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1.
Br J Haematol ; 205(1): 280-290, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38831752

RESUMEN

For patients with relapsed or refractory AML, sequential conditioning prior to allogeneic stem cell transplantation (alloSCT) is an established and potentially curative treatment option. Early response to treatment during conditioning indicates chemotherapy-responsive disease and may have prognostic value. We retrospectively evaluated blast clearance on day 5 after melphalan, administered 11 days prior to alloSCT as part of a sequential conditioning in 176 patients with active AML. Overall survival (OS) was 52% (95% confidence interval [CI] 45%-60%), and relapse-free survival (RFS) was 47% (95% CI 40%-55%) at 3 years. Patients who achieved early blast clearance did not show a significant improvement in OS and RFS (OS, hazard ratio [HR] HR 0.75, p 0.19; RFS, HR 0.71, p 0.09, respectively), but had a significantly lower non-relapse mortality rate (HR 0.46, p 0.017). HLA-mismatched donor, older age, adverse genetic risk and higher comorbidity scores were associated with inferior survival outcomes. A high initial blast count was only associated with inferior prognosis in patients receiving chemotherapy-only compared to total body irradiation containing conditioning therapy. These results indicate that for patients transplanted with active AML, sensitivity to chemotherapy might be of less importance, compared to other disease- and transplant-related factors.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Acondicionamiento Pretrasplante , Trasplante Homólogo , Humanos , Acondicionamiento Pretrasplante/métodos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidad , Persona de Mediana Edad , Masculino , Femenino , Adulto , Anciano , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/métodos , Adulto Joven , Adolescente , Pronóstico , Melfalán/administración & dosificación , Melfalán/uso terapéutico
2.
Br J Haematol ; 205(3): 1097-1107, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39049594

RESUMEN

Reduced-intensity conditioning regimens are commonly used in allogeneic haematopoietic cell transplantation for non-Hodgkin lymphoma (NHL); however, the optimal regimen remains unknown. In this study, the outcomes of adult patients with NHL who received fludarabine plus reduced-dose busulfan (6.4 mg/kg; Flu/Bu2) (n = 286) and fludarabine plus low-dose melphalan (80 or 100 mg/m2; Flu/Mel80-100) (n = 283) between January 2009 and December 2020 were compared using Japanese registry data. The primary end-point was the 5-year overall survival (OS). The 5-year OS was 53.8% (95% CI, 47.6-59.6) and 42.4% (95% CI, 35.6-49.0) in the Flu/Bu2 and Flu/Mel80-100 groups respectively (p = 0.030). After inverse probability of treatment weighting adjustment, the adjusted HR of Flu/Bu2 compared with Flu/Mel80-100 group for 5-year OS was 0.77 (95% CI, 0.60-0.99, p = 0.046), 0.97 (95% CI, 0.78-1.21, p = 0.798) for 5-year progression-free survival, 0.65 (95% CI, 0.45-0.94, p = 0.022) for 5-year cumulative risk of non-relapse mortality and 1.25 (95% CI, 0.95-1.64, p = 0.115) for 5-year cumulative risk of relapse. In this study, patients with NHL who received Flu/Bu2 were associated with better OS and lower non-relapse mortality than those who received Flu/Mel80-100.


Asunto(s)
Busulfano , Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin , Melfalán , Acondicionamiento Pretrasplante , Vidarabina , Humanos , Vidarabina/análogos & derivados , Vidarabina/administración & dosificación , Vidarabina/uso terapéutico , Busulfano/administración & dosificación , Busulfano/uso terapéutico , Melfalán/administración & dosificación , Melfalán/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Persona de Mediana Edad , Masculino , Femenino , Linfoma no Hodgkin/terapia , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Tasa de Supervivencia , Trasplante Homólogo
3.
J Clin Immunol ; 45(1): 6, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39264505

RESUMEN

BACKGROUND: IL10RA (IL10 receptor subunit alpha) deficiency is an autosomal recessive disease that causes inflammatory bowel disease during early infancy. Its clinical course is often fatal and the only curative treatment is allogeneic hematopoietic cell transplantation (HCT). In Japan, only case reports are available, and there are no comprehensive reports of treatment outcomes. METHODS: We retrospectively analyzed patients with IL10RA deficiency in Japan. RESULTS: Two newly identified and five previously reported patients were included in this study. Five patients underwent HCT; one untransplanted patient survived to age 14, and one died of influenza encephalopathy before transplantation. All five HCT recipients underwent HCT at the age before 2 years. They all were conditioned with fludarabine/busulfan- or fludarabine /melphalan-based regimens. The donor source was human leukocyte antigen haploidentical donor bone marrow (BM) for two patients and unrelated umbilical cord blood (CB) for two patients. One patient experienced graft failure with unrelated CB and required a second transplant with unrelated BM. All patients who underwent HCT survived and demonstrated an improved performance status. CONCLUSION: In cases of IL10RA deficiency, the need for transplantation should be promptly assessed, and early transplantation should be considered. (190/250).


