Incidence Of Relapse Research Articles

Treatment and long term follow-up results in patients with pulmonary vascular thrombosis related to COVID-19.

Pulmonary embolism is a complication of COVID-19 infection. The aim of this study is to assess prognosis and treatment response, including incidences of chronicity, relapse, and mortality among outpatients diagnosed with COVID-19-related pulmonary embolism between 2020 and 2022. A total of 101 patients with pulmonary embolism, started on anticoagulation during or within a month of COVID-19 infection, were included after testing positive by PCR. Data about comorbidities, Pulmonary Embolism Severity Index scores, PE diagnostic modalities, biochemical parameters, and transthoracic echocardiographic findings at diagnosis and at 24-month follow-up were collected. Cardiac catheterization parameters were recorded and compared between groups at diagnosis and at the 24-month follow-up. Groups were comparable with respect to gender, age, body mass index, and comorbidity score. Use of Q-SPECT for diagnosis was found significantly higher in patients with COVID-19-related pulmonary embolism (P < .001). The incidence of deep vein thrombosis was similar. In the study group, 43.6% of patients received anticoagulants for 3 months, with 49.1% using low molecular weight heparin and 50.9% using direct oral anticoagulants. At 24 months, rate of patients continuing treatment was comparable between groups. Specific pulmonary artery blockage value was found to be higher in patients with chronic thromboembolic pulmonary hypertension compared to those who demonstrated a response to pulmonary embolism treatment (P = .009). No adverse effects of anticoagulant therapy were observed during course of treatment. Over 24-month follow-up period, mortality, relapse, chronic thromboembolic hypertension and thromboembolic disease was observed in 2%, 2.2%, 4.9%, and 9.9% of patients, respectively.

Long-term follow-up of the TRED-HF trial

Abstract Background The TRED-HF trial (1) found that 44% of patients with recovered dilated cardiomyopathy (DCM) relapsed in the short term after withdrawal of medical therapy. The longer-term risk of relapse is uncertain. Purpose This follow-up aims to investigate the longer-term risk of relapse in patients with recovered DCM and any possible predictive factors. Methods TRED-HF trial participants were followed until May 2023. The primary outcome was DCM relapse defined as &amp;gt;10% reduction in left ventricular (LV) ejection fraction to &amp;lt;50%, doubling in N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) to &amp;gt;400ng/L, or clinical recurrence of heart failure (HF). Therapy intensity for HF was calculated using QUAD scores. The incidence of relapse was calculated using Kaplan-Meier estimates. Predictors of relapse were investigated using Cox proportional hazard modelling. Results For all fifty-one patients, median follow-up from enrolment was 6 (IQR: 6-7) years. Overall, thirty-three patients (65%) relapsed with an estimated 5-year relapse rate of 61% (95% CI 45-73). Twenty patients relapsed during the randomised trial, nine of whom had a recurrent relapse during follow-up (Figure 1). Thirteen patients relapsed for the first time after completion of the trial; of those, one patient did not have therapy withdrawn during the trial, 8 had restarted low intensity HF therapy and 4 patients stayed on no therapy. Five patients stayed off HF therapy and did not relapse. The overall mean intensity of HF therapy was lower after the trial compared to enrolment (mean difference in QUAD score -6 [-8 to -4]; p&amp;lt;0.001). A mean reduction in medication intensity was also seen at the point of relapse during the trial and during follow-up (Figure 2). Of relapses during follow-up, seven had identifiable triggers (arrhythmia (n=4), pregnancy (n=1), hypertension (n=1), infection (n=1)). Patients taking more HF medications at baseline or with higher baseline NT-pro-BNP were more likely to relapse. Corrected atrial fibrillation was associated with reduced future risk of relapse. Conclusions In patients with recovered DCM, the risk of relapse after therapy withdrawal increased with longer follow-up. Lower doses of HF medications and recurrent external triggers contributed to relapse. Few patients who stopped medications had sustained remission. Recovery of DCM after correction of AF was associated with a low risk of relapse provided atrial fibrillation did not recur.

