Oral Acyclovir Is an Effective in Decreasing the Incidence of Bortezomib Associated Herpes Zoster in Patients with Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4844-4844 ◽  
Author(s):  
Dawn DePaolo ◽  
Kena C. Miller ◽  
Amy Whitworth ◽  
Alice Mohr ◽  
Terry L. Mashtare ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Herpes Zoster ◽  
Side Effect ◽  
Historical Control ◽  
Oral Acyclovir ◽  
Significant Morbidity ◽  
Significant Difference ◽  
Acyclovir Prophylaxis ◽  
The Impact ◽  
First Time

Abstract Introduction: Bortezomib, a proteasome inhibitor is an effective antimyeloma therapy. We recently reported that multiple myeloma patients treated with bortezomib or bortezomib based regimen resulted in a higher incidence of herpes zoster (HZ). The exact etiology of this side effect remains unknown though our investigation demonstrated prolonged lymphopenia among patients treated with bortezomib. The high incidence of HZ among bortezomib treated patients prompted to prospectively investigate the role of antiviral prophylaxis in this patient population. Here we report for the first time the efficacy of acyclovir as prophylaxis for bortezomib associated HZ. Patients and Methods: We prospectively evaluated the impact of oral acyclovir (400mg PO twice daily for the duration of bortezomib therapy) on the incidence of HZ. All patients with multiple myeloma who were treated with bortezomib or bortezomib based regimens, and received prophylactic acyclovir were evaluable for this analysis. To compare the overall proportion of HZ among patients who received acyclovir prophylaxis and the historical control, Fisher exact test was used. Results: A total of 51 consecutive patients (27 M and 24 F) received acyclovir as prophylaxis. The median age was 61 (range 40–81 years), with advance stage MM noted in 86% (n=44) patients. Among these 69% had previously untreated MM while 31% had relapsed or refractory disease. Single agent bortezomib was given to 11 patients and 40 patients received bortezomib in combination with other antimyeloma agents (such as thalidomide, pegylated liposomal doxorubicin, dexamethasone, cyclophosphamide and/or lenalidomide). The overall incidence of HZ was 0% among patients receiving the acyclovir prophylaxis vs. 13% in the historical control. There was a significant difference in the overall proportion of HZ among patients who received acyclovir prophylaxis and the historical control (p = 0.0026). Conclusion: This is the first report on the efficacy of acyclovir for the prevention of bortezomib associated HZ in MM patients. While bortezomib is an effective antimyeloma therapy, an important side effect with significant morbidity is reactivation of HZ. Here we demonstrate for the first time that this side effect can be effectively prevented by oral acyclovir. Our observation warrants further evaluation. Considering significant morbidity associated with HZ we recommend the routine use of prophylactic acyclovir (or other antiviral agents) for patients being treated with bortezomib or bortezomib-based therapies.

Patients Who Attend Alone at a First Memory Consultation: Are They a Specific Population,or Is It an Instance of Confounding Bias?

2019 ◽  
Vol 81 (1-2) ◽  
pp. 81-86
Author(s):  
Pierre Koskas ◽  
Mouna Romdhani ◽  
Olivier Drunat
Keyword(s):  
Selection Bias ◽  
Confounding Bias ◽  
Significant Difference ◽  
Comparison Groups ◽  
Methodological Problems ◽  
Group 2 ◽  
The Impact ◽  
First Time ◽  
State Examination ◽  
Group 1

As commonly happens in epidemiological research, none of the reported studies were totally free of methodological problems. Studies have considered the influence of social relationships on dementia, but the mechanisms underlying these associations are not perfectly understood. We look at the possible impact of selection bias. For their first memory consultation, patients may come alone or accompanied by a relative. Our objective is to better understand the impact of this factor by retrospective follow-up of geriatric memory outpatients over several years. All patients over 70 who were referred to Bretonneau Memory Clinic for the first time, between January 2006 and 2018, were included in the study. The patients who came alone formed group 1, the others, whatever type of relative accompanied them, formed group 2. We compared the Mini-Mental State Examination (MMSE) scores of patients; and for all patients who came twice for consultation with at least a 60-day interval, we compared their first MMSE with the MMSE performed at the second consultation. In total, 2,935 patients were included, aged 79.7 ± 8.4 years. Six hundred and twenty-five formed group 1 and 2,310 group 2. We found a significant difference in MMSE scores between the 2 groups of patients; and upon second consultation in group 2, but that difference was minor in group 1. Our finding of a possible confounding factor underlines the complexity of choosing comparison groups in order to minimize selection bias while maintaining clinical relevance.

