Induction Therapy Group Research Articles

Real-life experiences of switching from intravenous to subcutaneous vedolizumab maintenance therapy in patients with inflammatory bowel disease.

A few prospective cohort studies support the safety of switching from intravenous to subcutaneous administration of vedolizumab during maintenance therapy in patients with inflammatory bowel disease. Real-life data on switching after intravenous induction therapy are lacking. The aim was to obtain real-world data on subcutaneous vedolizumab treatment in patients with inflammatory bowel disease after switching from intravenous vedolizumab induction or maintenance therapy, and to evaluate treatment persistence, safety, and changes in disease activity and serum vedolizumab concentrations. We performed a retrospective registry-based study of inflammatory bowel disease patients who received subcutaneous vedolizumab therapy in two tertiary centres. Altogether, 103 patients (26 Crohn's disease and 77 ulcerative colitis) switching from intravenous maintenance therapy (group 1) and 44 patients (14 and 30, respectively) switching from intravenous induction therapy (group 2) were included. At 6 months from baseline, 90.3% of the patients in group 1 and 90.9% of the patients in group 2 continued on subcutaneous vedolizumab. After the switch in group 1, disease activity remained stable. In group 2, clinical disease activity decreased significantly in ulcerative colitis patients ( P = 0.002). The median serum vedolizumab concentration was 34.00 µg/ml during subcutaneous maintenance therapy in group 1, which was significantly higher than the median concentration during intravenous therapy (17.00 µg/ml, P < 0.001), but remained unchanged in group 2 after the switch (31.50 µg/ml). Based on these data, subcutaneous vedolizumab treatment is well-tolerated and the treatment persistence remains high after switching from intravenous to subcutaneous vedolizumab therapy.

Effect of neoadjuvant therapy regimens on lymph nodes yield in rectal cancer.

Pathological nodal staging is relevant to postoperative decision-making and a prognostic marker of cancer survival. This study aimed to assess the effect of different total neoadjuvant therapy (TNT) regimens on lymph node status following total mesorectal excision (TME) for locally advanced rectal cancer (LARC). A retrospective cohort study of patients treated for node-positive clinical stage 3 LARC with TNT between January 2015 and August 2022. Patients were stratified into induction therapy and consolidation therapy groups. Variables collated included patient demographics, clinical and radiological characteristics of the tumor, and pathology of the resected specimen. Primary outcome was total harvested lymph nodes. Ninety-seven patients were included (57 [58.8%] males; mean age of 58.5 ± 11.4 years). The induction therapy group included 85 (87.6%) patients while 12 (12.4%) patients received consolidation therapy. A median interquartile range value of 22.00 (5.00-72.00) harvested lymph nodes was recorded for the induction therapy group in comparison to 16.00 (16.00-47.00) in the consolidation therapy arm (p = 0.487). Overall pathological complete response rate was 34%. Total harvested nodes from resected specimens were marginally lower in the consolidation therapy group. Induction therapy may be preferrable to optimize postoperative specimen staging.

Non-Contact Electric Field May Induced Higher CD4, CD8, Caspase-8, and Caspase-9 Protein Expression in Breast Tumor Tissue of Rats (Rattus norvegicus Berkenhout, 1769)

Non-contact electric field therapy has been studied as one of less invasive and safe alternative method in cancer therapy. Some studies reported that non-contact electric field therapy with low intensity (50 - 60 V/m) and medium frequency (150 kHz) could slower the rat’s breast tumor growth and did not cause significant damage on the rat's kidney and liver. However, further study needed to evaluate the potency of non-contact electric field to be developed into effective cancer therapy. Thus, we investigated the immune response of non-contact electric field therapy through the detection of CD4 and CD8 protein expression and the mechanism of apoptosis through the detection of caspase-8 and caspase-9 proteins on breast tumor tissue of rats. Twenty four rats were divided into 4 groups: 1. non-induction - non-therapy (NINT), 2. non-induction - therapy (NIT), 3. induction - non-therapy (INT), and 4. induction - therapy (IT). DMBA (7,12-dimethylbenz(α)anthracene) 20 mg/kg body weight was used to induced breast tumor formation. Rats with breast nodules that had reached 1 cm in size were exposed to an ECCT device with 150 kHz and 50 - 60 V/m electric fields. Further, the breast tissues were collected for routine histological and immunohistochemistry preparation for CD4, CD8, caspase 8, as well as caspase 9 detection. The data were statistically analyzed using Mann-Whitney U-Test method, with a significance level of p &lt; 0.05 using the SPSS 16.0 version. The scoring results were compared between the INT and IT groups. Our results showed that non-contact electric field therapy could suppress breast tumor growth and improved its histological structure. Interestingly, the breast tissue of IT group qualitatively had slightly more necrotic and apoptotic cells than that of INT group. Moreover, the IT group showed by higher CD4 and CD8 as well as higher caspase 8 and caspase 9 expression. Collecting all the data together, we concluded that non-contact electric field therapy potent to improve histological structure of breast tumor.