Comparison of neoadjuvant chemoimmunotherapy and neoadjuvant chemotherapy for resectable esophageal squamous cell carcinoma: a retrospective study with 3-year survival analysis

BackgroundNeoadjuvant chemoimmunotherapy (nCIT) for locally advanced esophageal squamous cell cancer (ESCC) has shown short-term benefits, but long-term survival outcomes are unclear. This study compares nCIT and neoadjuvant chemotherapy (nCT) in resectable ESCC.Patients and methodsA retrospective analysis was conducted on ESCC patients who underwent nCT or nCIT followed by esophagectomy. Propensity score matching (PSM) with a caliper of 0.02 was employed to minimize bias. The primary endpoints included disease-free survival (DFS) and overall survival (OS).ResultsA total of 131 comparable pairs of ESCC patients receiving nCT and nCIT were selected for the final analysis. The nCIT had higher rates of pathological complete response (pCR) and major pathological response (mPR) compared to nCT. Additionally, nCIT led to significant tumor down-staging, higher rates of R0 resection, and increased lymph node clearance during surgery. Patients who received nCIT exhibited improved disease-free survival (DFS) and overall survival (OS) at the 3-year follow-up. The incidence of distant and mixed relapses was lower in the nCIT group compared to the nCT group. However, the risk of locoregional relapse was comparable between the two groups. Subgroup analyses showed that the benefits of nCIT were generally observed across most patient subgroups. Interestingly, in patients without pCR or mPR, nCIT still demonstrated better survival benefits than nCT.ConclusionnCIT demonstrated superior pathological response rates and improved 3-year DFS and OS compared to nCT alone in locally advanced ESCC, but long-term survival validation is needed.

Relapse and survival after relapse among children with cancer in Denmark: 2001-2021.

In recent decades, new first and subsequent lines of anticancer treatment and supportive care have improved survival for children with cancer. We investigated recent temporal changes in the incidence of relapse and survival after relapse among children with cancer in Denmark. This register-based study included 2890 children diagnosed before age 15years with haematological cancers and solid tumours (2001-2021) and central nervous system (CNS) tumours (2010-2021). We used the Aalen-Johansen and Kaplan-Meier estimators to assess cumulative incidence of relapse-defined as cancer recurrence or progression-and survival probability after relapse. Comparing the periods 2001-2010 and 2011-2021, the 5-year cumulative incidence of relapse decreased from 14% to 11% among children with haematological cancers (p=.07), and from 21% to 18% among children with solid tumours (p=.26). Concurrently, the 5-year survival after relapse increased among children with haematological cancers (from 44% to 61%, p=.03) and solid tumours (from 38% to 46%, p=.25). Among children with malignant CNS tumours, the 5-year cumulative incidence of relapse and the 5-year survival after relapse remained stable (49% and 51%, p=.82; and 20% and 18%, p=.90) comparing 2010-2015 and 2016-2021. In recent decades in Denmark, improvements were observed in reducing relapse incidence and increasing survival after relapse in children with haematological cancers and solid tumours. However, the persistent survival gap between children who relapse and those who do not across all childhood cancers underlines the need for intensified and highly targeted treatments for children at high risk of relapse.

Comparative outcomes of various transplantation platforms, highlighting haploidentical transplants with post-transplantation cyclophosphamide for adult T-cell leukaemia/lymphoma.

This study retrospectively compared outcomes of various allogeneic haematopoietic cell transplantation (allo-HCT) platforms in patients with adult T-cell leukaemia/lymphoma. Platforms included human leukocyte antigen (HLA)-haploidentical-related donors using post-transplant cyclophosphamide (PTCY), HLA-matched related donors (MRD), HLA-matched unrelated donors (MUD) and cord blood transplantation (CBT). Patients who underwent their first allo-HCT between 2016 and 2021 were included. Outcomes analysed were overall survival (OS), relapse and non-relapse mortality (NRM). Seven hundred patients were included (PTCY, n = 121; MRD, n = 91; MUD, n = 160; CBT, n = 328). With a median follow-up of 794 days for survivors, 2-year OS was 48.1% (PTCY), 48.8% (MRD), 48.4% (MUD) and 34.6% (CBT); the respective 2-year cumulative incidence of relapse was 37.1%, 47.5%, 33.9% and 45.1% and that of NRM was 24.2%, 19.8%, 24.7% and 27.3%. PTCY was associated with delayed platelet engraftment relative to MRD and MUD. There was no increase in the incidence of severe acute or chronic graft-versus-host disease. In the PTCY group, poor performance status was a significant predictor of inferior OS, and infused CD34+ cell numbers of less than 5 × 106/kg were associated with delayed neutrophil and platelet engraftment. These results suggest that allo-HCT with PTCY is a safe and effective platform for patients with adult T-cell leukaemia/lymphoma.

Inotuzumab Ozogamicin and Low-Intensity Chemotherapy in Older Patients With Newly Diagnosed CD22+ Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia.

