The goal of this phase II trial was to evaluate safety and efficacy of a tandem autologous hematopoietic cell transplantation (auto-HCT) using sequentially total marrow irradiation (TMI) at the dose ...of 12 Gy (4 Gy on days -3, -2, and -1) and melphalan 200 mg/m
for patients with multiple myeloma (MM). TMI was performed using helical tomotherapy. Additional "boosts" (total 24 Gy) were applied for patients with active lesions as revealed by PET-FDG. Fifty patients with median age 58 years (41-64 years) were included and received tandem auto-HCT. TMI resulted in absolute neutropenia in all patients. Grade 3 infections were reported in 30% patients. Other toxicities were rare. Proportion of patients who achieved at least very good partial response increased from 46% before the first auto-HCT to 82% after tandem transplantation. Complete remission rates changed from 10% to 42%, respectively. The probabilities of overall and progression-free survival at 5 years were 74% and 55%, respectively. No patient died without progression. We conclude that conditioning with TMI ± PET-guided "boosts" represents personalized treatment approach in MM and is characterized by very good toxicity profile. Tandem auto-HCT using TMI in sequence with high-dose melphalan appears safe with encouraging early efficacy.
The optimal salvage therapy in relapsed/refractory Hodgkin lymphoma (R/R HL) has not been defined so far. The goal of this multicenter retrospective study was to evaluate efficacy and safety of BGD ...(bendamustine, gemcitabine, dexamethasone) as a second or subsequent line of therapy in classical R/R HL. We have evaluated 92 consecutive R/R HL patients treated with BGD. Median age was 34.5 (19–82) years. Fifty-eight patients (63%) had received 2 or more lines of chemotherapy, 32 patients (34.8%) radiotherapy, and 21 patients (22.8%) an autologous hematopoietic stem cell transplantation (autoHCT). Forty-four patients (47.8%) were resistant to first line of chemotherapy. BGD therapy consisted of bendamustine 90 mg/m
2
on days 1 and 2, gemcitabine 800 mg/m
2
on days 1 and 4, dexamethasone 40 mg on days 1–4. Median number of BGD cycles was 4 (2–7). The following adverse events ≥ 3 grade were noted: neutropenia (22.8%), thrombocytopenia (20.7%), anemia (15.2%), infections (10.9%), AST/ALT increase (2.2%), and skin rush (1.1%). After BGD therapy, 51 (55.4%) patients achieved complete remission, 23 (25%)—partial response, 7 (7.6%)—stable disease, and 11 (12%) patients experienced progression disease. AutoHCT was conducted in 42 (45.7%) patients after BGD therapy, and allogeneic HCT (alloHCT) in 16 (17.4%) patients. Median progression-free survival was 21 months. BGD is a highly effective, well-tolerated salvage regimen for patients with R/R HL, providing an excellent bridge to auto- or alloHCT.
Our aim was to prospectively assess the potential influence of pantoprazole therapy on the antiplatelet effects of acetylsalicylic acid (ASA) and clopidogrel (CLO) in stable angina pectoris (SAP) ...patients after percutaneous coronary intervention (PCI).
Forty-four patients with SAP (CCS I-III) and successful PCI with stent implantation were enrolled into the study. The patients were divided into group proton pump inhibitors (PPI): 23 patients with indications for PPI (F/M = 9/14; age = 64 ± 9; standard therapy + 20 mg pantoprazole) and the control group (group C): 21 patients (F/M = 6/15; age = 64 ± 8; standard therapy). The platelet function analysis in whole blood based on impedance aggregometry (ASPI, COL, ADP, TRAP tests) using Multiplate--V2.02.11 was performed 18-24 h after the PCI + CLO loading dose (600 mg) and 30 days after PCI.
Both baseline patient characteristics and clinical outcomes were comparable between the study groups. There were no differences in the mean values of the platelets (PTL) tests measured at the 30(th) day after PCI between both groups (PPI vs. C: ASPI: 24.6 ± 10.0 vs. 42.1 ± 14.8 U, COL: 32.9 ± 8.6 vs. 34.0 ± 7.7 U, ADP: 26.8 ± 12.4 vs. 30.4 ± 8.1 U, TRAP: 78.7 ± 16.6 vs. 78.1 ± 22.6 U, p = ns). The mean delta values of the PTL tests (18-24 h post-PCI/30 days post-PCI) were also comparable between the groups. The PTL aggregometry results were related to time (ADP, ASPI, TRAP vs. time, p = 0.001; COL vs. time, p = 0.03)--the baseline values of ADP, ASPI, COL and TRAP tests were smaller than those measured after the one-month observation.
Pantoprazole treatment does not impair the efficacy of dual antiplatelet therapy in patients with SAP after PCI.
Introduction. Although Hodgkin lymphoma (HL) is one of the most curable malignancies, 10-30% of patients experience resistance or relapse following initial response. Treatment options for ...relapsed/refractory (R/R) disease include usually multi-agent chemotherapy followed by autologous hematopoietic stem cell transplantation (autoHSCT). Although many chemotherapy-based regimens are used as salvage, the optimal one has not been defined so far. The goal of this study was to evaluate efficacy and safety of bendamustine in combination with gemcitabine and dexamethasone (BGD) in R/R HL.
Patients and Methods. This was a retrospective, single center study, including 30 consecutive R/R HL patients treated between 2016 and 2018. Median age was 33 (19-82) years. Ten patients (33%) had been pre-treated with at least 2 lines of chemotherapy; 11 patients (37%) with radiotherapy, 6 patients (20%) with autoHSCT while 4 patients (13%) with allogeneic (allo)HSCT. Six patients (20%) were resistant to previous salvage treatment.
