ABSTRACT
Currently, the role of DNA methylation in the IgM-monoclonal gammopathy disease spectrum remains poorly understood. In the present study, a multi-omics prospective analysis was conducted integrating DNA methylation, RNA-seq and WES data in 34 subjects [23 WM, 6 IgM-MGUS, 5 normal controls]. Analysis was focused on defining differences between IgM-gammopathies (WM/IgM-MGUS) compared to controls, and specifically between WM and IgM-MGUS. Between groups, genome-wide DNA methylation analysis demonstrated a significant number of differentially methylated regions which were annotated according to genomic region. Next, integration of RNA-seq data was performed to identify potentially epigenetically deregulated pathways. We found that pathways involved in cell cycle, metabolism, cytokine/immune signaling, cytoskeleton, tumor microenvironment, and intracellular signaling were differentially activated and potentially epigenetically regulated. Importantly, there was a positive enrichment of CXCR4 signaling pathway along with several interleukin (IL-6, IL-8, IL15) signaling pathways in WM compared to IgM-MGUS. Further assessment of known tumor suppressor genes and oncogenes uncovered differential promoter methylation of several targets with concordant change in gene expression, including CCND1 and CD79B. Overall, this report defines how aberrant DNA methylation in IgM-gammopathies may play a critical role in the epigenetic control of oncogenesis and key cellular functions.
ABSTRACT
Most patients with solitary bone plasmacytomas (SBP) progress to multiple myeloma (MM) after definitive radiation therapy as their primary treatment. Whether the presence of high-risk (HR) cytogenetic abnormalities by fluorescence in situ hybridization (FISH) in the clonal plasma cells, obtained either directly from the diagnostic SBP tissue or the corresponding bone marrow examination at the time of diagnosis, is associated with a shorter time to progression (TTP) to MM is unknown. This study evaluated all patients diagnosed with SBP at the Mayo Clinic from January 2012 to July 2022. The presence of del(17p), t(14;16), t(4;14), or +1q (gain or amplification) by FISH in clonal plasma cells was defined as HR. A total of 114 patients were included in this cohort, and baseline FISH was available for 55 patients (48%), of which 22 were classified as HR (40%). The median TTP to MM for patients with SBP and HR FISH was 8 months (95% confidence interval [CI], 6.3-26) compared with 42 months (95% CI, 25-not reached [NR]) in patients with SBP without HR FISH (P < .001). In a multivariate analysis, only HR FISH was a significant predictor for shorter TTP to MM, independent of minimal marrow involvement and an abnormal serum free light chain ratio at diagnosis. Deletion (17p) and gain 1q abnormalities were the most common FISH abnormalities responsible for the short TTP to MM. Thus, assessing for HR FISH abnormalities in clonal plasma cells derived from either the diagnostic SBP tissue or the staging bone marrow examination of patients with newly diagnosed SBP is feasible and prognostic for a shorter TTP to MM.
Subject(s)
Multiple Myeloma , Plasmacytoma , Humans , Plasmacytoma/genetics , In Situ Hybridization, Fluorescence , Chromosome Aberrations , Multiple Myeloma/diagnosis , Multiple Myeloma/genetics , Prognosis , Disease ProgressionABSTRACT
Smoldering multiple myeloma (SMM) is a precursor stage that precedes multiple myeloma (MM). SMM is heterogenous with nearly 40% of patients progressing to MM in the first 5 years. The high rate of progression of SMM patients highlights the need for early intervention, which underscores the importance of identifying SMM patients with the highest risk of progression. Several risk stratification models showed utility in identifying high-risk SMM patients; however, these systems showed limited sensitivity. To date, identifying high-risk SMM patients remains an important clinical need. In this study, we present the 3-dimensional telomere profiling as a structural biomarker capable of stratifying SMM patients as a function of genomic instability. Quantifying telomere dysfunction using the TeloView technology showed utility in risk stratification of cancer patients, particularly hematological malignancies. In this study, we analyzed 168 SMM patients. We report an AUC in ROC analysis of 0.8 using a subset of the patients as a training dataset. We then conducted a blind validation on a different cohort and demonstrated a positive predictive value of 85% and negative predictive value of 73%, with sensitivity and specificity of 83% and 76%, respectively. We examined the correlation between the TeloView prediction and the 20-2-20 scoring system, and cytogenetic abnormalities. We report a correlation of 53% with the 20-2-20 scores and over 60% correlation with cytogenetic abnormalities. The result of this study presents the telomere profiling as an effective biomarker able to stratify SMM patients to their respective risk groups with high sensitivity and specificity.