The Impact of Different Mobilization Strategies in the Setting of Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3254-3254
Author(s):  
Francesco Mazziotta ◽  
Gabriele Buda ◽  
Nadia Cecconi ◽  
Giulia Cervetti ◽  
Lorenzo Iovino ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Peripheral Blood ◽  
High Dose ◽  
Roc Curve Analysis ◽  
Cd34 Cells ◽  
Significant Difference ◽  
The Impact

INTRODUCTION Multiple myeloma (MM) is considered an incurable disease. Despite the introduction of novel agents allowed deeper response, high-dose chemotherapy and autologous stem cell transplantation (ASCT) remain the standard of care for patients (pts) in good clinical conditions. The most used strategies to mobilize stem cells from bone marrow (BM) into peripheral blood are high-dose cyclophosphamide (HD-CTX) plus G-CSF and G-CSF plus plerixafor (G-CSF+P). The goal of this retrospective study is to investigate whether the two different mobilization strategies have an impact on the clearance of monoclonal PCs in the apheresis products and on pts' outcome. PATIENTS AND METHODS We analyzed 62 pts (median age 61, range 41-75, 37 males and 25 women) diagnosed with MM and treated with ASCT between Mar 2014 and Mar 2018 at our Hematology Division (Pisa, Italy). All pts received induction therapy with at least 4 cycles of bortezomib, thalidomide and dexamethasone (VTD). 9/62 pts obtained a less than partial response (PR) and received lenalidomide-based regimens. After induction, 8 (12,9%) pts achieved complete remission (CR), 26 (41,9%) were in PR, 28 (45,2%) obtained a very good partial response (VGPR). 43/62 fit pts received HD-CTX (2-3 g/sqm) on day 1 followed by G-CSF (30 MU/day) started on day 4 until day 7, increased to 60 MU/day from day 8 until the end of apheresis. In 19/62 pts, after 4 days of G-CSF (60 MU/day) administration and not sufficient mobilization, we added plerixafor (0,24 mg/kgbw) for up to 4 consecutive days. In 43/62 pts we collected apheresis samples (10μl) analyzed through flow citometry to enumerate clonal residual PCs. The panel used to asses clonality included: CD138 Per-Cp, CD38 APC, CD19 PE-Cy7, CD45 APC-Cy7, cytoplasmic immunoglobulin K chain and L chain. RESULTS At the end of the peripheral blood stem cell (PBSC) collection, pts treated with HD-CTX presented a higher CD34+ absolute count (p=0.0489) and achieved the threshold of 5x106 CD34+ cells/kgbw in a significantly (p=0.006) higher percentage. We found a nearly significant (p=0.0517) lower count of CD34+ PBSCs in pts who received lenalidomide-based regimens before the mobilization. Performing flow citometry on apheresis samples, we observed that the number of the harvested clonal PCs showed a significant correlation (p=0.0115) with the occurrence of post-ASCT relapse. ROC curve analysis investigating the predictive effect of the number of pathological PCs on disease relapse showed an area under the curve of 0,6978 (95% CI 0.5392-0.8564; p=0.0267). Neither BM residual PCs detectable on BM biopsies performed before apheresis (r=-0.1323; p=0.609) nor the type of mobilization scheme (p=0.707) had an impact on the proportion of clonal PCs in the graft. Additionally, we did not observe any statistically significant difference in progression free- (PFS) (p=0.8276) and overall survival (OS) (p=0.2475) between the HD-CTX and G-CSF+P groups. DISCUSSION PBSC mobilization has a succession rate > 85%. Despite the use of HD-CTX to increase PBSC yields and decrease tumor burden, there is not clear evidence of a superior mobilization strategy. Additionally, HD-CTX has a not negligible toxicity and approximately 10% of the pts require hospitalization. Conversely, G-CSF+P is a safe and effective approach also in poor mobilizers. In our study, we observed a significative difference in the apheresis yields (p=0.0489) and in the percentage of pts who achieved the threshold of 5x106 CD34+ cells/kgbw (p=0.006) in favor of HD-CTX. Additionally, the detection of harvested residual clonal PCs could be a promising strategy to recognise pts more likely to relapse after ASCT. Nonetheless, we failed to demonstrate a superior effect of HD-CTX in the clearance of harvested clonal PCs, in agreement with the absence of a different pts' outcome amongst the two mobilization strategies. In conclusion, the choice between the two regimens is challenging and requires careful consideration of multiple factors. Overall, young fit pts, especially in the high-risk setting, should be treated with all appropriate modalities including chemiomobilization followed by double-ASCT. Conversely, in pts candidate to a single-ASCT it is reasonable to use G-CSF+P, since HD-CTX does not improve PFS and OS and add toxicity. The absence of an in-vivo purging effect on apheresis products of chemiomobilization further strengthens a chemotherapy-free mobilization. Disclosures Galimberti: Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau.

