SEARCH · PubMed Health

Results for “relapsed disease”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2026

Longitudinal analysis of circulating tumor DNA and CA19-9 dynamics in predicting disease relapse and monitoring treatment response in stage I-III pancreatic ductal adenocarcinoma: An interim analysis of a prospective observational study.

INTRODUCTION: Postoperative recurrence is the leading cause of mortality in resected pancreatic ductal adenocarcinoma (PDAC), yet reliable tools for early relapse detection and treatment response assessment remain lacking. METHODS: In a prospective cohort of 136 patients with resected stage I-III PDAC receiving adjuvant chemotherapy, we evaluated circulating tumor DNA (ctDNA) and CA19-9 as longitudinal biomarkers across multiple postoperative time windows. RESULTS: ctDNA consistently outperformed CA19-9 as an independent prognostic factor; ctDNA positivity at on-treatment and surveillance assessments achieved a positive predictive value of 91.7%, while persistent negativity identified the lowest-risk patients. Integrating CA19-9 with ctDNA resolved the ctDNA-alone gap in distinguishing treatment clearance from conversion, improving discrimination of responders from non-responders (HR 3.72; P = .008). A time-weighted dynamic ctDNA risk score (MinerVa-dynamic) further stratified ctDNA-negative patients into clinically distinct prognostic subgroups, achieving an area under the curve of 0.87 and 0.82 for one- and two-year disease-free survival prediction, respectively. CONCLUSIONS: These findings support a dual-biomarker longitudinal monitoring framework as a practical, individualized approach to postoperative surveillance and early therapeutic decision-making in PDAC.

CA19-9↗

PubMed1978

Immune competence in a patient with Hodgkin's disease and relapsing toxoplasmosis.

A 40 year old woman with Hodgkin's disease twice developed signs of encephalitis while being treated with prednisone and cyclophosphamide for 10 months. Since on both occasions her Toxoplasma dye test titer was 1 : 8000 or higher, she was treated on suspicion of toxoplasmosis with sulfadizine and pyrimethamine. Her tumor therapy was changed to bleomycin with lower doses of prednisone for 12 months. After death from central pontine myelinolysis, Toxoplasma and cytomegalovirus could be isolated, but no lesions attributable to these infectious agents were present. Maintenance of the patient's immune competence suggested an inquiry into the effects of the chemotherapeutic agents and of tumor infiltration for their respective interference with immunity. Using hamsters with chronic latent toxoplasmosis, it was found that both cortisone and cyclophosphamide caused recrudescence of chronic inapparent infection, that vinblastine and bleomycin interfered only slightly with the development of immunity, whereas in infiltrating lymphoma permitted immunity to develop normally. It is concluded that greater attention should be directed to the immunosuppressive effects of tumor treatment. By choice of an effective tumor therapy which is least immunosuppressive, and if necessary under cover of antimicrobial therapy, a patient with Hodgkin's disease can be aided in developing immunities which he may subsequently be able to maintain.

Adult↗

PubMed1979

The Princess Margaret Hospital study of ovarian cancer: stages I, II, and asymptomatic III presentations.

An analysis of 231 patients with stages I, II, and asymptomatic III ovarian cancer, studied in a prospective randomized-stratified trial, is presented. None of the stage IA patients with well-differentiated tumors have had disease relapses; one fourth of the patients with poorly differentiated tumors have had disease relapses throughout the peritoneal cavity. There is therefore little justification for pelvic radiation alone as postoperative therapy for stage IA ovarian carcinoma. For stage IB, II, and asymptomatic III presentations, patients with an incomplete initial pelvic operation had poor survival characteristics with all tested therapies. For patients in whom the operation was completed, abdominopelvic radiation was superior to pelvic radiation alone or followed by chlorambucil, with respect to long-term survival and control of abdominal disease. The effectiveness of abdominopelvic radiation was independent of stage or histology. The value of abdominopelvic radiation was most strikingly seen in patients with no visible residual tumor.

Cell Differentiation↗

PubMed1978

Biochemical markers in Hodgkin's disease and non-Hodgkin's lymphoma.

