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In patients with multiple myeloma (MM), the presence of high-risk cytogenetic abnormalities is associated with worse disease control and survival. Autologous stem cell transplant (ASCT) does benefit these patients. Tandem transplantation has been explored as a means to deepen responses and further improve survival however, its role remains controversial. This is particularly true in the era of novel agent induction and post-transplant maintenance therapy. The aim of this study was to use the Canadian Myeloma Research Group database and examine a large cohort of real-world patients comparing the outcomes of tandem versus single ASCT specifically in high-risk patients receiving novel agent-based induction and post-transplant maintenance. The data for this study was derived retrospectively from a comprehensive national-level database of Canadian patients with MM. High-risk cytogenetics was defined as presence of del17p, t(4;14), or t(14;16). Those receiving allogeneic transplant were excluded. Tandem transplantation was defined as a second ASCT performed consecutively without interim relapse or progression after first ASCT. Those with relapse or progressive disease within 3 months of completing a first transplant were excluded. We compared response depth, progression-free, and overall survival (OS) based on single or tandem transplantation procedures. The impact of covariates of interest was also assessed. A total of 381 patients with high-risk cytogenetics were identified. A total of 242 received single and 139 patients received tandem transplants. All received post-transplant maintenance. The most common induction regimen for these patients was cyclophosphamide, bortezomib, and steroids (CyBorD, 87%). Forty-one patients (10.8%) required reinduction prior to first ASCT. The best overall responses at any time were 98.3% (90.5% ≥ very good partial response [VGPR]) and 98.6% (89.9% ≥ VGPR) in the single and tandem ASCT groups, respectively. Survival outcomes were similar with the median progression-free survival for single or tandem ASCT of 35.2 and 35.3 months (P = .88) and the median OS were 92.6 and 88.9 months, respectively (P = .72). No statistically significant differences were seen based on type of cytogenetic abnormality or type of maintenance. This was confirmed on multivariate analysis. In the real-world setting, tandem ASCT does not improve outcomes for MM patients with high-risk cytogenetics. This may be driven by the use of effective pre- and post-ASCT therapies. The development of more potent induction and consolidation along with current nearly ubiquitous continuous maintenance therapies until disease progression does not support the use of a second high-dose procedure.
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There remains an unmet need to optimize the first-line treatment of patients with high-risk large B cell lymphoma (LBCL), particularly those with a high International Prognostic Index (IPI) score or a positive interim positron emission tomography (PET) scan who experience poor outcomes with R-CHOP. This study was conducted to evaluate the real-world effectiveness of consolidative autologous stem cell transplantation (ASCT) among patients with high-risk LBCL. This retrospective study included consecutive patients with LBCL and IPI score 4 or 5 who underwent consolidative ASCT as part of first-line therapy in Alberta, Canada. Progression-free survival (PFS), overall survival (OS), and disease-specific survival (DSS) were determined using the Kaplan-Meier method. The study cohort comprised 114 patients with median age of 60 years (range, 18 to 73 years), of whom 81 (71%) had an IPI score of 4 and 33 (29%) had an IPI score of 5. With a median follow-up of 5.6 years, the 5-year PFS was 72% (95% confidence interval [CI], 62% to 79%), 5-year OS was 74% (95% CI, 64% to 81%), and 5-year DSS was 80% (95% CI, 71% to 87%). There was no significant difference in PFS among patients with and patients without positive interim PET scans (n = 24), MYC and BCL2 and/or BCL6 rearrangements (n = 26), or central nervous system involvement (n = 15). Consolidative ASCT is associated with high cure rates and favorable survival outcomes in patients with high-risk LBCL and may overcome the adverse prognostic impact of a positive interim PET scan.