Subject(s)
Disease Progression , Smoldering Multiple Myeloma , Telomere , Humans , Smoldering Multiple Myeloma/genetics , Smoldering Multiple Myeloma/diagnosis , Female , Male , Middle Aged , Aged , Multiple Myeloma/genetics , Multiple Myeloma/diagnosis , Predictive Value of TestsABSTRACT
BACKGROUND: The BETTER intervention is an effective comprehensive evidence-based program for chronic disease prevention and screening (CDPS) delivered by trained prevention practitioners (PPs), a new role in primary care. An adapted program, BETTER HEALTH, delivered by public health nurses as PPs for community residents in low income neighbourhoods, was recently shown to be effective in improving CDPS actions. To obtain a nuanced understanding about the CDPS needs of community residents and how the BETTER HEALTH intervention was perceived by residents, we studied how the intervention was adapted to a public health setting then conducted a post-visit qualitative evaluation by community residents through focus groups and interviews. METHODS: We first used the ADAPT-ITT model to adapt BETTER for a public health setting in Ontario, Canada. For the post-PP visit qualitative evaluation, we asked community residents who had received a PP visit, about steps they had taken to improve their physical and mental health and the BETTER HEALTH intervention. For both phases, we conducted focus groups and interviews; transcripts were analyzed using the constant comparative method. RESULTS: Thirty-eight community residents participated in either adaptation (n = 14, 64% female; average age 54 y) or evaluation (n = 24, 83% female; average age 60 y) phases. In both adaptation and evaluation, residents described significant challenges including poverty, social isolation, and daily stress, making chronic disease prevention a lower priority. Adaptation results indicated that residents valued learning about CDPS and would attend a confidential visit with a public health nurse who was viewed as trustworthy. Despite challenges, many recipients of BETTER HEALTH perceived they had achieved at least one personal CDPS goal post PP visit. Residents described key relational aspects of the visit including feeling valued, listened to and being understood by the PP. The PPs also provided practical suggestions to overcome barriers to meeting prevention goals. CONCLUSIONS: Residents living in low income neighbourhoods faced daily stress that reduced their capacity to make preventive lifestyle changes. Key adapted features of BETTER HEALTH such as public health nurses as PPs were highly supported by residents. The intervention was perceived valuable for the community by providing access to disease prevention. TRIAL REGISTRATION: #NCT03052959, 10/02/2017.
Subject(s)
Nurses, Public Health , Female , Humans , Male , Middle Aged , Chronic Disease , Delivery of Health Care , Ontario , PovertyABSTRACT
BACKGROUND: Sarcopenia increases with age and is associated with poor survival outcomes in patients with cancer. By using a deep learning-based segmentation approach, clinical computed tomography (CT) images of the abdomen of patients with newly diagnosed multiple myeloma (NDMM) were reviewed to determine whether the presence of sarcopenia had any prognostic value. METHODS: Sarcopenia was detected by accurate segmentation and measurement of the skeletal muscle components present at the level of the L3 vertebrae. These skeletal muscle measurements were further normalized by the height of the patient to obtain the skeletal muscle index for each patient to classify them as sarcopenic or not. RESULTS: The study cohort consisted of 322 patients of which 67 (28%) were categorized as having high risk (HR) fluorescence in situ hybridization (FISH) cytogenetics. A total of 171 (53%) patients were sarcopenic based on their peri-diagnosis standard-dose CT scan. The median overall survival (OS) and 2-year mortality rate for sarcopenic patients was 44 months and 40% compared to 90 months and 18% for those not sarcopenic, respectively (p < .0001 for both comparisons). In a multivariable model, the adverse prognostic impact of sarcopenia was independent of International Staging System stage, age, and HR FISH cytogenetics. CONCLUSIONS: Sarcopenia identified by a machine learning-based convolutional neural network algorithm significantly affects OS in patients with NDMM. Future studies using this machine learning-based methodology of assessing sarcopenia in larger prospective clinical trials are required to validate these findings.
