Extramedullary Research Articles

Intra- and inter-operator reliability assessment of a novel extramedullary accelerometer-based smart cutting guide for total knee arthroplasty: an in vivo study

PurposeThe purpose is to verify the intra- and inter-operator reliability of an extramedullary (EM) accelerometer-based smart cutting guide for distal femoral resection during primary total knee arthroplasty (TKA). The hypothesis of the present study was that the use of the device would result in a good correlation between different operators with a difference between repeated measurements of less than 1°.MethodsTwenty-five not consecutive patients with knee osteoarthritis undergone to primary TKA using an EM inertial-based cutting guide to perform distal femoral resection. In order to assess the agreement in femoral axis definition of the device, two operators performed three time each the manoeuvres necessary to define axis. Inter-rater agreement was evaluated with Bland and Altman agreement test. Intra-rater repeatability was evaluated analysing average results distribution of repeated measurements. Accuracy of the device was evaluated comparing differences between intra-operative device data with final implant alignment measured on post-operative longstanding x-rays using Students’ t test.ResultsAgreement between the two operators was statistically significant (p < 0.05) with a bias of − 0.4° (95% CI − 0.6° to − 0.2°). Average difference between cut orientation measured with device and final implant position, measured on x-rays, was 0.2° (95% CI − 1.5° to 1.7°) with no statistical difference between the two measurements. Final implant alignment, measured on x-ray, was 90.2°, with 95% of cases distributed within range 88.0° to 92.0° for varus-valgus and 2.8° and with 95% of cases distributed within range 2.0° to 4.0° for flexion–extension.ConclusionsThe EM accelerometer-based smart cutting guide used to perform distal femoral resection during primary TKA demonstrated a good intra- and inter-operator reliability in the present in vivo study.

464 Local Extension of a Solitary Extra Medullary Nasal Plasmacytoma into the Orbit

AimExtramedullary plasmacytoma are rare neoplasms, which mainly occur in the head and neck, the most common site being the nasal cavity or septum. Patients may present with epistaxis, nasal obstruction, or rhinorrhoea. Extension into the orbit is rare but can lead to visual disturbances.MethodThis case report pertains to a 69-year-old female patient who initially presented with a 6-week history of recurrent sinusitis, with left sided cheek pain and diplopia.ResultsA CT and MRI scan was performed, which showed opacification of the left maxillary, ethmoid and sphenoid sinuses with bony destruction of the medial and anterior maxillary walls and into the anterior soft tissues. The mass was completely obstructing the left nasal cavity extending into the inferomedial orbit. Staging CT scans also showed nodal disease in the neck.Biopsy with histology was positive for CD138, with diffuse proliferation of plasma cells of varying maturity and atypia. Additionally, mono IgG kappa was also positive as was CD45 suggestive of a lymphoid neoplasm. Bone marrow biopsy and PET scan confirmed there was no systemic involvement.Radiotherapy was initiated after the patient recovered from COVID -19. A repeat MRI scan 6 weeks post radiotherapy showed a partial response with reduction in the size of the tumour, resolution of the intra-orbital extension and disappearance of paraprotein.ConclusionsThis case report illustrates need for earlier consideration of EMP diagnostically to reduce the risk of conversion of the plasmacytoma to multiple myeloma, which is a known possibility and to ensure minimal delay in the commencement of treatment.

PB2007: FACTORS ASSOCIATED WITH EARLY RELAPSE IN MYELOMA PATIENTS AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION

Background: Multiple myeloma (MM) is a clonal disease characterized by a neoplastic proliferation of plasma cells that make up approximately 10% of hematologic malignancies. Autologous hematopoietic stem cell transplantation (ASCT) after an induction regimen using combination of immunomodulatory drugs, proteasome inhibitors and dexamethasone is considered the standard treatment of newly diagnosed multiple myeloma in eligible patients. Aims: To demonstrate the pre-transplant factors associated with early relapse in MM patients undergoing ASCT. Methods: 27 adult MM patients who underwent ASCT at The Stem Cell Transplant Center of Dokuz Eylul University Hospital between October 2011 and August 2021 and who relapsed within 18 months of transplantation were included in this study. The data were compiled from the Dokuz Eylul Hematology archive and the Hospital Information Management System at Dokuz Eylul University Hospital and analyzed with SPSS v.24 (Statistical Package for Social Sciences). Mann-Whitney U test is used to compare kappa/lambda ratios, Kaplan Meier test is used to analyze survival and log-rank test is used to test significant difference between survival of two groups. Results: The median age at diagnosis is 57 (42-68) and 52% of patients were male (n=14). Patients received a median one line of treatment before ASCT (1-3). According to the ISS staging system, 9 patients were stage I, 9 patients were stage II and 9 patients were stage III. In 43% of patients (n=12), extramedullary (EM) disease involvement was present at the diagnosis. 33% had hypercalcemia (n=9), 19% had kidney involvement (n=5), 57% had anemia (n=16), and 75% had bone (n=21) at the time of diagnosis. Two patients achieved complete remission (CR) after 2 courses of induction therapy. But they lost this response pre-ASCT and they relapsed in 5th and 6th month after ASCT respectively. The median time to relapse post-ASCT was 6 (2-17) months. In 63% of these patients, clinical relapse was observed, treatment was started due to aggressive biochemical relapse in the rest. 25% (n=7) had EM disease involvement in relapse. In this patient group, the median survival after ASCT is 32 months (5-120). In 3 out of 10 patients with biochemical relapse, EM disease was not observed despite being present at the time of diagnosis. In 9 of the 17 patients with clinical relapse and EM disease at diagnosis, 7 patients relapsed with EM disease. Median Kappa/Lambda ratios at the time of diagnosis were 13.84 and 13.1 at the time of relapse. There was no statistically significant difference in kappa/lambda rates at the time of diagnosis and relapse of patients with biochemical and clinical relapse. Median progression-free survival (PFS) was 5 months in those with clinical relapse and 8 months in patients with biochemical relapse. Median overall survival (OS) was 19.2 months in those with clinical relapse and it was not reached in those with biochemical relapse (p=0.001) (Fig. 1). Image:Summary/Conclusion: It is known that in multiple myeloma, ASCT prolongs PFS. Early loss of response in patients who achieved CR after 2 courses of treatment may be a prognostic clue. OS and PFS are shorter in those with clinical relapses while biochemical relapses are more indolent. The fact that 43% of our patients have EM disease involvement in diagnosis indicates that this feature may be associated with early relapse. Outcomes of single and tandem ASCT in these patients should be examined in further studies.

The accuracy of an extramedullary femoral cutting system in total knee arthroplasty in patients with severe coronal femoral bowing: a radiographic study

BackgroundIntramedullary (IM) femoral alignment instrument is imprecise for the coronal alignment in total knee arthroplasty (TKA) in patients with severe lateral bowing of the femur, while the extramedullary (EM) alignment system does not depend on the structure of the femoral medullary cavity. The aim of this retrospective study was to compare the accuracy of postoperative limb alignment with the two femoral alignment techniques for patients with severe coronal femoral bowing.MethodsFrom January 2017 to December 2019, patients with end-stage knee osteoarthritis and coronal femoral bowing angle (cFBA) ≥ 5° who underwent total knee arthroplasty TKA at our institution were enrolled in the study. The postoperative hip-knee-ankle (HKA) alignment, femoral and tibial component alignment between the IM group and the EM group were compared on 5° ≤ cFBA < 10° and cFBA ≥ 10°.ResultsIn patients with 5° ≤ cFBA < 10°, no significant differences were observed in the EM group and IM group, including preoperative and postoperative parameters. However, when analyzing the patients with cFBA ≥ 10°, we found a significant difference in postoperative HKA (4.51° in the IM group vs. 2.23°in the EM group, p < 0.001), femoral component alignment angle (86.84° in the IM group vs. 88.46° in the EM group, p = 0.001) and tibial component alignment angle (88.69° in the IM group vs. 89.81° in the EM group, p = 0.003) between the two groups. Compared to the EM group, the IM group presents a higher rate of outliers for the postoperative HKA and femoral components.ConclusionsThe study showed that severe lateral bowing of the femur has an important influence on the postoperative alignment with the IM femoral cutting system. In this case, the application of EM cutting system in TKA will perform accurate distal femoral resection and optimize the alignment of lower limb and the femoral component.

Monoclonal B-cell lymphocytosis in the bone marrow: revisiting the criteria for chronic lymphocytic leukemia/small lymphocytic lymphoma