Arsenic Trioxide with Ascorbic Acid and High-Dose Melphalan for Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3090-3090 ◽  
Author(s):  
Muzaffar H. Qazilbash ◽  
Rima M. Saliba ◽  
Marilyn S. Davis ◽  
Floralyn L. Mendoza ◽  
Chitra Hosing ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Ascorbic Acid ◽  
Arsenic Trioxide ◽  
Cell Transplantation ◽  
Hematopoietic Progenitor Cell ◽  
High Dose ◽  
Significant Difference ◽  
Preparative Regimen ◽  
The Impact

Abstract Backround: Arsenic trioxide (ATO) has been shown to be synergistic with melphalan both in vitro and in vivo. We conducted a phase I/II trial to determine the safety and efficacy of a combination of arsenic trioxide, melphalan and ascorbic acid (AA) as preparative regimen in patients undergoing high-dose therapy (HDT) and autologous hematopoietic progenitor cell transplantation for multiple myeloma (MM). We also assessed the impact ATO levels on melphalan pharmacokinetics (PK), engraftment and toxicity. Methods: Forty-eight patients with secretory myeloma (23 females, 25 males; median age: 54, range: 3570) were treated between 4/04 and 8/05. All patient received melphalan 100 mg/m2 IV on days -4 and -3 and AA 1000 mg/day IV on days -9 to -3. Patients were randomized to 3 arms; no ATO (arm 1), ATO 0.15 mg/kg IV on days -9 to -3 (arm 2) and ATO 0.25 mg/kg IV on days -9 to -3 (arm 3). Twelve patients had disease progression or relapse after a prior autograft. Median CD34 cells dose infused was 4.5 x 106/kg (range 2.3–10.9). Results: Patients in all 3 arms were evenly matched. With a median F/U of 14.0 months (range 6–25) post autograft, no dose-limiting toxicity or non-relapse mortality was seen. Toxicity was limited to grade I or II nausea, vomiting and diarrhea. Median ATO levels on day 0 in arms 1, 2 and 3 were 0.2, 26.3 and 46.2 ng/ml, respectively. Melphalan PK was not altered by ATO pretreatment. Median time to neutrophil engraftment (ANC >500/ dl) was 9 days. There were no engraftment failures or delays in the ATO arms. CR rate for the entire group was 23%, and total response rate (CR + PR) was 75%. 1-year Progression-free survival (PFS) and overall survival (OS) were 75% and 95%, respectively. There was no significant difference in CR, RR, PFS or OS between the 3 arms (p = 0.9, 0.9, 0.4 and 0.6, respectively). A prior autologous transplant (p = 0.02) and abnormal cytogenetics at transplant (p = 0.04) were associated with a significantly shorter remission. Conclusions: ATO + melphalan + ascorbic acid is a safe, effective and well tolerated preparative regimen for patients with multiple myeloma undergoing an autotransplant. A longer follow up is needed to assess the impact of ATO on progression-free and overall survival.

Serum Concentrations of DKK-1 Correlate with the Extent of Bone Disease in Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3518-3518
Author(s):  
Martin Kaiser ◽  
Maren Mieth ◽  
Peter Liebisch ◽  
Susanne Rötzer ◽  
Christian Jakob ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Disease ◽  
Serum Levels ◽  
Conventional Radiography ◽  
Bone Lesions ◽  
X Rays ◽  
Myeloma Bone Disease ◽  
Lytic Lesions ◽  
Significant Difference ◽  
First Time

