Expression and Clinical Significance of β-Catenin in Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5010-5010
Author(s):  
Juan Li ◽  
Dian-Bao Zhang ◽  
Shao-kai Luo ◽  
Ying Zhao ◽  
Bei-Hui Huang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Clinical Significance ◽  
Healthy People ◽  
Expression Level ◽  
Stage Iii ◽  
Expression Levels ◽  
Mrna And Protein Expression ◽  
Expression Rate ◽  
The Relationship

Abstract OBJECTIVE: To detect the expression of β-catenin in mononuclears of bone marrow of healthy people, primary and relapsed/refractory multiple myeloma(MM), and analysis the clinical date and the curative effect of the MM patient, to open out the clinical significance of the expression of the β-catenin in MM. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and Wes tern blot were used to detect mRNA and protein expression of β-catenin in bone marrow samples of 12 primary MM patients, 14 relapsed/refractory MM patients, and 11 healthy people. RESULTS: The positive rates and the expression levels of β-catenin mRNA were significantly lower in healthy people than in MM patients (27.3% vs. 88.5%, 0.22±0.09 vs. 0.80±0.15, P <0.01), the expression level of β-catenin mRNA(β-catenin/β-actin) was significantly lower in newly diagnosed patients than in MM patients (0.7196±0.11 vs. 0.8517±0.16, P <0.05). β-catenin protein were not detected in all of the healthy people; while the positive rates of β-catenin was 69.2% in MM patients (P <0.01), and its expression levels was significantly higher in relapsed/refractory patients than in primary patients (0.3231±0.11 vs. 0.2065±0.08, P<0.05). In 10 primary MM patients which can be evaluated the curative effects, the expression rate in no response patients was significant lower than in response patients (14.3% vs. 100%, P <0.05). To stage the patients, the statistics show the expression of β-catenin protein in Durie/Salmon stage III was significant higher than stageII(87.5% vs. 40%, P <0.05) and in ISS stage III was significant higher than lor IIstage(100% vs. 45.5% or 33.3%). CONCLUSION: To analysis the relationship between β-catenin and β2-MG or serum LDH, we found the β-catenin protein was positive correlative with the expression level of β2-MG (r=0.688, P<0.01). and serum LDH(r=0.502, P<0.05).

scholarly journals Expression and Clinical Significance of CD137L in Multiple Myeloma Cells

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5616-5616
Author(s):  
Chengcheng Fu ◽  
Shuang Yan ◽  
Depei Wu
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Clinical Significance ◽  
Cell Lines ◽  
Myeloma Cell ◽  
Expression Level ◽  
Newly Diagnosed ◽  
Myeloma Cells ◽  
Low Level ◽  
Rpmi 8226