Vertical studies indicate that, in general, acute phase reactant proteins (APRP) reflect disease activity in both Hodgkin's disease and non-Hodgkin's lymphoma. Longitudinal studies of the selected APRP profile demonstrate the following: 1. The stable profile is characteristic of remission. 2. Considerable elevation of APRPs coincides with relapsed disease. 3. An unstable profile is a feature of relapsing disease and may give early warning of relapse. 4. Patients responding inadequately to treatment frequently have unstable APRP profiles.

Adult↗

PubMed1977

Reversible gonadotropin deficiency in male Cushing's disease.

Twelve adult males with documented active Cushing's disease were studied. Mean plasma testosterone (T) was significantly decreased: 1.8 +/- 0.3 (SEM) ng/ml (N=6.8 +/- 0.5); gonadotropin measurements in 8 patients, in basal conditions and under LH-RH iv, showed a significant decrease in both FSH and LH. A further study of 11 patients in remission of Cushing's disease indicated a significant increase in plasma T and gonadotropins up to the normal range. One patient with an initial low T value had a normalized T while in remission, then a dramatic decrease when the disease relapsed. We conclude: a hypogonadotropic hypogonadism is found in male Cushing's disease; it disappears as early as hypercortisolism is suppressed. Some possible mechanisms are discussed.

Adolescent↗

PubMed1977

Terminal deoxynucleotidyltransferase distribution in neoplastic and hematopoietic cells.

In the present study, terminal deoxynucleotidyltransferase was examined in the peripheral blood and (or) bone marrow of 115 children with a variety of neoplastic, hematologic, and other unrelated disorders. Terminal deoxynucleotidyltransferase activity was present at 4.08+/-0.74 U/108 cells in 23 morphologicall normal bone marrow samples from childhood controls. Terminal transferase was present at greater than 23 U/108 nucleated cells and at greater than31 U/108 blasts in the bone marrow of all children with acute lymphoblastic leukemia studied at initial diagnosis and at disease relapse. Terminal deoxynucleotidyltransferase was detectable at low levels, less than 7.5 U/108 cells, in all remission marrow smaples. Bone marrow terminal transferase activity was markedly elevated in all untreated acute lymphoblastic leukemia patients, whereas low levels which were difficult to interpret were present in the peripheral blood samples of two patients at diagnosis and six patients at relapse who had low absolute lymphoblast counts. Because of greater variation in the lymphoblast content of peripheral blood, bone marrow assays are more reliable in detecting disease activity. Marrow terminal deoxynucleotidyltransferase values obtained during the active phase of acute lymphoblastic leukemia were significantly greater than those found in other types of leukemia, bone marrow malignancies, and hematologic disorders. Terminal transferase determinations in blast cells of two patients with leukemic conversion of non-Hodgkin's lymphoma and in tumor cells from one patient with Burkitt's lymphoma were within the control range. These dat further define the usefulness of terminal deoxynucleotidyltrnasferase assay in the differentiation and classication of hematologic malignancies.

Adolescent↗

PubMed2026

KIT and FLT3-ITD mutations do not predict outcomes in pediatric core-binding factor acute myeloid leukemia: findings from the C-HUANAN-AML-15 multicenter cohort study.

