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1.
Sci Rep ; 14(1): 5716, 2024 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459150

RESUMO

Arsenic (As) is a significant contaminant whose unrestrained entrance into different ecosystems has created global concern. At the cellular level, As forms unsteady intermediates with genetic materials and perturbs different metabolic processes and proper folding of proteins. This study was the first in this region to explore, isolate, screen systematically, and intensively characterize potent As-tolerant bacterial strains from natural environments near Raiganj town of Uttar Dinajpur, West Bengal. In this study, two potent Gram-negative bacterial strains with high tolerance to the poisonous form of As, i.e., As(III) and As(V), were obtained. Both the isolates were identified using biochemical tests and 16S rRNA gene sequencing. These bacteria oxidized toxic As(III) into less poisonous As(V) and depicted tolerance towards other heavy metals. Comparative metabolic profiling of the isolates in control and As-exposed conditions through Fourier-transform infrared spectroscopy showed metabolic adjustments to cope with As toxicity. The metal removal efficiency of the isolates at different pH showed that one of the isolates, KG1D, could remove As efficiently irrespective of changes in the media pH. In contrast, the efficiency of metal removal by PF14 was largely pH-dependent. The cell mass of both the isolates was also found to favourably adsorb As(III). Whole genome sequence analysis of the isolates depicted the presence of the arsRBC genes of the arsenic operon conferring resistance to As. Owing to their As(III) oxidizing potential, high As bioaccumulation, and tolerance to other heavy metals, these bacteria could be used to bioremediate and reclaim As-contaminated sites.


Assuntos
Arsênio , Metais Pesados , Arsênio/metabolismo , Bioacumulação , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Ecossistema , Bactérias , Metais Pesados/análise , Biodegradação Ambiental , Genômica
3.
Cancer Med ; 13(3): e6906, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38205943

RESUMO

AIM: The aim of study was to investigate whether depression and anxiety symptoms and illness perception prior to hematopoietic stem cell transplantation (HSCT) predict health related quality of life (HRQOL) at Day 100 and 1 year following HSCT. METHODS: A total of 205 patients who underwent HSCT (N = 127 autologous transplants, N = 78 allogeneic transplants) were included in this prospective study. Baseline assessment was assessed prior to transplantation and post HSCT data were collected at Day 100 and 1 year. At baseline we assessed depressive symptoms (Patient Health Questionnaire-9), anxiety symptoms (Generalized Anxiety Disorder-7), illness perception (Brief Illness Perception Questionnaire), and HRQOL (Functional Assessment of Cancer Therapy-BMT). RESULTS: Patients who expressed a greater level of concern about the severity, course, and ability to exert control over one's illness (i.e., illness perception) and who reported a greater level of depression and anxiety symptoms prior to HSCT reported lower HRQOL at both Day 100 and 1 year posttransplant, with a similar degree of association observed at the two follow-up time points. CONCLUSIONS: Our findings suggest that pretransplant perceptions about their illness and negative mood are significant predictors of HRQOL following HSCT. Illness perception, depression, and anxiety are potentially modifiable risk factors for less than optimal outcome after HCSCT and intervention strategies should be explored.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Qualidade de Vida , Humanos , Estudos Prospectivos , Depressão/epidemiologia , Depressão/etiologia , Ansiedade/epidemiologia , Ansiedade/etiologia , Transtornos de Ansiedade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Percepção
4.
BMC Psychol ; 12(1): 40, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243338

RESUMO

PURPOSE: Loneliness may compromise health-related quality of life (HRQOL) outcomes and the immunological impacts of loneliness via neuroendocrinological mechanisms likely have consequences for patients who have undergone a hematopoietic stem cell transplantation (HSCT). RESEARCH APPROACH AND MEASURES: Loneliness (pre-transplant), immunological recovery (Day 30, Day 100, 1-year post-transplant), and HRQOL (Day 100, 1 year) were measured in a sample of 205 patients completing a HSCT (127 autologous, 78 allogenic). RESULTS: Greater levels of pre-transplant loneliness predicted poorer HRQOL at Day 100 and 1-year follow-up. Loneliness also was associated with higher absolute neutrophil to absolute lymphocyte (ANC/ALC) ratios in the entire sample at Day 30, which in turn was associated with Day 100 HRQOL. CONCLUSIONS: Findings demonstrate that pretransplant loneliness predicts HRQOL outcomes and associates with inflammatory immunological recovery patterns in HSCT patients. The balance of innate neutrophils to adaptive lymphocytes at Day 30 present a distinct profile in lonely individuals, with this immunity recovery profile predicting reduced HRQOL 100 days after the transplant. Addressing perceptions of loneliness before HSCT may be an important factor in improving immunological recovery and HRQOL outcomes.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Qualidade de Vida , Humanos , Solidão
5.
Br J Haematol ; 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38286472