Abstract 【 Background 】 Human CD137L molecule, a member of the TNF superfamily, was found to be expressed in a variety of malignant tumors, such as acute myeloid leukemia, non Hodgkin's lymphoma, associated with complete remission. Our previous experiments showed that high level of CD137L expressed on the surface of myeloma cell line RPMI-8226, U266, LP1, MY5 and KMS-11, as well as MM primary cell. However, we have no idea about the level of CD137L on MGUS (monoclonal gammapathy of undetermined significance) and the relation between the expression level and tumor stage, bionomics, prognosis of multiple myeloma. 【 Objective 】 (1) To determine expression and clinical significance of CD137L molecular in patients with MGUS and multiple myeloma cells; (2)To explore function of CD137L in multiple myeloma cell lines. 【 Methods 】 (1) The expression of CD137L molecule on myeloma cells/normal plasma cell surface was detected by flow cytometry; (2) Clinical significance of CD137L molecule expressed by multiple myeloma cells was accessed via rank sum test; expression level of high/low of CD137L on overall survival was evaluated through survival analysis and Log-Rank test; (3) SiRNA, the customization of SiRNA for CD137L gene, transfected myeloma cell lines U266, RPMI-8226, KMS-11 by Lipo3000.Then the expression of CD137L was detected by RT-PCR; cell cycle distribution after inhibition of CD137L signal was detected by PI; cell proliferation was detected by CCK8. 【 Results 】 (1) Fresh bone marrow specimens of 28 patients with newly diagnosed multiple myeloma patients were collected. The expression of CD137L molecule on CD45-/CD38+/CD138+ cell group in bone marrow was detected, and the median expression level was 29 (7-94)%; the expression of CD137L molecule on 9 patients with MGUS was 7 (2-57)%; (2) That the expression level of CD137L between patients with MGUS and newly diagnosed MM showed statistic difference indicated that it could be as a marker for differential diagnosis; the different expression level by rank sum test between those with newly diagnosed MM and post-treated MM, post-treated MM and RRMM indicated that it could be a marker for MRD; (3) The follow-up of patients found that after the treatment CD137L level of 11/13 patients decreased, and these patients at least achieved PR; (4) there is no related with the level of CD137L and type, ISS stage, DS stage, white blood cell count, hemoglobin concentration, platelet count, serum beta 2- microglobulin, lactate dehydrogenase, serum albumin, calcium concentration, the ratio of bone marrow plasma cell by correlation analysis; (5) According to median values of CD137L expression level, all the newly diagnosed patients were divided into two groups, low level expression and high level and survival analysis showed no significant difference by Log-Rank test. The 2 years survival rate of low level group and the high one was 84.7%, 74.1%; (6) KMS-11, RPMI 8226,U266 cells were transfected using Lipo3000 and only U266 cell line was inhibited obviously. Inhibition of CD137L induced cell proliferation by CCK8 test and a distribution change of G1 and S phase on cell cycle. 【 Conclusions 】 Multiple myeloma cell lines and primary myeloma cells had a high expression level of CD137L, MGUS cells had a low level while normal plasma cells surface without CD137L expression; CD137L can be a marker for diagnosis of MM and MGUS and for minimal residual disease; CD137L expression of MM patients had no correlation with clinical and biological features; In vitro the inhibition of CD137L signaling on U266 cells can induce cells proliferation. Disclosures No relevant conflicts of interest to declare.

scholarly journals Overexpression of Yin Yang 1 in bone marrow-derived human multiple myeloma and its clinical significance

2014 ◽  
Vol 45 (3) ◽  
pp. 1184-1192 ◽  
Author(s):  
SARA HUERTA-YEPEZ ◽  
HONG LIU ◽  
STAVROULA BARITAKI ◽  
MARIA DEL LOURDES CEBRERA-MUÑOZ ◽  
CLARA RIVERA-PAZOS ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Clinical Significance ◽  
Yin Yang 1 ◽  
Yin Yang ◽  
Human Multiple Myeloma

Personalized Treatment with low doses of Lenalidomide and Dexamethasone for Relapsed Multiple Myeloma in frail or Elderly Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5049-5049
Author(s):  
Angel Ruedas ◽  
Pablo Guisado ◽  
Beatriz Aguado ◽  
Ricardo Perez ◽  
Joaquin Martinez ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Elderly Patients ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Light Chains ◽  
Bone Marrow Toxicity ◽  
Low Doses ◽  
Very Elderly

