RESUMEN
Objective: To observe the treatment response of a two-dose regimen of inotuzumab ozogamicin (inotuzumab), a monoclonal antibody targeting CD22, for patients with heavily treated relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), including those failed or relapsed after chimeric antigen receptor (CAR) -T-cell therapy. Methods: Pediatric and adult patients who received two doses of inotuzumab and who were evaluated after inotuzumab treatment were included. Antibody infusions were performed between March 2020 and September 2022. All patients expressed CD22 antigen as detected by flow cytometry (>80% leukemic cells displaying CD22) before treatment. For adults, the maximum dosage per administration was 1 mg (with a total of two administrations). For children, the maximum dosage per administration was 0.85 mg/m(2) (no more than 1 mg/dose; total of two administrations). The total dosage administered to each patient was less than the standard dosage of 1.8 mg/m(2). Results: Twenty-one patients with R/R B-ALL were included, including five children (<18 years old) and sixteen adults. Seventeen patients presented with 5.0% -99.0% leukemic blasts in the bone marrow/peripheral blood or with extramedullary disease, and four patients were minimal residual disease (MRD) -positive. Fourteen patients underwent both CD19 and CD22 CAR-T-cell therapy, four underwent CD19 CAR-T-cell therapy, and three underwent blinatumomab therapy. Eleven patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). After inotuzumab treatment, 14 of 21 patients (66.7% ) achieved a complete response (CR, one was MRD-positive CR), and all four MRD-positive patients turned MRD-negative. Four of six patients who failed recent CD22 CAR-T-cell therapy achieved a CR after subsequent inotuzumab treatment. Seven patients (33.3% ) demonstrated no response. Grade 1-3 hepatotoxicity occurred in five patients (23.8% ), one child with no response experienced hepatic veno-occlusive disease (HVOD) during salvage transplantation and recovered completely. Conclusion: For patients with heavily treated R/R B-ALL, including those who had undergone allo-HSCT and CD19/CD22 CAR-T-cell therapy, the two-dose regimen of inotuzumab resulted in a CR rate of 66.7%, and the frequency of hepatotoxicity and HVOD was low.
Asunto(s)
Adulto , Humanos , Niño , Adolescente , Inotuzumab Ozogamicina , Receptores Quiméricos de Antígenos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Anticuerpos Monoclonales , Proteínas Adaptadoras Transductoras de Señales , Antígenos CD19 , Enfermedad Hepática Inducida por Sustancias y DrogasRESUMEN
Objective To investigate the effect of facet joint asymmetry on lumbar biomechanics in normal and patients with adolescent lumbar disc hemiation (ALDH). Methods Mimics 21.0, 3-Matic Medical 13.0, Geomagic Wrap 2017, HyperMesh 2019 and finite element software ABAQUS 2021 were combined to establish three-dimensional finite element models of nonnal lower lumbar spine and adolescent lumbar disc hemiation. According to the difference between the left and right facet joints, three cases of nonnal and ALDH patients aged 13-18 years old were selected, with a total of 6 cases. The stress of intervertebral disc under different torque loads (neutral position, lateral flexion and rotation) was analyzed and compared. Results 1. Three dimensional finite element models of L3-L, segments were established in 6 male nonnal and adolescent patients with lumbar disc herniation, and the stress and displacement nephogram of lumbar disc hemiation in nonnal neutral position, flexion, extension, lateral flexion and rotation were obtained; 2. The stress of L4_, annulus fibrosus increased when the facet joint angle of nonnal adolescents was symmetrical in the neutral position; 3. The stress of annulus fibrosus was greater than that of nucleus pulposus under different conditions, and the stress of annulus fibrosus was flexion > neutral position > extension; 4. In patients with ALDH, the left side of the facet joint was larger than the right 10 ° model, and the stress in the posterior side of the annulus fibrosus of L4_, segment increased significantly under extension condition. Under lateral flexion condition, the left stress of the left annulus fibrosus was compared with the right stress of the right annulus fibrosus, t = l. 575, P<0. 05, the difference was statistically significant, the right stress of the right annulus fibrosus was greater than the left stress of the left annulus fibrosus. Under the rotating condition, the stress on the left and right sides of the fiber ring was greater than that on the back side. Conclusion 1. Compared with nonnal and patients with ALDH, the stress of intervertebral disc increases under different postures, which ma)' increase the shear load of intervertebral disc and aggravate the process of intervertebral disc degeneration; 2. When the degree of left-right asymmetry of facet joint is more than 10 degrees, the stress on the side with small degree is greater. Facet joint asymmetry can lead to the overload of vertebral bod)' and intervertebral disc, leading to spinal instability; 3. The stress of intervertebral disc in extension is less than that in neutral position and flexion. Extension can relieve the pressure of intervertebral disc and play an auxiliary role in the recovery of patients with ALDH.
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Objective To measure the anatomical structure of the occipital condyle (OC) and the occipital foramen (FM) by three-dimensional reconstruction, and to analyze the morphological characteristics and relative positional relationship of the occipital condyle and occipital foramen, in order to provide anatomical parameters for the imaging diagnosis of the craniocervical junction and the choice of surgical approach. Methods Sixty normal subjects were selected with CT scans of the skull and upper cervical spine, including 30 males and 30 females, aged 20-65 (48. 18±16. 17) years old. The data were imported into the Syngo.via VB10B software, and the skull was reconstructed in three dimensions. To observe the shape of the occipital condyle and occipital foramen, and to measure the occipital condyle length, width, height, condyle inclination angle(CIA), longitudinal diameter, transverse diameter, area of the occipital foramen, the maximum distance between the cranial eyebrow and the posterior cranial point (SML), the crimson eyebrow on the SML line, the distance from the interpoint to the posterior margin of the occipital condyle (GOCP), the vertical distance between the anterior edge of the occipital foramen to the posterior margin of the occipital condyle (AOCP), and the distance from the medial margin of the left and right occipital condyles to the Y axis (OC-M), left and right occipital condyle posterior margin to X axis distance (OC-P); occipital condyle classification index (OCI), occipital condyle relative index of head (SOCI), midpoint on the SML straight line to the occipital condyle Marginal connection distance (COCP,COCP =GOCP-SML/ 2), and determine the type of relative positional relationship between left and right occipital condyles. Results The differences in anatomical length, width and height of the occipital condyle were statistically significant (P<0. 05), and men were larger than women; the occipital foramen area, longitudinal diameter of the occipital foramen, SML, GOCP, AOCP had statistical differences (P<0. 05). The lateral differences of occipital condyle inclination were statistically significant (P<0. 05), and the left side was greater than the right side. The differences in OC-M and OC-P sides were statistically significant (P<0. 05). The former was larger on the right than on the left; the latter was larger on the left than on the right. The longitudinal diameter of the occipital foramen was positively correlated with the area of the occipital foramen and AOCP; OCI classification result were as follows: typeⅠ(OCI<0. 45) had 8 cases (13. 33%), type Ⅱ (0. 45≤OCI<0. 50) had 47 cases (78. 33%), type Ⅲ (OCI≥0. 50) had 5 cases (8. 33%). SOCI classification result were as follows: type Ⅰ (SOCI< 0. 60) had 2 cases (3. 33%), type Ⅱ (0. 60≤SOCI<0. 75) had 54 cases (90. 00%), type Ⅲ (SOCI≥0. 75) had 4 cases (6. 67%). Conclusion The anatomical parameters of the occipital condyle in Inner Mongolia can be implanted with occipital condylar screws. The position of the occipital condyle relative to the foramen magnum and the skull is highly variable.