Abstract Objectives: Lytic bone disease is a hallmark of multiple myeloma (MM) and is caused by osteoclast activation and osteoblast inhibition. Secretion of Dickkopf (DKK)-1 by myeloma cells was reported to cause inhibition of osteoblast precursors. DKK-1 is an inhibitor of the Wnt/β-catenin signaling, which is a critical signaling pathway for the differentiation of mesenchymal stem cells into osteoblasts. So far there is no study showing a significant difference in serum DKK-1 levels in MM patients with or without lytic bone lesions. Methods: DKK-1 serum levels were quantified in 184 previously untreated MM patients and 33 MGUS patients by ELISA, using a monoclonal anti-DKK-1 antibody. For the evaluation of bone disease, skeletal X-rays were performed. Results: Serum DKK-1 was elevated in MM as compared to MGUS (mean 11,963 pg/mL versus 1993 pg/mL, P < 0.05). Serum DKK-1 levels significantly correlated with myeloma stage according to Durie and Salmon (mean 2223 pg/mL versus 15,209 pg/mL in stage I and II/III, respectively; P = 0.005). Importantly, myeloma patients without lytic lesions in conventional radiography had significantly lower DKK-1 levels than patients with lytic bone disease (mean 3114 pg/mL versus 17,915 pg/mL; P = 0.003). Of interest, serum DKK-1 correlated with the number of bone lesions (0 vs. 1–3 vs. >3 lesions: mean 3114 pg/mL vs. 3559 pg/mL vs. 24,068 pg/mL; P = 0.002). Conclusion: This is the largest study of DKK-1 serum levels in multiple myeloma patients and data show for the first time a correlation between DKK-1 serum concentration and the amount of lytic bone disease, suggesting that DKK1 is an important factor for the extent of bone disease and supporting the hypothesis of DKK-1 as a therapeutic target in myeloma bone disease.

TIMP-1 and TIMP-2 Levels Are Directly Correlated with Neoangiogenesis and Are Prognostic Factors in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4866-4866
Author(s):  
Luciana Correa Oliveira de Oliveira ◽  
Juliana Alves Uzuelli ◽  
Ana Paula Alencar de Lima Lange ◽  
Barbara Amelia Aparecida Santana-Lemos ◽  
Marcia Sueli Baggio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Disease ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 4866 Background Multiple myeloma (MM) is an incurable malignant disease, characterized by increased angiogenesis in the bone marrow (BM) microenvironment and aberrant BM metabolism. Matrix metalloproteinases (MMP) are a family of zinc-dependent endopeptidases implicated in tumour progression, invasion, metastasis and angiogenesis, via proteolytic degradation of extracellular matrix. MMPs are inhibited by tissue inhibitors of metalloproteinase (TIMP). Although recent studies have implicated MMP 9 in MM bone disease, little is known about the role of the TIMPs. Objectives a) to compare levels of sRANKL, OPG, MMP-2, MMP-9, TIMP-1, TIMP-2, VEGF, bFGF, microvessel density (MVD) between newly diagnosed MM patients and healthy controls; b) to determine the association of these molecules with disease progression, bone disease and neoangiogenesis and c) to evaluate the impact of these variables on survival. Patients and Methods As of July 2009 38 newly diagnosed and untreated multiple myeloma patients were enrolled in the study. The median age was 61years-old (range 39-91) with 24 (63%) males. Patients were diagnosed and categorized according The International Myeloma Working Group criteria and ISS, respectively. Bone involvement was graded according to standard X-ray: patients with no lesions, or with one/ two bones involved or diffuse osteoporosis were classified as low score, whereas patients with lesions in more than two bones or presence of bone fracture were classified as high score. MMP-2 and MMP-9 were determined by PAGE gelatin zymography from plasma as previously described. MMP-9, TIMP-1 and TIMP-2, OPG and sRANKL concentrations were measured by ELISA. The levels of VEGF, bFGF were obtained using cytometric bead array. Ten healthy volunteers were used as controls. Bone marrow MVD measured in hotspots was evaluated in 26 out of 38 patients at diagnosis and 15 patients with Hodgkin Lymphoma stage IA and IIA (used as controls) by staining immunohistochemically for CD34. Comparisons among groups were analyzed by ANOVA and the correlation by the Spearman's correlation coefficient. Cox regression were performed for overall survival (OS) analysis. Results Patients with MM had elevated TIMP-1, TIMP-2 and OPG values compared with controls. No significant difference was found between plasma sRANKL, pro-MMP2, pro-MMP9 and MMP-9 levels. We found that plasma TIMP-1 levels correlated positively with bFGF, VEGF, MVD, beta-2 microglobulin (B2M) and OPG (r: 0.514, p=0,001, r: 0.350, p=0,031; r: 0.610, p<0.0001; r: 0.760, p<0.0001 and r: 0.701, p<0.0001, respectively) and TIMP-2 levels with bFGF, DMV, B2M and OPG (r: 0.512, p=0.002; r: 0.595, p<0.0001; r: 0.587, p<0.0001 and r: 0.552, p<0.0001, respectively). TIMP-1 and TIMP-2 levels correlated with the ISS stage (p<0.0001, p=0.006, respectively). The only variables that correlated with clinical bone disease staging were hemoglobin, B2M and albumin levels, whereas TIMP-1, TIMP-2, bFGF, VEGF and OPG correlated with DMV. On the univariate analyses, age, gender, proMMP2, TIMP-1, TIMP-2, creatinine, B2M and MVD were significantly associated with overall survival. In Cox regression model, TIMP-1, TIMP-2 and B2M levels remained to be significantly associated with OS. In conclusion, our results suggest that TIMP-1 and TIMP-2 levels are strongly associated with neoangiogenesis and are independent prognostic factors in MM. Disclosures No relevant conflicts of interest to declare.