The use of inotuzumab ozogamicin (InO), a conjugated anti-CD22 monoclonal antibody, is becoming a promising frontline treatment for older patients with ALL. EWALL-INO is an open-label prospective multicenter phase II trial (ClinicalTrials.gov identifier: NCT03249870). Patients age 55 years and older with newly diagnosed CD22+ Philadelphia chromosome-negative (Ph-) B-cell precursor (BCP) ALL were eligible. After a prephase, a first induction consisting of vincristine, dexamethasone, and three injections of InO (0.8 mg/m2 day 1, 0.5 mg/m2 day 8/day 15) was followed by a second induction combining cyclophosphamide, dexamethasone, and two injections of InO (0.5 mg/m2 day 1/day 8). Responders received up to six cycles of chemotherapy consolidation and 18-month chemotherapy maintenance. Allotransplant was allowed after three consolidations. The primary end point was 1-year overall survival (OS). Between December 2017 and March 2022, 131 patients (median age 68 years) were included. Three patients died during induction 1 (n = 130), two from multiple organ failure and one from hemorrhage, and none during induction 2 (n = 120). After induction 2, 90% of the patients achieved complete remission (CR) or CR with incomplete platelet recovery (CRp) and 80% had measurable residual disease (MRD2) <10-4. Among responders (n = 119), 47 relapsed and 14 died in CR/CRp. One-year OS, relapse-free survival (RFS), and cumulative incidence of relapse (CIR) rates were 73.2%, 66%, and 25%, respectively. High-risk cytogenetics and lower CD22 expression (<70%) were associated with worse OS, while both high-risk cytogenetics and MRD2 ≥10-4 were associated with lower RFS and higher CIR. The 10 allotransplanted patients had very favorable outcomes (90% 2-year OS/RFS and no relapse). Only one nonfatal sinusoidal obstructive syndrome was documented during the study. Our results support InO's use in first-line regimens for older patients with CD22+ Ph- BCP-ALL.

Treatment Strategy for Catamenial and Endometriosis-Related Recurrent Spontaneous Pneumothorax

RELEVANCE. The problem of treating thoracic endometriosis complicated by recurrent spontaneous catamenial pneumothorax is associated with the widespread prevalence of endometriosis, the complexity of its treatment and unsatisfactory long-term outcomes. The diagnosis of catamenial pneumothorax can only be established with a carefully collected history and confirmation of its recurrent nature. Favorable results are achieved with complex therapy carried out by the thoracic surgeon and gynecologist, consisting of an adequate volume of surgical intervention and hormonal therapy with gonadotropin releasing hormone agonists.AIM OF STUDY. To improve the diagnosis of thoracic endometriosis and recurrent catamenial and endometriosis-related spontaneous pneumothorax. To optimize the currently available treatment tactics by reducing the incidence of early relapses of catamenial pneumothorax and creating favorable conditions for the formation of reliable pleurodesis.MATERIAL AND METHODS. We studied the immediate outcomes of complex treatment of 30 patients (14.7%) with right-sided recurrent catamenial (28) and endometriosis-related spontaneous pneumothorax (2), with a median age of 41 (37;44) years, for the period from 2011 to the first half of 2023. Surgical treatment via video-assisted thoracoscopic access was performed in 26 patients (86.7%). After surgery, all the patients were recommended a six-month course of hormonal therapy with gonadotropin releasing hormone agonists.RESULTS. Various types of mechanical pleurodesis were performed in 25 patients (96.1%), resection of the diaphragm — in 17 (65.4%), alloplastic reconstruction with a synthetic mesh implant — in 12 patients (46.1%), pulmonary resection — in 9 (34.6%). In 12 of 26 patients (46.1%) in the early postoperative period, 6 (3; 6.75) days after surgery, a recurrence of catamenial pneumothorax developed, which subsequently required repeated interventions. In 5 patients, the relapse clearly coincided with the menstrual cycle. Early recurrence of pneumothorax required repeated drainage of the pleural cavity in all the patients, chemical pleurodesis in 2, and prolonged drainage of the pleural cavity in 1.CONCLUSION. Surgeries involving resection and reconstruction of the diaphragm with a mesh implant, pleurectomy, lung resection do not ensure the removal of all endometrioid heterotopias of the diaphragm and lung, therefore, during the first mensis after surgery, in the early postoperative period, 46.1% of the patients had a recurrence of catamenial pneumothorax, with no formed pleurodesis, which contributes to the possibility of further recurrences of pneumothorax. Improving the immediate outcomes of complex treatment of catamenial pneumothorax is possible with the preventive administration of hormonal therapy 1.5–2 months before the planned surgical intervention, which requires a multidisciplinary approach of the thoracic surgeon and gynecologist.