Although core-binding factor acute myeloid leukemia (CBF-AML) is generally considered a favorable-risk subtype in children, disease relapse remains a significant concern. The prognostic relevance of co-occurring mutations, particularly KIT and FLT3-ITD, remains debatable, and treatment intensity may modulate their impact. This multicenter analysis included 289 children (< 14 years) with newly diagnosed CBF-AML enrolled in the C-HUANAN-AML-15 study (2015-2023). KIT and FLT3-ITD mutations were identified via cytogenetic analysis and targeted sequencing. Measurable residual disease (MRD) was evaluated by multiparameter flow cytometry (MFC) and quantitative polymerase chain reaction (PCR) following induction chemotherapy. Survival analyses were performed using Kaplan-Meier and Cox regression methods. This multicenter analysis included 289 children (< 14 years) with newly diagnosed CBF-AML enrolled in the C-HUANAN-AML-15 study (2015-2023). KIT and FLT3-ITD mutations were identified via cytogenetic analysis and targeted sequencing. Measurable residual disease (MRD) was evaluated by multiparameter flow cytometry (MFC) and quantitative polymerase chain reaction (PCR) following induction chemotherapy. Survival analyses were performed using Kaplan-Meier and Cox regression methods. KIT mutations were detected in 103 patients (35.6%), predominantly involving exon 17 (69.9%), and were associated with extramedullary disease, sex chromosome loss, and trisomy 22. No significant differences in 5-year event-free survival (EFS), overall survival (OS), or cumulative incidence of relapse (CIR) were observed between patients with and without KIT mutations. FLT3-ITD mutations (5.5% of patients) did not adversely affect outcomes. Neither mutation independently predicted survival. MRD positivity (MFC-MRD ≥ 0.1%) after the second induction cycle strongly predicted inferior EFS and OS and higher CIR, with corresponding results observed for molecular MRD and parallel findings for PCR-based MRD. In this large multicenter cohort, KIT and FLT3-ITD mutations did not adversely affect the prognosis of pediatric CBF-AML treated according to the C-HUANAN-AML-15 protocol. MRD after induction was the most powerful predictor of relapse and survival, underscoring its importance for risk stratification in future pediatric AML trials.

Humans↗

PubMed1976

Corticotropin and corticosteroids in generalized myasthenia gravis: comparative studies and role in management.

The effect of 310 courses of corticotropin, methylprednisolone, prednisone, and dexamethasone were studied in 62 patients with generalized myasthenia gravis who were poorly responsive to anticholinesterase medication and most of whom required assisted respiration. Improvement in strength and response to anticholinesterase medication occurred in 91% of the courses, and was moderate or marked in 63%. The incidence, degree, and duration of improvement appeared to be dose related. High doses of dexamethasone (20 mg orally each day for 10 days, repeated if necessary), which had 75% more glucocorticoid effect than any other regimen studied, produced the highest incidence of both improvement (100%) and moderate-to-marked improvement (75%), and the greatest duration of improvement (more than 3 months after 40% of the courses). The duration of improvement following intensive courses of any of the corticosteroids was approximately doubled by the subsequent administration of smaller doses of dexamethasone or prednisone on alternate days. Most patients with severe disease relapsed after 3 to 6 months of corticosteroid treatment, but increase in the dose of corticosteroid, and daily administration, which was more effective than alternate-day administratin, almost always again resulted in improvement. Corticotropin and corticosteroids were equally effective before and after thymectomy. High doses of corticotropin and corticosteroid produced an initial exacerbation of the disease in 80% of the courses, which was moderate or marked in 57%. Reduction in dose reduced the incidence of severe exacerbation, but did not prevent it, and also resulted in slower and less marked improvement. Withholding anticholinesterase medication did not prevent exacerbation or increase improvement, and afforded no advantage, though it was usually helpful to reduce the dose of this medication. Because of the hazard of initial exacerbation and the occurrence of other serious side effects in 15% of the patients. (bleeding ulcer, vertebral compression, aseptic necrosis of the femoral head or tibia, and subcapsular cataracts), it is recommended that corticosteroid treatment be limited to myasthenic patients who are not responding satifactorily to anticholinesterase medication, that smaller doses be employed in patients whose disease is not life threatening, and that higher doses be reserved for patients who are critically ill and are being managed, at least initially, in an intensive care unit.

Adolescent↗

PubMed2026

Independent prognostic value of semaphorin-4D, interleukin-1β and complement activation in newly diagnosed multiple myeloma patients.