Subject(s)
Deep Learning , Multiple Myeloma , Sarcopenia , Humans , Sarcopenia/complications , Sarcopenia/diagnostic imaging , Multiple Myeloma/complications , Multiple Myeloma/diagnostic imaging , Multiple Myeloma/pathology , Prospective Studies , In Situ Hybridization, Fluorescence , Retrospective Studies , Tomography, X-Ray Computed/methods , Muscle, Skeletal/diagnostic imaging , PrognosisABSTRACT
Not available.
ABSTRACT
Waldenström macroglobulinemia (WM) is a rare, indolent lymphoma, that predominately affects the elderly. We report the outcomes of young WM patients, evaluated over five decades, compared to their older counterparts, matched for the time of diagnosis. Between January 1, 1960 and October 31, 2013, 140 (11.8%) WM patients were ≤50 years of age at diagnosis in our database, and their estimated 10-year overall survival (OS) was 74%, with death attributable to WM in a higher proportion of patients compared to their older (≥65 years) counterparts (91% vs. 58%, p = .0001). Young patients were grouped into three cohorts based on the timing of the initiation of therapy: Group 1 (1960-1977, n = 12), Group 2 (1978-1995, n = 48), and Group 3 (1996-2013, n = 74). Among young patients, there was no disease-specific survival (DSS) difference across the three periods, [median DSS at 13 years (95% CI 5-23), 16 years (95% CI 14-22), and 15 years (95% CI 10-NR; p = .41), respectively]. However, DSS for the older cohort incrementally improved (Group 1, median 5.2 years, Group 2: 9.6 years, Group 3: 12 years; p = .05) over these periods. The estimated average years-of-life lost for the young cohort was 11.2 years from diagnosis, based on the expected survival for a normal age- and sex-matched population. Despite a protracted disease course, nearly all young patients succumb to their disease. In contrast to the improved survival of the elderly patient population, the evolving treatment strategies in WM have not impacted the outcome of young patients; however, the impact of Bruton tyrosine kinase inhibitors on this unique patient population remains to be determined.
Subject(s)
Waldenstrom Macroglobulinemia , Humans , Aged , Waldenstrom Macroglobulinemia/drug therapy , Waldenstrom Macroglobulinemia/diagnosis , Disease ProgressionABSTRACT
Lenalidomide-containing (R) triplet and quadruplet regimens are the standard of care for multiple myeloma (MM) and have been shown to increase the risk of thrombosis. The association between thromboembolism (TE) and survival in the novel multidrug era is not yet delineated. In this study, we evaluated the incidence of TE during the first year of MM diagnosis, its association with the type of induction regimen, and its impact on overall survival. We studied 672 newly diagnosed MM (NDMM) patients who received a triplet or quadruplet lenalidomide-based induction at the Mayo Clinic, Rochester. TE was diagnosed in 83 patients (12.4%). Of these, 56 (8.3%) had a deep venous thrombosis (DVT), 23 (3.4%) had a pulmonary embolism (PE) with or without the DVT, and 4 (0.6%) patients had a stroke. Carfilzomib-Rd (KRd) had the highest risk of TE (21.1%, 18/85), followed by quadruplets (11.1%, 5/45), bortezomib-Rd (9.6%, 51/531), and 0/11 (0%), treated with other lenalidomide-containing regimens. The difference in TE risk between KRd and the other regimens was statistically significant (OR = 2.6, p < .01). Nine patients developed a TE before being exposed to any treatment. Survival was significantly lower among patients that developed a TE (66 vs. 133 months, p < .01). The association of TE with reduced survival demonstrated in univariate analysis (HR = 2.2, 95% CI = 1.6-3.3) was maintained in the multivariable analysis adjusted for high-risk interphase fluorescence in situ hybridization (FISH), sex, age, receipt of an upfront transplant, the response at induction, and the International Staging System (ISS) (HR = 2.61, CI = 1.74-3.9). We conclude that TE is an important aspect of MM management, and effective management is especially relevant in the novel treatment era.