Haploidentical hematopoietic stem cell transplantation for hematologic malignancies: a novel conditioning regimen with anti-T lymphocyte immunoglobulin instead of anti-thymocyte globulin for in vivo T cell depletion.

We evaluated the safety and efficacy of a novel protocol for haploidentical stem cell transplantation (haplo-SCT) in 312 patients with hematologic malignancies. The protocol evolved from the Beijing platform replacing ATG with ATLG; adding Fludarabine and removing cytarabine and Simustine. GVHD prophylaxis combined Basiliximab and low-dose cyclophosphamide post-transplant; overall, the conditioning duration was shortened. Median times to neutrophil and platelet recovery were both 11 days. Graft rejection occurred in 0.96% of patients. Cumulative incidences of grades II-IV and III-IV acute GVHD by day 200 were 35.3% and 8.9%, respectively. Probabilities of total and extensive chronic GVHD at 2 years were 40.7% and 14.7%. CMV viremia was observed in 35.6% of patients, with a 1.9% 100-day CMV pneumonia incidence and no CMV-related mortality. Cumulative incidences of non-relapse mortality at 100 days, 1 year, and 2 years were 2.9, 4.4, and 6.6%. The 4-year OS, RFS, and GRFS rates were 78.9, 70.7, and 47.3%. Older recipient age was associated with higher NRM, while positive pre-transplant MRD predicted worse OS, RFS, and higher relapse incidence. Our novel protocol for haplo-SCT is associated with low infection rates and acceptable risks of graft failure, severe GVHD, and mortality, representing a safe and effective haploidentical transplantation strategy.

Correlation between MRI utilization and therapy switches in disease-modifying treatments for multiple sclerosis.

Studies measuring the role of magnetic resonance imaging (MRI) in therapeutic decision-making are rare in people with multiple sclerosis (pwMS). This study aimed to measure the association between MRI utilization and disease-modifying therapy (DMT) switches in pwMS. This retrospective cohort study identified pwMS in 2018 from a de-identified national claims database. PwMS who received MRI in 2018 were compared to pwMS not receiving MRI in 2018. PwMS were observed for six months to assess the incidence of DMT switches. The study sample consisted of 11,972 pwMS. 3,931 (32.8%) pwMS received at least one MRI in 2018. Overall, MRI utilization increased the odds of switching DMT (OR = 1.49, 1.79, and 3.01 for 1, 2, and ≥ 3 CNS locations imaged). For those on injectable or platform DMT, any MRI utilization increased the odds of switching DMT (OR = 1.54, 2.00, and 3.48 for 1, 2, and ≥ 3 locations imaged). For those on oral DMT, only receiving MRI of 2 or ≥ 3 locations increased the odds of a DMT switch (OR = 1.36, 1.89, and 2.40 for 1, 2, and ≥ 3 locations). Finally, for pwMS on infusible therapies, there was little evidence that MRI changed the odds of a DMT switch. Among pwMS on injectable or oral DMT, imaging more CNS locations increased the odds of switching DMT after adjusting for age and relapse incidence. For pwMS on high-efficacy infusible DMTs, MRI did not change the odds of switching DMT but remains essential for safety monitoring.

Biological Findings and Clinical Outcomes in Patients Treated With R-CHOP Plus High-Dose Methotrexate as First-Line Therapy in Large B-Cell Lymphoma With Testis Involvement.

Primary testicular lymphoma (PTL) is a rare occurrence of diffuse large B-cell lymphoma (DLBCL) that accounts for 1%-2% of all cases. Nodal DLBCL with testis involvement (DLBCL-T) and PTL are associated with poor prognosis, with high incidence of central nervous system relapse. Fifteen patients (median age 60 years) with PTL (n = 5) or DLBCL-T (n = 10) received high-dose methotrexate + R-CHOP. Overall, complete response (CR) rate was 73% and overall response rate 86%. With a 3.9-year median follow-up, 100% of patients with PTL had CR and none relapsed. On the contrary, 55% of DLBCL-T patients achieved CR among which only one was still in remission at the end of follow-up. Molecular parallels between PTL and Primary CNS Lymphoma (PCNSL) suggest shared origins, urging further research for tailored treatments and enhanced understanding of these lymphomas' biology.