How Induction Cycles before Remission Influence Long-Term Survival in Acute Myeloid Leukemia

Background ： Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by accumulation and expansion of immature myeloid cells in the bone marrow, peripheral blood and other tissues. Despite the progress made in mechanisms and approval of new therapeutics, the clinical outcome of AML remains suboptimal. The achievement of complete remission (CR) after induction chemotherapy is critical because the prognosis of refractory AML was especially unfavorable. However, little is known about the association between remission after first induction therapy and the overall survival (OS) in different subgroups of AML. Study Design and Methods: We retrospectively analyzed patients with newly diagnosed AML from January 2019 to August 2022. The diagnosis and treatment strategies were based on European Leukemia Net (ELN) criteria and National Comprehensive Cancer Network (NCCN) guideline. Composite complete remission (CRc) rate (CR+CR with incomplete recovery [CRi]) were assessed at the completion of induction or re-induction therapy. Minimal residual disease (MRD) was assessed using multiparameter flow cytometry with a minimum sensitivity of 0.1%. OS was measured from the day of diagnosis until death or the last follow-up date. Results : In total, 679 patients were included and the median age was 59.0 (range, 14.0-93.0) years old. There were 56.8% (386/679) of patients who achieved CRc after the induction therapy (group A), 18.1% (123/679) achieved CRc after the re-induction therapy (group B). The median follow-up period was 24.2 months. Even though there was no significant difference between group A and group B on OS, group A exhibited improved OS when censored at allogenic hematopoietic stem cell transplantation (HSCT) compared to that in group B (group A vs group B:3-year OS rates 65.7% vs 51.1%，p=0.004，Figure A). We further explored the effects of remission depth on survival. The results showed that, after induction therapy, patients achieved CR exhibited superior OS compared with that in CRi (CR vs. CRi, 3-year OS rates 69.4% vs 51.6%, p=0.006). Also, compared with these patients who failed to achieved MRD negativity within re-induction therapy, patients achieved MRD negativity within re-induction therapy showed superior OS when censored at HSCT (MRD- vs. MRD+, 3-year OS rates 64.7% vs 34.9%, p=0.040). After the first reduction therapy, patients achieved CRc but MRD positive benefit from HSCT (HSCT vs Non-HSCT, 3-year rates 83.0% vs 57.9%, p=0.017), but in patients with MRD negativity, HSCT did not improve the survival outcomes (HSCT vs Non-HSCT, 3-year rates 76.8% vs 65.7%, p=0.078). The next-generation sequencing (NGS) results were available in 520 patients. Based on the 2022 ELN risk stratification, the 3-year OS rates were 60.3%, 44.2% and 35.0% in favorable, intermediate and adverse group, respectively. Moreover, there were 43, 47, 60 patients in favorable, intermediate, and adverse subgroups underwent HSCT subsequently. In intermediate risk subgroup, patients who failed to achieve CRc after the first induction therapy, HSCT may serve as an effective intervention to prolong survival (3-year rates 100% vs 12.1%, P&amp;lt;0.001,). On the contrary, patients who achieved CRc in induction therapy, the overall survival were not influenced by HSCT status (3-year rates 81.5% vs 31.7%, p=0.153, Figure B). Conclusion: Our finding indicated that remission after the first cycle of induction therapy may be a prognostic factor for OS. Moreover, earlier and deeper remission may lead to improved survival. For those patients in intermediate risk group, who achieved CRc in induction therapy or achieved CRc with MRD negativity within re-induction therapy, HSCT may not influence the survival outcome.

Outcomes and challenges treating pediatric acute myeloid leukemia: a retrospective analysis of patients treated at the Fundación Valle del Lili between 2011 and 2020

IntroductionAcute myeloid leukemia is a challenging disease, due to a poor prognosis in developing countries. Herein, we aim to describe the clinical characteristics and outcomes after chemotherapy and transplantation. MethodsA retrospective analytic observational study was performed with patients under 18 years of age with newly diagnosed acute myeloid leukemia treated at a referral center in Colombia. Two groups were compared: induction therapy (IT) and induction therapy plus consolidation (IT + C). The survival analysis was performed using the Kaplan–Meier method. ResultsWe analyzed 34 patients diagnosed with acute myeloid leukemia; 20 received hematopoietic stem cell transplantation. Most were French-American-British (FAB) classification types M1, M5 and M0. The transplantation was haploidentical in 65%, conditioning was myeloablative in 67% and graft-versus-host disease prophylaxis was performed with post-transplant cyclophosphamide in 70%. Overall, the 5-year survival was 52% and the overall 5-year survival in the transplanted group was 80%. There were 16 deaths; in the IT group, n = 12, and in the IT + C group, n = 4. In the former, the main cause of death was septic shock and in the latter, it was relapse. ConclusionTransplantation is a safe option. Receiving treatment and supportive measures in hematopoietic stem cell transplantation units is necessary to avoid infections, especially during induction cycles.

