone marrow infiltration (P = 0.02) and bone pain (P = 0.002) as factors affecting 99mTc-MIBI pattern. In 22 patients with solitary myeloma, 99mTc-MIBI was positive in 86% of cases and detected more disease sites than X-ray. Among 168 scans performed during follow-up, 99mTc-MIBI presented high specificity in patients showing a complete response (CR; 86%), and correlated with myeloma activity and with response to therapy. At multivariate analysis, a positive pattern correlated with bone marrow infiltration (P = 0.002) and disease status other than CR (P = 0.03). We conclude that 99mTc-MIBI scanning is an additional diagnostic tool with a high specificity for the staging and the follow-up of multiple myeloma patients.

The Role of Whole-Body Magnetic Resonance Imaging in the Staging and Follow-Up of Bone Disease in Multiple Myeloma.

Radiographic skeletal survey (RSS) is the standard diagnostic tool for the screening of bone lesions in multiple myeloma (MM) at diagnosis and during the course of disease. Its major limitation is the low sensitivity in detecting minimal bone lesions and in differentiating active from inactive osteolyses. Several studies demonstrated the superiority of magnetic resonance imaging (MRI) over RSS for the detection of spinal and pelvis bone lesions. However, a significant proportion of patients develops bone lesions elsewhere, therefore MRI of spine and pelvis is inadequate for the staging and follow-up of patients. Recently, whole-body MRI (WB-MRI) has been used with promising results for the detection of secondary bone lesions in patients with non-haematological malignancies. The aims of this study were to evaluate the potential role of WB-MRI in the staging and follow-up of MM patients, using RSS as a standard of reference, and to study the correlation of MRI findings with biochemical markers of bone turnover. Characteristics of the 9 patients included in the study were the following: median age 57 years (46–67), 6 males and 3 females; 4 patients were untreated and asymptomatic, and 5 previously treated with chemotherapy. On the same day, all patients underwent RSS and WB-MRI, and blood sampling for serum osteocalcin (OC) as a marker of bone formation, and for carboxyterminal telopeptide of type I collagen (ICTP) as a marker of bone resorption. RSS and WB-MRI were read by two independent radiologists. WB-MRI was performed with a 1.5-T scanner (Magnetom Symphony Maestro Class). The skull, thorax, pelvis, femoral and lower leg bones were imaged in coronal planes, while sagittal images of the spine were acquired. T1-weighted spinecho (SE) and short-tau inversion time inversion recovery (STIR) sequences (TR 2670, TE 101, TI 150) with a maximum field of view of 450 mm and slice thickness of 5 mm were obtained. As reference standard contrast-enhanced MRI was performed in patients with discordant data at RSS and WB-MRI.RSS was negative in 5 patients, whereas in 4 revealed lytic lesions stable with respect to prior controls. In the group of RSS-negative patients, WB-MRI was positive in 3/5 cases, 2 of whom had marrow and serum progression at the time of evaluation. All 4 RSS-positive patients showed lytic lesions also at WB-MRI with an overlapping pattern of distribution. Only the lesions at humeral bones were not detected by WB-MRI, because humeri are outside the field of view. WB-MRI, however, was superior to RSS in identifying lytic lesions in the spine and pelvis. Biochemical markers of bone metabolism were evaluable in 8/9 cases. ICTP levels were high only in one patient without evidence of bone lesions both at RSS and WB-MRI. OC levels were low in 6 of 8 evaluable patients, and 5 of them had a positive WB-MRI.In conclusion, WB-MRI seems more sensitive than RSS for the detection of bone lesions in MM patients. In particular, it is more suitable for the initial staging of the disease in asymptomatic stage I MM and for the follow-up of patients with a stable picture of lytic lesions at RSS. There is no correlation between ICTP levels and the radiological findings, whereas OC levels are decreased in patients with extensive bone involvement.

Recovery of Polyclonal Immunoglobulin Synthesis after Autologous Stem Cell Transplantation in Multiple Myeloma Patients as a Prognostic Factor for Event-Free Survival.

Suppression of polyclonal immunoglobulin (Ig) synthesis is one feature of multiple myeloma (MM). To evaluate if recovery of polyclonal Ig synthesis after autologous stem cell transplantation (ABSCT) influences prognosis, we have retrospectively analyzed the prognostic value of clinical and laboratory variables of 348 multiple myeloma patients who underwent their first autologous stem cell transplantation between 06.1992 and 10.2002 at the University Hospital of Heidelberg. The median follow-up was 34 months (range, 3 to 136 months). The median number of chemotherapy courses prior to first ABSCT was 5 (range, 3 to 30). Twenty-two of 348 patients underwent altogether three ABSCTs (including 18 patients with tandem transplantations), 141 had two ABSCTs (including 87 tandem transplantations) and 29 patients were treated with allogeneic transplantation as second line treatment. Recovery of polyclonal Ig synthesis was studied by serumelectrophoresis on day 100 after first ABSCT (±30 days). Full polyclonal Ig recovery was observed in 93 of 348 patients (28%), partial recovery (reduced polyclonal Ig, no monoclonal Ig) in 58 (17%), no recovery (almost no polyclonal Ig and no monoclonal Ig) in 16 (5%), polyclonal Ig recovery associated with monoclonal Ig in 95 (27%) and monoclonal Ig without polyclonal Ig in 72 patients (21%) (data missing in 14 patients (4%)). On multivariate analysis (333 patients), using Cox proportional hazards regression model stratified with respect to tandem transplantation, superior event-free survival was observed with recovery of polyclonal Ig synthesis, low beta2-microglobulin at diagnosis (<2.5mg/L) and a high haemoglobin at diagnosis, whereas MM type IgA and a high number of chemotherapy courses prior to first ABSCT were identified as adverse prognostic factors. Regarding polyclonal recovery, patients with polyclonal Ig recovery associated with monoclonal Ig had a superior event-free survival compared to patients with only monoclonal Ig without any polyclonal Ig recovery. Overall survival was superior in patients with a low β2-microglobulin at diagnosis (<2.5mg/L) and a high haemoglobin at diagnosis, and worse in patients with a high number of chemotherapy courses prior to first ABSCT. We conclude that any recovery of polyclonal Ig synthesis even when associated with monoclonal Ig, improves event-free survival, and therefore can be used as a predictor of prognosis in the follow-up of multiple myeloma patients who underwent ABSCT.