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1.
Blood ; 142(22): 1871-1878, 2023 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-37494698

RESUMEN

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.


Asunto(s)
Mieloma Múltiple , Plasmacitoma , Humanos , Plasmacitoma/genética , Hibridación Fluorescente in Situ , Aberraciones Cromosómicas , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/genética , Pronóstico , Progresión de la Enfermedad
2.
Am J Respir Crit Care Med ; 209(5): 543-552, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38051944

RESUMEN

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.


Asunto(s)
Lesión Pulmonar , Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Humanos , Trasplante de Médula Ósea/efectos adversos , Lesión Pulmonar/complicaciones , Estudios de Cohortes , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/complicaciones , Insuficiencia Respiratoria/terapia
3.
Br J Haematol ; 204(5): 1825-1829, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38286472

RESUMEN

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.


Asunto(s)
Adenina , Protocolos de Quimioterapia Combinada Antineoplásica , Compuestos de Boro , Glicina , Piperidinas , Macroglobulinemia de Waldenström , Humanos , Compuestos de Boro/uso terapéutico , Compuestos de Boro/administración & dosificación , Compuestos de Boro/efectos adversos , Macroglobulinemia de Waldenström/tratamiento farmacológico , Glicina/análogos & derivados , Glicina/administración & dosificación , Glicina/efectos adversos , Glicina/uso terapéutico , Adenina/análogos & derivados , Masculino , Anciano , Persona de Mediana Edad , Femenino , Piperidinas/uso terapéutico , Piperidinas/administración & dosificación , Piperidinas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Anciano de 80 o más Años , Pirimidinas/efectos adversos , Pirimidinas/uso terapéutico , Pirimidinas/administración & dosificación , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Pirazoles/administración & dosificación , Adulto , Resultado del Tratamiento
4.
Anticancer Drugs ; 35(1): 63-69, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37067996

RESUMEN

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.


Asunto(s)
Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Lenalidomida/uso terapéutico , Dexametasona/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
5.
J Basic Microbiol ; 64(3): e2300351, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37847888

RESUMEN

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.


Asunto(s)
Bacillus , Mercurio , Mercurio/metabolismo , Suelo/química , Espectroscopía Infrarroja por Transformada de Fourier , Bacillus/metabolismo , Bacterias/metabolismo
6.
Am J Hematol ; 98(8): 1277-1285, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37334773

RESUMEN

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.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Melfalán , Mieloma Múltiple/tratamiento farmacológico , Trasplante Autólogo , Acondicionamiento Pretrasplante/métodos , Trasplante de Células Madre
7.
Am J Hematol ; 98(1): 49-55, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36226510

RESUMEN

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].


Asunto(s)
COVID-19 , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Mieloma Múltiple , Humanos , Vacunas contra la COVID-19 , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/complicaciones , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/terapia , Mieloma Múltiple/complicaciones , Mieloma Múltiple/terapia , Factores de Riesgo
8.
Hematol Oncol ; 40(4): 695-703, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35488778

RESUMEN

Therapeutic strategies that target novel pathways are urgently needed for patients with relapsed/refractory multiple myeloma (RRMM). Ibrutinib is an oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in MM cells. This phase 1 dose-escalation study examined various doses of ibrutinib in combination with standard doses of lenalidomide (25 mg) and dexamethasone (40 mg) using a standard 3 + 3 design in RRMM patients. The primary objective was to determine the maximum tolerated dose (MTD) of ibrutinib in combination with lenalidomide and dexamethasone. Patients (n = 15) had received a median of 4 prior regimens, 53% were triple-class exposed, 33% were penta-exposed, and 54% were lenalidomide-refractory. The MTD of ibrutinib was 840 mg (n = 6) and only 1 dose-limiting toxicity; a grade 3 rash possibly related to ibrutinib was noted. The most common ≥ grade 3 adverse events were rash in 2 (13%), lymphopenia in 2 (13%), leukopenia, neutropenia, thrombocytopenia, and anemia all occurring in 3 (20%) patients each. One patient achieved a partial response for an overall response rate of 7%. The clinical benefit rate was 80%. The median time to progression was 3.8 months. Ibrutinib, lenalidomide and dexamethasone appears to be a safe and well-tolerated regimen with reasonable efficacy in heavily pretreated RRMM patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Mieloma Múltiple , Recurrencia Local de Neoplasia , Agammaglobulinemia Tirosina Quinasa , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/administración & dosificación , Exantema/inducido químicamente , Humanos , Lenalidomida/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Resultado del Tratamiento
9.
J Natl Compr Canc Netw ; 20(5): 436-442, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35545171