BGD therapy consisted of bendamustine 90mg/m2 on days 1 and 2, gemcitabine 800 mg/m2 on days 1 and 4, dexamethasone 40 mg on days 1-4. Best response after at least 2 courses of therapy was the primary study end-point.
Results. Median number of BGD cycles was 4 (2-7). Nineteen (63%) patients achieved complete remission (CR) confirmed by FDG-PET, while 6 patients (20%) achieved partial response (PR), accounting for 83% overall response (OR) rate. Stable disease was reported in 3 patients and progressive disease - in 2 cases. Many patients achieved CR (33%) or PR (33%) after 2 cycles of BGD. The OR rate was 85% for patients in whom BGD was administered as first salvage and 80% when used in more advanced stages of the disease. Fourteen patients proceeded to autoHSCT while 4 patients were subsequently treated with alloHSCT.
Six patients experienced infections of the upper respiratory tract while two patients had allergic skin reactions. No organ toxicity was reported. One patient required transfusion of red blood cells while none was treated with platelet transfusions.
Conclusion. BGD is a highly effective, well-tolerated salvage regimen for patients with R/R HL. The protocol may be used as a bridge to autoHSCT or alloHSCT. Further, prospective studies are warranted to define its role in future treatment algorithms.
No relevant conflicts of interest to declare.
Background: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a standard of care for patients with high risk acute myeloid leukemia (AML). However, the procedure using conventional ...myeloablative conditioning regimens based on either busulphan (Bu) or total body irradiation (TBI) in combination with cyclophosphamide is associated with significant risk of non-relapse mortality (NRM). The use of reduced-intensity conditioning regimens results in improved tolerance but increased incidence of disease recurrence. In order to reduce toxicity while maintaining the anti-leukemic efficacy alternative conditioning regimens have been proposed including the use of Bu or TBI in combination with fludarabine (Flu). The goal of this retrospective, multicenter study was thus to compare Bu4Flu and TBI12Gy/Flu.
Patients and methods: Adult patients with AML treated with alloHSCT from either HLA-matched sibling (MSD) or unrelated donor (URD) between year 2012 and 2017 were included in the analysis. The following conditioning regimens have been selected for the comparison: intravenous Bu at the total dose 12.8 mg/kg (4 days) + Flu (Bu4Flu, N=60) or TBI at the total dose of 12 Gy given in three fractions + Flu (TBI12Flu, N=40).
Results: 100 patients (Bu4Flu, n=60; TBI4Flu, n=40) were included in the analysis. Median age was 42 (19-62) years in Bu4Flu group and 36 (19-64) for TBI12Flu group (p=0.01). Proportion of patients given transplant from URD was 72% and 70%, respectively (p=NS). The rates of patients treated with HSCT CR1, CR>1 and active disease were 75%, 25%, 0% in the Bu4Flu group while 82.5%, 10% and 7% in the TBI12Flu group (p=NS).
All patients engrafted except for one patient in the TBI12Flu group who died of infection before engraftment. Time to neutrophil recovery was significantly faster after TBI12Flu (median 15 days, range 11-24) compared to Bu4Flu (18, 12-36 days) (p=0.000007). With the median follow up of 18 months, the cumulative incidence of relapse at 2 years was 11% (+/-6) and 30% (+/-7), respectively (p=0.14) while NRM was 19% (+/-8) and 10 (+/-5%), respectively (p=0.34). The probability of OS was 76% (+/-8) after TBI12Flu and 71% (+/-7%) after Bu4Flu (p=0.69). The LFS rates were 70% (+/-8%) and 60% (+/-7%), respectively (p=0.53). No signficant differences regarding survival could be detected in analysis restricted to patients transplanted in CR.
Conclusion: Both Bu4Flu or TBI12Flu as conditioning regimens pre-alloHSCT for patients with AML are highly effective, which together with acceptable tolerance leads to survival rates of more than 70% at two years. TBI12Flu is associated with faster engraftment and a tendency to reduced risk of relapse. Prospective studies comparing both regiemens are needed.
No relevant conflicts of interest to declare.
Summary
The efficacy of salvage treatment of diffuse large B‐cell lymphoma (DLBCL) patients who relapse or progress (rrDLBCL) after initial therapy is limited. Efficacy and safety of ofatumumab with ...iphosphamide, etoposide and cytarabine (O‐IVAC) was evaluated in a single‐arm study. Dosing was modified for elderly patients. Patients received up to six cycles of treatment. The primary end‐point was the overall response rate (ORR). Patients were evaluated every two cycles and then six and 12 months after treatment. Other end‐points included progression‐free survival (PFS), event‐free survival (EFS), overall survival (OS) and safety. Seventy‐seven patients received salvage treatment with O‐IVAC. The average age was 56.8 years; 39% had an Eastern Cooperative Oncology Group (ECOG) performance status of at least 3; 78% had disease of Ann Arbor stage 3 or 4; 58% received one or more prior salvage therapies. The ORR for O‐IVAC was 54.5%. The median duration of study follow‐up was 70 months. The median PFS and EFS were 16.3 months each. The median OS was 22.7 months. Age, ECOG performance status and the number of prior therapy lines were independent predictors of survival. Treatment‐related mortality was 15.5%. O‐IVAC showed a high response rate in a difficult‐to‐treat population and is an attractive treatment to bridge to potentially curative therapies.
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