#4769 EFFECT OF EXTREMELY LONG DIALYSIS VINTAGE ON RENAL ALLOGRAFT SURVIVAL: A SINGLE-CENTER EXPERIENCE

Abstract Background and Aims Dialysis vintage is long in kidney transplant recipients (KTRs) due to the donor shortage in Turkey. We assessed the effect of pre-transplant dialysis duration (more than 10 years) on the outcomes of renal allografts. Method We retrospectively evaluated 480 KTRs who were grafted between January 2009 and October 2020 at Ankara University School of Medicine, Ibni Sina Hospital. KTRs were divided into two groups according to the duration of pre-transplant dialysis treatment: Group A, ≥10 years and Group B, &amp;lt;10 years. Data on demographics, comorbidities, immunologic properties and graft survivals were compared between the two groups. Results Group A included 60 patients and dialysis vintage was 288±60 months (Table 1). 420 patients in Group B had an average of 19 months period of dialysis treatment. While cadaveric transplantation was 78.3% in Group A, it was much lower in Group B (11.2%, p&amp;lt;0.001). Most of the patients were on hemodialysis treatment (95.0% vs. 58.3%, respectively, P = .001). Recipients’ age (P = .001), HLA mismatch number (P = .008) and PRA positivity (P = .001) were significantly higher in Group A. Although anti-human T-thymocyte globulin had been mostly chosen for induction therapy in Group A (p&amp;lt;0.001); almost all patients were under standard triple maintenance immunosuppression therapy. First year and late acute rejection rates were similar between two groups (p=1.000 and P = .407, respectively). Clinically important difference was demonstrated in graft loss, which was mostly seen in the ≥10 years dialysis group (Group A, 18.3% vs. Group B, 8.3%, P = .014). The 1-, and 5- years graft survival rates were 91.4%, and 81.3%, respectively, in Group A and 97.4%, and 93.4%, respectively, in Group B (P = .034 and P = .029, respectively). Patient loss was significantly higher in Group A (Group A, 28.3% vs. Group B, 14.3%, P = .018). Conclusion We demonstrated that pre-transplant dialysis duration for more than 10 years has adverse effects on post-transplant graft and patient outcomes, accompanied by high immunological risk. Updates of organ allocation system considering sensitized candidates and strategies to expand donor pool and donation rates are needed to reduce waiting times on dialysis.

The impact of induction therapy in low-immunological risk kidney transplant recipients regardless of HLA matching

BackgroundInduction agents have proved to reduce the rate of acute rejection (AR) in kidney transplant recipients (KTRs) without improving long-term graft and patient survival (PS). ObjectiveThis study evaluates the utility of induction therapy in low immunological risk KTRs regardless of donor-to-recipient HLA matching. MethodsWe retrospectively reviewed the records of 218 patients undergoing kidney transplantation (KT). These patients were divided into two groups according to the usage of induction therapy: 82 did not receive any induction therapy (Group I), and 136 patients received either Anti-IL2 receptor antibodies or anti-thymocyte globulin (Group II). All patients had panel reactive antibody (PRA) < 20% and absence of donor-specific antibodies (DSA). The difference in outcomes were assessed at different intervals following KT. ResultsThe rate of bacterial infections at one year (p-value = 0.032) and the frequency of CMV disease (p-value = 0.044) were significantly higher in Group II (with induction therapy). The duration of hospital stay, the rate and severity of acute rejection, the occurrence of delayed graft function, the rate and type of surgical complications at one year, and the graft function and survival at one and three years were similar between the two groups (p-value = NS). In addition, the financial burden is much less in Group I (without induction therapy), reducing the total cost of the transplant procedure. ConclusionWe conclude that induction therapy in low-immunological risk kidney transplant patients is not a must regardless of donor-to-recipient HLA matching. Therefore, induction therapy did not yield significant health results, but had negative financial consequences.

Effect of Daratumumab on Stem Cell Mobilization and Engraftment Kinetics Post Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma

Background: High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care therapy for patients with newly diagnosed multiple myeloma. Daratumumab, an anti-CD38 monoclonal antibody, is now frequently being incorporated as a part of induction therapy in clinical practice, on the basis of data from several clinical trials.1-3 Few studies have evaluated the impact of daratumumab on stem cell mobilization and engraftment with conflicting results. Delayed neutrophil engraftment was noted in patients who received daratumumab as a part of induction therapy in one study.4 However, no delay was reported in another retrospective study5 and at least one clinical trial.6 Lower numbers of stem cells collected were reported uniformly in all three studies with daratumumab use. We evaluated the impact of daratumumab on stem cell yield with mobilization therapy as well as engraftment kinetics. Methods: We retrospectively evaluated 353 patients with newly diagnosed multiple myeloma treated at Hackensack University Medical Center between 2019-2021, on an IRB approved protocol. As per institutional guidelines, a combination of granulocyte colony stimulating factor (GCSF) with plerixafor was used as the mobilizing regimen for patients >70 yrs; cyclophosphamide, etoposide and dexamethasone (CdE) with GCSF was used for patients <70. Plerixafor could be added after chemotherapy mobilization for patients failing to achieve the desired collection goals. All patients received melphalan at a dose of 200mg/m2 administered intravenously on day -1. Time to engraftment (TTE) was calculated from the day of stem cell infusion to neutrophil and platelet engraftment, each defined as an absolute neutrophil count (ANC) of over 500/uL for three sequential tests and a platelet level over 20,000/uL without transfusion support, respectively. Goal for stem cell collection was defined as >8 x 106 CD34+ cells for patients >65 years, >12 x 106 CD34+ cells for patients <65. Statistical analyses were performed using STATA v16.0 (Stata Corp, TX, USA). The differences in median times to engraftment were analyzed using the Wilcoxon signed-rank test. Neutrophil and platelet recovery over time were calculated and plotted using Kaplan-Meier survival analyses and log-rank test for equality of survival function. Differences were considered significant at p-values <0.05. Results: 47 patients received daratumumab as a part of their induction therapy (Group A) compared with 306 patients who did not (Group B). Both groups were well balanced with regards to number of cycles of remission-induction therapy, age, sex, and mobilization regimens (Table 1). A higher number of CD34+ cells were collected for Group B, compared with Group A (12 x 10^6 vs 9.5 x 10^6, p<0.001); a lower number of collection days were required to reach collection goal for Group B compared with Group A (2 days vs 3 days, p=0.01); more CD34+ cells were collected per day for Group B compared with Group A (4.9 x10^6 vs 3.0 x 10^6, p=0.01). 73.5% patients met their collection goal for Group A, compared with 46% for Group B (p<0.001). A second mobilization attempt was required for 7 (14.9%) of patients in Group A compared to 10 (3.3%) for Group B. No difference was noted with regards to TTE for ANC (11 days for both groups, p=0.005) (Figures A); TTE for platelets was noted to be delayed by 1 day for Group A (14 days vs 13 days, p=0.0168) (Figures B). Rates of bacteremia did not differ between the two groups. Results are summarized in Table 1. Conclusions In our single-center study, a lower number of CD34+ cells were collected for patients who received daratumumab as a part of induction therapy for myeloma despite the use of standard mobilization regimens. No difference was found with regards to ANC engraftment. Platelet engraftment occurred one day earlier for patients who did not receive daratumumab for induction. These observations are consistent with results published in two prior studies.5,6 Depending on the target goal for CD34+ cell collection, daratumumab should be used with caution in the upfront setting for multiple myeloma. This is particularly important if tandem stem cell transplantation, salvage transplantation, or stem cell boost post high dose therapy are being considered as prospective treatment options for patients with multiple myeloma. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

P1358: WILL COVID-19 PANDEMIC CHANGE MOBILIZATION STRATEGY OF HEMATOPOIETIC STEM CELLS IN MULTIPLE MYELOMA PATIENTS FOR THE BETTER?

Background: Autologous hematopoietic stem cell transplantation (ASCT) is the current standard of care for younger patients (pts) with multiple myeloma (MM), improving overall survival (OS) and progression free survival (PFS). According to EBMT, use of chemotherapy, typically cyclophosphamide (Cy), in combination with granulocyte colony-stimulating factor (G-CSF) is the preferred strategy for hematopoietic stem cell (HSC) mobilization to peripheral blood (PB). However, major disadvantages are therapy-related toxicity and higher mobilization failure. Plerixafor plus G-CSF has been shown to be superior to G-CSF alone, leading to higher CD34+ yields in fewer apheresis sessions; however there are few data in comparison to chemomobilization. Since the beginning of COVID-19 pandemic, our center adopted G-CSF ± Plerixafor as initial strategy to mobilize HSC in MM pts. Aims: To evaluate the efficacy, length of hospitalization and safety of G-CSF ± Plerixafor mobilization of HSC in MM pts, compared to chemomobilization. Methods: We performed a retrospective study of MM pts submitted to mobilization and 1st ASCT between 2018 and 2021. Pts who underwent mobilization with Cy (1.5 g/m2) plus pegylated G-CSF were included in group A; pts who received G-CSF ± Plerixafor were included in group B. Group B only received Plerixafor if they presented PB CD34+ cells < 15/mL on day 4 of mobilization with G-CSF. Results: We identified a total of 126 pts, excluded 4 (2 under hemodialysis and 2 receiving different protocols) and included 122 pts, 83 (68%) in group A and 39 (32%) in group B. Demographic characteristics and disease stage (ISS and R-ISS) were similar between the groups, presenting a male predominance (n=73, 60%) and a median age of 61 years. Since frontline protocol in MM changed recently, induction therapy in group A and B was, respectively, VCD 60 vs 26%; VRD 30 vs 75%; VTD 10 vs 0% (P<0.001). No differences were observed in pre-ASCT quality of responses (89.2 vs 89.7% ≥VGPR; P=0.532). The impact of apheresis in terms of length of hospitalization (4 vs 2 days, P<0.001) and median time from the 4th day of mobilization with G-CSF until first apheresis was lower in group B; 2 vs 1 days, P<0.001). There was no difference in the number of apheresis sessions (1 vs 1; P=0.260). The volume of DMSO was higher in group B (22 vs 30 mL, P=0.001). In group B, 16 (41%) pts did not need Plerixafor and there were no differences in length of hospitalization or the number of apheresis sessions compared with those who received Plerixafor. Mobilization failure was only seen in group A, (n=14, 17%, P=0.006). Poor mobilizers were remobilized with G-CSF + Plerixafor and presented longer hospitalization (4 vs 2 days, P=0.001) and number of apheresis sessions (2 vs 1 days, P=0.001) when compared to group B. During mobilization, grade ≥3 complications were observed in 8.4% (n=3) in group A, being febrile neutropenia the most frequent; mobilization was interrupted in 2 pts. All pts presented neutrophil and platelet engraftment and there was no difference in time of engraftment after ASCT between groups A and B (12 days in both, P=0.711). No differences were observed in PFS (74.5 vs 40 months, HR 0.8[0.2-2.9], P=0.782) or OS (82.6 vs NR, HR 1.1[0.2-6.0], P=0.839) between groups. Summary/Conclusion: The mobilization protocol changed, due to COVID-19 pandemic, from chemomobilization to G-CSF ± Plerixafor and resulted in less hospital resource utilization and less febrile neutropenia, without compromising ASCT success. Unlike prior reports, number of apheresis sessions after mobilization with G-CSF alone was similar to G-CSF + Plerixafor.