Association of PML Expression with Chemotherapy-Resistance In Multiple Myeloma Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2959-2959
Author(s):  
Daisuke Ohgiya ◽  
Makoto Onizuka ◽  
Hiromichi Matsushita ◽  
Naoya Nakamura ◽  
Hiroshi Kawada ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cellular Proliferation ◽  
Conflicts Of Interest ◽  
Alkylating Agents ◽  
Chemotherapy Resistance ◽  
Nuclear Body ◽  
Rank Test ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 2959 Background: Although several novel agents have improved the prognosis of patients with multiple myeloma (MM), it still remains an incurable disease because of the difficulty to eradicate MM cells by current therapeutic approaches. Recent studies have revealed that a subset of malignant cells, cancer stem cells, contribute to chemotherapy-resistance in cancer treatment. Promyelocytic leukemia gene product (PML), known as a tumor suppressor through a variety of cellular functions in a nuclear macromolecular structure called the PML nuclear body, has been reported to be responsible for the chemotherapy-resistance by regulating cell cycle in chronic myeloid leukemia. We therefore investigated the impact of PML expression on the cellular proliferation status of MM cells and patients' prognoses. Materials/Methods: Bone marrow clot sections from 48 patients with newly diagnosed MM from Jan 1998 to Dec 2009 before any therapy at diagnosis were obtained, and analyzed, according to appropriate procedure approved by IRB at the Tokai University School of Medicine (Kanagawa, Japan) with written informed consent. They were doubly-stained with a combination of anti-PML/anti-CD138 and anti-Ki67/anti-CD138. For evaluation of the relation between PML status and cellular proliferation, the positive rates of PML and Ki67 in CD138 positive cells were compared. For investigation of the impact of PML expression on the prognosis of MM, the patients were divided into 3 groups, according to the PML positive rates in the CD138 positive cells: negative/low (less than 25 percentile: 12 cases), intermediate (from 25 to 75 percentile: 24 cases) and high (more than 75 percentile: 12 cases). Their overall survivals were compared using log-rank test. Furthermore, the PML positive rates between before and after treatments were compared using paired t-test. Results: The median observation period of 48 cases was 915 days. The median age of the patients was 62.5 (38-76) at diagnosis. All the patients were underwent combination chemotherapies containing alkylating agents as initial therapies. Two and nine patients were underwent allogeneic and autologous stem cell transplantation during the clinical courses, respectively. The numbers of patients of international staging system (ISS) stage I, II and III were 17, 14 and 17 cases. The PML positive rates in each case ranged from 0% to 83.8%. They were not correlated with ISS stages (Spearman r = 0.083) and the Ki67 positive rates (Spearman r = -0.13). The PML positive rates in the negative/low, intermediate and the high groups were less than 22.1%, from 22.1 to 56.6% and more than 56.6%, respectively. No significant difference in overall survival was observed among the 3 groups (p>0.05). However, there were significant differences in two year survival rate when the 3 groups were compared (100%, 85.2% and 54.7%; p=0.015) (Fig. 1). In 13 patients whose bone marrow clot sections were sequentially collected, the PML positive rates after treatments were significantly higher than those at diagnosis (p=0.0042) (Fig. 2). Especially, PML positive rates in all the 3 patients from the negative/low group were progressively increased (0.3 to 82.6%, 14.1 to 100%, 19.0 to 37.5%), and 2 of them died due to disease progression. On the other hand, 2 patients whose PML positive rates decreased after treatment were alive more than 5 years without therapies. Conclusion: Our data indicated that the level of the PML expression at diagnosis was a possible prognostic factor for early course of the disease (2 years after diagnosis). Chemotherapies might induce PML expression in MM cells or select PML positive MM cells. These findings suggest that PML expression presumably reflect chemotherapy-resistance in MM cells. The molecular mechanism of the association is now under investigation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Immunophenotypic Response After Allografting In Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3371-3371 ◽  
Author(s):  
Luisa Giaccone ◽  
Lucia Brunello ◽  
Roberto Passera ◽  
Moreno Festuccia ◽  
Milena Gilestro ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
First Line ◽  
Significant Difference ◽  
The Impact