Abstract Abstract 5049 Background. Treatment of frail or elderly patients with relapsing symptomatic/active Multiple Myeloma (MM) is very difficult due to concomitant diseases, impaired bone marrow reserve, systemic toxicity, relatively decreased renal function and general problems of old age. Dexamethasone and new agents (thalidomide, lenalidomide, bortezomib and bendamustine) have been used in this setting, in most cases with doses adapted to the clinical situation. Aims. To retrospectively analyze the management of frail and/or very elderly MM patients with relapsed and active disease treated with reduced doses of the aforementioned agents in five hospitals in Madrid, Spain. Methods. The files of this group of MM patients were studied. The most common treatment has been the combination of low doses of lenalidomide (len) and of dexamethasone (dex), whereas treatment with reduced doses of other agents has been anecdotal; therefore we analyzed the results of len/dex combinations. Len and dex have been used in lower than standard doses, adapted to the individual initial situation of the patients and tailored according to effect and toxicity throughout treatment. There was no specific protocol and the management of the patients has depended exclusively on the practice and criteria of the treating physicians. Patient risk was stratified following the Salmon and Durie (S&D) score and the International Staging System (ISS). Response was assessed with the IMWG criteria. The study has been approved by the Ethics Committee of Hospital Ramon y Cajal, as coordinating center. Results. 38 patients were included in the study. Mean age was 79 years (range 68–90). 30 pts (79%) were older than 75 years and 10 pts had over 85 years. More than half of the patients (21) had two or more comorbidities. Patients had previously received 1 to 5 (m=1. 8) different treatment modalities, including steroids, melphalan (25), bortezomib (20), thalidomide (6) (or their combinations), and others or even APBSCT (3). 23 pts (60%) had IgG (m=4087 mg/dl, range 868–13000); 13 (34%) IgA (m=2115, range 355–4930) and 2 (5%) only light chains. 22 had κ and 15 λ light chains. 19 (50%) had BJ proteinuria. Mean Hemoglobin level was 10. 7 gr/dl (7. 5–14. 1) and mean creatinine level 1. 3 mg/dl (0. 4–12. 9); 28 (74%) had bone disease. 3 pts had S&D stage I, 22 stage II, and another 13 stage III. 13 pts had ISS stage I, 17 had stage II and 7 stage III. Patients received between 1 and 30 cycles of len/dex (m= 8). Median initial Len dose was 10 mg, the majority between 5 and 15mg, although 4 received 25 mg that were rapidly reduced. Mean initial dex dose was 20mg/day for 4 days. 4 pts (10. 5%) achieved Complete Remission (CR) (3 with negative IF), 27 (71%) Partial Remission (PR) (5 with VGPR) and 2 (5%) a significant, but lesser than 50%, reduction of the M-component (Stable Disease, Std). Altogether, overall response (CR+PR+Std) occurred in 33 pts (86%). The best response occurred after 2 to 9 cycles (m=4) of len/dex. Treatment was stopped in 15 patients due to neurological (4) or hematological (1) toxicity, pulmonary embolism (1), unrelated causes (4) and after achieving a plateau response (5). Time to next treatment was 1–30 months, (m=8 mo). 7 pts relapsed after 3–21 months (m=7). 10 patients died, 5 of related (disease progression, cardiac amyloidosis, renal progression to ESRF) and 5 of unrelated (cancer, sepsis, myocardial infarction, congestive heart failure) causes. Grade III-IV bone marrow toxicity occurred in 9 pts and neurological toxicity (PNP) in 5 (all of them had previously been treated with bortezomib or thalidomide). Conclusions. Personalized low doses of len/dex have been the most common treatment for frail/very elderly patients with relapsed MM in our centers and it is an active and tolerable option in this setting. The haematological toxicity was expectable and manageable, but prior treatments with bortezomib or thalidomide were associated with limiting neurotoxicity. Disclosures: No relevant conflicts of interest to declare.

Identification of a novel microRNA, miR-4449, as a potential blood based marker in multiple myeloma

2017 ◽  
Vol 55 (5) ◽  
Author(s):  
Xianjuan Shen ◽  
Yan Ye ◽  
Jing Qi ◽  
Wei Shi ◽  
Xinhua Wu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Growth ◽  
Real Time ◽  
Quantitative Pcr ◽  
Healthy Controls ◽  
Biological Processes ◽  
Expression Levels ◽  
Relative Expression ◽  
Real Time Quantitative Pcr

AbstractBackground:miRNAs act in diverse biological processes including development, cell growth, apoptosis, and hematopoiesis, suggesting their role in cancer.Methods:We examined the miRNAs perturbed in CD138+ primary multiple myeloma (MM) cells, using microarray analysis and real-time quantitative PCR (RT-qPCR). Serum miR-4449 expression levels were detected from 71 primary MM patients and 46 healthy controls by RT-qPCR.Results:Our analysis revealed up-regulation of 54 and down-regulation of 28 miRNAs in MM subjects compared to healthy controls. miR-4449 has not been reported in MM. It was found that the relative expression of bone marrow miR-4449 in MM patients (2.14±1.42) was higher than that in healthy controls (0.815±0.165) (U=8, p=0.0093). The relative expression of serum miR-4449 in MM patients (2.11±2.10) was significantly higher than that in healthy controls (0.357±0.235) (U=374, p<0.0001) and was significantly correlated with βConclusions:The expression levels of serum miR-4449 in MM patients were significantly higher than in healthy controls, suggesting that it may prove to be useful in the auxiliary diagnosis of MM.