Multiple myeloma represents a systemic disease of the bone marrow (BM) niche, in which immune and skeletal pathways are tightly interconnected. However, the independent prognostic significance of bone and immune-related markers in newly diagnosed multiple myeloma (NDMM) remains incompletely understood. Semaphorin (Sema) 4D, activin-A, and periostin ELISA, LEGENDplex™ Human Bone Metabolism Panel and proteomic analysis for novel biomarker identification were conducted in 71 consecutive samples from NDMM patients. In 25 patients, genomic analysis was performed on sorted clonal plasma cells. NDMM patients had a median age at diagnosis of 65 years and a median follow-up of 2.5 years. Interleukin (IL)-1β and Sema4D levels predicted progression-free survival (PFS), highlighting their role in disease relapse. Proteomic profiling revealed a systemic signature associated with worse prognosis, enriched in complement activation components. Complement C5 significantly affected PFS and time to progression (TTP). IL-1β and C5 predicted PFS independently of the second revision of the International Staging System (R2-ISS) stage, and a similar trend was noted for Sema4D. Myeloma bone disease (MBD) did not significantly affect overall survival, PFS, or TTP, suggesting that contemporary treatments mitigate its impact. Genomic analyses identified variants associated with inferior PFS, including HLA-DRB5 (c.300_306delinsCGGG) and HLA-DQB1 (c.317_319delinsCGG). Sema4D and the IL-1β-complement cascade emerged as key drivers of disease progression, independent of R2-ISS stage, representing potential prognostic and therapeutic targets in NDMM.

Journal Article↗

PubMed2025

Mutagenic Impact and Evolutionary Influence of Chemoradiotherapy in Hematologic Malignancies.

UNLABELLED: Ionizing radiotherapy (RT) is a widely used treatment strategy for malignancies. In solid tumors, RT-induced double-strand breaks lead to the accumulation of insertion-deletions (indels; ID), and their repair by nonhomologous end joining has been linked to the ID8 mutational signature in surviving cells. However, the extent of RT-induced mutagenesis in hematologic malignancies and its impact on their mutational profiles and interplay with commonly used chemotherapies has not yet been explored. In this study, we interrogated 580 whole-genome sequence (WGS) samples from patients with large B-cell lymphoma, multiple myeloma, and myeloid neoplasms and identified ID8 only in relapsed disease. Yet ID8 was detected after exposure to both RT and mutagenic chemotherapy (i.e., platinum and melphalan). Using WGS of single-cell colonies derived from treated lymphoma cells, we revealed a dose-response relationship between RT and platinum and ID8. Finally, using ID8 as a genomic barcode, we demonstrate that a single RT-surviving cell may seed distant relapse. SIGNIFICANCE: RT and the ID8 indel signature are related, but their genomic impact on hematologic malignancies is unclear. Leveraging WGS, we linked ID8 to both RT and mutagenic chemotherapy and validated that platinum can induce ID8. We used ID8 as a genomic barcode to reveal that RT-resistant cells may seed systemic relapse.

Humans↗

PubMed2025

Biallelic antigen escape is a mechanism of resistance to anti-CD38 antibodies in multiple myeloma.

Monoclonal antibodies targeting CD38 are a therapeutic mainstay in multiple myeloma (MM). Although they have contributed to improved outcomes, most patients still experience disease relapse, and little is known about tumor-intrinsic mechanisms of resistance to these drugs. Antigen escape has been implicated as a mechanism of tumor-cell evasion in immunotherapy. Yet, it is unknown whether MM cells can develop permanent resistance to anti-CD38 antibodies by acquiring genomic events leading to biallelic disruption of the CD38 gene locus. Here, we analyzed whole-genome and whole-exome sequencing data from patients 701 newly diagnosed MM, 67 patients at relapse with naivety to anti-CD38 antibodies, and 50 patients collected at relapse after anti-CD38 antibodies. We report a loss of CD38 in 10 of 50 patients (20%) after CD38 therapy, 3 of whom exhibited a loss of both copies. Two of these cases showed convergent evolution in which distinct subclones independently acquired similar advantageous variants. Functional studies on missense mutations involved in biallelic CD38 events revealed that 2 variants, L153H and C275Y, decreased binding affinity and antibody-dependent cellular cytotoxicity of the commercial antibodies daratumumab and isatuximab. However, a third mutation, R140G, conferred selective resistance to daratumumab, while retaining sensitivity to isatuximab. Clinically, patients with MM are often rechallenged with CD38 antibodies after disease progression and these data suggest that next-generation sequencing may play a role in subsequent treatment selection for a subset of patients.