Subject(s)
Multiple Myeloma , Thromboembolism , Thrombosis , Humans , Multiple Myeloma/complications , Multiple Myeloma/drug therapy , Lenalidomide/therapeutic use , In Situ Hybridization, Fluorescence , Dexamethasone/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bortezomib/therapeutic use , Thrombosis/etiology , Thrombosis/drug therapy , Thromboembolism/drug therapyABSTRACT
Extramedullary multiple myeloma (EMM) can present either at initial diagnosis (de novo) or at disease relapse (secondary) and confers an aggressive clinical course. Limited data exist for choosing the optimal therapy for EMM and this remains an area of unmet clinical need. After excluding paraskeletal multiple myeloma and primary plasma cell leukemia, we identified 204 (68%) patients with secondary EMM and 95 (32%) with de novo EMM between January 01, 2000 and 31 December, 2021. The median overall survival (OS) was 0.7 (95% CI: 0.6-0.9) years for secondary EMM and 3.6 (95%CI: 2.4-5.6) years for de novo EMM. The median progression-free survival (PFS) with initial therapy was 2.9 months (95% CI: 2.4-3.2 months) for secondary EMM and 12.9 months (95% CI: 6.7-18 months) for de novo EMM. Patients with secondary EMM treated with CAR-T therapy (n = 20) achieved a partial response (PR) or better in 75% with a median PFS of 4.9 months (3.1 months-not reached; NR). Patients with EMM treated with bispecific antibodies (n = 12) achieved a ≥ PR in 33%, with a median PFS of 2.9 months (95%CI: 2.2 months-NR). In a matched cohort, multivariate logistic regression analysis demonstrated younger age at diagnosis, 1q duplication, and t(4;14) at diagnosis of MM to be independent predictors of development of secondary EMM. Presence of EMM was independently associated with inferior OS in the matched cohorts for both de novo (HR 2.9 [95% CI: 1.6-5.4], p = .0007) and secondary EMM (HR 1.5 [95% CI: 1.1-2], p = .001).
Subject(s)
Multiple Myeloma , Humans , Multiple Myeloma/drug therapy , Treatment Outcome , Chromosome Aberrations , Retrospective StudiesABSTRACT
Patients with multiple myeloma (MM) have a lower efficacy from COVID-19 vaccination and a high rate of mortality from COVID-19 in hospitalized patients. However, the overall rate and severity of COVID-19 infection in all settings (including non-hospitalized patients) and the independent impact of plasma cell-directed therapies on outcomes needs further study. We reviewed the medical records of 9225 patients with MM or AL amyloidosis (AL) seen at Mayo Clinic Rochester, Arizona, and Florida between 12/01/2019 and 8/31/2021 and identified 187 patients with a COVID-19 infection (n = 174 MM, n = 13 AL). The infection rate in our cohort was relatively low at 2% but one-fourth of the COVID-19 infections were severe. Nineteen (10%) patients required intensive care unit (ICU) admission and 5 (3%) patients required mechanical ventilation. The mortality rate among hospitalized patients with COVID-19 was 22% (16/72 patients). Among patients that were fully vaccinated at the time of infection (n = 12), two (17%) developed severe COVID-19 infection, without any COVID-related death. On multivariable analysis, treatment with CD38 antibody within 6 months of COVID-19 infection [Risk ratio (RR) 3.6 (95% CI: 1.2, 10.5), p = .02], cardiac [RR 4.1 (95% CI: 1.3, 12.4), p = .014] or pulmonary comorbidities [RR 3.6 (95% CI 1.1, 11.6); p = .029] were independent predictors for ICU admission. Cardiac comorbidity [RR 2.6 (95% CI: 1.1, 6.5), p = .038] was an independent predictor of mortality whereas MM/AL in remission was associated with lower mortality [RR 0.4 (95% CI: 0.2-0.8); p = .008].
