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Science Advances Nov 2023Choroidal melanoma, a common intraocular malignant tumor, relies on local radiotherapy and enucleation for treatment. However, cancer recurrence and visual impairment...
Choroidal melanoma, a common intraocular malignant tumor, relies on local radiotherapy and enucleation for treatment. However, cancer recurrence and visual impairment remain important challenges. Here, a therapeutic artificial vitreous body (AVB) hydrogel based on tetra-armed poly(ethylene glycol) was developed to control the recurrence of choroidal melanoma and preserve vision after vitrectomy. AVB loaded with melphalan (Mel) and anti-programmed cell death ligand-1 (αPDL1), was injected after surgical resection in the choroidal melanoma mouse model. Afterwards, the sequentially released Mel and αPDL1 from AVB could achieve a synergistic antitumor effect to inhibit tumor recurrence. AVB with similar physical properties to native vitreous body could maintain the normal structure and visual function of eye after vitrectomy, which has been evidenced by standard examinations of ophthalmology in the mouse model. Thus, the immunotherapeutic AVB may be a promising candidate as an infill biomaterial to assist surgical treatment of intraocular malignant tumors.
Topics: Animals; Mice; Vitreous Body; Vitrectomy; Hydrogels; Neoplasm Recurrence, Local; Melanoma; Choroid Neoplasms; Melphalan; Immunotherapy
PubMed: 37910617
DOI: 10.1126/sciadv.adh1582 -
Ocular Oncology and Pathology Sep 2023The aim of the study was to describe the successful conservative management of diffuse infiltrating retinoblastoma (DIR). Identification of pathogenic variant was done...
INTRODUCTION
The aim of the study was to describe the successful conservative management of diffuse infiltrating retinoblastoma (DIR). Identification of pathogenic variant was done after cell-free DNA (cfDNA) analysis in aqueous humor.
CASE PRESENTATION
Herein, we report 2 patients with unilateral, non-familial DIR with anterior and posterior involvement. Both patients underwent liquid biopsy for tumor cfDNA analysis in aqueous humor. Treatment consisted of a combination of systemic and intra-arterial chemotherapy, with consecutive intracameral and intravitreal injections of melphalan. One patient also required iodine-125 brachytherapy. In both cases, tumor cfDNA analysis revealed biallelic somatic alterations of the gene. These alterations were not found in germline DNA. Both patients retained their eyes and had a useful vision after a follow-up of 2 years.
CONCLUSION
In selected cases, conservative management of DIR is safe and effective. Tumor cfDNA analysis in aqueous humor is an effective technique to disclose somatic alterations that guide the germline molecular explorations and improve genetic counseling after conservative treatment.
PubMed: 37900191
DOI: 10.1159/000531233 -
Cancers Oct 2023Even with liver-targeted therapies, uveal melanoma with hepatic metastasis remains a challenge. The aim of this study was to compare the outcome of patients treated with...
Even with liver-targeted therapies, uveal melanoma with hepatic metastasis remains a challenge. The aim of this study was to compare the outcome of patients treated with either SIRT or CS-PHP. We included 62 patients with hepatic metastasized uveal melanoma (n = 34 with SIRT, receiving 41 cycles; n = 28 with CS-PHP, receiving 56 cycles) that received their treatments between 12/2013 and 02/2020 at a single center. We evaluated their response according to the RECIST 1.1, as well as progression-free survival (PFS) and overall survival (OS), after the initiation of the first cycle of the liver-directed treatment using Cox regression, adjusted via propensity score analysis for confounders, including the amount of hepatic involvement. The disease control rate was 18% for SIRT and 30% for CS-PHP. The median (range) of PFS was 127.5 (19-1912) days for SIRT and 408.5 (3-1809) days for CS-PHP; adjusted Cox regression showed no significant difference ( = 0.090). The median (range) of OS was 300.5 (19-1912) days for SIRT and 516 (5-1836) days for CS-PHP; adjusted Cox regression showed a significant difference ( = 0.006). In our patient cohort, patients treated with CS-PHP showed a significantly longer OS than patients treated with SIRT. CS-PHP might therefore be preferable for patients with liver-dominant metastatic uveal melanoma.
PubMed: 37894309
DOI: 10.3390/cancers15204942 -
Journal of Clinical Medicine Oct 2023Isolated limb perfusion (ILP) for soft tissue sarcomas (STS) is usually performed with tumor necrosis factor alpha (TNF-α) and melphalan. ILP regularly leads to a total...
BACKGROUND
Isolated limb perfusion (ILP) for soft tissue sarcomas (STS) is usually performed with tumor necrosis factor alpha (TNF-α) and melphalan. ILP regularly leads to a total blood loss (BLt) of 1.5-2 L/patient. Blood inflow from the central blood circulation to the limb is influenced by unstable pressure gradients and pain reactions after the administration of melphalan. With perioperative regional anesthesia (RA), pain levels can be reduced, and the pressure gradient stabilized resulting in a reduced BLt. The aim of this study was to compare the BLt with and without RA in patients with ILP during circulation of drugs.