Humans↗

PubMed1977

The role of radiation therapy in localized resectable intestinal non-Hodgkin's lymphoma in children.

Forty children with localized resectable intestinal non-Hodgkin's lymphoma were seen between 1948 and 1974. Survival was related to the extent of disease at presentation and to therapy. No deaths occurred after 15 months and no recurrences occurred after 13 months after diagnosis. Six of eight stage IE patients (75%) and nine of 29 stage IIE patients (31%) have survived a minimum of 2 years; one of the three stage IVE patients has survived 17 years. Unfavorable prognostic findings at surgery were serosal involvement, presence of tumor at the surgical margins, mesenteric nodal involvement, and the presence of abdominal fluid or blood. Paraortic nodal involvement or multiple primary foci were universally fatal. Eight of 11 patients (73%) treated with surgery and whole abdominal irradiation (greater than or equal 2000 rad) with or without chemotherapy have survived. Seven of 18 patients (39%) treated with surgery and low dose chemotherapy have survived. One of seven patients treated with surgery and localized or low dose radiation therapy with or without chemotherapy has survived. Four patients treated with surgery alone died. Bone marrow and central nervous system involvement occurred after previous disease relapse elsewhere.

Adolescent↗

PubMed2026

Therapy induced senescence promotes immunogenicity in acute myeloid Leukemia through reduced EZH2 activity.

Chemotherapy resistance and disease relapse are major determinants of treatment failure in acute myeloid leukemia (AML). Therapy-induced senescence (TIS) is one outcome of chemotherapy, but its immunological consequences in AML remain unclear. Here we show that ex vivo chemotherapy induces senescence in a subset of therapy-naïve AML samples. TIS is marked by elevated interferon signaling, upregulation of human leukocyte antigen (HLA) class I and II molecules, and increased presentation of leukemia- and senescence-associated peptides, conferring AML cells antigen-presenting cell-like features. These changes enhance autologous CD4+ and CD8+ T cell responses against AML, both ex vivo and in patient-derived xenograft models. TIS also restores AML sensitivity to immune checkpoint blockade therapy. Mechanistically, we identify reduced Polycomb Repressive Complex 2 (PRC2) activity as central to TIS induction and its immunogenicity. PRC2 inhibition reactivates senescence-related genes and HLA expression in non-senescent AML cells, enabling T cell activation. These findings uncover a senescence-driven immune mechanism with potential to improve therapy outcomes in AML.

Humans↗

PubMed2025

Identification of multicohort-based predictive signature for NMIBC recurrence reveals SDCBP as a novel oncogene in bladder cancer.

BACKGROUND: Despite surgical and intravesical chemotherapy interventions, non-muscle invasive bladder cancer (NMIBC) poses a high risk of recurrence, which significantly impacts patient survival. Traditional clinical characteristics alone are inadequate for accurately assessing the risk of NMIBC recurrence, necessitating the development of novel predictive tools. METHODS: We analyzed microarray data of NMIBC samples obtained from the ArrayExpress and GEO databases. LASSO regression was utilized to develop the predictive signature. We combined gene signature and clinicopathological factors to construct a clinical nomogram for estimating NMIBC recurrence in a local cohort. Finally. the biological functions and potential mechanisms of SDCBP in bladder cancer were investigated experimentally in vitro and in vivo. RESULTS: An 8-gene signature was developed, and its efficiency for predicting NMIBC recurrence was evaluated using Kaplan-Meier and time-dependent ROC curves in both training and validation datasets. Immunohistochemical testing revealed elevated levels of ACTN4 and SDCBP in recurrent NMIBC tissues. We integrated the two proteins with clinical factors to develop a nomogram model, which showed superior accuracy compared to individual parameters. Gene Set Variation Analysis and Gene Set Enrichment Analysis unveiled SDCBP exerted cancer-promoting biological processes, such as angiogenesis, EMT, metastasis and proliferation. Experimental procedures demonstrated that silencing SDCBP attenuated cell growth, glucose metabolism and extracellular acidification rate, accompanied by decreased expression of p-AKT, p-ERK1/2, LDHA and Vimentin. CONCLUSIONS: The established 8-gene signature holds promise as a tool for predicting NMIBC recurrence, while targeting SDCBP may represent a potential strategy for delaying disease relapse.

