BACKGROUND: The prognosis of patients with refractory or relapsed AML (R/R-AML) is very limited. To (re)achieve complete remission, there has recently been increasing evidence that the combination of venetoclax (VEN) with chemotherapy is associated with improved outcomes.
METHODS: Our retrospective, single-center study of 53 R/R-AML patients with a median follow-up time of 11.0 months compared standard salvage chemotherapy (FLAG-Ida or HAM in n = 35 patients) with a combination of venetoclax (VEN) and FLAG-Ida (FLAVIDA in n = 18 patients) concerning safety and efficacy.
RESULTS: Regarding the primary endpoints, there was a statistically significant increased event free survival (EFS) in the FLAVIDA group compared to patients with standard chemotherapy based on the univariate log-rank-test and in the multivariate Cox regression analysis (HR 0.22 [95% CI 0.05, 0.97]). There were no differences between the two groups in terms of patients developing febrile neutropenia CTCAE III° and IV° or a delay in hematological recovery. In addition, a clear trend towards an improved overall response rate (78% vs. 51%) was demonstrated in the FLAVIDA group.
CONCLUSIONS: The FLAVIDA regimen represents a promising treatment alternative for R/R AML patients with a high response rate and significantly improved EFS compared to standard chemotherapy.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is primarily manifested by persistent inflammation affecting the musculoskeletal system and the skin. The treatment of SAPHO syndrome remains a challenge. Tofacitinib is a Janus kinase (JAK) inhibitor that inhibits a range of cytokines. Here, we report a patient who had been diagnosed with SAPHO syndrome refractory to initial treatment and responded well to tofacitinib. An 18-year-old male was presented to our center with polyarthritis, associated with sternal and clavicular pain. There was a nine-month history of skin lesions affecting his chest and back and was diagnosed with a case of SAPHO syndrome. Nonsteroidal anti-inflammatory drugs, conventional disease-modifying antirheumatic agents, and biological drugs were unhelpful. After five weeks of starting tofacitinib at 5mg twice daily in combination with methotrexate, the patient reported significant improvement in dermatological and osteoarticular symptoms. JAK inhibitors, especially tofacitinib, can be a good choice for the treatment of SAPHO refractory to disease-modifying antirheumatic drugs (DMARDs) and tumor necrosis factor (TNF) inhibitors.

The optimal treatment for patients with severe aplastic anemia (SAA) who fail an initial course of antithymocyte globulin (ATG) plus cyclosporine has not yet been established. We compared the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n = 36) with repeated immunosuppressive therapy (IST) (n = 33) for relapsed/refractory SAA between 2007 and 2022. In the IST group, patients were retreated with ATG (n = 16) or high-dose cyclophosphamide (n = 17). The overall response rate was 57.6% at 6 months and 60.6% at 12 months. In the allo-HSCT group, patients received a transplant from a matched sibling donor (n = 6), matched unrelated donor (n = 7), or haploidentical donor (n = 23). All patients achieved neutrophil engraftment, and there were no cases of primary graft failure. The cumulative incidences (CIs) of grades II-IV and III-IV acute graft-versus-host disease (GVHD) were 36.1% ± 0.7% and 13.9% ± 0.3% at day +100, respectively. The 4-year CI of chronic GVHD (cGVHD) was 36.2% ± 0.7%, with moderate to severe cGVHD at 14.9% ± 0.4%. Compared with IST, HSCT recipients showed much higher hematologic recovery rate at 3, 6, and 12 months (63.9%, 83.3%, and 86.1%, respectively, p < 0.001). The estimated 4-year overall survival (OS) (79.8% ± 6.8% vs. 80.0% ± 7.3%, p = 0.957) was similar; however, the failure-free survival (FFS) was significantly better in the HSCT group (79.8% ± 6.8% vs. 56.6% ± 8.8%, p = 0.049). Of note, children in the HSCT cohort were all alive without treatment failures, exhibiting superior OS (100% vs. 50.0% ± 17.7%, p = 0.004) and FFS (100% vs. 50.0% ± 17.7%, p = 0.004) than children in the IST cohort. Subgroup analysis revealed that younger patients (age ≤ 35 years), especially children, and those with refractory SAA benefited more from HSCT. Therefore, for these patients, salvage HSCT may be more preferable than a second course of IST.