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Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Transplante Autólogo , Intervalo Livre de Doença , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/terapia , AlbertaAssuntos
Amiloidose , Amiloidose de Cadeia Leve de Imunoglobulina , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Amiloidose de Cadeia Leve de Imunoglobulina/genética , Bortezomib/uso terapêutico , Amiloidose/diagnóstico , Amiloidose/tratamento farmacológico , Ácidos Borônicos , Dexametasona , Resultado do TratamentoRESUMO
BACKGROUND AIMS: Although calcineurin inhibitors (CNIs) have a well-established role in the prevention of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT), their use can be limited by significant toxicities, which may result in premature treatment discontinuation. The optimal management of patients with CNI intolerance is unknown. The objective of this study was to determine the effectiveness of corticosteroids as GVHD prophylaxis for patients with CNI intolerance. METHODS: This retrospective single-center study included consecutive adult patients with hematologic malignancies who underwent myeloablative peripheral blood allogeneic HCT with anti-thymocyte globulin, CNI, and methotrexate GVHD prophylaxis in Alberta, Canada. Multivariable competing-risks regression was used to compare cumulative incidences of GVHD, relapse, and non-relapse mortality between recipients of corticosteroid versus continuous CNI prophylaxis, and multivariable Cox proportional hazards regression was applied to compare overall survival, relapse-free survival (RFS) and moderate-to-severe chronic GVHD and RFS. RESULTS: Among 509 allogeneic HCT recipients, 58 (11%) patients developed CNI intolerance and were switched to corticosteroid prophylaxis at median 28 days (range 1-53) after HCT. Compared with patients who received continuous CNI prophylaxis, recipients of corticosteroid prophylaxis had significantly greater cumulative incidences of grade 2-4 acute GVHD (subhazard ratio [SHR] 1.74, 95% confidence interval [CI] 1.08-2.80, P = 0.024), grade 3-4 acute GVHD (SHR 3.22, 95% CI 1.55-6.72, P = 0.002), and GVHD-related non-relapse mortality (SHR 3.07, 95% CI 1.54-6.12, P = 0.001). There were no significant differences in moderate-to-severe chronic GVHD (SHR 0.84, 95% CI 0.43-1.63, P = 0.60) or relapse (SHR 0.92, 95% CI 0.53-1.62, P = 0.78), but corticosteroid prophylaxis was associated with significantly inferior overall survival (hazard ratio [HR] 1.77, 95% CI 1.20-2.61, P = 0.004), RFS (HR 1.54, 95% CI 1.06-2.25, P = 0.024), and chronic GVHD and RFS (HR 1.46, 95% CI 1.04-2.05, P = 0.029). CONCLUSIONS: Allogeneic HCT recipients with CNI intolerance are at increased risks of acute GVHD and poor outcomes despite institution of corticosteroid prophylaxis following premature CNI discontinuation. Alternative GVHD prophylaxis strategies are needed for this high-risk population.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Inibidores de Calcineurina/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Transplantados , Recidiva Local de Neoplasia/etiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/patologia , Corticosteroides/uso terapêuticoRESUMO
Although autologous stem cell transplantation (ASCT) can achieve durable responses in eligible patients with follicular lymphoma (FL), long-term follow-up is needed to determine if it has curative potential. This retrospective, multicenter study included 162 patients who received ASCT for relapsed FL in Alberta, Canada. With a median (range) follow-up time of 12.5 years (0.1-27.9), the 12-year time-to-progression (TTP) was 57% (95% confidence interval [CI] 49%-65%), time-to-next-treatment was 61% (95% CI 52%-69%), progression-free survival was 51% (95% CI 42%-59%) and overall survival was 69% (95% CI 60%-76%). A plateau emerged on the TTP curve at 57% starting 9 years after ASCT with no relapses occurring beyond this timepoint. Ten patients remained in remission 20 years or more after ASCT. Patients undergoing ASCT at first or second relapse had superior outcomes compared to third or later relapse (12-year TTP 61% vs. 34%), as did patients without progression of disease within 24 months (POD24) of frontline treatment versus those with POD24 (12-year TTP 67% vs. 50%). ASCT achieves high rates of durable remission in relapsed FL, with long-term follow-up revealing that more than 50% of transplanted patients may be functionally cured of their lymphoma. The optimal timing to consider ASCT is at first or second relapse, regardless of POD24 status.