Adaptive stereotactic radiosurgery for cerebral metastases of non-small cell lung cancer: a retrospective study

INTRODUCTION: Non-small cell lung cancer (NSCLC) is a common cause of brain metastases (BM). Adaptive stereotactic radiosurgery (ASRS) may be a useful option in the treatment of patients with large unresectable brain metastases (BM), but to date there are only a limited number of studies evaluating the effectiveness of this method.OBJECTIVE: To analyze the effectiveness of ASRS in patients with large BM NSCLC not subject to surgical resection.MATERIAL AND METHODS: We retrospectively analyzed data from 37 patients suffering from NSCLC with 45 large (&gt;2 cm in diameter, volume &gt;4 cm3) unresectable BM treated with the Gamma Knife Perfexion model using two- and three-fraction ASRS. Of these, 14 foci (31.1%) were metastases of squamous cell lung cancer, 31 (68.9%) were metastases of adenocarcinoma. The median volume of lesions treated with ASRS was 9.8 (range 4.6–30.6 cm3). The dynamics of volume changes between fractions and the cumulative incidence of local relapses (CILR) were studied, and ROC analysis was performed for the tumor volume parameter. Intracranial progression-free survival (iPFS) and overall survival (OS) were assessed. Statistics: To establish statistical significance of differences for related variables, the Wilcoxon test for pairwise comparisons and the Friedman test for three or more groups were used. The Kaplan-Meier method was used to calculate local control, PFS, and OS rates. The log-rank test was used to compare survival data in two groups.RESULTS: The median follow-up period was 19.4 months. With two-fraction ASRS, the median volume of metastasis decreased by 28.6% by the second session, with three-fraction — by 40.0% by the third session. The 1-year and 2-year CILR rates were 8.6±6.1%, respectively; 26.1±12.3%. In ROC analysis, the area under the curve (AUC) for tumor volume was 0.80 (95% CI 0.6– 1.0) with an optimal cutoff of 18.5 cm3. The differences in CILR between the groups with metastasis volume &lt;18.5 cm3 and ≥18.5 cm3 were statistically significant (p&lt;0.001). Median iPFS was 8.3 (95% CI 5.9–10.7) months, 1-year iPFS was 33.5±8.1%;2-year — 7.8±5.2%. Median OS was 13.2 (95% CI 9.0–17.4) months; 1-year OS — 52.9±8.7%, 2-year — 22.4±8.8%.DISCUSSION: Using two- and three-fraction ASRS, we delivered doses to large BM sufficient for a high level of local control with an acceptable risk of neurotoxicity: 1-year local control was 91.4%; 2-year — 73.9%; the incidence of radionecrosis is 8.5%. A statistically significant effect of lesion volume ≥18.5 cm3 on the risk of local recurrence was found. The iPFS and OS indicators after ASRS can be considered satisfactory for this group of patients.CONCLUSION: ASRS is an effective and perhaps optimal strategy for the treatment of large unresectable BM in patients with NSCLC, but comparison with other modern radiotherapy modalities such as stereotactic hypofractionated radiotherapy and WBRT with simultaneous integrated boost is needed.

Infection Mortality in Acute Promyelocytic Leukemia in Children

Abstract Background Acute promyelocytic leukemia (APL) is a rare entity in children. The percentage of APL patients is 5-7% of all pediatric acute myeloid leukemia cases; a higher frequency (about 20%) is reported in children of Latino/Hispanic ancestry. The introduction of trans retinoic acid has been crucial for both antileukemic efficacy in APL and for prevention of early deaths. Furthermore, the use of arsenic trioxide (ATO) demonstrated to be highly effective in achieving high cure rates with reduced toxicity. However, there is a paucity of data concerning infection related deaths in APL. The objective was to describe the percentage of infection-related-deaths in APL in children; to describe the event free survival (EFS) and describe other main complications observed. Methods We identified 30 patients, as part of the Hospital Alejandro Posadas registry from a single center. We conducted a retrospective observational descriptive analysis. The patients were treated with the GIMEMA-AIDA 2000 protocol (n=23, 76.7%) and 1-LPA pediatrico-18-GALTA/CLEHOP (n=6, 20%). One patient died before treatment was given. The patients were diagnosed between 2000 to 2022. We used frequencies for descriptive variables, Chi2 /Fisher test for categorical data and time to event techniques for survival analysis. Any cause of mortality was extracted and analyzed. Results There were 66.7% of males; and median age was 12-year (IQR 8-15). PML-Rar alfa was positive (cytogenetics) in 23 (76.7%); Negative 6 (20%) and failed in 1 patient (3.3%). 100% had positive molecular biology for PML-rarAlfa transcript. Median white cells were 3.35x 109 /l (IQR 1.675-13.25). The patients were classified as high-risk (n=10, 33.3%) and standard risk (n=20, 66.7%). Four patients showed molecular relapse, 2 had CNS and one bone marrow involvement. Three patients died (10%), 2 due to endocranial hemorrhage, 1 as a consequence of complications of a hematological relapse. No patient died due to microbiologically documented infection or febrile neutropenia. With a mean estimated survival time (median not achieved) in years of 17.7 years, (CI 95% 14.6-20.7) the event free survival was 79% (SE 0.75), with 6 events. Cumulative competitive incidence of relapse 14% (SE 0.65). Conclusion In patients with APL, we could not find infections as cause of death. The overall results of APL management were very promising. Figure 1. Event Free Survival Acute Promyelocytic Leukemia.