RESUMEN

The NCCN Guidelines for Hematopoietic Growth Factors provide recommendations for the appropriate use of growth factors in the clinical management of febrile neutropenia (FN), chemotherapy-induced thrombocytopenia (CIT), and chemotherapy-induced anemia (CIA). Management and prevention of these sequelae are an integral part of supportive care for many patients undergoing cancer treatment. The purpose of these guidelines is to operationalize the evaluation, prevention, and treatment of FN, CIT, and CIA in adult patients with nonmyeloid malignancies and to enable the patient and clinician to assess management options for FN, CIT, and CIA in the context of an individual patient's condition. These NCCN Guidelines Insights provide a summary of the important recent updates to the NCCN Guidelines for Hematopoietic Growth Factors, with particular emphasis on the incorporation of a newly developed section on CIT.


Asunto(s)
Anemia , Antineoplásicos , Neoplasias , Adulto , Anemia/inducido químicamente , Anemia/tratamiento farmacológico , Antineoplásicos/efectos adversos , Factores de Crecimiento de Célula Hematopoyética/uso terapéutico , Humanos , Neoplasias/tratamiento farmacológico
10.
J Oncol Pharm Pract ; 28(2): 425-433, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33719723

RESUMEN

OBJECTIVE: Outcomes in multiple myeloma (MM) have significantly improved necessitating focus on survivorship. METHODS: We undertook a web-based survey in collaboration with International Myeloma Foundation (IMF) to explore patient awareness and psycho-physical impacts of MM. The survey was viewed on the IMF website by 1,324 individuals from 32 countries. RESULTS: The survey responses were available from 959 individuals, with 62% who completed the survey. Treating doctors were the most frequent source of MM-related information. Only 56% patients admitted full compliance with treatment. Treatment side effects bothered 86% responders, including >50% admitting to pain, peripheral neuropathy and asthenia. Majority (57%) reported some degree of depression, 82% had discontent with their quality of life and only 35% reported being satisfied with their coping mechanisms. Patients ≥65 years of age reported more peripheral neuropathy (p = 0.007) and difficulty with ability to work (p = 0.015). CONCLUSIONS: We report the prevalence of psychologic, social and physical domains as well as patient-physician relationship dynamics. This knowledge can help improve MM survivorship.Introduction.


Asunto(s)
Mieloma Múltiple , Humanos , Internet , Mieloma Múltiple/terapia , Estudios Prospectivos , Calidad de Vida , Encuestas y Cuestionarios
11.
Ann Hematol ; 100(3): 735-741, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33438047

RESUMEN

Plasma cell disorders including plasmacytomas and multiple myeloma (MM) are exquisitely radiosensitive, and thus, radiation therapy (XRT) is used effectively in their management. The role of XRT in the setting of novel MM therapeutics has not been explored. The 2016 National Cancer Database (NCDB) for MM with patients diagnosed between 2004 and 2013 was studied. Association between utilization of XRT as part of initial therapy and patient, disease, or treating facility characteristics was studied. A total of 111,281 cases with 91.6% MM, 7% osseous plasmacytoma (PLA-O), and 1.4% extramedullary plasmacytoma (PLA-E) were identified. XRT was utilized as part of initial therapy in 25.4% cases, including 69.3% of PLA-O, 60% of PLA-E, and 21.5% of MM patients. Patients with PLA-E and MM were significantly less likely to receive XRT as compared to PLA-O (p < 0.001). A significantly decreased use of XRT was noted over time (p < 0.001), and for advancing patient age (p < 0.001), women (p < 0.001), and blacks (p < 0.001), and with increasing income (p = 0.015). Patients with Medicare were less likely to receive XRT (OR 0.86, 95% CI 0.78, 0.94) as compared to uninsured as were those with initial treatment at academic or high-volume facilities and facilities performing stem cell transplant. There was overall decreased utilization of XRT in recent years, possibly due to advent of efficacious systemic agents for MM therapy, with a higher XRT utilization for plasmacytomas. Patterns of XRT use need to be explored prospectively, so that uniform standards of healthcare delivery can be maintained and treatment heterogeneity can be minimized.