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Transplante de Células-Tronco Hematopoéticas , Linfoma Folicular , Humanos , Seguimentos , Estudos Retrospectivos , Transplante Autólogo , Linfoma Folicular/tratamento farmacológico , Intervalo Livre de Doença , Recidiva Local de Neoplasia/terapia , Recidiva Local de Neoplasia/patologia , Transplante de Células-Tronco , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMO
BACKGROUND: Higher cumulative dose of bortezomib, a key component of Multiple Myeloma (MM) treatment regimens, has been shown to improve outcomes in MM patients, but must be balanced with toxicities including peripheral neuropathy. In this study, we studied the effect of cumulative bortezomib dose on survival, depth of response, and discontinuation rate in transplant ineligible MM patients. PATIENTS AND METHODS: Data from 70 patients treated with Cyclophsophamide, Bortezomib, and Dexamethasone (CyBorD) in a single Canadian center were grouped according to above vs below median cumulative bortezomib dose and analyzed for progression-free survival (PFS), overall survival (OS), depth of response, and discontinuation rate. RESULTS: There was a trend for lower discontinuation rate (45.7% vs. 68.6%, P = .052) and significantly lower rate of neuropathy-related discontinuation (5.7% vs. 22.9%, P = .035) in patients who received higher than 43.1 mg/m² of bortezomib. The higher-dose group showed a trend for higher rate of complete response (14.3% vs. 5.7%, P = .225) and significantly higher rate of very good partial response or better (77.1% vs. 51.4%, P = .024). There was significantly longer PFS (24.3 vs. 9.1 months, P = .012) and a trend for longer OS (22.4 vs. 61.3 months, P = .061) in the higher-dose group. In landmark analysis after 180 days, PFS (23.5 vs. 24.3 months, P = .941) and OS were similar in both groups. CONCLUSION: Higher cumulative bortezomib dose showed a lower rate of discontinuation, longer survival, and deeper response. Determining risk of treatment intolerance remains important for treatment.
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Mieloma Múltiplo , Doenças do Sistema Nervoso Periférico , Humanos , Bortezomib/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Canadá , Ciclofosfamida/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Dexametasona/efeitos adversos , Resultado do TratamentoRESUMO
Rituximab is commonly used as prevention, preemption, or therapeutically for post-transplant lymphoproliferative disorder (PTLD) after hematopoietic cell transplantation (HCT). Although it is generally assumed that rituximab toxicity (ie, infections resulting from hypogammaglobulinemia and neutropenia) is negligible in relation to mortality due to PTLD, limited evidence supports the validity of this assumption. We sought to determine the impact of rituximab on immunoglobulin levels, neutrophil count, infection density, and mortality outcomes. This study retrospectively analyzed 349 HCT recipients, 289 of whom did not receive rituximab and 60 of whom received rituximab preemptively or therapeutically at a median of 55 days post-transplantation. IgM, IgG, and IgA levels at 6 months and 12 months post-transplantation were lower in patients who received rituximab compared with those who did not (significant at P < .05 for IgM and IgA at 6 months and for IgM and IgG at 12 months). Rituximab recipients also had a higher incidence of severe neutropenia (<.5/nl) between 3 and 24 months (subhazard ratio [SHR], 2.3; P = .020). Regarding non-Epstein-Barr viral infections/PTLD, the rituximab group had a higher infection density between 3 and 24 months compared with the no-rituximab group (3.8 versus 1.6 infections per 365 days at risk; incidence rate ratio, 2.2; P < .001). The rituximab group also had a higher incidence of fatal infections (SHR, 3.1; P = .026), higher nonrelapse mortality (SHR, 2.4; P = .006), and higher overall mortality (hazard ratio, 1.7; P = .033). There were no significant between-group differences in the incidence of clinically significant graft-versus-host disease, graft failure, or relapse. Based on this study, rituximab given for PTLD is associated with substantial morbidity and mortality. Whether the benefit of preemptive rituximab outweighs the risk remains to be determined. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