Reduced Intensity Conditioning Prior Autologous Stem Cell Transplantation in Elderly DLBCL Patients.

High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is widely used in patients with diffuse large B-cell lymphoma. HDCT/ASCT is associated with increased morbidity in elderly/unfit patients. We retrospectively evaluated the use of reduced intensity conditioning in DLBCL patients. Our study included 146 patients aged 60 years and older treated at our institution between 2005 and 2019; 86 patients received standard intensity conditioning (SI group) with BEAM or TEAM (BCNU or thiotepa, etoposide, cytarabine, melphalan). Sixty patients received reduced intensity high-dose conditioning (RI group) with BM (BCNU, melphalan, 43.3%), TM (thiotepa, melphalan, 16.7%), BCNU or busulfan thiotepa (38.4%), or bendamustine melphalan (1.7%). Median follow-up was 62.4 months. We observed comparable toxicities in the SI and RI groups. The cumulative incidence of relapse at 3 years was higher in the RI group (30.8% vs. 23.4%, p = 0.034). There was no difference in nonrelapse mortality (NRM). In univariate analyses, SI vs. RI conditioning resulted in superior progression-free survival (PFS) (HR 1.80 CI 1.11-2.92, p = 0.017) but not in superior overall survival (OS) (HR 1.48 CI 0.86-2.56, p = 0.152). On multivariate analysis, we observed no difference in PFS (HR 0.74 CI 0.40-1.38, p = 0.345) and a trend toward better OS with RI conditioning (HR 0.45 CI 0.22-0.94, p = 0.032). Age 60-69 versus ≥ 70 years and remission prior to ASCT were the only factors predicting better PFS. Factors associated with better OS were RI conditioning, age 60-69 versus ≥ 70 years, ECOG 0 versus ≥ 1 performance status, bulky disease, and prior lines 1 versus ≥ 2. In conclusion, RI conditioning prior to ASCT may be feasible in elderly patients and led to a comparable outcome when corrected for several significant confounders.

Outcomes of haploidentical transplants with PT-CY vs 10/10 MUD transplants with ATG in Germany

AbstractAllogeneic stem cell transplantation (allo-HSCT) is the best curative treatment modality for many malignant hematologic disorders. In the absence of a matched related donor, matched unrelated donors (MUDs) and haploidentical donors (Haplo-Tx) are the most important sources of stem cells. However, multicenter real-life data that compare 10/10 MUD transplantations with Haplo-Tx are still limited. In this registry-based retrospective study, we compared the outcomes of allo-HSCTs from 10/10 MUDs with antithymocyte globulin (ATG)–based regimens (n = 7050) vs Haplo-Tx using posttransplant cyclophosphamide (PT-CY Haplo; n = 487) in adult patients with hematologic malignancies between 2010 and 2020. Cox proportional hazard models and competing risks regression models were formed to compare the outcomes of the groups. Overall survival (OS), Disease-free survival (DFS), and graft-versus-host disease (GVHD)–free and relapse-free survival (GRFS) were superior for 10/10 MUDs (OS [hazard ratio (HR), 1.27; confidence interval (CI), 1.10-1.47; P = .001]; DFS [HR, 1.17; CI, 1.02-1.34; P = .022]; GRFS [HR, 1.34; CI, 1.19-1.50; P < .001]). The risk of acute GVHD (aGVHD) grade 2 to 4, aGVHD grade 3 to 4, and chronic GVHD (cGVHD) was higher in the PT-CY Haplo group than the 10/10 MUD group (aGVHD grade 2-4 [HR, 1.46; CI, 1.25-1.71; P < .001]; aGVHD grade 3-4 [HR, 1.74; CI, 1.37- 2.20; P < .001]; cGVHD [HR, 1.30; CI, 1.11-1.51; P = .001]). A lower incidence of relapse was observed in the PT-CY Haplo group (relapse: HR, 0.83; CI, 0.69-0.99; P = .038). Unrelated 10/10 matched transplantation with ATG treatment leads to lower GVHD rates and improved survival rates compared with PT-CY Haplo transplantation in Germany.