Follow up examination of multiple sclerosis patients treated with alemtuzumab in Multiple Sclerosis Centre, Szeged

Therapeutic strategy of relapse-remitting multiple sclerosis has changed significantly during the past decade. While earlier escalating therapy was widely applied, recently, in case of high disease activity, induction therapy has become available. In our study, we processed the data of our alemtuzumab treated patients from our register. Alte-ra-tions in relapse rate and MRI activity due to the treatment were determined. These data were compared in patients treated with alemtuzumab as an escalating and as an induction therapy. We noted the observed side effects. The 49 patients observed in the study had undergone two cycles of alemtuzumab therapy. The drug was applied as an induction therapy in 9 cases. Average relapse rate during the two years was 1.4±1.0, which decreased to 0.1±0.3 in the two years following the therapy. The average EDSS before therapy was 2.7±2.2 in the induction therapy group and 2.7±1.7 in the escalating therapy group. After the treatment, this score decreased to 1.6±0.6 and 2.5±1.8 in the induction and the escalating therapy group, respectively. We found clinical and MRI progression in case of 4 patients. As regards to side effects, cytokine release was detected in 51.0% of the patients following the first cycle, and 24.5% of the patients following the second cycle of the therapy. Infection related to the therapy was observed in 28.6%, while autoimmune thyreoiditis was diagnosed in 18.3% of the patients. The tight follow-up of the treated patients and the precise documentation of the register enable the comparison of results yielded by placebo controlled clinical studies with daily practice, as well as to gain information on the benefits of induction therapy as a paradigm shift in treating MS patients.

Antithymocyte globulin is associated with a lower incidence of de novo donor-specific antibody detection in lung transplant recipients: A single-center experience.

PurposeInduction immunosuppression has improved the long‐term outcomes after lung transplant. This is the first report exploring the association of induction immunosuppression with the development of de novo donor‐specific human leukocyte antigen (HLA) antibodies (DSA) in lung transplant recipients (LTR).MethodsSixty‐seven consecutive primary LTR were followed for 3 years posttransplant. A total of 41/67 (61%) LTR‐received induction immunosuppression using a single dose of rabbit Antithymocyte Globulin (rATG; 1.5 mg/kg) within 24 h of transplant. All recipients had a negative flow cytometry crossmatch on the day of transplant. Serum samples at 1, 3, 6, and 12 months posttransplant were assessed for the presence of de novo HLA DSA.ResultsDe novo HLA DSA were detected in 22/67 (32.8%) LTR within 1‐year posttransplant. Of these, 9/41 (21.9%) occurred in the induction therapy group and 13/26 (50%) in the noninduction group. Class II DSA were detected in 3/41 (7.3%) LTR who received induction compared to 9/26 (34.6%) LTR without induction immunosuppression (p = .005). Differences in overall survival or freedom from chronic lung allograft dysfunction rates between the two groups were not statistically significant.ConclusionInduction immunosuppression utilizing a modified regimen of single‐dose rATG is associated with a significant reduction in de novo DSA production in LTR.

Clinical Correlates and Outcomes of Dual Basiliximab and Antithymocyte Globulin Induction in Kidney Transplant Recipients: A National Study.