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Infecções por Vírus Epstein-Barr , Transtornos Linfoproliferativos , Neutropenia , Humanos , Rituximab/efeitos adversos , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/epidemiologia , Herpesvirus Humano 4 , Estudos Retrospectivos , Fatores de Risco , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/tratamento farmacológico , Neutropenia/complicações , Neutropenia/tratamento farmacológico , Imunoglobulina G , Imunoglobulina M/uso terapêutico , Imunoglobulina A/uso terapêuticoRESUMO
BACKGROUND AIMS: The value of routine chimerism determination after myeloablative hematopoietic cell transplantation (HCT) is unclear, particularly in the setting of anti-thymocyte globulin (ATG)-based graft-versus-host disease (GVHD) prophylaxis. METHODS: Blood samples were collected at 3 months post-HCT from 558 patients who received myeloablative conditioning and ATG-based GVHD prophylaxis. Chimerism was assessed using multiplex polymerase chain reaction of short tandem repeats in sorted T cells (CD3+) and leukemia lineage cells (CD13+CD33+ for myeloid malignancies and CD19+ for B-lymphoid malignancies). ATG exposure was determined using a flow cytometry-based assay. The primary outcomes of interest were relapse and chronic GVHD (cGVHD). RESULTS: Incomplete (<95%) T-cell chimerism and leukemia lineage chimerism were present in 17% and 4% of patients, respectively. Patients with incomplete T-cell chimerism had a significantly greater incidence of relapse (36% versus 22%, subhazard ratio [SHR] = 2.03, P = 0.001) and lower incidence of cGVHD (8% versus 25%, SHR = 0.29, P < 0.001) compared with patients with complete chimerism. In multivariate modeling, patients with high post-transplant ATG area under the curve and any cytomegalovirus (CMV) serostatus other than donor/recipient seropositivity (non-D+R+) had an increased likelihood of incomplete T-cell chimerism. Patients with incomplete leukemia lineage chimerism had a significantly greater incidence of relapse (50% versus 23%, SHR = 2.70, P = 0.011) and, surprisingly, a greater incidence of cGVHD (45% versus 20%, SHR = 2.64, P = 0.003). CONCLUSIONS: High post-transplant ATG exposure and non-D+R+ CMV serostatus predispose patients to incomplete T-cell chimerism, which is associated with an increased risk of relapse. The increased risk of cGVHD with incomplete B-cell/myeloid chimerism is a novel finding that suggests an important role for recipient antigen-presenting cells in cGVHD pathogenesis.
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Infecções por Citomegalovirus , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia , Humanos , Doença Enxerto-Hospedeiro/prevenção & controle , Soro Antilinfocitário , Quimerismo , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Fatores de Risco , Doença Crônica , Citomegalovirus , RecidivaRESUMO
Severe acute respiratory syndrome coronavirus (SARS-CoV2) and associated COVID-19 infection continue to impact patients globally. Patients with underlying health conditions are at heightened risk of adverse outcomes from COVID-19; however, research involving patients with rare health conditions remains scarce. The amyloidoses are a rare grouping of protein deposition diseases. Light-chain and transthyretin amyloidosis are the most common disease forms, often present with systemic involvement of vital organs including the heart, nerves, kidneys, and GI tracts of affected individuals. The Amyloidosis Program of Calgary examined 152 ATTR patients and 103 AL patients analyzing rates of vaccination, COVID-19 testing, infection outcomes, influence referrals, and excess deaths. Results showed 15 total PCR-confirmed COVID-19 infections in the tested population of amyloid patients, with a higher frequency of infections among patient with AL compared to the ATTR cohort (26.2% vs 5.1%). Four patients (26.6%) required hospital admission for COVID-19 infection, 2 ATTR, and 2 AL patients. Of the confirmed cases, 1 (0.07%) unvaccinated ATTR patient died of a COVID-19 infection. An excess of deaths was found in both the ATTR and AL cohorts when comparing pre-pandemic years 2018 and 2019 to the pandemic years of 2020 and 2021. The finding suggests that amyloidosis patients are likely at a high risk for severe COVID-19 infection and mortality, especially those of advanced age, those on an active treatment with chemotherapy, and those with concomitant B-cell or plasma cell disorder. The impact of virtual healthcare visits and pandemic measures on the excess of deaths observed requires further research.