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Japón , Masculino , Femenino , Lactante , Resultado del Tratamiento , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodos , Adolescente , Preescolar , Subunidad alfa del Receptor de Interleucina-10/genética , Subunidad alfa del Receptor de Interleucina-10/deficiencia , Niño , Enfermedades Inflamatorias del Intestino/terapia
4.
Ann Surg Oncol ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39174837

RESUMEN

BACKGROUND: Uveal melanoma often metastasizes to the liver, portending a poor prognosis. Melphalan/hepatic delivery system (HDS) via percutaneous hepatic perfusion (PHP) is a minimally invasive means of circulating high-dose chemotherapy through the affected liver. This study evaluated melphalan/HDS use as either first-line or second-line treatment to guide treatment sequencing. PATIENTS AND METHODS: A retrospective review included patients with hepatic-dominant metastatic uveal melanoma who underwent melphalan/HDS treatment via PHP from 2008 to 2023. RESULTS: A total of 30 patients were identified; 53.3% female, with a median age of 63.5 years (37-78 years). Median follow-up time was 14.5 months. First-line therapies included melphalan/HDS (n = 17), liver-directed (n = 7), and immunotherapy (n = 6). Second-line therapies included melphalan/HDS (n = 6), immunotherapy (n = 5), and liver-directed (n = 3). Median hepatic progression-free survival (hPFS) for first-line melphalan/HDS, immunotherapy, and liver-directed therapy was 17.6/8.8/9.2 months, respectively (P = 0.002). Median hPFS for second-line melphalan/HDS, immunotherapy, and liver-directed therapy was not reached/14.7/7.5 months, respectively (P < 0.001). Median overall PFS for first-line melphalan/HDS, immunotherapy, and liver-directed therapy was 15.4/8.8/9.2 months, respectively (P = 0.04). Median overall PFS for second-line melphalan/HDS, immunotherapy, and liver-directed therapy was 22.2/14.7/7.5 months, respectively (P = 0.001). CONCLUSIONS: Melphalan/HDS via PHP for metastatic uveal melanoma to the liver was found to have significantly improved hPFS and overall PFS when used as first-line therapy compared with immunotherapy or liver-directed therapy. PHP continued to demonstrate improved hPFS and PFS when used as second-line therapy compared with second-line immunotherapy or liver-directed therapy.

5.
Ann Hematol ; 103(1): 269-283, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37880484

RESUMEN

Autologous stem cell transplantation (ASCT) remains the mainstay of the treatment in newly diagnosed transplant-eligible multiple myeloma (MM) patients. This retrospective study was performed to investigate the potential prognostic markers which may modify transplant course in a total of 256 ASCT recipients [median age: 58 (30-74) years; male/female: 138/118], including pretransplant (PET0) and day + 60 (PET2) PET/CT assessments and comparative analysis of melphalan (Mel) dose. Better responses with significantly higher complete response/very good partial response rates were achieved in patients who proceeded to transplant within 301 days from diagnosis (p < 0.001). Patients who had received < 1.5 lines of treatment prior to transplant had significantly higher probability of overall survival (OS) (p = 0.004) and progression-free survival (PFS) (p < 0.001). The probability of OS was significantly higher in patients with low Eastern Cooperative Oncology Group (ECOG) performance score (PS = 0-1) (p = 0.003) and HCT-Comorbidity Index (HCT-CI = 0) (p = 0.011). The number of involved areas (p = 0.028) and maximum standardized uptake value (SUVmax) (p = 0.021) in PET0 represented significant impact on OS. The probabilities of OS (p < 0.001) and PFS (p = 0.01) were significantly better with Mel200 mg/m2 conditioning compared to Mel140 mg/m2. Conditioning with Mel200 mg/m2, early and upfront ASCT and low pretransplant treatment burden were found to be significantly associated with ASCT outcome in MM patients. Despite its predictor impact on survival and prognosis, further studies are warranted to standardize PET/CT-based response assessments before being used as a guide for treatment decisions in clinical practice.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Masculino , Femenino , Persona de Mediana Edad , Mieloma Múltiple/terapia , Mieloma Múltiple/tratamiento farmacológico , Trasplante Autólogo , Estudios Retrospectivos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Nivel de Atención , Acondicionamiento Pretrasplante , Melfalán/uso terapéutico , Trasplante de Células Madre , Resultado del Tratamiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
6.
Cancer Control ; 31: 10732748241246898, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38605434