We used national transplant registry data to study clinical correlates and outcomes of single versus dual induction therapy in adult kidney-only transplant recipients in the United States (2005-2018). The risk of death and graft loss at 1 and 5 y, according to induction therapy type, was assessed using multivariate Cox regression analysis (adjusted hazard ratio with 95% upper and lower confidence limits [LCLaHRUCL]). Of the 157 351 recipients included in the study, 67% were treated with ATG alone, 29% were treated with IL2rAb alone, and 5% were treated with both. Compared with IL2rAb alone, the strongest correlates of dual induction included Black race, calculated panel reactive antibody ≥80%, prednisone-sparing maintenance immunosuppression, more recent transplant eras, longer cold ischemia time, and delayed graft function. Compared with ATG alone, dual induction was associated with an increased 5-y risk of death (aHR 1.071.151.23; P < 0.0001), death-censored graft failure (aHR 1.051.131.22; P < 0.05), and all-cause graft failure (aHR 1.061.121.18; P < 0.0001). Further research is needed to develop risk-prediction tools to further inform optimal, individualized induction protocols for kidney transplant recipients.

Comparing the effect of induction therapy with or without antithymocyte globulin on renal allograft outcomes in live-donor kidney transplant recipients

Background: This study aimed to investigate the effectiveness of antithymocyte globulin (ATG) in low-risk live-donor kidney transplant recipients (LDKTRs). Methods: In this cohort study, 114 LDKTRs were analyzed in 2 groups of ATG induction therapy (n=77) and control (n=37). In this study, 500 mg pulse therapy with methylprednisolone was provided for both groups for 3 days. In addition, one mg/kg of daily ATG was prescribed for 4 days in ATG induction group. Serum creatinine (Cr) was measured at 3, 7, 30, 90, and 180 days after surgery and discharge day. Acute rejection (AR) was confirmed based on biopsy or rise in serum Cr by three-tenths from baseline if other causes had been ruled out. Survival analysis was used by Stata14 and p < 0.05 was considered significant. Results: Cr changes were not significantly different between ATG induction therapy and control group in all follow-up periods (2.26 and 1.07 in ATG vs 2.26 and 1.03 in control group from the third day; (p=0.999) to the sixth month (p=0.735)). There was no significant difference between the 2 study groups in AR incidence (11.7% in ATG vs 10.8% in control group, P = 0.890) and its time (9.6 in ATG vs 9.8 in control group, p=0.695). Recipients factors were baseline Cr >10 mg/dL (p=0.055), blood group AB (p=0.007), no postoperative pulse therapy with methylprednisolone (PM) (p=0.005); and donors’ factors were age ≤ 30 years (p=0.022) and blood group AB (p=0.006). Also, based on the log rank analysis, recipient-donor weight difference of 0 to 5 kg (p=0.047) had a significant association with earlier AR. Exploring these effects simultaneously by Cox regression analysis showed only significant results for recipients' baseline Cr (p=0.040) and postoperative therapy with PM (p=0.014). Conclusion: Both strategies of induction therapy had the same good results based on Cr decrease. Recipients' baseline Cr and postoperative therapy with PM were the predictors of survival time of the kidney (AR).

Comparing the effect of induction therapy with or without antithymocyte globulin on renal allograft outcomes in live-donor kidney transplant recipients

Background: This study aimed to investigate the effectiveness of antithymocyte globulin (ATG) in low-risk live-donor kidney transplant recipients (LDKTRs). Methods: In this cohort study, 114 LDKTRs were analyzed in 2 groups of ATG induction therapy (n=77) and control (n=37). In this study, 500 mg pulse therapy with methylprednisolone was provided for both groups for 3 days. In addition, one mg/kg of daily ATG was prescribed for 4 days in ATG induction group. Serum creatinine (Cr) was measured at 3, 7, 30, 90, and 180 days after surgery and discharge day. Acute rejection (AR) was confirmed based on biopsy or rise in serum Cr by three-tenths from baseline if other causes had been ruled out. Survival analysis was used by Stata14 and p < 0.05 was considered significant. Results: Cr changes were not significantly different between ATG induction therapy and control group in all follow-up periods (2.26 and 1.07 in ATG vs 2.26 and 1.03 in control group from the third day; (p=0.999) to the sixth month (p=0.735)). There was no significant difference between the 2 study groups in AR incidence (11.7% in ATG vs 10.8% in control group, P = 0.890) and its time (9.6 in ATG vs 9.8 in control group, p=0.695). Recipients factors were baseline Cr >10 mg/dL (p=0.055), blood group AB (p=0.007), no postoperative pulse therapy with methylprednisolone (PM) (p=0.005); and donors' factors were age ≤ 30 years (p=0.022) and blood group AB (p=0.006). Also, based on the log rank analysis, recipient-donor weight difference of 0 to 5 kg (p=0.047) had a significant association with earlier AR. Exploring these effects simultaneously by Cox regression analysis showed only significant results for recipients' baseline Cr (p=0.040) and postoperative therapy with PM (p=0.014). Conclusion: Both strategies of induction therapy had the same good results based on Cr decrease. Recipients' baseline Cr and postoperative therapy with PM were the predictors of survival time of the kidney (AR).