Subject(s)
COVID-19 , Immunoglobulin Light-chain Amyloidosis , Multiple Myeloma , Humans , COVID-19 Vaccines , Immunoglobulin Light-chain Amyloidosis/complications , Immunoglobulin Light-chain Amyloidosis/therapy , Multiple Myeloma/complications , Multiple Myeloma/therapy , Risk FactorsABSTRACT
Movements of four adult giant trevally Caranx ignobilis were tracked using passive acoustic telemetry after being released from uShaka Sea World Aquarium in Durban, South Africa, where they had been kept on display for a period of 8 years. All four individuals were detected on a large network of deployed acoustic receivers for a minimum of 3 months to a maximum of over 6 years. Their movements were compared to 43 wild-caught and tagged C. ignobilis over a similar period and two individuals adopted movement behavior similar to that of their conspecifics, including repeated annual seasonal migrations to a known spawning aggregation site. This study shows that with good animal husbandry, indigenous fish kept in captivity can be released back into the wild and not only survive but adopt natural movement behavior and contribute to future generations of their species.
ABSTRACT
Thromboses are prevalent in POEMS syndrome, but few risk factors for POEMS-associated thrombosis have been identified. The objective of this study is to identify novel risk factors for POEMS-associated thrombosis. In this retrospective cohort of 230 POEMS patients, 27% developed thrombosis. Arterial events were slightly more common than venous. Stroke accounted for 26% of all thromboses and 53% of arterial events. There were differences in baseline features between the thrombosis group and the no thrombosis group, and these were driven by patients with arterial thrombosis. Risk factors for arterial thrombosis included thrombocytosis, elevated hemoglobin/hematocrit, extravascular volume overload, and splenomegaly. Hyperprolactinemia appeared to be a risk factor for venous thrombosis. The risk of thrombosis was most striking among men with elevated hemoglobin (32% vs. 5%, p < .001) and hematocrit (42% vs. 5%, p < .001) compared to men without. Most thromboses occurred prior to POEMS directed therapy, and most that occurred during therapy happened within 3 months of diagnosis. Twenty-one percent of patients with thrombosis had recurrence. In recognition of high overall rates of thrombosis in this population, all patients with POEMS syndrome should receive prophylactic antiplatelet therapy, and clinicians should consider anticoagulation in patients with risk factors for POEMS-associated thrombosis.
Subject(s)
POEMS Syndrome/complications , Thrombosis/etiology , Adult , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Thrombosis/diagnosisABSTRACT
Achievement of a complete response (CR) in multiple myeloma (MM) correlates with improvement in survival outcomes; however, its impact on prognostic variables at baseline outside of clinical trial settings is not well described. We sought to determine the impact of achieving a CR within 2 years from diagnosis, its effect on the prognostic value of fluorescence in situ hybridization (FISH) and International Staging System (ISS) risk, and examined additional predictors of outcome among those achieving a CR in a routine clinical setting. We evaluated 1869 newly diagnosed MM patients who had ≥ 2 monoclonal protein immunofixation studies in the serum and urine available within 24 months from diagnosis, categorizing those with ≥ 2 negative serum and urine immunofixations as achieving CR. With a landmark at 24 months, median progression-free survival (PFS) for CR versus non-CR patients was 29.8 versus 20.9 months (p ≤ .0002); median overall survival (OS) was 104 versus 70 months (p < .0001). The impact of achieving a CR was retained after adjusting for FISH, ISS, sex, transplant status, and involved heavy chain. Baseline FISH and ISS stage were not associated with PFS or OS among patients achieving a CR. The following variables were found as predictors of inferior OS within the CR cohort: age > 75 years, male gender, hypoalbuminemia, and non-immunoglobulin G involved heavy chain. Our study confirms that achievement of CR within 2 years from diagnosis is associated with improvement in survival outcomes and neutralization of the impact of FISH and ISS risk, thereby confirming observations from the clinical trial setting among a clinical practice cohort.
