Relapse Pattern in Club Foot Treated with Ponseti Technique - A Prospective Observational Study from Kerala, India

BACKGROUND Though the Ponseti method has become the popular and standard of care for clubfoot correction, relapse of clubfoot deformity following correction is not uncommon. The relapsed feet can progress from flexible to rigid if left untreated and can become as severe as the initial deformity. The purpose of this study was to analyse the relapse pattern in clubfeet that have undergone treatment with the Ponseti method. METHODS Between 2015 and 2017, 78 children (134 feet), 58 boys and 20 girls were included in this study. It was a prospective observational study of relapse patterns in idiopathic clubfoot after one year of completion of the Ponseti method of treatment. Pirani scoring system was used to identify the relapse. RESULTS Dynamic, fixed, and complete relapse patterns were observed in this study. Patients were categorised into two groups - bilateral and unilateral. In the bilateral group, 18 children (36 feet i.e. 23 %) had decreased ankle dorsiflexion, 5 had (10 feet i.e. 6 %) rigid equinus, 22 had (44 feet i.e., 29 %) dynamic forefoot adduction or supination and 5 had (10 feet i.e. 6 %) fixed adduction in forefoot and midfoot. Six children from the bilateral group showed complete relapse. Among the unilateral group, 8 children (8 feet i.e. 36 %) presented with decreased ankle dorsiflexion, 4 had (4 feet i.e. 18 %) rigid equinus relapse, 6 had (6 feet i.e. 27 %) dynamic forefoot adduction or supination and 4 had (4 feet i.e. 18 %) showed fixed forefoot adduction. CONCLUSIONS Dynamic forefoot adduction or supination pattern is common to relapse pattern in the bilateral group and dynamic hind-foot relapse was common in the unilateral group. Age at initial presentation, initial Pirani score, and the number of casts required were not significantly related to the incidence of relapse. KEYWORDS Club Foot, CTEV, Ponseti Method, Relapse Pattern

Prognostic Implications of Epilepsy Onset Age According to Relapse Pattern in Patients with Four-Year Remission

A total of 472 epilepsy patients with a 4-year remission period were divided into 10-year age groups according to age of onset. The relapse patterns during at least 3 years of follow-up were classified as early relapse (ER), late relapse (LR), and seizure-free (SF). The remission probability and multiplicity of prognostic factors were evaluated using univariate and multivariate multinomial logistic analyses. The weighted risk score based on odd ratios (ORs) was used for comparisons of the relative risk of relapse between groups. The group with onset in their 20s had the lowest remission probability among the groups. The risks of relapse in the LR patients and the relative weighted risk score of ER patients in the group with onset in their 20s were 3.11 and 19.44, respectively, which was the highest risk among the age groups. Patients without remission within 1 year had the highest relapse risk, with an OR of 7.18 in ER patients. The OR of relapse in patients with >10 generalized tonic–clonic (GTC) seizures was the second most important prognostic factor in LR patients. The distinct risk and corresponding prognostic factors in LR and ER patients reflected inherent differences between these relapse patterns.

GCT-38. RELAPSE PATTERNS OF INTRACRANIAL GERMINOMAS BEFORE AND AFTER ENDOSCOPIC ERA

PURPOSE We evaluated the relapse patterns of CNS germinomas before and after introducing neuroendoscopic biopsy in 2000. METHODS We retrospectively assessed the relapse patterns of 57 patients treated as pure germinoma or germinoma with STGC between 1980 and 2019 at University of Tsukuba, partially containing the patients of the previous report (Takano S et al., World Neurosurg, 2015). Median age was 15 y.o.(7y.o.~38y.o.), and men was 80.7%. Tumor locations were pineal 35, sellar 19, basal ganglia 3, others 11. Group A;1980~1999 was 20, and group B;2000~2019 was 37. From 1980 to 1994, whole brain irradiation(WB) 30.6 Gy plus whole ventricle irradiation(WV) 19.8 Gy. From 1995 to 1999, WV 26~30.6 Gy with Chemotherapy(Chem) or Chem alone. Since 2000, Chem for 3 kurr with WV 24~30.6 Gy, and 6–19.8 Gy as local boost to residual lesion. RESULTS Follow up periods were median 121 M(4.5M~386M; group A), and median 89 M(4 M~231 M; group B). Six patients(30%) recurred in the group A, as ex field 4(1;brain and extramedullary, 1;brain and paranasal sinus, 1;LV & third ventricle, 1;extramedullary), in field 1(LV). Chem only 1(LV & third ventricle). Two patients(5.4%) recurred in the group B, as ex field 2(1;intramedullary, 1;extramedullary). The group A showed CR;18, PR;1, Dead;1(Dissemination), and the group B showed CR;35, PR;1 Dead;1(Encephalopathy). CONCLUSION WV and Chem prevented extrafield recurrence keeping good quality of life. Neuroendscopy biopsy with ETV did not increase CSF seeding.