Monoclonal B-cell lymphocytosis is a clonal B-cell population in the peripheral blood (PB) of <5x10ˆ9/L without extramedullary (EM) disease, often with a chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) phenotype. The degree of bone marrow (BM) involvement is not currently a part of the diagnostic criteria for MBL or CLL/SLL, but CLL-type MBLs in BM can be seen in patients lacking PB lymphocytosis. Data are limited on the outcome of such cases. We assessed the clinicopathologic characteristics of isolated BM CLL-type MBL in patients who did not meet criteria for CLL/SLL. We evaluated BMs from 2006 to 2018 with CLL-like clonal B-cell populations in patients with a PB absolute lymphocyte count or monoclonal B-cell count of <5×109/L and without definite evidence of EM disease. We investigated the extent and pattern of marrow involvement, PB counts, flow cytometric data, genetics, concurrent hematopoietic diseases, and outcomes including progression and treatment. Thirty cases with BM MBL but <5x10E9/L PB monoclonal B cells and no EM disease were identified. Thirteen of 30 had additional hematopoietic neoplasms. The mean patient age was 74.1 years (median: 77 years, range: 43-91 years). No patients had lymphadenopathy (LAD) or splenomegaly by physical examination. By imaging, nine of 18 had LAD (8/9<1.5cm) and four of 18 had splenomegaly but with other attributable etiologies. Mean PB absolute lymphocyte count (ALC) was 1.8×10E9/L (range: 0.5-5.0×10E9/L). Twenty-four of 30 (80%) had low-level (<20%) BM involvement by MBL, and among these, none with available follow-up data progressed to diagnostic CLL/SLL. Six of 30 (20%) had >20% marrow involvement by MBL. Four of 6 were treated for CLL/SLL due to cytopenias, despite not meeting diagnostic criteria, and all 4 were CD38 or ZAP70 positive and had cytogenetic abnormalities, including trisomy 12. One of 6 developed overt CLL/SLL 3 years later and had cytogenetic abnormalities at the time of MBL diagnosis. One of 6 was monitored without treatment but had no cytogenetic abnormalities.Isolated BM CLL-type MBL represents a diagnostic gray area, and this study highlights the range of clinical outcomes. All cases with <20% BM involvement did not require CLL-specific treatment or progress to CLL/SLL. In the 4 cases where treatment was initiated due to cytopenias, patients had ≥20% BM involvement, CD38 or ZAP70 expression, and cytogenetic abnormalities but lacked a PB ALC of ≥5x10E9/L or LAD ≥1.5cm, suggesting that not all patients with clinically significant disease will meet criteria for CLL/SLL. The results also show that concurrent hematopoietic disorders can complicate the diagnosis, as the disease course or treatment may result in leukopenia, precluding PB absolute lymphocytosis. Though larger studies are needed, the degree of BM involvement, in conjunction with flow cytometric prognostic markers, and cytogenetic abnormalities may be a useful addition to the current diagnostic criteria for CLL/SLL which only considers a PB numerical cutoff and EM involvement.

Tisagenlecleucel outcomes in relapsed/refractory extramedullary ALL: a Pediatric Real World CAR Consortium Report

AbstractChimeric antigen receptor (CAR) T cells have transformed the therapeutic options for relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia. Data for CAR therapy in extramedullary (EM) involvement are limited. Retrospective data were abstracted from the Pediatric Real World CAR Consortium (PRWCC) of 184 infused patients from 15 US institutions. Response (complete response) rate, overall survival (OS), relapse-free survival (RFS), and duration of B-cell aplasia (BCA) in patients referred for tisagenlecleucel with EM disease (both central nervous system (CNS)3 and non-CNS EM) were compared with bone marrow (BM) only. Patients with CNS disease were further stratified for comparison. Outcomes are reported on 55 patients with EM disease before CAR therapy (CNS3, n = 40; non-CNS EM, n = 15). The median age at infusion in the CNS cohort was 10 years (range, <1-25 years), and in the non-CNS EM cohort it was 13 years (range, 2-26 years). In patients with CNS disease, 88% (35 of 40) achieved a complete response vs only 66% (10 of 15) with non-CNS EM disease. Patients with CNS disease (both with and without BM involvement) had 24-month OS outcomes comparable to those of non-CNS EM or BM only (P = .41). There was no difference in 12-month RFS between CNS, non-CNS EM, or BM-only patients (P = .92). No increased toxicity was seen with CNS or non-CNS EM disease (P = .3). Active CNS disease at time of infusion did not affect outcomes. Isolated CNS disease trended toward improved OS compared with combined CNS and BM (P = .12). R/R EM disease can be effectively treated with tisagenlecleucel; toxicity, relapse, and survival rates are comparable to those of patients with BM-only disease. Outcomes for isolated CNS relapse are encouraging.