Asunto(s)
Oncología Médica/tendencias , Mieloma Múltiple/radioterapia , Pautas de la Práctica en Medicina/tendencias , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Humanos , Masculino , Oncología Médica/estadística & datos numéricos , Persona de Mediana Edad , Mieloma Múltiple/epidemiología , Pautas de la Práctica en Medicina/estadística & datos numéricos , Puerto Rico/epidemiología , Factores Socioeconómicos , Estados Unidos/epidemiología
12.
Eur J Haematol ; 107(1): 48-53, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33655560

RESUMEN

INTRODUCTION: Hypoalbuminemia is a known adverse prognostic factor in lymphomas. Yet, it is unknown if axicabtagene ciloleucel (axi-cel) overcomes the adverse prognostic impact of hypoalbuminemia in relapsed/refractory large B-cell lymphoma. METHODS: We conducted a retrospective analysis across three Mayo Clinic centers to assess the relationship of hypoalbuminemia (defined as a serum albumin (SA) levels ≤ 3.5 g/dL) on outcomes of patients treated with axi-cel. RESULTS: This analysis included 81 patients. Two patients had no available SA levels preceding axi-cel infusion. Eighteen patients (22.8%) had hypoalbuminemia with a median SA of 3.3 g/dL. Patients with normal SA had a statistically higher ORR than those without hypoalbuminemia (P = .018). There was no difference in 1-year PFS and OS between the group with hypoalbuminemia and the group with normal SA levels (48% vs 49%, P = .81) and (74% vs 73%, P = .97), respectively. There was no difference in the severity or median duration of cytokine release syndrome or neurotoxicity between the two groups. CONCLUSION: Notwithstanding the limitations related to the relatively small sample size, axi-cel therapy appears to overcome the adverse effect of hypoalbuminemia on OS and PFS. Large multicenter clinical studies are certainly needed to validate these findings.


Asunto(s)
Antígenos CD19/biosíntesis , Productos Biológicos/uso terapéutico , Síndrome de Liberación de Citoquinas , Hipoalbuminemia/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adulto , Anciano , Productos Biológicos/efectos adversos , Citocinas/metabolismo , Femenino , Humanos , Hipoalbuminemia/complicaciones , Inmunoterapia Adoptiva , Inflamación , Linfoma de Células B Grandes Difuso/complicaciones , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Albúmina Sérica/biosíntesis , Resultado del Tratamiento
13.
Am J Hematol ; 96(8): 945-953, 2021 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-33909933

RESUMEN

Comparative data guiding initial therapy for Waldenström macroglobulinemia (WM), an infrequently encountered non-Hodgkin lymphoma, are sparse. We evaluated three commonly used rituximab-based frontline regimens: rituximab-bendamustine (R-Benda); dexamethasone, rituximab, cyclophosphamide (DRC); and bortezomib, dexamethasone, rituximab (BDR) in 220 treatment-naïve patients with WM, seen at Mayo Clinic between November 1, 2000 and October 31, 2019. The median follow-up was 4.5 (95%CI: 4-5) years. The R-Benda cohort (n = 83) demonstrated superior overall response rate (ORR: 98%), in comparison to DRC (n = 92, ORR: 78%) or BDR (n = 45, ORR: 84%) cohorts, p = 0.003. Similarly, longer progression-free survival (PFS) was evident with R-Benda use [median 5.2 vs. 4.3 (DRC) and 1.8 years (BDR), p < 0.001]. The time-to-next therapy (TTNT) favored R-Benda [median, not-reached, 4.4 (DRC) and 2.6 years (BDR), p < 0.001). These endpoints were comparable between the DRC and BDR cohorts. Overall survival (OS) was similar across the three cohorts, p = 0.77. In a subset analysis of 142 patients genotyped for MYD88L265P mutation, the ORR, PFS and TTNT were unaffected by the patients' MYD88 signature within each cohort. In conclusion, ORR, PFS and TTNT with R-Benda are superior compared to DRC or BDR in treatment-naïve patients with active WM. The patient outcomes with any one of these three regimens are unaffected by the MYD88L265P mutation status.


Asunto(s)
Macroglobulinemia de Waldenström/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad
14.
Biol Blood Marrow Transplant ; 26(1): 76-82, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31494227