RESUMEN

BACKGROUND: Percutaneous Hepatic Perfusion (PHP) is a liver directed regional therapy recently FDA approved for metastatic uveal melanoma to the liver involving percutaneous isolation of liver, saturation of the entire liver with high-dose chemotherapy and filtration extracorporeally though in line filters and veno-venous bypass. The procedure is associated with hemodynamic shifts requiring hemodynamic support and blood product resuscitation due to coagulopathy. OBJECTIVE: To assess the cardiac safety and subsequent clinically significant sequalae of this therapy. METHODS: Consecutive PHP procedures done at our center between 2010-2022 were assessed retrospectively. Cardiac risk factors, post procedural cardiac enzymes, electrocardiograms, and transthoracic echocardiograms along with 90-day cardiac outcomes were reviewed. All data were reviewed by cardio-oncologists at our institution. RESULTS: Of 37 patients reviewed, mean age was 63 years and 57% were women. 132 procedures were performed with an average of 3.57 procedures per patient. 68.6% of patients had elevated troponin during at least 1 procedure. No patients were found to have acute coronary syndrome, heart failure, unstable arrhythmias, or cardiac death. No patients had notable echocardiographic changes. 10.8% of patients with positive troponin had asymptomatic transient electrocardiographic changes not meeting criteria for myocardial infarction. One patient had non-sustained ventricular tachycardiac intra-operatively which did not recur subsequently. Three patients died from non-cardiac causes within 90-days. There was no oncology treatment interruption, even in those with troponin elevation. In multivariable analysis, a history of hyperlipidemia was a predictor of postoperative troponin elevation. (P = .042). CONCLUSION: Percutaneous Hepatic Perfusion is safe and associated with a transient, asymptomatic troponin elevation peri-operatively without major adverse cardiac events at 90 days. The observed troponin elevation is likely secondary to coronary demand-supply mismatch related to procedural hemodynamic shifts, hypotension, and anemia.


Percutaneous hepatic perfusion using melphalan in patients with uveal melanoma and liver metastases carries no significant cardiac adverse events.


Asunto(s)
Neoplasias Hepáticas , Melanoma , Melfalán , Neoplasias de la Úvea , Humanos , Femenino , Persona de Mediana Edad , Masculino , Antineoplásicos Alquilantes , Estudios Retrospectivos , Quimioterapia del Cáncer por Perfusión Regional/métodos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Recurrencia Local de Neoplasia/tratamiento farmacológico , Perfusión
7.
Eur J Haematol ; 112(3): 402-411, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37968873

RESUMEN

Melphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone demonstrated superior progression-free survival (PFS), but not overall survival (OS), versus pomalidomide plus dexamethasone in relapsed/refractory multiple myeloma in the OCEAN study. Time to progression (TTP) <36 months after a prior autologous stem cell transplantation (ASCT) was a negative prognostic factor for OS with melflufen. This post hoc exploratory analysis evaluated patients refractory to prior alkylators (e.g., cyclophosphamide and melphalan) in OCEAN. In 153 patients refractory to prior alkylators (melflufen, n = 78; pomalidomide, n = 75), the melflufen and pomalidomide arms had similar median PFS (5.6 months [95% CI, 4.2-8.3] vs. 4.7 months [95% CI, 3.1-7.3]; hazard ratio [HR], 0.92 [95% CI, 0.63-1.33]) and OS (23.4 months [95% CI, 14.4-31.7] vs. 20.0 months [95% CI, 12.0-28.7]; HR, 0.92 [95% CI, 0.62-1.38]). Among alkylator-refractory patients with a TTP ≥ 36 months after a prior ASCT or no prior ASCT (melflufen, n = 54; pomalidomide, n = 53), the observed median PFS and OS were longer in the melflufen arm than the pomalidomide arm. The safety profile of melflufen was consistent with previous reports. These results suggest that melflufen is safe and effective in patients with alkylator-refractory disease, suggesting differentiated activity from other alkylators.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Melfalán/análogos & derivados , Mieloma Múltiple , Fenilalanina/análogos & derivados , Talidomida/análogos & derivados , Humanos , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Melfalán/uso terapéutico , Alquilantes/uso terapéutico , Dexametasona/efectos adversos , Trasplante Autólogo , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
8.
Bioorg Med Chem Lett ; 97: 129549, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37952597