Characteristics of intramedullary nail breakage in pertrochanteric femur fractures: a summary of 70 cases

ObjectiveTo reveal noteworthy characteristics of intramedullary (IM) nail breakage in pertrochanteric femur fractures.Materials and methodsThe data from 6 patients with IM nail breakage in our hospital between August 2008 and May 2018 were reviewed retrospectively. With an additional 64 cases reported in articles in the PubMed database prior to October 2019, a total of 70 cases were reviewed and analysed; epidemiological patient data and data on the initial trauma, fracture type, nail selected for the original surgery, time from surgery to breakage, mechanism and location of breakage, status of fracture healing, salvage treatment and prognosis were assessed.ResultsSeventy patients with pertrochanteric fractures, including 2 stable fractures and 68 unstable fractures, experienced IM nail breakage at a mean of 9.4 months after the initial surgery. Among them, 9 (12.9%) occurred within 3 months, 23 (32.9%) between 3 and 6 months and 38 (54.3%) after 6 months. The mean age was 72.3 years, and 16 (22.9%) patients were younger than 65 years old. When nail breakage occurred, 66 fractures (94.3%) exhibited delayed union/non-union. Self-dynamisation was found in 12 cases (17.1%). The salvage procedures included 4 partial/total implant removal procedures, 17 hemi/total hip arthroplasty procedures, 3 conservative treatment procedures, and 46 revised osteosyntheses, of which 7 cases (15.2%) sustained secondary implant failure. No significant differences were found between the failure rates of IM nails and extramedullary(EM) devices (odds ratio [OR], 3.429; 95% confidence interval [CI], 0.632–18.877; p = 0.330).ConclusionIM nail breakage is a rare complication lack of time regularity and mostly occurs in unstable pertrochanteric fractures in the presence of delayed union/non-union. Osteosynthesis revision can be conduct by a new IM nail or EM device but considerable secondary failure rate is noteworthy. Self-dynamisation may be a warning sign of nail breakage.

Patterns and Outcomes of Relapse Treated With Radiotherapy Following Total Marrow and Lymphoid Irradiation in High-Risk and/or Relapsed/Refractory Acute Leukemia

Total Marrow and Lymphoid Irradiation (TMLI) is a promising component of the preparative regimen for hematopoietic cell transplantation in patients with high-risk and/or relapsed/refractory acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), which has poor 5-yr OS at ∼15%. Extramedullary (EM) relapse rates in patients treated with this regimen has been reported to be ∼13%. This study evaluates patterns and outcomes of radiotherapy (RT) used to treat patients with EM relapse previously treated with TMLI.An IRB-approved analysis of 5 prospective TMLI trials was interrogated (IRB 04199, 05013, 05021, 14012, and 14106). Pre-transplant conditioning consisted of TMLI and etoposide (VP-16)/cyclophosphamide, fludarabine/melphalan, or bulsulfan/VP-16. TMLI targeted bones and major lymphoid tissues using image-guided tomotherapy, with total dose ranging from 12 to 20Gy delivered twice daily. EM recurrences were treated at the discretion of the hematologist and radiation oncologist using RT ± chemotherapy. Descriptive statistics and survival analysis were then performed on this cohort.In total, 254 patients with AML or ALL were treated with TMLI at our institution between 2006 and 2018. 21 of these patients were identified as receiving at least one subsequent course of radiation. A total of 67 relapse sites (median = 2 sites/patient, range = 1-16) were treated (6 lymph node, 34 soft tissue, 23 bone, and 4 CNS). At time of transplant, median age was 31 yrs (21-61 years). The median follow-up from date of transplant of these patients was 32.2 mo (3.9-154.1 mo). Of the 21 patients, 17 had active disease (MRD+ and/or bone marrow+) at transplant and 6 had prior history of EM disease. 12 patients had EM relapse only without BM relapse, while 5 had prior BM relapse and 4 had simultaneous EM and BM relapse. 12 recurrences were treated with systemic therapy prior to RT. The median mean TMLI dose to these sites was 12.0 Gy (4.0-20.8 Gy). 1-yr and 5-yr estimates of OS were 80.9% (95% CI = 56.9-92.4%) and 35.6% (95% CI = 13.8-58.3%), respectively. 1 and 2-yr OS following salvage RT to the first site of EM recurrence was 45.4% (95% CI = 23.1-65.3%) and 38.9% (95% CI = 17.7-59.8%), respectively. The median salvage RT dose was 24 Gy (6-30 Gy). Following RT, 86.6% of the sites had durable local control.To our knowledge, this is the largest analysis to date of patients treated with TMLI. Relapse incidence was as frequent in regions receiving ≥12 Gy as those receiving < 12 Gy, suggesting TMLI is not associated with an increased EM relapse risk. These patients did not have significantly different OS compared to historical controls. RT is an effective modality to treat EM relapse in patients with acute leukemia who were previously treated with TMLI.