RESUMEN

Mycosis fungoides and Sézary syndrome are the most common types of primary cutaneous T cell lymphomas. The clinical presentation of mycosis fungoides is generally indolent, whereas Sézary syndrome represents a more aggressive disease variant. Stage at diagnosis is the most important determinant of long-term survival outcome. Although most patients present with early-stage disease, those who develop progressive disease or have an advanced stage represent a therapeutic challenge because of a lack of effective therapies. Allogeneic hematopoietic cell transplantation (allo-HCT) has been used as a potentially curative treatment modality with encouraging long-term outcomes. However, a lack of randomized controlled data remains, and the published literature is limited to mostly retrospective studies. We performed a comprehensive search of the medical literature using PubMed/Medline, EMBASE, and Cochrane reviews on September 13, 2018. We extracted data on clinical outcomes related to benefits (overall [OS] and progression-free [PFS] survival) and harms (relapse and nonrelapse mortality [NRM]) independently by 2 authors. Our search strategy identified 289 references. Five studies (266 patients) were included in this systematic review and meta-analysis. Reduced-intensity and nonmyeloablative regimens were more commonly prescribed (76%). Mobilized peripheral blood stem cells were the preferred graft source (78%). The pooled OS and PFS rates were 59% (95% confidence interval [CI], 50% to 69%) and 36% (95% CI, 27% to 45%), respectively. Pooled relapse rate was 47% (95% CI, 41% to 53%) and pooled NRM rate 19% (95% CI, 13% to 27%). Results of this systematic review and meta-analysis show that allo-HCT yields encouraging OS and PFS rates; however; relapse remains a significant cause of allo-HCT failure. Novel strategies to further improve outcomes should focus on offering allo-HCT before the development of resistant disease and reducing relapse by incorporating post-transplant maintenance therapies.


Asunto(s)
Quimioterapia de Mantención , Micosis Fungoide , Trasplante de Células Madre de Sangre Periférica , Síndrome de Sézary , Aloinjertos , Supervivencia sin Enfermedad , Humanos , Micosis Fungoide/mortalidad , Micosis Fungoide/terapia , Recurrencia , Síndrome de Sézary/mortalidad , Síndrome de Sézary/terapia , Tasa de Supervivencia
15.
Cytotherapy ; 22(1): 16-20, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31879152

RESUMEN

BACKGROUND AIMS: Baseline platelet count has been shown to be a sensitive predictor of autologous peripheral blood progenitor cell collection yield in patients with multiple myeloma mobilized with granulocyte colony-stimulating factor (G-CSF). Patients who mobilize poorly with G-CSF are often treated with plerixafor to enhance mobilization. There are no surrogate markers available to predict response to plerixafor. METHODS: We retrospectively analyzed data from 73 patients with multiple myeloma who did not have adequate mobilization with G-CSF alone and were treated with plerixafor as a rescue agent. RESULTS: We found that baseline platelet count directly correlated with peripheral blood CD34+ (PB-CD34+) count after plerixafor treatment (r = 0.36, P < 0.0001) and the number of PB-CD34+ cells collected on the first day of apheresis and inversely correlated with the number of apheresis sessions needed to collect the target number of PB-CD34+ cells (P = 0.0015). Baseline platelet count of 153 000/µL or less was associated with 90% specificity of predicting poor response to plerixafor with a sensitivity of 33%. CONCLUSIONS: Baseline platelet count is a good predictor of mobilization response to plerixafor in patients with multiple myeloma.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Movilización de Célula Madre Hematopoyética , Compuestos Heterocíclicos/uso terapéutico , Mieloma Múltiple/terapia , Recuento de Plaquetas , Adulto , Anciano , Bencilaminas , Biomarcadores , Eliminación de Componentes Sanguíneos , Ciclamas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Autólogo
16.
J Natl Compr Canc Netw ; : 1-4, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32871558

RESUMEN

Hematopoietic growth factors, including erythrocyte stimulating agents (ESAs), granulocyte colony-stimulating factors, and thrombopoietin mimetics, can mitigate anemia, neutropenia, and thrombocytopenia resulting from chemotherapy for the treatment of cancer. In the context of pandemic SARS-CoV-2 infection, patients with cancer have been identified as a group at high risk of morbidity and mortality from this infection. Our subcommittee of the NCCN Hematopoietic Growth Factors Panel convened a voluntary group to review the potential value of expanded use of such growth factors in the current high-risk environment. Although recommendations are available on the NCCN website in the COVID-19 Resources Section (https://www.nccn.org/covid-19/), these suggestions are provided without substantial context or reference. Herein we review the rationale and data underlying the suggested alterations to the use of hematopoietic growth factors for patients with cancer in the COVID-19 era.

17.
J Natl Compr Canc Netw ; 18(1): 12-22, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31910384

RESUMEN

Management of febrile neutropenia (FN) is an integral part of supportive care for patients undergoing cancer treatment. The NCCN Guidelines for Hematopoietic Growth Factors provide suggestions for appropriate evaluation, risk determination, prophylaxis, and management of FN. These NCCN Guidelines are intended to guide clinicians in the appropriate use of growth factors for select patients undergoing treatment of nonmyeloid malignancies. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines regarding the incorporation of newly FDA-approved granulocyte-colony stimulating factor biosimilars for the prevention and treatment of FN.