RESUMO

This phase II study evaluated time-limited (24 cycles) treatment with ibrutinib and ixazomib in newly diagnosed (NDWM; n = 9) and relapsed/refractory (RRWM; n = 12) Waldenström macroglobulinaemia (WM). The overall response rate (ORR) was 76.2% (n = 16) in 21 evaluable patients with no patient achieving a complete response (CR). The median duration of treatment was 15.6 months, and after a median follow-up time of 25.7 months, the median progression-free survival (PFS) was 22.9 months. While the primary end-point was not met (CR rate at any time) and 28.5% discontinued treatment due to toxicity, ibrutinib plus ixazomib led to a clinically meaningful ORR and PFS. Combined Bruton's tyrosine kinase (BTK) and proteasome inhibition merits further evaluation in WM.

6.
Anticancer Drugs ; 35(1): 63-69, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37067996

RESUMO

Daratumumab is an anti-CD38 mAb, used frequently in combination with lenalidomide and pomalidomide. No studies compared daratumumab plus lenalidomide and dexamethasone (DRd) to daratumumab plus pomalidomide and dexamethasone (DPd) in lenalidomide-exposed multiple myeloma. We identified 504 consecutive multiple myeloma patients who received daratumumab at Mayo Clinic between January 2015 and April 2019. We excluded patients who received daratumumab in the first line, received more than four lines of therapy prior to daratumumab use, did not receive lenalidomide prior to daratumumab, or had an unknown status of lenalidomide exposure, and patients who received daratumumab combinations other than DRd or DPd. We examined the impact of using DRd compared to DPd on progression-free survival (PFS) and overall survival (OS) in patients with relapsed/refractory multiple myeloma. Out of 504 patients, 162 received DRd or DPd and were included; 67 were lenalidomide-exposed and 95 were lenalidomide-refractory. DRd was used in 76 (47%) and DPd in 86 (53%) patients. In lenalidomide-exposed multiple myeloma, there was no difference in median PFS; 34.2 months [95% confidence interval (CI), 22.8-44.6] for DRd compared to 25.2 months (95% CI, 4.9-35.3) for DPd, P  = 0.2. In lenalidomide-refractory multiple myeloma, there was no difference in median PFS; 18.6 months (95% CI, 13-32) for DRd compared to 9 months (95% CI, 5.2-14.6) for DPd, P  = 0.09. No difference in median OS was observed in DRd compared to DPd. Our study shows combining daratumumab with lenalidomide in patients with prior lenalidomide use is a viable and effective treatment option.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Lenalidomida/uso terapêutico , Dexametasona/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
7.
Am J Respir Crit Care Med ; 209(5): 543-552, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38051944

RESUMO

Rationale: Pulmonary complications contribute significantly to nonrelapse mortality following hematopoietic stem cell transplantation (HCT). Identifying patients at high risk can help enroll such patients into clinical studies to better understand, prevent, and treat posttransplantation respiratory failure syndromes. Objectives: To develop and validate a prediction model to identify those at increased risk of acute respiratory failure after HCT. Methods: Patients underwent HCT between January 1, 2019, and December 31, 2021, at one of three institutions. Those treated in Rochester, MN, formed the derivation cohort, and those treated in Scottsdale, AZ, or Jacksonville, FL, formed the validation cohort. The primary outcome was the development of acute respiratory distress syndrome (ARDS), with secondary outcomes including the need for invasive mechanical ventilation (IMV) and/or noninvasive ventilation (NIV). Predictors were based on prior case-control studies. Measurements and Main Results: Of 2,450 patients undergoing stem cell transplantation, there were 1,718 hospitalizations (888 patients) in the training cohort and 1,005 hospitalizations (470 patients) in the test cohort. A 22-point model was developed, with 11 points from prehospital predictors and 11 points from posttransplantation or early (<24-h) in-hospital predictors. The model performed well in predicting ARDS (C-statistic, 0.905; 95% confidence interval [CI], 0.870-0.941) and the need for IMV and/or NIV (C-statistic, 0.863; 95% CI, 0.828-0.898). The test cohort differed markedly in demographic, medical, and hematologic characteristics. The model also performed well in this setting in predicting ARDS (C-statistic, 0.841; 95% CI, 0.782-0.900) and the need for IMV and/or NIV (C-statistic, 0.872; 95% CI, 0.831-0.914). Conclusions: A novel prediction model incorporating data elements from the pretransplantation, posttransplantation, and early in-hospital domains can reliably predict the development of post-HCT acute respiratory failure.