Additional Reduction Screw Fixation Technique for Pertrochanteric Hip Fractures: A Novel Method to Prevent Excessive Sliding in Cephalomedullary Nail Surgery

Extramedullary (EM) reduction, defined as the medial cortex of the head-neck fragment located outside the medullary canal of the distal shaft fragment, has been introduced to prevent excessive postoperative sliding or failure of the lag screw in pertrochanteric fracture surgeries. Favorable EM reduction results have recently been reported in several clinical and biomechanical studies. Despite these efforts, maintaining the head-neck fragment in an EM position is periodically a difficult and challenging problem. Herein, the technique for reduction and maintenance of the head-neck fragment was introduced in an EM position using a Kirschner wire and partially threaded cannulated screw fixation via screw fixation from EM to the head-neck fragment, which was positioned inferior to the lag screw on the femoral calcar, also called the reduction screw. The authors utilized this reduction screw in 34 pertrochanteric fracture surgeries using a cephalomedullary nail and fracture union was acheive in all cases by a minimum one-year follow-up period without surgical complications.

Abstract LB147: Updates on clinical safety and efficacy result of GC027, the first-in-human, “Off-the-Shelf” CD7 CAR-T stand-alone therapy for adult patients with relapsed/refractory T-cell lymphoblastic leukemia (r/r T-ALL)

Abstract Introduction: T-ALL represents an area of high unmet medical need. Once relapsed, patients have limited treatment options. We first reported data from a single-arm, open-label, multi-center, investigator-initiated study in adults with r/r T-ALL (ChiCTR1900025311) treated with TruUCAR™ GC027, an off-the-shelf CAR-T product at AACR 2020. Here we report long term follow-up results and preliminary results of additional patients treated. Methods: Between July 2019 to Feb 2021, a total of 6 r/r T-ALL patients (19-38 yrs) with a median of 6 prior lines were treated with a single infusion of GC027 at 3 different dose levels after Lymphodepletion over 6 days: DL1 (6x106 cells/kg, n=2), DL2 (1x107 cells/kg, n=3), DL3 (1.5x107 cells/kg, n=1) including a primary refractory T-ALL pt with extramedullary (EM) disease. Results: All 6 pts treated showed molecular expansions of CAR-T cells and peaked day 6-11 in peripheral blood (by qPCR, median 416,905 copies/ug DNA). Robust cellular expansion (by FACS) was observed in 5 pts (median 648 cells/ul). Clinically, 5/6 pts achieved MRD-CR/CRi at the month 1 assessment, including 1 pt with EM disease at several locations including neck, axilla, mediastinum and pancreas. His EM lesions were reassessed by PET-Scan on day 47 after treatment, confirming a complete response. Long-term follow-up (n=5): All pts evaluable at day 28 (n=4) reconstituted all blood cell lineages as assessed by blood cell count. At 6 months, 3/5 pts had maintained MRD- CR. At data cut-off Feb. 4, 2021, 1 pt continued to be in MRD-CR at 16.8 months (day 505) post treatment. 1 pt maintained CR until day 267, when he was found CD7 partial negative (by FACS) relapsed (BM). 1 pt with primary refractory disease (no response to VDP) maintained MRD- CR until month 7 (day 217) and was found relapsed by BM and PB assessment with CD7 partial negative (FACS). He received HSCT on day 255, achieved MRD- CR but relapsed again 5 months post HSCT. Safety (n=6): Overall safety findings were consistent with previous observations reported. TEAEs occurred were grade 3 febrile neutropenia (6/6), grade 4 neutropenia (4/6), grade 4 thrombocytopenia (4/6) and grade 3 anemia (3/6). All TEAE resolved after treatment with SOC and best supportive care, neutropenia improved with G-CSF treatment. Non-hematological TEAE presented as grade≤2 hypoalbuminemia (6/6), grade 3 pulmonary infection (3/6), grade≤2 AST increase (4/6) and grade≤2 ALT increase (3/6). 6/6 pts developed grade ≥ 3 CRS (ASBMT consensus grading), which was manageable in all cases and resolved after treatment. No Grade 5, ICANs or aGvHD were observed. Conclusion: The allogeneic off-the-shelf TruUCAR™ CAR-T GC027 shows promising efficacy as standalone therapy in heavily pretreated R/R T-ALL pts with a manageable safety profile. A single infusion of GC027 was able to induce deep, durable responses, with the longest duration of response (MRD-CR) 18 months post treatment still ongoing without any additional therapy during remission. GC027 warrants further evaluation in larger clinical studies. Citation Format: Shiqi Li, Lei Gao, Zhongtao Yuan, Kun Wu, Lin Liu, Le Luo, Yao Liu, Cheng Zhang, Yu Li, Duanpeng Wang, Zhimin Li, Xu Tan, Ruihao Huang, Dingsong Zhang, Youcheng Wang, Xinxin Wang, Jia Liu, Martina Sersch, Sanbin Wang, Xi Zhang. Updates on clinical safety and efficacy result of GC027, the first-in-human, “Off-the-Shelf” CD7 CAR-T stand-alone therapy for adult patients with relapsed/refractory T-cell lymphoblastic leukemia (r/r T-ALL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB147.