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Neuropatias Amiloides Familiares , COVID-19 , Amiloide/metabolismo , Teste para COVID-19 , Humanos , RNA Viral , SARS-CoV-2RESUMO
INTRODUCTION: Despite the common use of cyclosporine (CsA) for acute graft-versus-host disease (aGVHD) prophylaxis following allogeneic stem cell transplant, the optimal CsA trough target remains unknown. MATERIALS AND METHODS: Here, we report on outcomes of adult patients following myeloablative conditioning to identify an optimal CsA trough target and characterize the most relevant timeframe post-transplant for CsA trough targeting to minimize aGVHD. We retrospectively reviewed 399 consecutive patients who underwent first peripheral blood allogeneic stem cell transplant for hematological malignancies between January 2009 and December 2018. RESULTS: In the unadjusted and adjusted analyses, the incidence of grades 2-4 aGVHD was significantly higher among patients with an average CsA trough concentration <250 mcg/L compared to patients with an average CsA trough concentration ≥250 mcg/L during days 15-28 post-transplant (31.5% versus 18.8%, P = 0.037), with an odds ratio (OR) of 1.97 (95% confidence interval 1.04-3.71). In contrast, no correlations between CsA trough concentration and relapse, non-relapse mortality and overall survival was found. CONCLUSION: In conclusion, early post-transplant CsA trough concentrations are an important factor in the prophylaxis against aGVHD. Our findings suggest that CsA trough concentrations should be maximized between days 15-28 post-myeloablative transplant.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Aguda , Adulto , Ciclosporina/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunossupressores/uso terapêutico , Recidiva Local de Neoplasia/etiologia , Estudos Retrospectivos , Transplante de Células-Tronco , Condicionamento Pré-Transplante/efeitos adversosRESUMO
A number of tricyclic antidepressants (TCAs) are commonly prescribed off-label for the treatment of neuropathic pain. The blockade of neuronal calcium ion channels is often invoked to partially explain the analgesic activity of TCAs, but there has been very limited experimental or theoretical evidence reported to support this assertion. The N-type calcium ion channel (CaV2.2) is a well-established target for the treatment of neuropathic pain and in this study a series of eleven TCAs and two closely related drugs were shown to be moderately effective inhibitors of this channel when endogenously expressed in the SH-SY5Y neuroblastoma cell line. A homology model of the channel, which matches closely a recently reported Cryo-EM structure, was used to investigate via docking and molecular dynamics experiments the possible mode of inhibition of CaV2.2 channels by TCAs. Two closely related binding modes, that occur in the channel cavity that exists between the selectivity filter and the internal gate, were identified. The TCAs are predicted to position themselves such that their ammonium side chains interfere with the selectivity filter, with some, such as amitriptyline, also appearing to hinder the channel's ability to open. This study provides the most comprehensive evidence to date that supports the notion that the blockade of neuronal calcium ion channels by TCAs is at least partially responsible for their analgesic effect.
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BACKGROUND: Stable isotope labeling is a non-invasive, sensitive means of monitoring metabolic flux in plants. The most physiologically meaningful information is obtained from experiments that take advantage of the natural photosynthetic carbon assimilation pathway to introduce a traceable marker with minimal effects on the physiology of the organism. The fundamental substrate in isotopic labeling experiments is 13CO2, which can reveal the earliest events in carbon assimilation and realistically portray downstream metabolism when administered under conditions suitable for making kinetic inferences. Efforts to improve the accuracy and resolution of whole plant labeling techniques have focused on improvements in environmental control, air flow characteristics, and harvesting methods. RESULTS: Here we present a dynamic flow cuvette designed for single Arabidopsis thaliana labeling experiments. We have also verified its suitability for labeling Nicotiana benthamiana and essential oils in Pelargonium graveolens. Complete plans for fabrication of this device are included. The design includes three important innovations. First, uniform, circular air flow over the rosette surface is accomplished by a fan and deflector that creates a mini-cyclone effect within the chamber interior. Second, a network of circulating canals connected to a water bath provides temperature control to within ± 0.1 ºC under variable irradiance, humidity, and air flow conditions. When photosynthetically active radiation (PAR) was varied over a range of 1000 µEinsteins m-2 s-1 with no adjustment to the external temperature control system, the abaxial leaf temperature changed by < 3 ºC/1000 PAR. Third, the device is fully compatible with liquid nitrogen quenching of metabolic activity without perturbation of the light environment. For short labeling experiments (< 10 s), the most critical variable is the half-life (t1/2) of the atmosphere within the chamber, which determines the maximum resolution of the labeling system. Using an infrared gas analyzer, we monitored the atmospheric half-life during the transition from 12CO2 to 13CO2 air at different flow rates and determined that 3.5 L min-1 is the optimal flow rate to initiate labeling (t1/2 ~ 5 s). Under these conditions, we observed linear incorporation of 13C into triose phosphate with labeling times as short as 5 s. CONCLUSIONS: Advances in our ability to conduct short term labeling experiments are critical to understanding of the rates and control of the earliest steps in plant metabolism. Precise kinetic measurements in whole plants using 13CO2 inform metabolic models and reveal control points that can be exploited in agricultural or biotechnological contexts. The dynamic labeling cuvette presented here is suitable for studying early events in carbon assimilation and provides high resolution kinetic data for studies of metabolism in intact plants under physiologically realistic scenarios.