Correlation of Vitamin D3 with the Expression of RORγt and Foxp3 mRNAs in the Peripheral Blood of Myasthenia Gravis Patients

2020 ◽  
pp. 1-7
Author(s):  
Pan Huang ◽  
Xiao-ying He ◽  
Min Xu
Keyword(s):  
Myasthenia Gravis ◽  
Peripheral Blood ◽  
Normal Subjects ◽  
Orphan Receptor ◽  
Expression Level ◽  
Control Group ◽  
Foxp3 Mrna ◽  
Expression Levels ◽  
Relative Expression ◽  
The Relationship

<b><i>Objectives:</i></b> to investigate the expression levels of 1,25(OH)<sub>2</sub>D<sub>3</sub> in the peripheral blood from patients with myasthenia gravis (MG) and to correlate levels with retinoid-related orphan receptor γt (RORγt) and forkhead or winged-helix transcription factor 3 (Foxp3) mRNA expression. <b><i>Methods:</i></b> Sixty-seven patients with MG were enrolled in the experimental group, and 50 normal subjects were selected as the control group. The expression levels of 1,25(OH)<sub>2</sub>D<sub>3</sub> and RORγt and Foxp3 mRNAs were measured in the serum of the 2 patient groups and the relationship between factors were correlated with the severity score of MG. The relationship between the levels of 1,25(OH)<sub>2</sub>D<sub>3</sub> and the relative expressions of RORγt and Foxp3 mRNAs was determined. <b><i>Results:</i></b> There were no differences between groups regarding patient’s baseline data. 1,25(OH)<sub>2</sub>D<sub>3</sub> and RORγt and Foxp3 mRNAs are differentially expressed in the MG group and the control group (<i>p</i> &#x3c; 0.05). QMG score is negatively correlated with the expression level of peripheral blood 1,25(OH)<sub>2</sub>D<sub>3</sub> and Foxp3 mRNA (<i>r</i> = −0.797, −0.543; <i>p</i> &#x3c; 0.01) and positively correlated with the relative expression level of RORγt mRNA (<i>r</i> = 0.539; <i>p</i> &#x3c; 0.01). 1,25(OH)<sub>2</sub>D<sub>3</sub> expression level was negatively correlated with the relative expression of RORγt mRNA (<i>r</i> = −0.559; <i>p</i> &#x3c; 0.01) and positively correlated with the relative expression of Foxp3 mRNA (<i>r</i> = 0.390; <i>p</i> &#x3c; 0.01). <b><i>Conclusions:</i></b> The levels of 1,25(OH)<sub>2</sub>D<sub>3</sub> were shown to be lower in patients with MG compared to normal controls. The observed low levels of 1,25(OH)<sub>2</sub>D<sub>3</sub> may lead to changes in the expression of RORγt and Foxp3 mRNAs involved in MG.

Clinical and Prognostic Impact of (11;14)(q13;q32) Translocation on Patients with Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5507-5507
Author(s):  
Daisuke Miura ◽  
Kentaro Narita ◽  
Ayumi Kuzume ◽  
Rikako Tabata ◽  
Toshiki Terao ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Tumor Cells ◽  
Clinical Characteristics ◽  
Mononuclear Cells ◽  
Plasma Cells ◽  
Stage Iii ◽  
Prognostic Impact ◽  
Cd20 Expression ◽  
The Impact