Different Kinetics and Risk Factors for Isolated Extramedullary Relapse after Allogeneic Hematopoietic Stem Cell Transplantation in Children with Acute Leukemia

Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most frequent cause of post-transplantation mortality. Isolated extramedullary (EM) relapse (iEMR) after HSCT is relatively rare and not well characterized, particularly in pediatric patients. We retrospectively analyzed 1527 consecutive pediatric patients with acute leukemia after allo-HSCT to study the incidence, risk factors, and outcome of iEMR compared with systemic relapse. The 5-year cumulative incidence of systemic relapse (either bone marrow [BM] only or BM combined with EMR) was 24.8%, and that of iEMR was 5.5%. The onset of relapse after allo-HSCT was significantly longer in EM sites than in BM sites (7.19 and 5.58 months, respectively; P=.013). Complete response (CR) 2+/active disease at transplantation (hazard ratio [HR], 3.1; P < .001) and prior EM disease (HR, 2.3; P=.007) were independent risk factors for iEMR. Chronic graft-versus-host disease reduced the risk of systemic relapse (HR, 0.5; P=.043) but did not protect against iEMR. The prognosis of patients who developed iEMR remained poor but was slightly better than that of patients who developed systemic relapse (3-year overall survival, 16.5% versus 15.3%; P=.089). Patients experiencing their first systemic relapse continued to have further systemic relapse, but only a minority progressed to iEMR, whereas those experiencing their iEMR at first relapse developed further systemic relapse and iEMR at approximately similar frequencies. A second iEMR was more common after a first iEMR than after a first systemic relapse (58.8% versus 13.0%; P=.001) and was associated with poor outcome. iEMR has a poor prognosis, particularly after a second relapse, and effective strategies are needed to improve outcomes.

Isolated Extramedullary (EMD) Blastic Transformation of Chronic Myeloid Leukemia (CML-BP) in the TKI Era: Characteristics, Treatments and Outcomes

Isolated Extramedullary (EMD) Blastic Transformation of Chronic Myeloid Leukemia (CML-BP) in the TKI Era: Characteristics, Treatments and Outcomes

Molecular annotation of extramedullary acute myeloid leukemia to identify prevalence of targetable mutations.

7024 Background: Extramedullary (EM) involvement, including myeloid sarcoma (MS) and leukemia cutis (LC), is uncommon in patients with acute myeloid leukemia (AML). Mutational landscape of EM-AML is not well characterized, including concordance of sequencing data from EM vs. non-EM site (blood or bone marrow) and the potential for personalized targeted therapy in this patient cohort. Methods: In a multicenter retrospective study, clinical and genomic data were collected on EM-AML patients treated at Moffitt Cancer Center, Memorial Healthcare System, and University of Miami, as well as sequenced cases at a central laboratory. Next generation sequencing (NGS) data come from panels that interrogated 24- 406 genes, with 15 genes covered by all panels, including notably, IDH1, IDH2, KIT, KRAS, NPM1, NRAS, and TP53. Survival estimates using Kaplan-Meier statistics and multivariate analysis with Cox-regression were performed in SPSS (v.26). Results: Our study included 58 patients with EM-AML. Median age at diagnosis was 62 years; 55% of patients were males. In our cohort, 34 (59%) patients had MS, and 19 (33%) had LC. EM-AML was noted during relapse in 60% of evaluable patients (n=45), and 31% had isolated EM disease. Patients with LC had a significantly worse median overall survival (OS) than those with MS (5.7 months vs. 21.9 months, p= 0.008); Pattern of EM involvement (MS vs. LC) remained an independent prognostic factor for OS (p= 0.04) in a multivariate analysis including disease setting (new diagnosis vs. relapse) and ELN risk category. Results of NGS performed during EM presentation were available in 48 patients, 19 of which had NGS data from EM site. Most commonly mutated genes were NRAS on EM site NGS (37%) and NPM1 on non-EM site NGS (28%). Based on EM NGS, 52% patients had a targetable genomic alteration, with 37% mutations in IDH, 21% NPM1, 5% FLT3, and 11% MLL-PTD. Five (two with concurrent M+EM disease) out of nine evaluable patients had significant discordance in targetable mutations between EM and non-EM NGS at EM-AML. Three of four patients who received treatment with IDH1/2 inhibitors based on EM NGS achieved complete response. Conclusions: EM-AML has a distinct molecular architecture with an inferior OS in LC vs. MS patients. We conclude that EM site NGS is critical in patients with EM-AML, as 52% have potentially targetable mutations and could benefit from specific targeted therapies.[Table: see text]

Novel Design of Minimal Incision Double Oblique Device for Osteosynthesis (DODO) of Hip: Results of an In-silico Study Based on the Femur Morphometrics of the Northeast (NE) Indian population.