Characterization of relapse patterns in patients with acute lymphoblastic leukemia treated with blinatumomab

Introduction Blinatumomab is a CD19/CD3 bispecific T-cell engager (BiTE) antibody that simultaneously binds CD19 on the surface of B-cells and CD3 on the surface of T-cells, resulting in tumor cell lysis. It is approved for the treatment of patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and in patients with minimal residual disease after intensive induction chemotherapy. Relapse patterns after treatment with blinatumomab have not been well characterized. Methods We reviewed patients treated with blinatumomab with relapsed, refractory or minimal residual disease-positive B-ALL from 1 December 2014 to 31 December 2018 at a single academic medical center. Patient demographics, blast percentage prior to blinatumomab initiation, prior lines of therapy, blinatumomab treatment duration, sites of relapse, progression free survival, and overall survival were collected. Results A total of 20 patients were identified. Four (20%) patients developed extramedullary relapse following blinatumomab. The median time from treatment initiation to extramedullary relapse was 179 days (range 47–241). Sites of extramedullary relapse included the pancreas, adrenal gland, kidneys, liver, parotid gland, and brain. Conclusion Extramedullary relapse occurs frequently following treatment of B-ALL with blinatumomab. Further studies aimed at preventing extramedullary relapse following blinatumomab treatment are warranted.

Paired Analyses of AML at Diagnosis and Relapse By Single-Cell RNA Sequencing Identifies Two Distinct Relapse Patterns

Introduction: Despite achievement of complete remission (CR) following chemotherapy, Acute Myelogenous Leukemia (AML) relapses in the majority of adult patients. While relapsed AML is almost always clonally related to the disease at diagnosis, the actual molecular and cellular contributors to chemotherapy resistance and to AML relapse remain incompletely understood. Some molecular determinants of relapse have been identified in genomic, epigenetic and proteomic aberrations, while cellular relapse reservoirs have been identified in leukemia stem cells as well as in more mature leukemic cell compartments. Here, we set out to determine the cellular composition, gene mutation status and gene expression of paired AML specimens procured at diagnosis and at relapse aiming at a better understanding of the AML relapse process. Methods: We employed the drop-seq 3' single cell RNA sequencing (scRNA-seq) method (Macosko 2015) with minor modifications to analyze the mRNA expression in single cells derived from 12 paired AML specimens procured at diagnosis and at relapse from prior CR. We obtained scRNA-seq data on 1000-2000 single cells per sample detecting approximately 2000-3000 unique molecular identifiers (UMIs) and 800-1500 genes per cell. Using WES or panel-based sequencing we determined mutations in known driver genes. Subsequently, we optimized novel methods for detection and mapping of mutated driver genes to individual cells using mutation specific PCR conditions and novel bioinformatics approaches. We annotated scRNA-seq expression profiles of the diagnosis and relapsed AML specimens individually using publicly available data for cell type-specific RNA markers derived from sorted normal cell populations and further compared the scRNA-seq data to scRNA-seq data of 5 pooled normal human bone marrows generated for this study. Results: Through analyses of scRNA-seq data of paired diagnosis and relapse AML specimens via principle components analyses (PCA) or t-distributed stochastic neighbor embedding (t-SNE) we detected varying degrees of separation of cell clusters in all cases analyzed indicative of substantial changes in single cell gene expression between AML diagnosis and relapse. A few of these observed cluster shifts were paralleled by gain or loss of mutated genes (e.g. FLT3-ITD) at relapse while most others lacked obvious clonal genomic markers. Through subsequent comparison of the expression similarities of single AML cells to sorted normal human bone marrow cells we detected two distinct AML relapse patterns: i) a pattern of relapse suggesting simple leukemia regrowth as evidenced by similar proportions of leukemia cells mapping onto discrete normal bone marrow cells (e.g. monocyte-like or GMPs or CMPs), and, ii) a pattern of relapse whereby the gene expression of relapsed cells (but not diagnosis cells) had similarity to normal hematopoietic cells that are conventionally placed more apical in the classical hematopoiesis differentiation cascade (HSCs, MPPs, CMPs; a phenotypic shift to immaturity). In addition, no leukemia sample mapped to just one classically defined bone marrow cell type but instead to multiple cell types, suggesting that most AML leukemia cells harbor aberrant hybrid cell gene expression patterns. Finally, we detected quantitative shifts in T cells and NK cells in some samples at relapse, which will be analyzed in greater detail. Conclusions: The comparative analysis of scRNA-seq data of paired AML specimens procured at diagnosis and relapse, identifies frequent and previously unrecognized changes in gene expression in leukemia cells at relapse. Through a comparison of gene mutation and gene expression at single cell resolution we identify two distinct AML relapse patterns in adult AML. Disclosures No relevant conflicts of interest to declare.