Introduction. Translocations involving chromosome 14 at band q32, the immunoglobulin heavy chain (IgH) locus, are considered to be the most important initiating events for the development of multiple myeloma (MM). Among the IgH translocations in MM, t(11;14)(q13;q32) is the most frequently reported, and associated with a lymphoplasmacytic morphology. This translocation have been traditionally considered as standard-risk chromosomal abnormality compared to other translocations such as t(4;14) or t(14;16), although some controversies on the prognostic impact of this translocation still remain. This study aimed to clarify the clinical and prognostic impact of t(11;14) in Japanese patients in relation to other clinical variables such as immunophenotype of the tumor cells, other cytogenetic abnormalities, and use of stem cell transplantation (SCT). Patients and methods. Among the 244 consecutive patients with newly diagnosed MM, treated at Kameda Medical Center between April 2009 and July 2019, 234 patients, having cytogenetic analysis data (including t(11;14), t(4;14), t(14;16), and del(17p) by interphase fluorescence in situ hybridization (iFISH)) fully available, were included in this study. Data regarding the patients' clinical and laboratory characteristics, including the International Staging System (ISS), immunophenotype of the tumor cells, baseline circulating plasma cells (CPCs), treatment responses, disease progression, and survival status, were collected. iFISH was performed with CD138-purified bone marrow plasma cells, and the cut off values for translocation were ≥ 10% and for del(17p) ≥ 20%. Using multicolor flow cytometry, surface marker analysis of bone marrow samples and quantification of pre-treatment CPCs on peripheral blood mononuclear cells were simultaneously performed. CPCs were reported as the percentage of total mononuclear cells. Patients were considered to be negative for clonal CPCs at a sensitivity of 10−4 (0.01%) clonal plasma cells for all events evaluated. Results. The incidence of patients harboring t(11;14) was 24.4% (n = 57); t(11;14) was detected significantly high in light-chain-only subtypes (P < 0.001). We compared clinical characteristics of patients carrying t(11;14) with others. Myeloma cells with t(11;14) were associated with negative expression of CD56 (P < 0.001), CD117 (P = 0.046), and CD200 (P = 0.006), and positive expression of CD20 (P = 0.01) and CD81 (P = 0.035). Patients with t(11;14) were associated with positive CPCs (P = 0.011). In order to focus on the impact of t(11;14), we divided the patients into 4 groups: (A) no specific cytogenetic abnormality listed above (n = 137), (B) t(11;14) group (n = 57), (C) t(4;14) or t(14;16) group (n = 29), and (D) del(17p) only (n = 10), and the clinical characteristics and survival of the patients were compared across the three groups (A), (B), and (C). Almost all the patients (> 95%) in this cohort received bortezomib-based therapy. Median progression-free survival (PFS) and overall survival (OS) of patients in (A), (B), and (C) groups were 55.6, 34.2, and 30.2 months (m) (A vs. B, P = 0.036, and A vs. C, P = 0.031), and not reached, 51.2, and 79.8 m (A vs. B, P = 0.11, and A vs. C, P = 1.00), respectively. However, patients harboring t(11;14) were further divided into CD20-positive and -negative groups, the latter having poor prognosis (36.1 vs. 26.7, P = 1.0 for median PFS, and not reached vs. 44.2, P = 0.029 for median OS). Compared to other groups, patients without CD20 expression had significantly shorter OS (vs. A, vs. B, P = 0.024, 0.035, respectively), whereas those with CD20 expression tended to have longer OS, without statistical significance (Figure 1).Univariate analysis revealed ISS stage III, creatinine > 2.0 mg/dL, use of SCT, t(11;14) without CD20 expression, and age ≥ 70 years to be associated with shorter OS, whereas multivariate analysis demonstrated ISS stage III, use of SCT, and t(11;14) without expression CD20 (HR 1.88; 95% CI 1.10-3.21; P = 0.021) to be independent prognostic factors for poor OS. Conclusions. Our findings demonstrated that patients harboring t(11;14) had distinct clinical and immunophenotypic characteristics, two subsets of the disease entities with a clearly different survival according to CD20 expression. Disclosures Matsue: Ono Pharmaceutical: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Novartis Pharma K.K: Honoraria; Celgene: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria.