RESUMEN

Therapeutically active lipids in drug delivery systems offer customization for enhanced pharmaceutical and biological effects, improving safety and efficacy. Biologically active N, N-didodecyl-3,4-dimethoxy-N-methylbenzenaminium lipid (Q) was synthesized and employed to create a liposome formulation (FQ) encapsulating melphalan (M) through a thin film hydration method. Synthesized cationic lipids and their liposomal formulation underwent characterization and assessment for additive anti-cancer effects on myeloma and melanoma cancer cell lines. These effects were evaluated through various studies, including cytotoxicity assessments, cell cycle arrest analysis, apoptosis measurements, mitochondrial membrane potential depolarization, DNA fragmentation, and a significant reduction in tumorigenic potential, as evidenced by a decrease in both the number and percentage area of cancer spheroids.


Asunto(s)
Antineoplásicos , Liposomas , Humanos , Línea Celular , Sistemas de Liberación de Medicamentos , Lípidos , Melfalán/farmacología , Neoplasias/tratamiento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacología
9.
Int J Mol Sci ; 25(14)2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39063245

RESUMEN

The clinical impact of therapy-related acute leukemias is increasing with the extension of cancer-related survival; however, the origins remain largely unknown. Acute erythroleukemia (AEL), a rare unfavorable type of myeloid neoplasia, may also develop secondary to cytotoxic therapy. The disorder is featured by specific genetic alterations, most importantly multi-allelic mutations of the TP53 gene. While AEL might appear as a part of the therapy-related MDS/AML, spectrum information regarding the genetic complexity and progression is largely missing. We present two AEL cases arising after cytotoxic therapy and melphalan-based myeloablation/autologous peripheral stem cell transplantation due to multiple myeloma (MM). As stated, multiple pathogenic TP53 variants were present unrelated to preexisting MM, in parallel with uninvolved/wild-type hemopoiesis. Potential mechanisms of leukemic transformation are discussed, which include (1) preexisting preneoplastic hemopoietic stem cells (HSC) serving as the common origin for both MM and AEL, (2) the generation and intramedullary survival of p53-deficient post-chemotherapy HSCs, (3) reinoculation of mobilized autologous TP53 mutated HSCs, and (4) melphalan treatment-related late-onset myelodysplasia/leukemia with newly acquired TP53 mutations.


Asunto(s)
Leucemia Eritroblástica Aguda , Mieloma Múltiple , Trasplante Autólogo , Mieloma Múltiple/terapia , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Humanos , Persona de Mediana Edad , Leucemia Eritroblástica Aguda/genética , Leucemia Eritroblástica Aguda/patología , Leucemia Eritroblástica Aguda/terapia , Masculino , Proteína p53 Supresora de Tumor/genética , Trasplante de Células Madre Hematopoyéticas/métodos , Transformación Celular Neoplásica/genética , Mutación , Femenino , Melfalán/uso terapéutico , Melfalán/administración & dosificación , Anciano , Quimioradioterapia/métodos , Neoplasias Primarias Secundarias/etiología , Neoplasias Primarias Secundarias/terapia , Neoplasias Primarias Secundarias/genética
10.
Ann Hematol ; 102(8): 2233-2240, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37392367

RESUMEN

Despite the development of effective agents for multiple myeloma (MM), the management of patients with high-risk MM (HRMM) is challenging. High-dose treatment followed by autologous stem cell transplantation (ASCT) is regarded as upfront treatment for transplant-eligible patients with HRMM. In the present study, we retrospectively investigated the efficacies of two conditioning regimens for upfront ASCT in newly diagnosed patients with MM and high-risk features: high-dose melphalan (HDMEL; 200 mg/m2) and busulfan plus melphalan (BUMEL). In total, 221 patients underwent ASCT between May 2005 and June 2021; among these 221 patients, 79 had high-risk cytogenetic abnormalities. In patients with high-risk cytogenetics, BUMEL showed a tendency toward longer overall survival (OS) and progression-free survival (PFS) compared to HDMEL (median OS; not reached vs. 53.2 months; P = 0.091, median PFS; not reached vs. 31.7 months; P = 0.062). Additionally, multivariate analysis revealed that BUMEL was significantly associated with PFS (hazard ratio = 0.37, 95% confidence interval = 0.15-0.89, P = 0.026). We compared BUMEL with HDMEL in patients with other high-risk features, such as high lactate dehydrogenase level, extramedullary disease, and poor response to frontline therapy. Notably, among patients with less than very good partial response (VGPR) to frontline therapy, median PFS was significantly longer in the BUMEL group than in the HDMEL group (55.1 vs. 17.3 months, respectively; P = 0.011). These findings indicate that BUMEL may be an effective conditioning regimen for upfront ASCT in MM patients with high-risk cytogenetics; BUMEL may be more appropriate than HDMEL for patients with less than VGPR to frontline therapy.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Melfalán , Mieloma Múltiple/tratamiento farmacológico , Busulfano , Estudios Retrospectivos , Trasplante Autólogo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Acondicionamiento Pretrasplante , Trasplante de Células Madre
11.
Pediatr Blood Cancer ; 70(8): e30444, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37243382