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Subsequent malignancies (SMs) present a significant burden of morbidity and are a common cause of late mortality in survivors of allogeneic hematopoietic cell transplant (allo-HCT). Previous studies have described total body irradiation (TBI) as a risk factor for the development of SMs in allo-HCT survivors. However, most studies of the association between TBI and SM have examined high-dose TBI regimens (typically ≥600 cGy), and thus little is known about the association between low-dose TBI regimens and risk of SMs. Our goal, therefore, was to compare the cumulative incidence of SMs in patients of Alberta, Canada, who received busulfan/fludarabine alone vs busulfan/fludarabine plus 400 cGy TBI. Of the 674 included patients, 49 developed a total of 56 malignancies at a median of 5.9 years' posttransplant. The cumulative incidence of SMs at 15 years' post-HCT in the entire cohort was 11.5% (95% confidence interval [CI], 8.5-15.6): 13.4% (95% CI, 9.1-19.3) in the no-TBI group and 10.8% (95% CI, 6.6-17.4) in the TBI group. In the multivariable model, TBI was not associated with SMs, whereas there was an association with number of pre-HCT cycles of chemotherapy. The standardized incidence ratio for the entire cohort, compared with the age-, sex-, and calendar year-matched general population, was 1.75. allo-HCT conditioning that includes low-dose TBI does not seem to increase risk of SMs compared with chemotherapy-alone conditioning.
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Transplante de Células-Tronco Hematopoéticas , Neoplasias , Bussulfano , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Condicionamento Pré-Transplante/efeitos adversos , Irradiação Corporal Total/efeitos adversosRESUMO
Post-transplant lymphoproliferative disorder (PTLD) is a potentially serious complication that occurs following hematopoietic cell transplantation (HCT), in which B cells transformed by Epstein-Barr virus (EBV) proliferate uncontrollably. It is unknown whether risk factors for the incidence of PTLD are identical to those for mortality due to PTLD, a clinically more important outcome. We sought to determine the risk factors influencing the incidence of PTLD and those influencing mortality due to PTLD in a cohort of 1184 allogenic HCT recipients. All patients were predisposed to PTLD, because their graft-versus-host disease (GVHD) prophylaxis included antithymocyte globulin. The overall PTLD incidence was 9.0%, and mortality due to PTLD was 1.1%. In multivariate analysis, risk factors for PTLD incidence include donor+/recipient- (D+/R-) EBV serostatus (subhazard ratio [SHR], 3.3; P = .002), use of a donor other than an HLA-matched sibling donor (non-MSD) (SHR, 1.7; P = .029), receipt of total body irradiation (TBI; SHR, 3.3; P = .008), and the absence of GVHD (SHR, 3.3; P < .001). The sole risk factor for mortality due to PTLD among all patients was D+/R- serostatus (SHR, 5.8; P = .022). Risk factors for mortality due to PTLD among patients who developed PTLD were use of a bone marrow (BM) graft (compared with peripheral blood stem cells [PBSCs]; SHR, 22.8; P < .001) and extralymphatic involvement (SHR, 14.6; P < .001). Interestingly, whereas the absence of GVHD was a risk factor for PTLD incidence, there was a trend toward the presence of GVHD as a risk factor for PTLD mortality (SHR, 4.2; P = .093). Likewise, whereas use of a BM graft was a risk factor for PTLD mortality, there was a trend toward use of a PBSC graft as a risk factor for PTLD incidence (SHR, 0.44; P = .179). Some risk factors for the incidence of PTLD are identical to the risk factors for mortality due to PTLD (ie, D+/R- serostatus), whereas other risk factors are disparate. Specifically, TBI was identified as a risk factor for PTLD incidence but not for PTLD mortality; the absence of GVHD was a risk factor for PTLD incidence, whereas the presence of GVHD was possibly a risk factor for PTLD mortality; and receipt of a PBSC graft was possibly a risk factor for PTLD incidence, whereas receipt of a BM graft was a risk factor for PTLD mortality.