Abstract Background Minimal residual disease (MRD) by multiparameter flow-cytometry recently showed a promising role in predicting outcomes in patients with multiple myeloma. However, data on immunophenotypic response (IR) after allografting are lacking. Aim To evaluate the impact of IR and compare it to conventional complete remission (CR) following allografting in myeloma patients. Methods Sixty-six consecutive patients, median age 54 years (35-66), who underwent an allograft between January 2000 and December 2011 with a follow-up of at least 3 months were included. Disease response was evaluated by serum and urine electrophoresis, and bone marrow aspirate at baseline, 3, 6, 12, 18, 24 months after transplant and yearly thereafter. Skeletal survey or MRI were performed yearly or as clinically indicated (overt relapse or complaints of bone pain). Bone marrow aspirates had to contain at least 13000 cells/µL for flow-cytometry studies and IR was defined as absence of monoclonal plasma-cells detected by 4 or 6-colour staining with the following antibodies: CD38, CD138, CD56, CD19, CD45, cyKappa, cyLambda. CR was defined according to standard criteria (Durie et al, Leukemia 2006; 20:1467-73). Results Conditioning regimen was non-myeloablative 2Gy TBI-based in 55 patients, reduced intensity (fludarabine-melphalan-based) in 10 and myeloablative in 1 patient. Post-grafting immunosuppression consisted of cyclosporine with mycophenolate mofetil or methotrexate. Donors were HLA identical siblings in 58 patients and unrelated in 8. Only 1 patient received bone marrow as source of stem cells. Thirty-five/66 (53%) received the allograft as part of the first line treatment, whereas the remaining 31/66, (47%) were transplanted at relapse. At the time of transplant, 5/66 were both in IR and CR, 16 were only in IR and 4 patients were only in clinical CR. All 21 patients in IR at the time of transplant maintained it, while 26/45 (58%) entered IR after the allograft. Among patients surviving at least 3 months, overall treatment related mortality was 10.6% at 3 years. After a median follow-up of 69 months (range 19-147), the incidence of acute and chronic graft-versus-host disease was 45.6% and 49.3% without significant difference between responsive and non-responsive patients. At follow-up, overall, 24 patients achieved CR and IR (CR/IR group), 21 achieved IR but not CR because of persistence of urine/serum M-component (noCR/IR group), and 21 did not achieve either CR or IR (noCR/noIR group). Interestingly, none achieved CR without IR. Median overall survival (OS) and event-free survival (EFS) in patients who achieved IR were 96 and 55 months versus 36 and 7 months in those who did not (p<0.001). Median OS and EFS were not reached and 59 months in the CR/IR group, 77 and 15 months in the noCR/IR, and 30 and 5 months in the noCR/noIR respectively (p<0.001 for both EFS and OS-fig.1). In univariate analysis, being in the CR/IR group was the only significant predictor for prolonged OS and EFS (p<0.001). Of note, cumulative incidence of extra-medullary disease at first relapse after the allograft was 4% in the CR/IR, 32% in the noCR/IR and 15% in the noCR/noIR groups respectively (p<0.001). Receiving the allograft as first line therapy or later during the disease course did not significantly impact on OS and EFS. Conclusion The achievement of IR confers a favorable impact on OS and EFS after allografting. A higher incidence of extra-medullary in the noCR/IR group (some 30% of our patient cohort) may suggest that myeloma cells escape immune control outside the bone marrow. In this group, imaging studies such as positron emission tomography may clinically be indicated during follow-up to detect early relapse. Disclosures: No relevant conflicts of interest to declare.