METHODS
Patients were treated according to the following protocol: After the establishment of limb circulation, ILP was started with the administration of TNF-α. Half the dose of melphalan was given as a bolus after 30 min, and the remaining dose was continuously administered in the following 30 min. The extremity was washed out after 90 min. ILP with perioperative RA (supraclavicular plexus block/peridural catheter) was performed prospectively in 17 patients and compared to a matched retrospective control group of 17 patients without RA. BLt was documented and perioperative anesthesiological data were analyzed for response rates after the application of melphalan (RaM).
RESULTS
BLt and RaM tended to be lower for the intervention group with RA if compared to the control group without RA in all analyses. The trend of lower BLt and RaM in ILP with RA was more pronounced for the upper extremity compared to the lower extremity. Results were not statistically significant.
CONCLUSION
These findings indicate that the use of RA can help to stabilize hemodynamic anesthetic management and reduce the BLt in ILP, especially during perfusion of the upper extremities.
PubMed: 37892681
DOI: 10.3390/jcm12206542 -
Blood Advances Feb 2024Outcomes in patients with relapsed diffuse large B-cell lymphoma (DLBCL) who undergo autologous stem cell transplant (auto-SCT) are poor. Blinatumomab is a CD3/CD19...
Outcomes in patients with relapsed diffuse large B-cell lymphoma (DLBCL) who undergo autologous stem cell transplant (auto-SCT) are poor. Blinatumomab is a CD3/CD19 bispecific T-cell engager that directs cytotoxic T cells to CD19+ cells. Here, we performed a pilot study of blinatumomab consolidation after auto-SCT for 14 patients with DLBCL or transformed follicular lymphoma. All patients underwent standard-of-care auto-SCT with carmustine, etoposide, cytarabine, and melphalan (BEAM) conditioning followed by 1 cycle (4 weeks continuous infusion) of blinatumomab consolidation starting at day 42 after auto-SCT. All 14 patients treated on study completed BEAM auto-SCT and 1 cycle of posttransplant blinatumomab. Five patients developed grade 1 cytokine release syndrome (CRS), with no grade 2 or higher CRS. Immune effector cell-associated neurotoxicity syndrome was not observed. Patients were followed up for 3 years after auto-SCT, with median follow-up of 37 (range, 12-65) months. One-hundred days after auto-SCT (1 month after blinatumomab consolidation), 12 patients (86%) had achieved complete remission. At 1 year after auto-SCT, 7 patients (50%) remained in CR, and 1 patient had died of progressive disease. Patients who relapsed had a lower CD8:CD4 T-cell ratio before starting blinatumomab than patients who remained in remission. This pilot study demonstrates blinatumomab consolidation after auto-SCT is safe and well tolerated. Strategies to increase the CD8:CD4 ratio and use additional cycles of consolidation in a larger randomized trial are needed to confirm the efficacy of consolidation with blinatumomab after auto-SCT. This trial was registered at www.clinicaltrials.gov as #NCT03072771.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Pilot Projects; Remission Induction; Transplantation, Autologous; Neoplasm Recurrence, Local; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Stem Cell Transplantation; Antibodies, Bispecific
PubMed: 37871306
DOI: 10.1182/bloodadvances.2023011130 -
Journal of Clinical Medicine Sep 2023Melphalan was poorly available in mainland China. The aim of this study is to explore the dose-adjusted busulfan/cyclophosphamide (BU/CY) as an alternative regimen in...
BACKGROUND
Melphalan was poorly available in mainland China. The aim of this study is to explore the dose-adjusted busulfan/cyclophosphamide (BU/CY) as an alternative regimen in auto stem cell transplantation (ASCT) for multiple myeloma (MM).
METHODS
A total of 105 newly diagnosed MM patients undergoing ASCT during May 2012 and August 2017 were retrospectively analyzed. The BU/CY regimen was applied to 64 patients. Busulfan (9.6 mg/kg or 8.0 mg/kg in total) and cyclophosphamide (3.6 g/m or 3.0 g/m in total) were administered according to the creatinine clearance rate (CCR). A high-dose melphalan (HDMEL) regimen (200 mg/m) was given to the other 41 patients.
RESULTS
At a median follow-up of 65 (1~119) months, estimated overall survival (OS) and progression-free survival (PFS) at 104 months in the BU/CY and HDMEL groups were 35.6% vs. 20.5% ( = 0.263) and 20.2% vs. 2.4% ( = 0.035), respectively. The median overall survival (OS) and PFS of the HDMEL and BU/CY groups were 55 vs. 70.5 months and 26 vs. 46.5 months, respectively. In multivariate analysis, the BU/CY regimen was found to be the only protective factor for PFS. No lethal toxicity was found in the BU/CY group, and treatment-related mortality (TRM) in 100 days was similar to the HDMEL group.
CONCLUSIONS
MM patients may also benefit from the dose-adjusted BU/CY regimen.
PubMed: 37834886
DOI: 10.3390/jcm12196239 -
JPMA. the Journal of the Pakistan... Sep 2023A retrospective study was conducted for which records of patients with Retinoblastoma (RB), treated at Lahore General Hospital between 2017 and 2021, were retrieved on...