Subject(s)
Multiple Myeloma , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , In Situ Hybridization, Fluorescence , Male , Middle Aged , Multiple Myeloma/mortality , Multiple Myeloma/therapy , Multiple Myeloma/urine , Remission Induction , Retrospective Studies , Survival RateABSTRACT
Castleman disease (CD) is a rare lymphoproliferative disease characterized by diverse clinical and pathologic features. Due to its rarity, there are limited studies comparing currently available therapies. The role of autologous stem cell transplantation (ASCT) in CD has not yet been established. In this paper, we describe the clinical characteristics, treatment choices, and outcomes in 34 Mayo Clinic patients diagnosed with multicentric CD from July 1, 2003 to April 30, 2018. Eighteen patients (53%) also met the criteria for POEMS, including 14 with the osteosclerotic variant. The first-line treatments included: steroid monotherapy (4), cytotoxic chemotherapy (6), rituximab alone (8) or with chemotherapy (2), anti-IL6 treatment (3), and ASCT (10). The median follow-up was 4.8 (range: 0.1-15.2) years. The 5- and 10-year overall survival rates were 84% and 71%, respectively. Sixteen patients received high-dose chemotherapy followed by ASCT during their disease course. Among those, 14 had multicentric CD associated with POEMS. There were no transplant-related deaths. All patients had at least a partial response to ASCT, most of whom achieved a complete response. The favorable outcomes seen with ASCT in this cohort suggest that transplantation may have a role in multicentric CD, particularly for patients with multicentric CD associated with POEMS.
Subject(s)
Castleman Disease , Hematopoietic Stem Cell Transplantation , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Castleman Disease/diagnosis , Castleman Disease/therapy , Humans , Retrospective Studies , Rituximab/therapeutic use , Stem Cell Transplantation , Transplantation, AutologousABSTRACT
Gain of 1q22 at diagnosis portends poorer outcomes in multiple myeloma (MM), but the prognostic significance of acquired 1q22 gain is unknown. We identified 63 MM patients seen at Mayo Clinic from 1/2004 to 12/2019 without 1q22 gain at diagnosis who acquired it during follow up and compared them to 63 control patients who did not acquire 1q22 gain with similar follow up. We also compared outcomes in the acquired 1q22 gain group with outcomes in 126 patients with 1q22 gain present at diagnosis. The incidence of acquired 1q22 gain was 6.1% (median follow-up 6.8 years); median time to acquisition was 5.0 years (range: 0.7-11.5 years). Abnormalities on baseline fluorescence in situ hybridization (FISH) included trisomies (54%) and monosomy 13 (39%); 16 (25%) had high-risk (HR) translocations or del(17p). Median progression-free survival with front line therapy was 29.5 months in patients with acquired 1q22 gain, versus 31.4 months in control patients (p = .34) and 31.2 months in patients with de novo 1q22 gain (p = .04). Median overall survival (OS) from diagnosis was 10.9 years in patients with acquired 1q22 gain, versus 13.0 years in control patients (p = .03) and 6.3 years in patients with de novo 1q22 gain (p = .01). Presence of HR FISH at baseline increased risk of 1q22 gain acquisition. We demonstrate that acquisition of 1q22 gain is a significant molecular event in MM, associated with reduced OS. Among HR patients for whom this clonal evolution is determined, a risk-adapted approach and/or clinical trial should be considered.