Does Induction Therapy Increase Anastomotic Complications in Bronchial Sleeve Resections?

Sleeve lobectomy represents a safe and effective treatment for central NSCLC to avoid the risks of pneumonectomy. Induction therapy (IT) may be indicated in advanced stages; however, the effect of IT on bronchial anastomoses remains uncertain. The purpose of the study was to evaluate the impact of IT on the complications of the anastomoses. Between 2000 and 2012, 159 consecutive patients were submitted to sleeve lobectomy for NSCLC at our Institution. We retrospectively compared the results of patients who underwent IT before operation with those who received upfront surgery. In the study period, 49 (30.8%) patients received IT (37 chemotherapy, 1 radiotherapy and 11 chemo-radiotherapy) and 110 (69.2%) patients were directly submitted to surgery (S). The two groups were comparable for sex, age, comorbidities, ASA score, pulmonary function, side, type of procedure and histology. Pathological stage was statistically higher for IT group (p = 0.001). No differences between IT and S groups were observed in terms of post-operative mortality (2% vs 0%, p = NS), morbidity (45% vs 38%, p = NS), including early (6% vs 9%, p = NS) and long-term (16% vs 14%, p = NS) bronchial complication rates. Patients undergoing induction mediastinal radiotherapy, however, are at higher risk of bronchial complications. In our experience, the use of induction chemotherapy did not significantly increase mortality and morbidity rates, in particular, neither for early nor for late anastomotic complications. We, therefore, conclude that sleeve lobectomy after induction chemotherapy is safe and reliable procedure for the treatment of locally advanced NSCLC.

Pneumonectomy in Stage IIIA-N2 NSCLC: Should It Be Considered After Neoadjuvant Chemotherapy?

BackgroundOwing to the expected poor long-term outcomes and high postoperative morbidity and mortality, patients with stage IIIA-N2 tumors candidate to pneumonectomy (PN) are usually excluded from surgery. This study aims to analyze the outcome of patients who underwent PN to prove its safety and feasibility. Patients and MethodsWe retrospectively analyzed data from 233 patients who underwent PN for N2 non–small-cell lung cancer (NSCLC) between 1998 and 2015. Eighty-five patients were occult N2 disease (group 1), whereas 148 patients underwent induction therapy (IT) for stage IIIA-N2 (group 2). ResultsOverall morbidity, postoperative mortality, and 90-day mortality rates were 46.8%, 2.6%, and 8.6%, respectively. The 2 groups (group 1 vs. 2) had similar postoperative and 90-day mortality rates: 2.4% versus 2.7% (P = 1.00), and 9.4% versus 8.1% (P = .81), respectively. The incidence of major morbidity was higher and statistically significant in group 2 compared with group 1: 23% versus 12.9% (P = .1). Postoperative bronchopleural fistula occurred in 4.7% (4/85) of patients with occult N2 (group 1) and in 10.1% (15/148) of patients undergoing IT (group 2) (P = .10). Median overall survival (OS) was 2.2 years, with a 3 and 5-year OS of 43.4% and 31.6%, respectively. Disease-free survival (DFS) was 1.5 years, with 3 and 5-year DFS of 41.6% and 32%, respectively; no difference in OS and DFS between the 2 groups was found. ConclusionsConsidering the acceptable morbidity and mortality rate and the long-term survival, PN should not be excluded for selected patients with stage IIIA-N2 NSCLC as a matter of principle.

Induction therapy for clinical stage T2N0M0 esophageal cancer: A systematic review and meta-analysis.

It is still controversial whether patients with clinical T2N0M0 (cT2N0M0) esophageal cancer are treated with induction therapy. The aim of this study was to determine the effect of induction therapy on cT2N0M0 esophageal cancer. We searched PubMed, Embase, the Cochrane Library, and Medline databases from inception up to May 1, 2017. This meta-analysis was performed to compare odds ratios (OR) for 5-year overall survival (OS), pathologically understaged and overstaged after esophagectomy. Eight retrospective studies of 2646 patients were included in the meta-analysis. Data showed that no statistically significant difference in 5-year over survival was observed between induction therapy group and direct operation group. The pooled OR and 95% confidence interval (CI) for 5-year OS were 0.92 (95% CI = 0.72-1.18; P = .52). Whereas, compared with induction therapy group, direct operation group had more pathologically understaged and less overstaged after esophagectomy. Currentclinical staging for T2N0M0 esophageal carcinoma remains inaccurate. In this study, we found that direct operation group had more pathologically understaged and less overstaged after esophagectomy compared with induction therapy group. Induction therapy could degrade the tumor staging but not improve the patient's survival.