RESUMEN

BACKGROUND: Access to intra-arterial chemotherapy for retinoblastoma in low- and middle-income countries (LMICs) is limited. There is a need to optimize the efficacy of systemic chemotherapy for advanced intraocular retinoblastoma, particularly in LMICs. The aim was to compare the efficacy of standard versus higher dose carboplatin-based intravenous chemotherapy for group D and E retinoblastoma. METHODS: The single-center, single-blinded, randomized study was conducted during 2019-2021. Patients with newly diagnosed group D or E retinoblastoma were randomized to receive vincristine, etoposide, and standard versus higher dose (<36 months: 18.6 vs. 28 mg/kg; ≥36 months: 560 vs. 840 mg/m2 ) carboplatin. Examination under anesthesia and ultrasonography was performed at diagnosis and following three cycles of chemotherapy. Group E eyes with poor likelihood of globe/vision salvage at diagnosis were excluded. RESULTS: Thirty-two eyes of 30 patients were analyzed: 17 group D and 15 group E eyes. The tumor response to chemotherapy with regards to regression pattern (p = .72), tumor shrinkage (diameter: p = .11, height: p = .96), subretinal seeds (p = .91), and vitreous seeds (p = .9) were comparable between the two treatment arms. The globe salvage (group D [82% vs. 67%; p = .58]; group E [12.5% vs. 29%; p = .57]) and salvage of meaningful vision (group D [100% vs. 75%; p = .13]; group E [100% vs. 50%; p = .48]) were comparable between standard and higher dose arms. No excess treatment-related toxicity was observed in the higher dose arm. CONCLUSIONS: Higher dose carboplatin-based intravenous chemotherapy did not result in superior globe or vision salvage in group D or E retinoblastoma.


Asunto(s)
Neoplasias de la Retina , Retinoblastoma , Humanos , Lactante , Retinoblastoma/patología , Carboplatino , Neoplasias de la Retina/patología , Melfalán , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento
12.
J Biochem Mol Toxicol ; 37(8): e23374, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37086025

RESUMEN

The success of chemotherapy regimens has led to an increase in cancer survival rate over the last decades. Melphalan has been widely used for the treatment of several types of cancers despite its gonadotoxic effects. Due to its ability to cause mutations in the spermatogonial stem cells and spermatids, melphalan can exert a negative impact on male reproductive health in young cancer survivors. ß-aminoisobutyric acid (BAIBA), a myokine released by skeletal muscles, has been reported to have beneficial effects in diabetic nephropathy, cardiomyopathy and hepatic toxicity. However, the exact role of BAIBA in chemotherapy-induced germ cell toxicity is still unexplored. The present study aims to determine the dose-dependent (25, 50, and 100 mg/kg) effects of BAIBA on melphalan-induced (1.5 mg/kg) germ cell toxicity in sprague-dawley (SD) rats. The evaluation parameters included quantification of oxidative stress biomarkers, sperm count, sperm motility and head morphology, sperm and testicular DNA damage, sperm mitochondrial membrane potential, ultrastructural changes in sperms, histological and protein expression studies in testes. Melphalan treatment significantly altered all the above-mentioned parameters and the high dose (100 mg/kg) of BAIBA restored melphalan-induced toxicity in a significant manner by exerting antioxidant, anti-inflammatory and antiapoptotic effects. However, the medium dose (50 mg/kg) of BAIBA decreased the toxicity of melphalan and the low dose (25 mg/kg) of BAIBA failed to counteract the melphalan-induced male germ cell toxicity as well as the peripheral blood micronucleus induction. The antioxidant, anti-inflammatory and antiapoptotic role of BAIBA in melphalan-induced gonadal damage is a novel finding in an experimental rat model.