Assuntos
Lesão Pulmonar , Síndrome do Desconforto Respiratório , Insuficiência Respiratória , Humanos , Transplante de Medula Óssea/efeitos adversos , Lesão Pulmonar/complicações , Estudos de Coortes , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/complicações , Insuficiência Respiratória/terapia
8.
Curr Oncol ; 30(11): 9627-9633, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37999117

RESUMO

While immunotherapies, such as CAR T therapy and bi-specific antibodies, have revolutionized the treatment of multiple myeloma (MM), patients with AL amyloidosis have been excluded from trials with these agents due to concerns of underlying autonomic, cardiac, and renal dysfunction, leading to potentially fatal toxicities from these therapies. In this communication, we described the outcomes of two patients with AL amyloidosis and concurrent MM with underlying cardiac and/or renal dysfunction who underwent anti-BCMA CAR T cell therapy with ide-cel or cilta-cel, received cytokine release syndrome prophylaxis, and tolerated therapy well with manageable toxicities and achieved a MRD-negative state. We described the preliminary efficacy and safety of CAR T in patients with AL amyloidosis and highlighted the importance of patient selection and medical optimization of cardiac and renal function prior to CAR T.


Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina , Nefropatias , Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Humanos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/tratamento farmacológico , Imunoterapia Adotiva/efeitos adversos , Receptores de Antígenos Quiméricos/uso terapêutico , Amiloidose de Cadeia Leve de Imunoglobulina/complicações , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Antígeno de Maturação de Linfócitos B/uso terapêutico , Terapia Baseada em Transplante de Células e Tecidos , Nefropatias/etiologia
9.
J Investig Med High Impact Case Rep ; 11: 23247096231209543, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37919949

RESUMO

Factor VII (FVII) is an important, vitamin K-dependent clotting factor. Acquired FVII deficiency is a rare entity that is associated with serious bleeding complications. We report a case of acquired FVII deficiency in a patient with recurrent chronic myeloid leukemia in blast crisis who developed bilateral retinal hemorrhages. The coagulopathy was corrected with the initiation of chemotherapy and subsequent reduction in peripheral blast count.


Assuntos
Deficiência do Fator VII , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Deficiência do Fator VII/complicações , Crise Blástica/complicações , Crise Blástica/tratamento farmacológico , Fator VII/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Vitamina K/uso terapêutico
10.
Cureus ; 15(9): e45629, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37868472

RESUMO

INTRODUCTION: Utilized in the healthcare sector, social media offers numerous benefits. However, its drawbacks encompass the variable quality of unregulated and unsupervised content. Thus, we aimed to evaluate the information in content related to chest pain found across Instagram and analyze the quality and reliability of chest pain-related content via Instagram posts. METHODOLOGY: Instagram posts with content related to chest pain were analyzed with the help of a structured questionnaire that included the Global Quality Scale (GQS) and DISCERN score (DS). To collect Instagram posts, several distinct hashtags were employed: #chestpain, #chestpains, #angina, #anginatreatment, #heartattack, #heartattacksurvivor, #heartattackprevention. RESULTS: A total of 262 posts were included, of which 29.7% of the total posts (n=78) contained information that describes the etiology of the disease. 27.8% of the total posts (n = 73) enclosed promotional content. Posts were found to be uploaded by doctors (18.7%), hospitals (15.6%), patients (17.9%), dieticians (11.1%), healthcare organizations (9.2%), and others (27.5%). Both Global Quality and DISCERN scores were statistically significant with a p-value of 0.001. CONCLUSIONS: The findings of this study revealed that most of the Instagram content on chest pain posted via physicians were highly reliable and had a better global quality score. Information regarding various causes, symptoms and preventive measures on Instagram can be considered as an acceptable source for patients to surf on. A major limitation is that only English content was analyzed. In the future, the use of higher quality posts produced by healthcare professionals could potentially contribute to enhancing patient education via Instagram.