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.
Topics: Male; Female; Humans; Infant; Child, Preschool; Retinoblastoma; Retinal Neoplasms; Retrospective Studies; Tertiary Care Centers; Developing Countries; Edema
PubMed: 37817703
DOI: 10.47391/JPMA.7689 -
Bone Marrow Transplantation Jan 2024
Topics: Humans; Aged; Multiple Myeloma; Bortezomib; Melphalan; Thalidomide; Pyrazines; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone
PubMed: 37816907
DOI: 10.1038/s41409-023-02119-9 -
Journal of Clinical Oncology : Official... Jan 2024The GMMG-CONCEPT trial investigated isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in transplant-eligible (TE) and transplant-noneligible (TNE)...
PURPOSE
The GMMG-CONCEPT trial investigated isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in transplant-eligible (TE) and transplant-noneligible (TNE) patients with newly diagnosed multiple myeloma (NDMM) with exclusively high-risk disease for whom prospective trials are limited, aiming to induce minimal residual disease (MRD) negativity.
METHODS
This academic, investigator-initiated, multicenter, phase II trial enrolled patients with high-risk NDMM (HRNDMM) defined by mandatory International Staging System stage II/III combined with del17p, t(4;14), t(14;16), or more than three 1q21 copies as high-risk cytogenetic aberrations (HRCAs). Patients received Isa-KRd induction/consolidation and Isa-KR maintenance. TE patients received high-dose melphalan. TNE patients received two additional Isa-KRd cycles postinduction. This prespecified interim analysis (IA) reports the primary end point, MRD negativity (<10, next-generation flow), at the end of consolidation. The secondary end point was progression-free survival (PFS).
RESULTS
Among 125 patients with HRNDMM (TE-intention-to-treat [ITT]-IA, 99; TNE-ITT, 26) of the IA population for the primary end point, the median age was 58 (TE-ITT-IA) and 74 (TNE-ITT) years. Del17p was the most common HRCA (TE, 44.4%; TNE, 42.3%); about one third of evaluable TE/TNE patients presented two or more HRCAs, respectively. The trial met its primary end point with MRD negativity rates after consolidation of 67.7% (TE) and 54.2% (TNE) of patients. Eighty-one of 99 TE-ITT-IA patients reached MRD negativity at any time point (81.8%). MRD negativity was sustained for ≥1 year in 62.6% of patients. With a median follow-up of 44 (TE) and 33 (TNE) months, median PFS was not reached in either arm.
CONCLUSION
Isa-KRd effectively induces high rates of sustainable MRD negativity in the difficult-to-treat HRNDMM population, regardless of transplant status, translating into a median PFS that was not yet reached after 44/33 months.
Topics: Humans; Middle Aged; Multiple Myeloma; Lenalidomide; Prospective Studies; Dexamethasone; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37753960
DOI: 10.1200/JCO.23.01696 -
HemaSphere Oct 2023We conducted a registry analysis including adult acute myeloid leukemia (AML) patients in remission who had received thiotepa, busulfan, and fludarabine (TBF) or...
Thiotepa-busulfan-fludarabine Compared to Treosulfan-based Conditioning for Haploidentical Transplant With Posttransplant Cyclophosphamide in Patients With Acute Myeloid Leukemia in Remission: A Study From the Acute Leukemia Working Party of the EBMT.
We conducted a registry analysis including adult acute myeloid leukemia (AML) patients in remission who had received thiotepa, busulfan, and fludarabine (TBF) or treosulfan-based (Treo) conditioning for haplo-hematopoietic stem cell transplant (HSCT) with posttransplant cyclophosphamide (PTCy) between 2010 and 2020. A total of 1123 patients met the inclusion criteria (968 received TBF and 155 received Treo). A 1:1 matched-pair analysis was performed on 142 TBF and 142 Treo patients. In the Treo group, 68% of patients received treosulfan at a dose ≥36 g/m and 54% of patients received a second alkylator (thiotepa or melphalan). We observed a trend toward increased incidence of grade II-IV acute (a) graft-versus-host disease (GVHD) at 180 days in the TBF group compared with Treo (29% versus 20%; = 0.08), while incidence of grade III-IV aGVHD was not statistically different. Similarly, the incidence of chronic (c) GVHD was not statistically different in the 2 groups. Incidence of nonrelapse mortality at 2 years was 19% in TBF and 14% in Treo ( = 0.4). Relapse incidence at 2 years was not statistically different in the 2 groups (16% and 18% in TBF and Treo, respectively; = 0.9). Leukemia-free survival, overall survival, and GVHD-free, relapse-free survival was 65% versus 68% ( = 0.6), 73% versus 76% ( = 0.5), and 54% versus 53% ( = 0.8) in TBF versus Treo, respectively. In conclusion, we did not find a significant difference between the 2 conditioning in the present study; Treo and TBF represent 2 valid alternative regimens for haplo-HSCT with PTCy for AML in remission.
PubMed: 37746158
DOI: 10.1097/HS9.0000000000000952