Asunto(s)
Antioxidantes , Melfalán , Ratas , Masculino , Animales , Melfalán/toxicidad , Antioxidantes/farmacología , Motilidad Espermática , Semen , Células Germinativas , Inflamación/inducido químicamente , Ratas Sprague-Dawley , Estrés Oxidativo , Testículo , Apoptosis
13.
Support Care Cancer ; 31(9): 521, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37581845

RESUMEN

PURPOSE: Oral cryotherapy is an effective method to prevent oral mucositis (OM) induced by chemotherapeutic agents, such as melphalan (Mel). However, there is limited data about cryotherapy in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients; thus, the current study aimed to examine the efficacy of cryotherapy among allo-HSCT recipients treated with Mel-containing regimens. METHODS: Medical records of 78 consecutive allo-HSCT recipients were retrospectively analyzed. Baseline characteristics and clinical courses between the patients who received cryotherapy (cryotherapy group, n = 42) and those who did not (control group, n = 36) were compared, especially focusing on methotrexate (MTX) use as a part of graft-versus-host disease (GVHD) prophylaxis. RESULTS: Binary logistic regression analysis revealed that a higher dose of Mel (OR, 3.82; 95%CI, 1.085-13.46; P = 0.037) or MTX use (OR, 7.61; 95% CI, 2.41-23.97; P < 0.001) was associated with the incidence of OM. MTX use was also significantly associated with the duration of OM (ß = 0.515; 95% CI, 9.712-21.636; P < 0.001). Among 31 patients without MTX use, cryotherapy was associated with a significant reduction of OM development (0% in the cryotherapy group vs 35% in the control group, P = 0.021). We did not find such an association in 47 patients with MTX use. CONCLUSION: Cryotherapy was useful to prevent the incidence of OM in allo-HSCT recipients in the cases without MTX for GVHD prophylaxis.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Estomatitis , Humanos , Melfalán/efectos adversos , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Estomatitis/prevención & control , Estomatitis/inducido químicamente , Metotrexato/uso terapéutico , Crioterapia/métodos , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodos , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control
14.
Graefes Arch Clin Exp Ophthalmol ; 261(4): 1167-1175, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36401651

RESUMEN

PURPOSE: To evaluate the efficacy and toxicity of intravitreal carboplatin plus melphalan for the treatment of vitreous seeds in eyes with retinoblastoma (RB). METHODS: This retrospective series at a tertiary referral center included 22 consecutive RB patients who had received intravitreal carboplatin (16 µg per 0.05 ml) combined with melphalan (30 µg in 0.03 ml) [IVi (Ca-Me)] for treatment of vitreous seeds. Tumor control and drug toxicities were recorded. RESULTS: There were 22 eyes of 22 patients, divided into primary group (n = 13) without history of previous intravitreal chemotherapy (IViC) and refractory group (n = 9) with history of previous IViC using melphalan and/or topotecan. The demographics and clinical findings of the primary and refractory groups did not differ significantly. The 6-month follow-up revealed complete vitreous seed control (77% vs. 89%, p = 0.47). Vitreous seed recurrence was detected in 1 eye of each group at 6 months. During the next 18-month follow-up period, no recurrence of seed was observed. The response to IVi (Ca-Me) was not significantly influenced by previous IViC (p = 0.70), primary systemic or intra-arterial chemotherapy (p = 0.45), or the type of regression (p = 0.35). The most common tumor treatment complications were retinal detachment (RD) (n = 2), early hypotony (n = 2) and late hypotony (n = 4, unrelated), cataract (n = 2), and severe pigment dispersion (n = 1). Enucleation was performed in 8 eyes, for total RD (n = 1), phthisis bulbi (n = 5), and extensive solid tumor recurrence (n = 2). There was no case of orbital invasion, systemic metastasis, or death. CONCLUSION: Based on this interventional case series for primary and refractory vitreous RB seeds, carboplatin plus melphalan therapy may be effective with few toxic side effects.