WT1 Transcripts Is a Powerful Leukemia Marker to Predict Early Relapse After Allogeneic Haematopoietic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4488-4488
Author(s):  
Carlo Messina ◽  
Cristina Tresoldi ◽  
Maria Teresa Lupo Stanghellini ◽  
Alessandro Crotta ◽  
Stefania Girlanda ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Expression Level ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Early Relapse ◽  
Expression Levels ◽  
Donor Chimerism ◽  
Before And After

Abstract Abstract 4488 Introduction Definition of leukemia remission requires the lack of disease markers at sub-microscopic level. This is highly important after a potentially curative approach as allogeneic hematopoietic stem cell transplant (HSCT), where early detection of relapse at molecular level may lead to modulation of immunosuppressive therapy or donor lymphocyte infusion (DLI). In AML various approaches has been used to define MRD, but still the majority of AML cases do not have a useful and sensitive MRD marker. Over-expression of Wilms' tumor gene 1 (WT1) in leukemic blasts has been reported in >80% of AML and >40% of MDS. Physiologic hematopoietic stem cell compartments also express WT1, however, a ‘malignant’ WT1 expression can be clearly distinguished based on quantitative detection methods such as semiquantitative RT-PCR. Quantification of WT1 expression levels can detect frequencies of leukemic cells in bone marrow (BM) and peripheral blood (PB) as low as 10-3 and 10-5, respectively. Therefore WT1 expression levels provide a new marker for leukemic blast cells regardless of the type of leukemia especially in the relevant percentage of patients that lacks a specific molecular marker of their disease and thus may be a useful marker MRD and may predict the relapse after allogeneic HSCT. Materials and methods We measured quantitative expression of WT1 at diagnosis, before and after allogeneic transplant monthly for the first six months and then every three months. The quantitative assessment of the WT1 transcript amount was performed by real-time quantitative polymerase chain reaction (RQ-PCR). Results Our study included 19 AML and 6 MDS pts who underwent allogeneic HSCT in our Institute between 12/2007 and 6/2009. Median age at diagnosis was 49 years (range 22-68). Bone marrow samples at diagnosis showed a WT1 median expression level of 5851.66 copies (range 77.98-31203.57). Fifteen pts (60%) had a specific cytogenetic marker that could allow MRD monitoring. At HSCT 17 pts (68%) were in CR, 5 (20%) had a refractory or relapsed disease, while 3 (12%) were transplanted upfront. Six pts (24%) received grafts from a matched sibling donors, 6 (24%) were transplanted from a matched unrelated donor (MUD), 10 (40%) from a familiar haploidentical donor and 3 (12%) received a cord blood unit. Myeloablative conditioning regimen consisted of Treosulfan 42 g/sqm, Fludarabine 150 mg/sqm, ALG 30 mg/kg and Rituximab 500 mg (last two drugs only for alternative donors). After HSCT a rapid decline of WT1 expression levels was observed in all pts that obtained or maintained a condition of CR. Two pts (8%) relapsed and both had an increase in WT1 expression before relapse. In the first relapsed pt, analysis of WT1 showed a dramatically increase between pre transplant level and day +28, while STR showed 100% donor chimerism. Relapse occurred on day +43, still on IST, with 69% of blast at AM evaluation and 40% donor chimerism. This pt was successfully reinduced with chemotherapy followed by allogeneic PBSC infusion without GvHD profilaxys obtaining a rapid reduction of WT1 (43.66). The pt developed GvHD that required a new IST, confirming a strong immune-surveillance of HSCT. The second pt was still on immunosuppressive treatment (IST) at the time of relapse (+136). WT1 in BM on day +30 was 30 cp and then increased gradually to 167 and 190 cp on day +67 and +102, respectively. Cytogenetic analysis and STR chimerism still showed a cCR with 100% donor chimerism. At relapse AM showed 10% blasts, WT1 expression level was 7447 cp with >95% donor chimerism. IST was discontinued and one month later WT1 expression level decreased to 1640 with >95% donor chimerism. In this situation we reasoned that DLI was the best available treatment. The total dose of donor T cell infused was 5 ×105 CD3/Kg. This procedure allowed an immune-mediated leukemia control with reduction of WT1 (1.58), cCR and 100% donor chimerism. Conclusions These data show that WT1 may be useful as a non-specific leukemia marker for monitoring MRD in AML and MDS after allogeneic HSCT and should enable the detection of early relapse allowing intervention at a more favourable stage than at overt relapse. We observed a complete concordance between WT1 expression levels and status of AML before and after allogeneic HSCT. Based on these results cases with increase of WT1 levels after HSCT and without GVHD may be candidate to immune intervention such as discontinuation of immunosuppression and/or DLI. Disclosures: Bonini: MolMed S.p.A.: Consultancy.