Asunto(s)
Biosimilares Farmacéuticos/uso terapéutico , Neutropenia Febril Inducida por Quimioterapia/tratamiento farmacológico , Factores de Crecimiento de Célula Hematopoyética/uso terapéutico , Neoplasias/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biosimilares Farmacéuticos/economía , Biosimilares Farmacéuticos/normas , Neutropenia Febril Inducida por Quimioterapia/etiología , Aprobación de Drogas , Costos de los Medicamentos , Educación Médica Continua , Factores de Crecimiento de Célula Hematopoyética/economía , Factores de Crecimiento de Célula Hematopoyética/normas , Humanos , Oncología Médica/educación , Oncología Médica/normas , Neoplasias/sangre , Oncólogos/educación , Organizaciones sin Fines de Lucro/normas , Factores de Riesgo , Estados Unidos , United States Food and Drug Administration/legislación & jurisprudencia
18.
Psychosomatics ; 61(4): 363-370, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32359775

RESUMEN

BACKGROUND: Hematopoietic cell recipients are reported to have a high prevalence of depression and anxiety. The impact of depression and anxiety on opioid use has not been well characterized. This is of significance as the opioid epidemic continues, and over 60% of deaths secondary to drug overdose involve the use of opioids. OBJECTIVE: In this retrospective, single-center study of 275 patients who underwent hematopoietic cell transplantation (HCT) (allogeneic and autologous) for hematological malignancies, we explore the impact of depression and anxiety on opioid use. RESULTS: Patients who were both anxious and depressed at admission for HCT had increased odds of receiving an opioid (odds ratio of 4.50 [95% confidence interval: 1.75, 11.56]) compared with patients who were neither depressed nor anxious. However, patients who were either depressed or anxious did not have different odds of receiving an opioid compared with those who were neither depressed nor anxious. Autologous HCT recipients had reduced odds of receiving an opioid (odds ratio of 0.17 [95% confidence interval: 0.08, 0.38]) compared with patients undergoing allogeneic HCT. Patients with lower Karnofsky performance status (<90 on a scale of 1-100) had an increased incidence of receiving a higher Morphine milligram equivalent daily dosage (incidence rate ratio of 2.59 [95% confidence interval: 1.18, 5.67]) when modeled by zero truncated negative binomial regression. CONCLUSION: Presence of depression and anxiety impacts opioid use in patients undergoing HCT.


Asunto(s)
Analgésicos Opioides/uso terapéutico , Ansiedad/epidemiología , Depresión/epidemiología , Trasplante de Células Madre Hematopoyéticas/psicología , Hospitalización , Adulto , Anciano , Analgésicos Opioides/efectos adversos , Femenino , Florida/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
19.
Blood ; 130(10): 1198-1204, 2017 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-28684537

RESUMEN

This phase 1/2 trial evaluated the maximum tolerated doses, safety, and efficacy of pomalidomide, bortezomib, and dexamethasone (PVD) combination in patients with relapsed lenalidomide-refractory multiple myeloma (MM). In phase 1, dose level 1 consisted of pomalidomide (4 mg by mouth on days 1 to 21), IV or subcutaneous bortezomib (1.0 mg/m2 on days 1, 8, 15, and 22), and dexamethasone (40 mg by mouth on days 1, 8, 15, and 22) given every 28 days. Bortezomib was increased to 1.3 mg/m2 for dose level 2 and adopted in the phase 2 expansion cohort. We describe the results of 50 patients. Objective response rate was 86% (95% confidence interval [CI], 73-94) among all evaluable patients (stringent complete response, 12%; complete response, 10%; very good partial response, 28%; and partial response, 36%) and 100% among high-risk patients. Within a median follow-up of 42 months, 20% remain progression free, 66% are alive, and 4% remain on treatment. Median progression-free survival was 13.7 months (95% CI, 9.6-17.7). The most common toxicities were neutropenia (96%), leukopenia (84%), thrombocytopenia (82%), anemia (74%), and fatigue (72%); however, the majority of these were grade 1 or 2. The most common grade ≥3 toxicities included neutropenia (70%), leukopenia (36%), and lymphopenia (20%). Deep vein thrombosis occurred in 5 patients. In conclusion, PVD is a highly effective combination in lenalidomide-refractory MM patients. Weekly administration of bortezomib enhanced tolerability and convenience. Toxicities are manageable, mostly consisting of mild cytopenias with no significant neuropathy. This trial was registered at www.clinicaltrials.gov as #NCT01212952.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Dexametasona/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Talidomida/análogos & derivados , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Lenalidomida , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Talidomida/uso terapéutico , Resultado del Tratamiento
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