Asunto(s)
Neoplasias de la Retina , Retinoblastoma , Humanos , Lactante , Retinoblastoma/diagnóstico , Retinoblastoma/tratamiento farmacológico , Melfalán/efectos adversos , Neoplasias de la Retina/diagnóstico , Neoplasias de la Retina/tratamiento farmacológico , Carboplatino/uso terapéutico , Estudios Retrospectivos , Antineoplásicos Alquilantes/efectos adversos , Recurrencia Local de Neoplasia/patología , Cuerpo Vítreo/patología , Siembra Neoplásica , Inyecciones Intravítreas
15.
J Oncol Pharm Pract ; 29(6): 1398-1403, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36245321

RESUMEN

High-dose melphalan-based autologous stem cell transplant (ASCT) remains a standard of care for plasma cell disorders (PCDs). Currently, there is variability in the literature surrounding the timing of melphalan administration to avoid potential cytotoxic effects, although the administration has been safely proposed when given at least 8 hours prior to stem cell infusion. The objectives of this study were to assess differences in safety and efficacy outcomes between day -1 and day -2 single-dose melphalan administration in patients undergoing ASCT for PCDs. A retrospective chart review was performed at our institution comparing patients receiving melphalan on day -1 to an equal number of patients receiving melphalan on day -2. The primary endpoint was time to neutrophil engraftment from stem cell infusion. Univariate analyses were performed. Mean time to neutrophil engraftment from stem cell infusion was identical at 10.7 days for both cohorts (p = 0.88). Mean time to platelet engraftment from stem cell infusion was shorter with day -1 administration (17.4 vs. 18.6 days, p = 0.06). Mean time to neutrophil and platelet engraftment from melphalan infusion were significantly shorter with day -1 administration. Similar outcomes were observed for length of hospitalization, infection- and mucositis-related toxicities, hematologic response, transplant-related mortality, and overall survival. Our findings show no difference in time to neutrophil engraftment from stem cell infusion and a trend toward shorter time to platelet engraftment with day -1 administration. Based on our study, day -1 melphalan administration is an acceptable and safe practice.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Melfalán , Estudios Retrospectivos , Células Plasmáticas , Trasplante Autólogo , Trasplante de Células Madre , Acondicionamiento Pretrasplante/efectos adversos
16.
Int J Mol Sci ; 24(4)2023 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-36835401

RESUMEN

Melphalan (Mel) is an antineoplastic widely used in cancer and other diseases. Its low solubility, rapid hydrolysis, and non-specificity limit its therapeutic performance. To overcome these disadvantages, Mel was included in ß-cyclodextrin (ßCD), which is a macromolecule that increases its aqueous solubility and stability, among other properties. Additionally, the ßCD-Mel complex has been used as a substrate to deposit silver nanoparticles (AgNPs) through magnetron sputtering, forming the ßCD-Mel-AgNPs crystalline system. Different techniques showed that the complex (stoichiometric ratio 1:1) has a loading capacity of 27%, an association constant of 625 M-1, and a degree of solubilization of 0.034. Added to this, Mel is partially included, exposing the NH2 and COOH groups that stabilize AgNPs in the solid state, with an average size of 15 ± 3 nm. Its dissolution results in a colloidal solution of AgNPs covered by multiple layers of the ßCD-Mel complex, with a hydrodynamic diameter of 116 nm, a PDI of 0.4, and a surface charge of 19 mV. The in vitro permeability assays show that the effective permeability of Mel increased using ßCD and AgNPs. This novel nanosystem based on ßCD and AgNPs is a promising candidate as a Mel nanocarrier for cancer therapy.


Asunto(s)
Nanopartículas del Metal , beta-Ciclodextrinas , Melfalán , Plata , beta-Ciclodextrinas/química , Solubilidad
17.
J Pak Med Assoc ; 73(9): 1881-1883, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37817703

RESUMEN

A retrospective study was conducted for which records of patients with Retinoblastoma (RB), treated at Lahore General Hospital between 2017 and 2021, were retrieved on February 1, 2022. Staging of RB, neuroimaging, RetCam images, and treatment were analysed. The study included 47 patients (22 females and 25 males). Mean age of presentation was 26.5±15 months. Records of 84 eyes (37 bilateral and 10 unilateral) were examined. Family history was positive in only (n=3) 6.3% cases. Mean follow-up was 22.94±14.4 months. Leucocoria was the commonest presentation, seen in 72 (85.7%) eyes, proptosis in 8 (9.5%), huge fungating mass in 2 (2.4%), while tumour was diagnosed because of screening in 2 (2.4%) patients. Posttreatment complications included cataract in two patients, Ischaemic chorioretinal toxicity, transient macular oedema, orbital oedema and transient intra cranial oedema in one patient each. Two patients had metastasis and underwent systemic chemotherapy. The study showed that patients with retinoblastoma can achieve better results if diagnosed early and treated with newer treatment options.