RELAPSE AFTER ORTHODONTIC TREATMENT

Orthodontic treatment results are prone to relapse over time, which is the unfavorable change in position of teeth to its original position before orthodontic treatment. With that said, retention is an important part of almost every case of orthodontic treatment. There are many contributing factors to the incidence of a relapse. This article aims to explain the incidence and prevention of relapse after orthodontic treatment through reviewing literature published during 2012 to 2022 which discusses topics that are appropriate and related to relapse and retention. Sources were taken from textbooks, journals and websites that can be accessed through Google Scholar and PubMed databases. A total of 30 references were found, and 9 articles were included in the integrative review after further analysis. This article concludes that relapse is a common occurrence after orthodontic treatment because of gingival and periodontal factors, occlusal factors, soft tissue factors, hard tissue factors, and growth factors, and its prevention requires the use of retainers, either removable or fixed, depending on the case.

Incidence of Relapses After Meningococcal Vaccination in Clinical Trials of Eculizumab and Ravulizumab in Anti-Aquaporin-4 Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD)

Incidence of Relapses After Meningococcal Vaccination in Clinical Trials of Eculizumab and Ravulizumab in Anti-Aquaporin-4 Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD)

Measurable residual disease assessment prior to allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia and myelodysplastic syndromes: a 20-year monocentric study.

Patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) who undergo allogeneic hematopoietic stem-cell transplantation (alloHSCT) can have divergent survival outcomes while all in morphological complete remission (CR). Techniques of measurable residual disease (MRD) have allowed us to refine their prognosis in two categories: MRD-positive and MRD-negative patients. We conducted a monocentric retrospective study (01/2000-12/2020) to assess the prognosis of pretransplant MRD status measured by multiparametric flow cytometry (MFC) and molecular biology assessed by PCR. 192 patients were included. The median follow-up period was 77months. Among patients undergoing alloHSCT in CR, overall survival (median-OS: 130.6 vs. 16.0months, P < 0.001), disease-free survival (median-DFS: 109.6 vs. 7.1months, P < 0.001) and cumulative incidence of relapse (12-month CIR: 7.3% vs. 33.7%, P < 0.0001) were significantly different between MRD-negative and MRD-positive patients. Patients with discordant intermethod results had intermediate DFS. MRD-negative patients according to molecular PCR-based techniques, WT1 overexpression and MFC had longer median-DFS, compared to MRD-positive patients (P = 0.001, P < 0.001, P < 0.001, respectively). Looking into subgroups, MRD-positive patients among the ELN2017 adverse-category (P < 0.0001), myeloablative and reduced-intensity conditioning regimens (P < 0.0001, P = 0.005), < 60-year patients (P < 0.001) and AML patients (P < 0.001) were associated with lower DFS. This difference was not found in ≥ 60-year patients (P = 0.27) and MDS patients (P = 0.70). MRD-positive patients within the favorable/intermediate ELN2017 category trended toward lower DFS (P = 0.05). We confirmed that MRD status prior to alloHSCT is a strong prognostic factor for OS, DFS and CIR. Combining MFC and molecular-PCR techniques to assess MRD seems primordial as inter-method discordance can be consequential.

Measurable residual disease monitoring in AML with FLT3-ITD treated with intensive chemotherapy plus midostaurin

AbstractMeasurable residual disease (MRD) monitoring in acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITDpos]) has been hampered by the broad heterogeneity of ITD mutations. Using our recently developed FLT3-ITD paired-end next-generation sequencing (NGS)–based MRD assay with a limit of detection of 10−4 to 10−5, we evaluated the prognostic impact of MRD at different time points in 157 patients with FLT3-ITDpos AML who were enrolled in the AMLSG16-10 trial and who were treated with a combination of intensive chemotherapy and midostaurin, followed by midostaurin maintenance. Achievement of MRD negativity (MRDneg) after 2 cycles of chemotherapy (Cy2), which was observed in 111 of 142 (78%) patients, was predictive of superior 4-year rates of cumulative incidence of relapse (CIR) (4y-CIR; 26% vs 46%; P = .001) and overall survival (OS) (4y-OS; 70% vs 44%; P = .012). This survival advantage was also seen among patients who underwent allogeneic hematopoietic-cell transplantation during first complete remission (4y-CIR, 14% vs 39%; P = .001; 4y-OS, 71% vs 49%; P = .029). Multivariate models for CIR and OS after Cy2 revealed FLT3-ITD MRDneg as the only consistent favorable variable for CIR (hazard ratio [HR], 0.29; P = .006) and OS (HR, 0.39; P = .018). An NPM1 co-mutation correlated with a deeper molecular response as reflected by stronger MRD reduction and a higher rate of FLT3-ITD MRDneg after Cy2. During follow-up, conversion from MRDneg to MRDpos was a strong, independent factor for inferior CIR (HR, 16.64; P < .001) and OS (HR, 4.05; P < .001). NGS-based FLT3-ITD MRD monitoring allows for the identification of patients at high risk for relapse and death following treatment with intensive chemotherapy and midostaurin. Using NGS-based technology, FLT3-ITD emerges as a novel, highly clinically relevant target for MRD monitoring. This trial was registered at www.ClinicalTrials.gov as #NCT01477606.