Subject(s)
Multiple Myeloma/genetics , Aged , Chromosome Duplication , Chromosomes, Human, Pair 1 , Female , Humans , Male , Multiple Myeloma/diagnosis , Prognosis , Survival AnalysisABSTRACT
BACKGROUND: Transversus abdominis plane (TAP) block and local anaesthetic wound infiltration are used to relieve pain after caesarean section. OBJECTIVES: To determine whether TAP block or local anaesthetic wound infiltration is the better analgesic option after caesarean section. DESIGN: Systematic review and meta-analysis with trial sequential analysis. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Clinical Trials, Web of Science up to June 2020. ELIGIBILITY CRITERIA: We retrieved randomised controlled trials comparing TAP block with wound infiltration after caesarean section. Primary outcome was pain score during rest (analogue scale, 0 to 10) at 2âh postoperatively, analysed according to the TAP block technique (ultrasound-guided/landmark-guided), anaesthetic strategy (spinal/general), intrathecal fentanyl (yes/no) and multimodal analgesia (yes/no). Secondary pain-related outcomes included pain scores during rest at 12 and 24âh, and total intravenous morphine consumption at 2, 12 and 24âh. We sought rates of block complications, including postoperative infection, haematoma, visceral injury and local anaesthetic systemic toxicity. RESULTS: Seven trials, totalling 475 patients, were identified. There was no difference in pain score during rest at 2âh between groups. Subgroup analyses revealed no differences related to TAP block technique (Pâ=â0.64), anaesthetic strategy (Pâ=â0.53), administration of intrathecal fentanyl (Pâ=â0.59) or presence of multimodal analgesia (Pâ=â0.57). Pain score during rest at 12âh and intravenous morphine consumption at 2 and 12âh were identical in both groups. Data were insufficient to compare block complications. Overall quality of evidence was moderate. CONCLUSION: There is moderate level evidence that TAP block and wound infiltration provide similar postoperative analgesia after caesarean section. TRIAL REGISTRY NUMBER: PROSPERO CRD42020208046.
Subject(s)
Analgesia , Cesarean Section , Abdominal Muscles/diagnostic imaging , Analgesics, Opioid , Anesthetics, Local , Cesarean Section/adverse effects , Female , Humans , Pain, Postoperative/diagnosis , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , PregnancyABSTRACT
BACKGROUND: Multiple myeloma (MM) with the translocation t(11;14) may have inferior outcomes in comparison with other standard-risk MM, and it has been suggested to portend a worse prognosis in African Americans in comparison with Whites. This study used the Center for International Blood and Marrow Transplant Research (CIBMTR) database to examine the impact of t(11;14) on the clinical outcomes of patients with MM of African American and White descent. METHODS: This study evaluated 3538 patients who underwent autologous hematopoietic cell transplantation (autoHCT) for MM from 2008 to 2016 and were reported to the CIBMTR. Patients were analyzed in 4 groups: African Americans with t(11;14) (n = 117), African Americans without t(11;14) (n = 968), Whites with t(11;14) (n = 266), and Whites without t(11;14) (n = 2187). RESULTS: African Americans with t(11;14) were younger, had lower Karnofsky scores, and had more advanced stage MM with a higher Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI). Fewer African Americans with t(11;14) (21%) had a coexistent high-risk marker in comparison with Whites with t(11;14) (27%). In a multivariate analysis, race and t(11;14) had no association with progression-free survival. However, overall survival was superior among African Americans with t(11;14) in comparison with Whites with t(11;14) (hazard ratio, 0.53; 95% confidence interval, 0.30-0.93; P = .03). Survival was also associated with female sex, stage, time from diagnosis to transplant, a low HCT-CI, and receipt of maintenance. CONCLUSIONS: Race may have a differential impact on the survival of patients with t(11;14) MM who undergo autoHCT and needs to be further studied.
Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Multiple Myeloma/epidemiology , Multiple Myeloma/therapy , Translocation, Genetic/genetics , Transplantation Conditioning/methods , Transplantation, Autologous/methods , Black or African American , Female , Humans , Male , Middle Aged , Multiple Myeloma/pathology , Prospective Studies , United States , White PeopleABSTRACT
Patients with asymptomatic/smouldering Waldenström macroglobulinaemia (SWM) have a variable risk of progression to active WM. Our study evaluated 143 patients with SWM consecutively seen between January 1996 and December 2013. With a median [95% confidence interval (CI)] follow-up of 9·5 [8·1-11·5] years, the cumulative rate of progression was 11% at 1 year, 38% at 3 years and 55% at 5 years. On multivariate analysis, haemoglobin (Hb) ≤123 g/l [risk ratio (RR) 2·08; P = 0·009] and ß2 -microglobulin (ß2 M) ≥2·7 µg/ml (RR 2·0; P = 0·01) were independent predictors of a shorter time-to-progression (TTP) to active WM. Patients with myeloid differentiation factor 88 wild type (MYD88WT ) genotype (n = 11) demonstrated a trend toward shorter TTP [median (95% CI) 1·7 (0·7-8·7) vs. 4·7 (2·4-7·7) years for the MYD88L265P cohort, n = 42; P = 0·11]. The presence of C-X-C chemokine receptor type 4 (CXCR4) mutation (n = 29) did not impact the TTP (median: 3 years for CXCR4WT vs. 5·6 years for CXCR4MUT , P = 0·34). The overall survival (OS) for patients with SWM (median: 18·1 years) was comparable to an age-, sex- and calendar year-matched USA population (median: 20·3 years, P = 0·502). In conclusion, Hb and ß2 M at diagnosis represent independent predictors of progression to active WM. Comparable survival of SWM and a matched USA population argues against pre-emptive intervention in this patient population.
Subject(s)
Hemoglobins/analysis , Myeloid Differentiation Factor 88/genetics , Waldenstrom Macroglobulinemia/genetics , beta 2-Microglobulin/blood , Aged , Biomarkers/analysis , Disease Progression , Female , Follow-Up Studies , Genotype , Humans , Male , Middle Aged , Multivariate Analysis , Mutation , Predictive Value of Tests , Receptors, CXCR4/genetics , Retrospective Studies , Risk Factors , Survival , Waldenstrom Macroglobulinemia/blood , Waldenstrom Macroglobulinemia/diagnosis , Waldenstrom Macroglobulinemia/pathologyABSTRACT
Measurable residual disease (MRD) assessment by marrow-based next-generation flow cytometry (NGF) following autologous stem cell transplantation (ASCT) may lead to false-negative results due to patchy marrow involvement and extramedullary disease in patients with multiple myeloma. We assessed the value of simultaneous MRD evaluation with NGF and serum matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MASS-FIX). Of all 61 complete responders who were NGF-negative for MRD, around day-100 post ASCT, 59% were MASS-FIX-positive. At median follow-up of 26 months, 69% of MASS-FIX(+)/NGF(-) patients were alive and progression-free versus 96% of MASS-FIX(-)/NGF(-) patients, P = 0·02. MASS-FIX, a simple peripheral blood-based assay complements marrow-based NGF to accurately prognosticate patients with myeloma.
Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Multiple Myeloma/diagnosis , Multiple Myeloma/therapy , Neoplasm, Residual/blood , Paraproteinemias/blood , Adult , Aged , Bone Marrow/metabolism , False Negative Reactions , Female , Flow Cytometry/methods , Follow-Up Studies , Humans , Immunoglobulin Subunits/blood , Male , Middle Aged , Multiple Myeloma/pathology , Neoplasm, Residual/diagnosis , Prognosis , Progression-Free Survival , Retrospective Studies , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methodsABSTRACT
In this review, two types of soft-tissue involvement in multiple myeloma are defined: (i) extramedullary (EMD) with haematogenous spread involving only soft tissues and (ii) paraskeletal (PS) with tumour masses arising from skeletal lesions. The incidence of EMD and PS plasmacytomas at diagnosis ranges from 1·7% to 4·5% and 7% to 34·4% respectively. EMD disease is often associated with high-risk cytogenetics, resistance to therapy and worse prognosis than in PS involvement. In patients with PS involvement a proteasome inhibitor-based regimen may be the best option followed by autologous stem cell transplantation (ASCT) in transplant eligible patients. In patients with EMD disease who are not eligible for ASCT, a proteasome inhibitor-based regimen such as lenalidomide-bortezomib-dexamethasone (RVD) may be the best option, while for those eligible for high-dose therapy a myeloma/lymphoma-like regimen such as bortezomib, thalidomide and dexamethasone (VTD)-RVD/cisplatin, doxorubicin, cyclophosphamide and etoposide (PACE) followed by SCT should be considered. In both EMD and PS disease at relapse many strategies have been tried, but this remains a high-unmet need population.