11.
J Basic Microbiol ; 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37847888

RESUMO

Mercury (Hg) is a highly toxic heavy metal and Hg-resistant indigenous bacterial isolates may offer a green and cost-effective bioremediation strategy to counter Hg contamination. In this study, a potent Hg-resistant bacterium was isolated from the forest soil of a bird sanctuary. Identification using matrix-assisted laser desorption ionization-time of flight mass spectrometry depicted the isolate as a strain of Bacillus tropicus, validated by morphological, biochemical, and molecular studies. The isolate demonstrated biological Hg removal efficiency and capacity of 50.67% and 19.76 mg g-1 , respectively. The plasmid borne resistance determinant, merA, encoding mercuric reductase, was detected in the bacterium endowing it with effective Hg volatilization and resistance capability. A Fourier-transform infrared spectroscopic comparative metabolic profiling revealed the involvement of various functional groups like -COOH, -CH2 , -OH, PO4 - and so on, resulting in differential spectral patterns of the bacterium both in control and Hg-exposed situations. A temporal variance in metabolic signature was also observed during the early and mid-log phase of growth in the presence of Hg. The bacterium described in this study is the first indigenous Hg-resistant strain isolated from the Uttar Dinajpur region, which could be further explored and exploited as a potent bioresource for Hg remediation.

12.
Cancer Med ; 12(18): 19013-19020, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37587868

RESUMO

INTRODUCTION: Health information technology (HIT) has the potential to improve healthcare delivery and engagement. Studying racial-ethnic disparities in HIT engagement will help understand and overcome challenges to healthcare utilization. METHODS: We undertook a patient-reported survey among patients with lymphoid malignancies at two campuses of Mayo Clinic, Florida to explore HIT-related disparities. Variables between Whites and non-Whites, and non-Whites from the two campuses were compared. RESULTS: The survey was completed by 1004 respondents, with 71% whites, 27% non-Whites (race-ethnicity not reported by 2%). Non-Whites included 30% responders at the main campus and 64% at an inner-city campus. Whites were significantly older and had higher education, while non-Whites had lesser access to a computer. Only 51% of non-Whites were registered to use electronic medical records (EMR) as compared to 72% Whites (p < 0.001) and significantly lesser number of non-Whites even knew that EMR existed (81% vs. 92%, p < 0.001). Encouragingly, a higher number of non-Whites wanted to engage in EMR. Non-Whites from the main campus were older, more educated and had more access to a computer as compared to those from the inner-city campus. Similar disparate factors were noted among minorities from the two campuses, suggesting impact of socioeconomic backgrounds on EMR usage among non-Whites. Linguistic barriers were more striking among inner-city campus non-Whites. CONCLUSIONS: Non-Whites continue to struggle with suboptimal utilization of the healthcare system and barriers related to integration in HIT, including disparities representing socioeconomic differences. Efforts need to be made at several levels to help racial-ethnic minorities overcome awareness, access, and linguistic barriers to HIT utilization.

13.
Blood ; 142(22): 1871-1878, 2023 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-37494698

RESUMO

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.


Assuntos
Mieloma Múltiplo , Plasmocitoma , Humanos , Plasmocitoma/genética , Hibridização in Situ Fluorescente , Aberrações Cromossômicas , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Prognóstico , Progressão da Doença
14.
Bone Marrow Transplant ; 58(10): 1130-1136, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37479753