Hip fractures account for a large proportion of hospitalization among the trauma cases. Low cost, simple technique, easy removal, and high rate of the bone union makes extramedullary (EM) fixation techniques a preferred choice. A close-fit bone and plate are essential for the success of such implantation. Various studies have found femur morphometry being related to regional features and social differences. Most of the available commercial implants are developed based on the data of the Caucasian population. In the herein study, a novel design, Double Oblique Device for Osteosynthesis of hip (DODO), is proposed while considering the regional morphometry of the Northeast (NE) population of India. This study employs finite element (FE) analysis to compare the biomechanical outcome of the new device with that of proximal femoral locking plate (PFLP) and variable angle dynamic hip screw (VA-DHS) on a femur having an Evans type-I intertrochanteric fracture. The stress shielding was substantially high for the PFLP and VA-DHS in the distal bone fragment (lateral aspect) and for DODO in the femoral head. The difference in axial displacement between the post-implanted DODO-fixed femur and its respective intact femur was predicted to be almost the same as that of PFLP-fixed femur and its respective intact femur. The computational results found the new device to be a viable alternative to the conventional plating techniques, especially for the NE population of India, and predicted better to comparable biomechanical characteristics.

No Significant Difference Between Intramedullary and Extramedullary Button Fixation for Distal Biceps Brachii Tendon Rupture After Cyclic Loading in a Cadaver Model

PurposeTo biomechanically compare intramedullary (IM) versus extramedullary (EM) distal biceps button fixation under cyclic loading conditions, which is most representative of postoperative physiologic status.MethodsThis controlled laboratory study used 13 fresh-frozen matched paired cadaver elbows. One specimen from each pair was randomized to either IM (unicortical) or EM (bicortical) distal biceps button fixation via onlay technique. A servohydraulic actuator was used to cycle each specimen from full extension to 90° of flexion at 0.5 Hz for 3,000 cycles. All specimens were subsequently loaded to failure to simulate an acute postoperative load.ResultsDuring cyclic loading, the mean change in force from cycle 5 to cycle 3000 was 2.1 ± 3.2 N for the IM group and 0.6 ± 4.2 N for the EM group (P = .19). The increase in tendon gap for the IM group was 1.02 mm and for the EM group was 1.83 mm (P = .37). During failure loading, the IM group had a mean failure load of 154.9 ± 44.5 N and the EM group a mean failure load of 191.1 ± 62.6 N (P = .16).ConclusionsNo significant differences exist between the IM and EM techniques in loss of force and tendon gap formation under cyclic loading or load to failure conditions. Thus, IM fixation may adequately facilitate optimal bone-tendon apposition, with less risk of iatrogenic injury to the posterior interosseous nerve that can be seen with bicortical extramedullary fixation.Clinical RelevanceThe most common major complication following distal biceps repair is PIN palsy. IM fixation may be sufficient in facilitating optimal bone-tendon apposition and healing with onlay technique, while minimizing risk of iatrogenic PIN injury associated with EM fixation.

Expert review on soft-tissue plasmacytomas in multiple myeloma: definition, disease assessment and treatment considerations.

In this review, two types of soft-tissue involvement in multiple myeloma are defined: (i) extramedullary (EMD) with haematogenous spread involving only soft tissues and (ii) paraskeletal (PS) with tumour masses arising from skeletal lesions. The incidence of EMD and PS plasmacytomas at diagnosis ranges from 1·7% to 4·5% and 7% to 34·4% respectively. EMD disease is often associated with high-risk cytogenetics, resistance to therapy and worse prognosis than in PS involvement. In patients with PS involvement a proteasome inhibitor-based regimen may be the best option followed by autologous stem cell transplantation (ASCT) in transplant eligible patients. In patients with EMD disease who are not eligible for ASCT, a proteasome inhibitor-based regimen such as lenalidomide-bortezomib-dexamethasone (RVD) may be the best option, while for those eligible for high-dose therapy a myeloma/lymphoma-like regimen such as bortezomib, thalidomide and dexamethasone (VTD)-RVD/cisplatin, doxorubicin, cyclophosphamide and etoposide (PACE) followed by SCT should be considered. In both EMD and PS disease at relapse many strategies have been tried, but this remains a high-unmet need population.