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Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Transtornos Linfoproliferativos , Infecções por Vírus Epstein-Barr/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 4 , Humanos , Incidência , Transtornos Linfoproliferativos/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: The impact of coronavirus disease-19 on the management of multiple myeloma (MM) has been recognized. However, the real effect on clinical outcomes remains poorly understood. OBJECTIVE: We describe a local experience of the management of MM patients and report their outcomes during the current pandemic. METHODS: All consecutive symptomatic MM patients seen at our center since 03/20 were evaluated. RESULTS: A cohort of 156 patients diagnosed from 01/19 to 12/20 was analyzed to interrogate differences in presentation patterns. A total of 553 MM patients were seen and/or treated at Tom Baker Cancer Center in the year of 2020. From those, 47.1% (n = 261) were tested for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Sixteen patients tested positive and data are presented. In addition, a decrease of 21.7% in the rate of new smoldering MM/MM diagnosis was observed in 2020 as compared to 2019. Further, an increase in deaths was also observed in 2020. CONCLUSIONS: Our study confirms an increase lethality for MM patients infected with SARS-CoV-2. A balance between safety and need for cancer control should be emphasized.
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COVID-19 , Mieloma Múltiplo , COVID-19/complicações , COVID-19/mortalidade , Canadá/epidemiologia , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/epidemiologia , Pandemias , SARS-CoV-2RESUMO
The use of cyclophosphamide, bortezomib and dexamethasone (CyBorD) is widely accepted in the treatment of AL amyloidosis (AL). Recently, the substitution of dexamethasone by methylprednisolone (CyBorMe) appeared to improve response rates and survival outcomes. All consecutive newly diagnosed AL amyloidosis treated with CyBorMe from 01/19 to 08/20 were evaluated. A historic cohort of patients treated with CyBorD was used for comparison (01/13-08/20). Methylprednisolone was given IV at 500 mg weekly for 4 weeks in the CyBorMe group. 43 patients were treated with CyBorD and 14 with CyBorMe. After a median of 4 cycles of CyBorD and 3 cycles of CyBorMe, Hematological Response was seen in 90.6% and 92.8% of cases, including CR in 28.5% and 35.7%, VGPR in 33.3% and 35.7% and PR in 30.9% and 21.4% for CyBorD and CyBorMe, respectively. Time to first response was faster in the CyBorMe group (4 vs. 6 weeks) and cardiac response was observed in 44% and 31% of patients treated with CyBorMe and CyBorD, respectively. CyBorMe appeared to be efficacious and well tolerated in patients with AL amyloidosis. Prospective studies with CyBorMe in the stage III/IV group are warranted aiming to minimize toxicity.
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Background: Patients with monoclonal gammopathy of undetermined significance (MGUS) have clinical features including older age, presence of medical comorbidities, susceptibility to infections, and thrombotic tendencies which are relevant when assessing their risk during the coronavirus disease (COVID-19) pandemic. Objective: To study the vulnerability of patients with MGUS during the COVID-19 pandemic, we assessed the local management of MGUS patients and their clinical outcomes. Methods: Retrospective chart reviews were performed for all patients with MGUS seen at a university medical center clinic (2014-2020). Results: A total of 228 MGUS patients were included; 211 patients are alive, 7 patients died before the pandemic, and 10 patients died since the pandemic declaration. The mean age and the overall survival (OS) of the patients who died before versus during the pandemic were 83.0 versus 75.2 years, p = 0.4, and OS 40.6 versus 53.2 months, p = 0.3, respectively. One patient died of COVID-19. Nine patients had venous thromboembolisms (VTE), all of which occurred before the pandemic onset. Conclusions: There were no significant differences found in the mean age or OS of the MGUS patients who died before versus after the pandemic onset. An increase in VTE rates was not seen. Study results are limited by small patient numbers.