RESUMO

Due to the advent of effective novel therapies for multiple myeloma (MM), the use of cryopreserved autologous peripheral blood hematopoietic cells (APBHC) for a salvage autologous transplant (auto-HCT) is in decline. We evaluated utilization trends and costs associated with cryopreserved APBHC in patients with MM. We retrospectively evaluated the clinicopathologic data from 440 patients with MM who underwent APBHC mobilization and collection at Mayo Clinic Florida between 2010 and 2019. Based on institution-specific charges as of May 2021, the cost of 1 session of APBHC collection/apheresis was $4,680 and the cost of 1 year of APBHC cryopreservation was $4,790 per patient. Out of 347 patients who had APBHC in cryopreservation, 5 (1.4%) underwent a salvage auto-HCT and 61% of patients had ≥1 excess collection sessions for APBHC that ultimately went unused. The median cost of excess collection sessions was $4,680 per patient (range, $4,680-$32,760) and the median total cost for excess collection sessions plus costs for storage was $23,840 per patient (range, $4,680-$85,450). The sum of costs of excess collection sessions was $2,077,920 and the sum of costs of cryopreservation was $5,812,665. Institutional policies regarding universal APBHC collection and long-term storage should be reevaluated in the era of novel therapeutics.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/patologia , Estudos Retrospectivos , Transplante Autólogo , Autoenxertos/patologia , Mobilização de Células-Tronco Hematopoéticas
15.
Am J Hematol ; 98(8): 1277-1285, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37334773

RESUMO

In this phase 1/2 study, carfilzomib was added to high-dose melphalan conditioning prior to autologous stem cell transplantation (ASCT) in patients with multiple myeloma that had been treated with ≤2 prior lines of therapy. Carfilzomib was escalated at doses of 27, 36, 45, and 56 mg/m2 on days -6, -5, -2, and -1 before ASCT in the phase 1 component of the study. In addition, all the patients received melphalan 100 mg/m2 on days -4 and -3. The primary endpoint of the phase 1 component was to identify the maximum tolerated dose, and the primary endpoint of the phase 2 component was the rates of complete response (≥CR) at 1 year after ASCT. The phase 1 dose escalation cohort included 14 patients, and 35 patients were included in the phase 2 cohort. The maximum tested dose was 56 mg/m2 (MTD). The median time from diagnosis to study enrollment was 5.8 (range 3.4-88.4) months, and 16% of patients had obtained a ≥CR prior to ASCT. The best response within 1 year after ASCT was a ≥ CR rate in 22% for the entire cohort, and 22% for patients treated at the MTD. The ≥VGPR rates improved from 41% before ASCT to 77% by 1 year after ASCT. One patient had a grade 3 renal adverse event, and renal function returned to baseline with supportive care. The rate of grade 3-4 cardiovascular toxicity was 16%. The addition of carfilzomib to melphalan conditioning was safe and resulted in deep responses after ASCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Melfalan , Mieloma Múltiplo/tratamento farmacológico , Transplante Autólogo , Condicionamento Pré-Transplante/métodos , Transplante de Células-Tronco
16.
Hematol Oncol Stem Cell Ther ; 16(4): 407-411, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37363981

RESUMO

BACKGROUND: Multiple myeloma (MM) is the second most common hematologic malignancy, with 34,470 estimated new cases in 2022. High-dose therapy followed by autologous hematopoietic cell transplantation (auto-HCT) remains a standard treatment for MM even in the era of novel therapies. This is usually performed in hospital-based settings, either in the inpatient or outpatient units. Advanced Care at Home (ACH) represents a virtual hybrid hospital-at-home program that combines a virtual provider-staffed command center with a vendor-mediated supply chain capable of delivering high-acuity care in the comfort of the patients' own homes. In our program, we used the existing ACH platform to deliver post-HCT care for recipients of auto-HCT. PATIENTS AND METHODS: Four patients (female = 2, 50%) with MM, with a median age of 60 (range, 40-74) years, were admitted to the inpatient Blood and Marrow Transplant (BMT) unit. The conditioning regimen consisted of melphalan 200 mg/m2, administered on day -2. All patients received stem cell infusion (day 0) in the inpatient setting, with a median dose of 3.64 (range, 2.92-8.22) × 106/kg CD34 cells. RESULTS: Patients were discharged to their homes after completing the infusion on day 0 or day +1 at the latest. Post-infusion care was provided by the ACH team in coordination with the BMT team. The median time intervals to absolute neutrophil count and platelet engraftment were 12 (range, 11-13) and 11 (range, 9-16) days, respectively. All patients were successfully discharged from the ACH program at a median of day +14 (range, day +14 to day +15). CONCLUSIONS: Our results highlight the feasibility of delivering post-HCT care for auto-HCT recipients in the home setting and confirm the generalizability of this approach.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Transplante de Células-Tronco Hematopoéticas/métodos , Resultado do Tratamento , Mieloma Múltiplo/terapia , Transplante Autólogo , Melfalan , Condicionamento Pré-Transplante/métodos
17.
Transplant Cell Ther ; 29(5): 327.e1-327.e9, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36758832