Outcome of patients with diffuse large B-cell lymphoma and testicular involvement - real world data.

Patients with testicular lymphoma are at an increased risk of central nervous system (CNS) disease. Optimal strategy for CNS relapse prevention is unknown. We analyzed treatment strategies, cumulative incidence of CNS relapse and prognosis in 229 patients with diffuse large B-cell lymphoma (DLBCL) and testicular involvement: 157 primary testicular lymphomas (PTL) in clinical stages IE/IIE and 72 patients in advanced stages (T-DLBCL) IIIE/IV. Treatments for PTL vs. T-DLBCL included: rituximab-based chemotherapy (80.9% vs. 90.3%), orchiectomy (94.3% vs. 65.3%) and contralateral testicular irradiation (59.8% vs. 44.4%). Majority (84.3%) received CNS prophylaxis with similar rates of prophylactic methotrexate (intravenous 19.1% vs. 16.6%, intrathecal 40.8% vs. 40.4%, or both 24.2% vs. 27.8%) between PTL and T-DLBCL (p = 0.89). Median follow-up was 51.8 months. CNS relapses occurred in 14 (6.1%) of 63 relapsing patients. The 5-year cumulative incidence of CNS relapse in PTL was 4.5% and in T-DLBCL 12.1%. Median time to CNS relapse was 21.9 months. In univariate analyses, orchiectomy was the single significant factor associated with lower risk of CNS relapse in PTL (HR = 0.11 [95% CI, 0-0.124], p = 0.001). Rituximab significantly reduced CNS relapse risk in T-DLBCL (HR = 0.1002, p = 0.0005). Median progression-free survival (PFS) and overall survival (OS) following CNS relapse was dismal in T-DLBCL compared to PTL (PFS 1.6 vs. 37.8 months, p = 0.04 and OS 2.3 vs. 37.8 months, p = 0.05). This study confirmed a favorable impact of rituximab in prevention of CNS relapse in T-DLBCL. Methotrexate prophylaxis did not alter CNS relapse risk. Prognosis of CNS relapse is particularly poor in T-DLBCL.

The real-world use and effectiveness of avacopan in routine practice for the treatment of ANCA vasculitis. First experiences in Spain.

ANCA-associated vasculitis (AAV) are chronic diseases with relapses that associate organic damage because of the disease and its treatment. Avacopan is a new treatment indicated for AAV. We present the first experiences with avacopan in Spain as part of an Early Access program. Patients with AAV who started avacopan between June 2022-September 2023 were included. For comparison, a historical cohort of patients diagnosed with AAV around the same time and treated without avacopan was also included. 29 patients treated with avacopan were analyzed. Twelve patients (41.4%) were male, median age was 56 years. Most of patients were ANCA MPO positive (21/29, 72.4%). The most frequently affected organ was the kidney (23/29, 79.31%), with a mean eGFR of 23.2 ml/minMedian follow-up was 456.8 ± 181.7 days with a remission rate of 86.2%. eGFR increased from 23.2 ± 11.2-38.38 ± 18.55 ml/min after 12 months of diagnosis.2 patients had Adverse Events related to avacopan as severe neutropenia and a gastrointestinal affectation , 13 infections were reported and 1 death.Patients treated with avacopan received a significantly lower cumulative dose of prednisone at 6 and 12 months (p-values of 0.02 and <0.01, respectively) compared with historical controls. The evolution of GFR at 1 year of follow-up and the incidence of relapse were similar in both groups. The combination of avacopan in clinical practice presents a good safety profile and provides added value by contributing to the control of AAV activity, increase GFR, and removal of steroids.