Urinary Bladder Neoplasms↗

PubMed1979

The pattern of spread and treatment of metastases in testicular seminoma.

The results of treatment of 199 patients referred to the Royal Marsden Hospital with testiclar seminoma from 1963 to 1975 are described. Of 190 previously untreated patients 16 (8.4%) have died of seminoma, 3 (1.5%) of teratoma and 9 (4.9%) of intercurrent disease. Of 121 Stage I patients the only death was due to a second testicular tumour. In orchiectomy and volume of abdominal node metastases. This was not, however, prognostically significant. Death from seminoma occurred in 6 out of 38 patients (15.8%) with nodal metastases less than or equal to 5 cm in diameter and 3 out of 16 patients (18.7%) with metastases greater than 5 cm in diameter; 2 of 8 Stage III patients died of seminoma. Thus radiation controlled nodal metastases in more than 80% of Stage I, II and III patients. In Stage IV patients and patients referred with disease relapse, 12 out of 16 patients died of seminoma. Chemotherapy experience is briefly reviewed. Cyclophosphamide as a single agent has produced a 50% response rate. There is no evidence to suggest a radiation-related increase in mortality from the group of long-term tumour-free survivors.

Castration↗

PubMed1979

Cytogenetic remission in a Ph1-positive case of chronic myelogenous leukaemia.

Unusual cytogenetic findings in a case of chronic myelogenous leukaemia in the course of an aplastic crisis induced by busulfan therapy are reported. The proportion of Ph1-positive cells in bone marrow aspirates fell from 100% before treatment to 8.6% following aplasia. It increased gradually during recovery, and normal cells still represented 25.7% of the metaphases 20 months later. After a 38-months' remission without therapy the disease relapsed and the Ph1 chromosome was found in 100% of the bone marrow cells.

Adult↗

PubMed1979

Clonal identification in acute lymphoblastic leukemia.

In a case of acute lymphoblastic leukemia, two distinct types of leukemia blast cells could be identified throughout the course of the disease. The initially dominant type of blast cell was sensitive to chemotherapy; the other was drug-resistant, gradually becoming dominant as the disease progressed. The cell types could be clearly separated by their morphologic and surface membrane marker characteristics. The same chromosomal constitution was present in both types of blast cells, indicating a common clonal origin. Additional chromosomal abnormalities were present in the later stages of the disease, demonstrating that a distinct subclone had proliferated. This study illustrates that in some cases of acute leukemia, disease relapse is caused by growth of drug-resistant subclones that may be clearly identified by changes in morphology and surface membrane marker characteristics.

Adult↗

PubMed1979

Role of plasma carcinoembryonic antigen in evaluating patients with breast cancer treated with adjuvant chemotherapy.

Serial plasma carcinoembryonic antigen (CEA) levels were determined in 84 patients with breast cancer who were receiving postsurgical adjuvant chemoimmunotherapy or adjuvant chemotherapy. CEA values were correlated with clinical status, scintiscans, alkaline phosphatase, LDH, and SGOT. CEA values greater than 2.5 ng/ml were considered abnormal. Thirty patients had normal serial CEA values; all remain disease-free. In 54 patients one or more abnormal CEA values were recorded; nine of 54 developed overt metastatic disease. Relapses occurred in four of 38 patients in whom values up to 5 ng/ml were recorded, in three of 14 patients in whom values up to 10 ng/ml were recorded, and in two of two patients in whom values greater than 10 ng/ml were recorded.

Antineoplastic Agents↗