RESUMO

Post-transplantation cyclophosphamide (PTCy) and calcineurin inhibitor (CNI)-based graft versus host disease (GVHD) prophylaxis has been associated with lower rates of acute and chronic GVHD compared with the traditional prophylaxis of CNI and methotrexate (MTX) in matched related donor (MRD) and matched unrelated donor (MUD) allogeneic hematopoietic cell transplantation (allo-HCT). The combination of PTCy with sirolimus (PTCy-Siro) as CNI-free GVHD prophylaxis has shown promising results, with cumulative rates of grade II-IV acute and chronic GVHD in the range of 15% to 27% and 20% to 27%, respectively, in patients undergoing MRD, MUD, and haploidentical allo-HCT. We report a single-center, nonrandomized comparison of patients undergoing matched donor allo-HCT receiving PTCy-Siro with those receiving the standard GVHD prophylaxis of tacrolimus and methotrexate (Tac-MTX). One hundred and sixteen consecutive patients who had undergone an MRD or MUD allo-HCT between January 2018 and January 2021 and received either PTCy-Siro (n = 29) or Tac-MTX (n = 87) as GVHD prophylaxis regimens were eligible for inclusion. Patients receiving PTCy-Siro had a significantly shorter median time to immunosuppression withdrawal than patients receiving Tac-MTX (138 days [range, 37 to 312 days] versus 232 days [range, 66 to 1120 days]; P < .001). There was no significant difference between the 2 arms in the incidence of grade II-IV acute GVHD, grade III-IV acute GVHD, steroid-refractory acute GVHD, or clinical infections. At a median follow-up of 1.1 years (range, 0 to 1.8 years), patients receiving PTCy-Siro were significantly less likely to have chronic GVHD, with 2-year freedom from GVHD of 75% (95% confidence interval [CI], 58% to 98%) versus 20% (95% CI, 10% to 40%) for those receiving Tac-MTX (P = .005).


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Inibidores de Calcineurina/uso terapêutico , Calcineurina , Metotrexato/uso terapêutico , Doadores não Relacionados , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/tratamento farmacológico , Ciclofosfamida/uso terapêutico
18.
Cancers (Basel) ; 15(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36672426

RESUMO

Bcl-2 and Mcl-1 proteins play a role in multiple myeloma (MM) cell survival, for which targeted inhibitors are being developed. AT-101 is an oral drug, which disrupts Bcl-2 and Mcl-1 function, impedes mitochondrial bioenergetic processes and induces apoptosis in MM cells. When combined with lenalidomide and dexamethasone (Rd), AT-101 significantly reduced tumor burden in an in vivo xenograft model of MM. These data provided rationale for a phase I/II study to establish the effective dose of AT-101 in combination with Rd (ARd regimen) in relapsed/refractory MM. A total of 10 patients were enrolled, most with high-risk cytogenetics (80%) and prior stem cell transplant (70%). Three patients were lenalidomide-refractory, 2 were bortezomib-refractory and 3 were daratumumab-refractory. The ARd combination was well tolerated with most common grade 3/4 adverse events being cytopenia's. The overall response rate was 40% and clinical benefit rate was 90%. The median progression free survival was 14.9 months (95% CI 7.1-NE). Patients responsive to ARd showed a decrease in Bcl-2:Bim or Mcl-1:Noxa protein complexes, increased CD8+ T and NK cells and depletion of T and B-regulatory cells. The ARd regimen demonstrated an acceptable safety profile and promising efficacy in patients with relapsed/refractory MM prompting further investigation in additional patients.

20.
Am J Hematol ; 98(1): 49-55, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36226510

RESUMO

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].


Assuntos
COVID-19 , Amiloidose de Cadeia Leve de Imunoglobulina , Mieloma Múltiplo , Humanos , Vacinas contra COVID-19 , Amiloidose de Cadeia Leve de Imunoglobulina/complicações , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Mieloma Múltiplo/complicações , Mieloma Múltiplo/terapia , Fatores de Risco
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