Impact of t (11;14) on the outcome of autologous hematopoietic cell transplantation (Auto-HCT) in multiple myeloma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8040-8040
Author(s):  
Koji Sasaki ◽  
Gary Lu ◽  
Chitra Hosing ◽  
Uday R. Popat ◽  
Sairah Ahmed ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Chromosomal Abnormalities ◽  
Normal Karyotype ◽  
Cancer Center ◽  
Induction Treatment ◽  
High Dose ◽  
Significant Difference ◽  
The Impact

8040 Background: Approximately 15-20% of patients with multiple myeloma (MM) present with t(11;14)(q13;q32) involving IgH and CCND1-XT genes. In this study, we report the impact of the t(11;14) on the outcome of patients with MM. Methods: We performed a retrospective chart review on patients with MM who underwent high-dose chemotherapy followed by auto-HCT at the M.D. Anderson Cancer Center between 2/2000 and 8/2010, and had conventional cytogenetic (CC) or fluorescent in situ hybridization (FISH) results available before transplant. The primary objective was to compare the progression free survival (PFS) and overall survival (OS) of patients with t(11;14) to patients without chromosomal abnormalities. Results: CC or FISH studies were available for 1239 patients: 863 normal, 28 with t(11;14), 348 with other abnormalities. Concurrent high-risk abnormalities on CC or FISH were seen in 15/28 patients with t(11;14): del(13q) in 11 , del(17p) in 3, and t(14;16)(q32;q23) in 1. Induction treatment in patients with t(11;14) was: bortezomib + dexamethasone +/- thalidomide/lenalidomide : 15 (53%), thalidomide or lenalidomide + dexamethasone: 11 (39%), others 2 (8%); they received auto-HCT after a median of one line (1-7) of therapy. Median follow up in surviving patients was 39 months. There was no significant difference in median time from diagnosis to auto-HCT from diagnosis (6.9 vs. 7.7 months, p=1.0), disease status at auto HCT (>PR1: 82 vs. 76%, <PR1: 7 vs. 11%, relapsed 10 vs. 13%), complete remission (CR: 21% vs. 32%; p=0.30), very good partial remission (VGPR: 29% vs. 21%; p=0.23) or overall response (75% vs. 85%; p=0.18) between patients with t(11;14) and normal karyotype. Median PFS in patients with t(11;14) and normal karyotype was 15.7 months and 35.9 months, respectively (p=0.017). Median OS in patients with t(11;14) and normal karyotype was 51.4 months and 88.4 months, respectively (p=0.03). There was no difference in PFS (p=0.25) or OS (p=0.71) in patients with t(11;14), with or without other high-risk chromosomal abnormalities. Conclusions: In this large single center study with a long follow up, we demonstrated that t(11;14) in MM is associated with a shorter PFS and OS in the context of auto-HCT.

Variable Risk of Second Primary Malignancy In Multiple Myeloma Patients of Different Ethnicities

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 678-678
Author(s):  
Pedram Razavi ◽  
Gaurav Patel ◽  
Asher Chanan-Khan ◽  
Sikander Ailawadhi
Keyword(s):  
Multiple Myeloma ◽  
Conflicts Of Interest ◽  
Latency Period ◽  
Incidence Rates ◽  
Second Primary ◽  
Solid Organ ◽  
Specific Patient ◽  
Significant Difference ◽  
Race Ethnicity ◽  
The Impact