Lung Resection after Definitive and Neo-Adjuvant Chemoradiation for Stage IIIA/B Locally Advanced Non-Small Cell Lung Cancer: a Retrospective Analysis

The outcomes of so called "salvage" resections after definitive chemoradiation vs. curative resections after neoadjuvant chemoradiation therapy (IT-resection) in patients with stage IIIA/B locally advanced non-small cell lung cancer have rarely been compared. The aim of our study was to compare perioperative results, postoperative and recurrence-free survival and to identify relevant prognostic survival factors for both therapy strategies. Between June 2008 and May 2017, 43 patients underwent pulmonary resection following induction therapy (group 1) and 14 patients underwent salvage resection after definitive chemoradiation (group 2). Retrospective analysis was performed of demographic factors, tumour stage and location, initial therapy, preoperative regression status, perioperative morbidity and mortality, postoperative and recurrence-free survival. In group 2, significantly higher radiation dose was applied (p < 0.001) and the interval between chemoradiation and lung resection was significantly longer (p = 0.02). In addition, significantly higher perioperative blood loss and more frequent blood transfusions were noted (p = 0.003 and 0.005, respectively). Perioperative morbidity and mortality were statistically comparable in the two groups (p = 0.72 and 0.395, respectively). Postoperative 5 year survival in group 1 was 55%, in group 2 48% (log-rank p = 0.353). Five year recurrence-free survival in group 1 was 53%, in group 2 42% (log-rank p = 0.180). Diffuse metastasis occurred mostly in group 2, whereas in group 1 oligometastasis was more frequently noted. Postoperative outcome after salvage resection seems statistically comparable to results following curative resection after induction therapy. Diffuse distant metastasis is frequently noted. Careful patient selection is required.

Rituximab Maintenance Therapy Reduces Rate of Relapse of Pancreaticobiliary Immunoglobulin G4-related Disease

IgG4-related disease (IgG4-RD), a multi-organ fibroinflammatory syndrome, typically responds to steroids. However, some cases are steroid resistant, and pancreaticobiliary IgG4-RD commonly relapses after steroid withdrawal. Rituximab induces remission of IgG4-RD, but the need for and safety of maintenance rituximab treatment are unknown. We compared outcomes of patients with pancreaticobiliary IgG4-RD treated with or without maintenance rituximab therapy. We performed a retrospective study of patients with pancreaticobiliary IgG4-RD treated with rituximab at the Mayo Clinic in Rochester, Minnesota, from January 2005 through December 2015. The cohort was divided into patients who received only rituximab induction therapy (group 1, n= 14) and patients who received rituximab induction followed by maintenance therapy (group 2, n= 29). We collected data on recurrence of IgG4-RD symptoms and findings, as well as information on evaluations, treatment, and adverse events. Median follow-up times were similar between group 1 (34 mo) and group 2 (27 mo) (P= .99). Thirty-seven patients (86%) were in steroid-free remission 6 months after rituximab initiation. A higher proportion of patients in group 1 had disease relapse (3-year event rate, 45%) than in group 2 (3-year event rate, 11%) (P= .034). Younger age, higher IgG4 responder index score after induction therapy, and increased serum levels of alkaline phosphatase at baseline or after rituximab induction were associated with relapse. Infections developed in 6 of 43 patients, all in group 2 (P= .067 vs group 1); all but 1 occurred during maintenance therapy. In a retrospective study of patients with pancreaticobiliary IgG4-RD, we found rituximab maintenance therapy prolongs remission. Relapses are uncommon among patients receiving maintenance therapy, but maintenance therapy may increase risk of infection. Patients with factors that predict relapse could be candidates for rituximab maintenance therapy.

Impact of induction chemoradiotherapy on pulmonary function after lobectomy for lung cancer

ObjectiveOur study aim was to determine whether there are differential changes in whole-lung and regional lung functions after lobectomy for lung cancer between propensity score-matched patients treated with and without induction chemoradiotherapy, by using single-photon emission computed tomography lung perfusion. MethodsThis study was a retrospective matched cohort study of consecutively acquired data. Pulmonary function test and perfusion scintigraphy were conducted before lobectomy and 6 months after lobectomy in patients treated with induction therapy (n = 72) and in those not treated (n = 170), for measuring functional changes of whole lung, contralateral lung, and lobes. After exact matching on resected lobe site, propensity scores for age, smoking status, preoperative pulmonary functions, and predicted postoperative pulmonary function were used to match the groups. ResultsAfter the matching, 46 patients were selected from the groups. Standardized mean differences of the 5 matched variables were <0.1. Whole lung function significantly decreased after lobectomy in the induction therapy group than in the noninduction therapy group (P < .001). Although ipsilateral preserved lobe function before surgery was not different between the groups (P = .33), postoperative value was significantly lower in the induction therapy group than in the noninduction therapy group (P < .001). Although both groups showed a significant increase of contralateral lung function after lobectomy (P < .01), the increases were not significantly different between the groups (P = .81). ConclusionsInduction chemoradiotherapy was associated with reduced pulmonary function after lobectomy because of a decrease in ipsilateral preserved lobe function, which could be caused by the chronic effects of the induction chemoradiotherapy.