Asunto(s)
Neoplasias de la Retina , Retinoblastoma , Masculino , Femenino , Humanos , Lactante , Preescolar , Retinoblastoma/epidemiología , Retinoblastoma/terapia , Neoplasias de la Retina/epidemiología , Neoplasias de la Retina/terapia , Estudios Retrospectivos , Centros de Atención Terciaria , Países en Desarrollo , Edema
18.
Rinsho Ketsueki ; 64(11): 1397-1403, 2023.
Artículo en Japonés | MEDLINE | ID: mdl-38072424

RESUMEN

The IFM/DFCI group reported that VRD induction followed by up-front autologous peripheral blood stem cell transplantation (ASCT) and maintenance therapy led to median PFS of 50 months, which established up-front ASCT as the standard of care even in the era of novel agents. We conducted a retrospective analysis on outcomes of patients who received triplet induction therapy followed by up-front ASCT at our institution. A total of 124 patients received ASCT between November 2016 and December 2021 at Japanese Red Cross Medical Center. Patient characteristics, treatment response before and after ASCT, and PFS and OS were retrospectively analyzed. VRD-based induction therapy was used for 94%. Among 118 evaluable patients, 116 (98%) received either consolidation and/or maintenance therapy. Best responses were ≥CR 77% and ≥VGPR 94%, respectively. Sixty-eight out of 104 patients achieved MRD-negativity by multiparameter FCM (<10-5). Five-year estimated PFS and OS were 54.7% and 80.2%, respectively. Age ≥65, high-risk cytogenetic abnormalities, and

Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib/uso terapéutico , Quimioterapia de Inducción , Mieloma Múltiple/tratamiento farmacológico , Estudios Prospectivos , Estudios Retrospectivos , Trasplante Autólogo , Resultado del Tratamiento , Anciano
19.
Khirurgiia (Mosk) ; (7): 94-99, 2023.
Artículo en Ruso | MEDLINE | ID: mdl-37379411

RESUMEN

Uveal melanoma accounts for 80% of all ocular melanomas, and 30-60% of patients have metastases to the liver. A few patients are candidates for liver resection, and this disease is associated with poor prognosis. There are few data on optimal management of metastatic uveal melanoma. Isolated hepatic perfusion is a perspective method for regional treatment of inoperable metastatic liver lesions with uveal melanoma. We present a patient with uveal melanoma who underwent previous enucleation of the eye. Cancer progressed 15 years later as an isolated inoperable metastatic liver lesion. The patient underwent isolated liver perfusion with melphalan, hyperthermia and oxygenation. Subsequently, the patient received systemic therapy with pembrolizumab. Partial response was achieved 1 month after the procedure. There was no progression for 20 months after surgery under systemic therapy with pembrolizumab. Thus, isolated liver chemoperfusion with melphalan is advisable in these patients.


Asunto(s)
Neoplasias Hepáticas , Melanoma , Humanos , Melfalán/uso terapéutico , Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamiento farmacológico , Quimioterapia del Cáncer por Perfusión Regional/métodos , Melanoma/diagnóstico , Melanoma/tratamiento farmacológico , Perfusión
20.
Br J Haematol ; 196(3): 639-648, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34671975

RESUMEN

Relapsed/refractory multiple myeloma (RRMM) is known to have a high burden of disease and complications associated with refractoriness to prior lines of therapy. Severe pain and fatigue symptoms and impairments in physical and emotional functioning have been strongly linked to reduced health-related quality of life (HRQoL) in patients with RRMM. Assessment of patient reported-outcome measures from the pivotal, Phase II HORIZON study (OP-106; NCT02963493) in patients with RRMM (n = 64) demonstrated that melphalan flufenamide (melflufen) plus dexamethasone treatment preserved HRQoL. Patients had clinically meaningful improvements, even after eight treatment cycles, in relevant scales such as global health status/QoL, physical functioning, emotional functioning, pain, and fatigue. Patients with triple-class-refractory disease (n = 50) displayed similar improvements. Patient-reported outcome deterioration was delayed for a substantial amount of time in patients who experienced a response to melflufen plus dexamethasone treatment relative to patients who did not experience a response. These findings support the notion that treatment with melflufen plus dexamethasone may sustain or improve HRQoL over time in patients with RRMM, including in patients with triple-class-refractory disease for whom outcomes are generally worse. The clinical benefits observed in patients from the HORIZON trial are encouraging and supportive of translation into real-world practice.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores de Tumor , Dexametasona/administración & dosificación , Femenino , Humanos , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/epidemiología , Mieloma Múltiple/etiología , Clasificación del Tumor , Estadificación de Neoplasias , Medición de Resultados Informados por el Paciente , Resultado del Tratamiento
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