Abstract Abstract 678 Background: Second primary malignancies (SPM) among multiple myeloma (MM) patients have been reported with an estimated incidence varying from 1%–15%. We have previously reported that significant disparity exists in MM survival across patients of different ethnicities. We undertook a Surveillance Epidemiology and End Results (SEER) based analysis to describe the incidence of SPM among MM patients of different ethnicities, in order to explore the variable impact that SPM might have on MM outcomes of patients across racial subgroups. Methods: SEER database was used to examine the standardized incidence rates (SIR) of SPM among MM patients diagnosed between 1973–2008. Observed to expected ratio (O/E) of SPM was calculated using incidence rates of cancers for the general population. The 95% confidence limits (CI) were constructed using Fisher's exact test. The analysis was restricted to patients with MM as first primary, microscopic confirmation of diagnosis, reporting sources not coded as autopsy- or death-certificate-only, and SPM reported more than 2 month after MM diagnosis. Mutually exclusive race/ethnicity categories were: African-Americans (AA), Asians/Pacific Islanders (API), Hispanic whites (HW), Non-Hispanic whites (NHW), and others. The risk of SPM among MM patients was explored by ethnicity, type of SPM, and latency period. Results: A total of 3090 cases of MM with SPM were diagnosed between 1973–2008, of which, 2021 patients met our inclusion criteria. Stratification of SPM by ethnicity revealed: 387 AA (19%), 72 API (4%), 51 HW (3%), 1500 NHW (74%) and 11 other (<1%) cases. There was an average 4.7-year latency period between diagnosis of MM and SPM (mean age 68.2 and 72.9 years, respectively). The latency period was not significantly different by type of SPM (solid organ vs. hematological) or ethnicity. AA had the youngest age at diagnosis for both, MM and SPM (65.6 and 70.1 year, respectively). (Figure 1) For all SPM sites analyzed together, there was no significant difference between the observed and expected incidence (O/E 0.98; 95% CI 0.94–1.02). However, O/E risk was significantly decreased for solid organ SPM (N=1695; O/E 0.92; 95% CI 0.88–0.96) and increased for hematological malignancies (N=263; O/E 1.63; 95% CI 1.44–1.84). Highest excess risk among all SPM was noted for acute non-lymphocytic leukemia (ANLL) (O/E 6.51; 95% CI 5.37–7.83). The overall risk of observed SPM was not different from expected rates by ethnicity, with the exception of HW who had a significantly decreased overall SPM risk. Table 1 summarizes significant results of O/E risk of SPM by race and site. HW and NHW were less likely to develop overall solid organ SPM. Within solid organ sites, HW had a significantly decreased O/E risk of developing lung/bronchus and prostate SPM. NHW were the only ethnic subgroup with an increased O/E risk of developing melanoma of skin, while the O/E risk of developing SPM of kidney/renal pelvis was increased only among AA. The risk of ANLL as SPM was significantly increased among AA, API, and NHW, while risk of NHL as SPM was only increased among NHW. Conclusion: Exploring potential causes of outcome disparities is important for evaluating disease characteristics and optimal triaging of healthcare resources for specific patient populations. We have performed the largest population-based analysis for the risk of SPM in MM patients stratified by race/ethnicity. We found that the risk of developing SPM among MM patients is variable depending on the patient's ethnic background. This warrants further exploration of the impact of SPM on outcomes of MM patients across different racial subgroups. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Impact of the Second Wave of COVID-19 on Outcomes in Hip Fracture Patients: An Observational Study

2021 ◽  
Vol 11 (24) ◽  
pp. 11589
Author(s):  
Mattia Morri ◽  
Cristiana Forni ◽  
Andrea Evangelista ◽  
Tania Broggian ◽  
Elisa Ambrosi ◽  
...  
Keyword(s):  
Observational Study ◽  
Recovery Time ◽  
Pressure Ulcers ◽  
Healthcare Outcomes ◽  
Average Complexity ◽  
Femur Fractures ◽  
Significant Difference ◽  
The Impact ◽  
First Time ◽  
Second Wave

The aim of this work was to measure the healthcare outcomes for patients undergoing surgery for femur fractures during the second wave of the COVID-19 pandemic within a context of orthopaedic surgery units and living with the pandemic and compare them with pre-pandemic outcomes. A retrospective observational study was conducted. The incidence of pressure ulcers and deambulation recovery time were the main outcome. The pre-pandemic group consisted of 108 patients and the second wave pandemic group included 194 patients. The incidence of pressure ulcers increased from 10% in the pre-pandemic period to 21% in the second wave (p = 0.016) and the crude relative risk (RR) was 2.06 (p = 0.023). The recovery of deambulation showed no significant difference in the recovery time in terms of days needed to walk the first time (3 days vs. 2 days; p = 0.44). During the second wave of COVID-19, the risk of pressure ulcers for patients undergoing femur fracture surgery increased significantly. This variation could be explained by the absence of a caregiver for these patients and the increased average complexity of the patients managed in the orthopaedic setting. The hospital management should take into account these aspects when restoring the hospital’s normal surgical activities.

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