Tailored Low Dose Lenalidomide with Low Dose Dexamethasone (len/dex) in Previously Treated Patients with Multiple Myeloma Older Than 70 Years Requiring Treatment.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4950-4950
Author(s):  
Angel Ruedas ◽  
Ricardo Perez ◽  
Valentin Garcia ◽  
Alicia Smucler ◽  
Pilar Bravo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Elderly Patients ◽  
Low Dose ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Bone Marrow Toxicity ◽  
Low Doses ◽  
Previously Treated

Abstract Abstract 4950 Background & Aims The management of elderly patients with Multiple Myeloma (MM) previously treated requiring further therapy (although in most cases palliative) is very difficult due to the presence of concomitant diseases, decreased bone marrow reserve, systemic toxicity, relatively decreased renal function and general problems of old age. As in this setting the tolerability of standard doses of conventional chemotherapy, high doses of dexamethasone or IMiDs is a concern, we report the preliminary results of the combination of tailored low doses of lenalidomide (len) and low doses of dexamethasone (dex). Methods We retrospective analyze the results of the combination of low dose lenalidomide and low dose of dexamethasone (len/dex) in 14 patients aged over 70 years with pretreated MM and progressive disease. Low doses of len (5-10 mg daily for 21days) were initially given and flexibly modified in subsequent cycles according to response and toxicity, along with low doses of dex (20-40 mg/day for 4 days) in most (12) patients. G-CSF and red cell transfusions were used when needed. Patient risk was stratified following the Salmon and Durie (S&D) score and the International Staging System (ISS). Response was assessed with the IMWG criteria. Results Median age was 80 years (70-90). All patients had received between 2-5 different previous modality treatments (m=2), including bortezomib (7), thalidomide (4) or PBSCT (2). 11 pts had IgG, m=3397mg/dl (868-4990), 2 IgA m=1460 (1050-1870) and another one BJ. 9 pts had κ and 4 » light chains. Median Hemoglobin level was 10 gr/dl (7.2-11.4) and median creatinine level 1.19 mg/dl (0.75-1.63). 11 (78%) had bone disease. 9 pts had S&D stage II, 4 stage III and another one stage I. 7 pts had ISS stage II, 4 had stage I and 2 stage III. Patients received between 2 and 13 cycles of len/dex (m=6.8). 11 pts (78%) achieved Partial Remission (PR) and 2 (14%) achieved significant, but lesser that 50%, reduction of the M-component (Stable Disease: Std). Overall response (PR+Std) occurred in 13/14 patients (92.8%). The best response occurred between 2-12 cycles of len/dex. Grade III-IV bone marrow toxicity occurred in 5 pts (35 %) and neurological toxicity (PNP) in 5 pts (35%) (all of them had received previous bortezomib or thalidomide). Treatment was stopped in 6 pts: for unrelated causes (1), due to neurological (3) or haematological (1) toxicity and in 2 pts after achieving Std and both relapsed after 3 months. Conclusions Treatment with tailored low doses of lenalidomide and low doses of dexamethasone (len/dex) is an active and tolerable option for previously treated elderly patients with symptomatic MM. Low lenalidomide doses can be flexibly modified according to the quality of the response and the hematological toxicity that is expectable and manageable. Previous treatments with bortezomib or thalidomide is associated with neurotoxicity. Disclosures No relevant conflicts of interest to declare.

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