Postoperative alignment in revision total knee arthroplasty, a comparison between intra and extra-medullary tibial alignment

BackgroundRevision total knee arthroplasty commonly involves stemmed components. If the diaphysis is engaged, this technique may be problematic for mechanical alignment (MA) in cases of tibial bowing, which are not infrequent (up to 30%).The aim of this study is to compare an intra-medullary(IM) and extra-medullary(EM) alignment method. We hypothesized that IM technique and canal-filling stems may result more frequently in valgus MA. On the other hand, an EM technique could produce less valgus knees but is at risk of creating MA outliers. MethodA retrospective radiographic analysis of revision TKAs was performed. The patients were divided to either the EM or IM alignment group and compared on the overall post-operative MA. The following parameters were measured on standing, long leg x-rays: Hip-knee-Ankle angle (HKA), mechanical lateral distal femoral angle and mechanical medial proximal tibial angle (mMPTA). Results119 cases of revision TKAs were included (EM = 80, IM = 39). There was a difference between the EM and IM group for the mean mMPTA (89.94° vs 90.92°, effect size = 0.45, p = 0.013) and HKA angle (1.64° vs 0.05°, effect size = 0.52, p = 0.0064). A higher proportion of IM patients were in overall valgus alignment (16/39, 41%) vs EM group (16/80, 20%, p = 0.0134). Both techniques showed the same proportion of outliers, defined as HKA angle more than 5 degrees from neutral mechanical alignment (11/80 vs 5/39, p = 0.286). ConclusionThe extra-medullary alignment method with short cemented stems creates less valgus mechanical alignment than the intra-medullary technique with press-fit stems, without creating more MA outliers.

Parietal Abcess Revealing Several Foci of Extramedullary Hematopoiesis: A Case Report

In children, Extra Medullary Hematopoiesis (EMH) is a compensatory response to severe chronic anemia, particularly in the context of B thalassemia. Its localization, variable, is mainly hepatic, splenic and ganglionic but all the other organs, including the skin, can be reached. Rare, most often asymptomatic, EMH can be manifested by a mass syndrome. The anamnesis and the imaging bring arguments in favor of the diagnosis, sometimes difficult to establish, without resorting to invasive examinations. Thanks to therapeutic progress, the surgical treatment has become rare, reserved for certain special cases. We report the case of a patient with major B thalassemia, in whom the appearance of an abscessed abdominal mass has revealed several foci of EMH.

Evaluation of the Survival Outcomes of Multiple Myeloma Patients According to Their Plasmacytoma Presentation at Diagnosis

Objective:Multiple myeloma (MM) associated with extramedullary (EM) plasmacytoma has a poor therapeutic response and poor outcomes when treated with conventional chemotherapy. EM plasmacytoma is divided into two groups: the first group comprises tumors that are extending directly from osteolytic bone lesions (EM-B, bone-related), while the second results from plasmacytoma infiltration into soft tissues with no relationship to the bone (EM-S, soft tissue-related). This study aimed to compare the general characteristics and survival outcomes of transplant-eligible MM patients who had EM-S or EM-B and MM patients who did not have plasmacytoma at the time of diagnosis.Materials and Methods:This study was performed in a retrospective manner. The MM patients who were treated at our tertiary care center between January 2003 and January 2017 were evaluated retrospectively for the presence of plasmacytoma at diagnosis.Results:There were 141 (78.3%) MM patients who did not have plasmacytoma, 22 (12.2%) MM patients who had EM-B, and 17 (9.4%) MM patients who had EM-S at the time of diagnosis in this study. The 5-year overall survival was 63% in patients who had bone EM-B, 63% in patients who had EM-S, and 80% in patients who did not have plasmacytoma (p=0.02). The 5-year disease-free survival was 47% in patients who had EM-B, 35% in patients who had EM-S, and 54% in MM patients who did not have plasmacytoma (p=0.15).Conclusion:These findings lead us to suggest that MM patients with EM plasmacytoma at the time of diagnosis have poorer prognosis than patients without plasmacytoma, even if autologous stem cell transplantation is performed. The presence of EM involvement negatively affects survival outcomes.

Azacitidine (AZA) with Nivolumab (Nivo), and AZA with Nivo + Ipilimumab (Ipi) in Relapsed/Refractory (R/R) Acute Myeloid Leukemia: Clinical and Immune Biomarkers of Response

Azacitidine (AZA) with Nivolumab (Nivo), and AZA with Nivo + Ipilimumab (Ipi) in Relapsed/Refractory (R/R) Acute Myeloid Leukemia: Clinical and Immune Biomarkers of Response