Ewing sarcoma (ES) is a malignant tumor of bone and soft tissue that most often occurs in children, adolescents, and young adults. Debate and controversy remain in the management of relapsed/refractory ES (RR-ES). The authors leveraged the expertise assembled by the National Ewing Sarcoma Tumor Board, a multidisciplinary virtual tumor board that meets monthly to discuss challenging cases of ES. In this review, they focus on select topics that apply to the management of patients with RR-ES. The specific topics covered include the initial approach of such patients and discussion of the goals of care, the role of molecular testing, chemotherapy regimens and novel agents to consider, the role of maintenance therapy, and the use of high-dose chemotherapy with autologous stem cell rescue. The data referenced are often limited to subgroup analyses and/or compiled from multiple sources. Although not intended to replace the clinical judgement of treating physicians, these guidelines are intended to support clinicians and provide some clarity and recommendations for the management of patients with RR-ES. PLAIN LANGUAGE SUMMARY: Ewing sarcoma (ES) is a bone and soft tissue cancer that most often occurs in teenagers and young adults. This article uses the experience of the National Ewing Sarcoma Tumor Board, a multi-institution, multidisciplinary virtual tumor board that meets monthly to discuss challenging cases of ES and to address questions related to the treatment of patients with relapsed ES. Although not intended to replace the clinical judgement of treating physicians and limited by available data, these consensus recommendations will support clinicians who treat patients with this challenging malignancy, made even more difficult when it recurs.

The FMS-related tyrosine kinase 3 (FLT3) inhibitor gilteritinib is standard therapy for relapsed/refractory (R/R) FLT3-mutated (FLT3mut) acute myeloid leukemia (AML) but the overall survival (OS) is only approximately 20 % and few patients achieve deep and/ or durable response. We retrospectively analyzed 29 R/R FLT3mut AML patients treated on triplet regimens (gilteritinib+ venetoclax［VEN] +azacitidine［AZA]). Nineteen patients (65.5 %) had received prior FLT3 inhibitor therapy. The modified composite complete remission (mCRc) rate was 62.1 % (n = 18; CR, 4/29,13.8 %; CRi, 6/29, 20.7 %; MLFS, 8/29, 27.6 %). Among 18 patients achieved mCRc, FLT3-PCR negativity was 94.4 % (n=17), and flow-cytometry negativity was 77.7 % (n=14). The mCRc rate was 70 % (n=7) in 10 patients without prior FLT3 TKI exposure and 57.8 % (n=11) in 19 patients with prior FLT3 TKI exposure (P=0.52). At the end of the first cycle, the median time to ANC > 0.5× 109/L was 38 days and platelet > 50× 109/L was 31 days among responders, but 60-day mortality was 0 %. The estimated 2-year OS was 60.9 % for all R/R FLT3mut patients. The 1-year OS was 80 % and 58.8 % in patients without and with prior FLT3 TKI exposure, respectively (P=0.79). The estimated 2-year OS was 62 % in 19 (65.5 %) patients who received allo-HSCT after triplet therapy and 37 % in 10 patients who did not receive allo-HSCT (P=0.03). In conclusion, triplet therapy with gilteritinib, VEN, and AZA is effective and safe and an excellent frontline option for R/R FLT3mut AML.

OBJECTIVE: To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with regorafenib (hereafter, TACE-regorafenib) or camrelizumab (hereafter, TACE-camrelizumab) for treating hepatocellular carcinoma (HCC) with untreatable progression after TACE and sorafenib therapy.
METHODS: The medical records of patients with HCC who received TACE-regorafenib or TACE-camrelizumab between September 2018 and December 2023 were retrospectively evaluated. Therapeutic response, overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were compared between the two groups.
RESULTS: A total of 76 patients were enrolled in this study, with 41 and 35 patients in the TACE-regorafenib and TACE-camrelizumab groups, respectively. The objective response rates in the TACE-regorafenib and TACE-camrelizumab groups were 9.8% and 8.6%, respectively, with no statistically significant difference between the two groups (P = 0.859). Similarly, there was no statistically significant difference in disease control rates between the two groups (61.0% vs 68.6%, P = 0.838). The median OS was 11 months in the TACE-regorafenib group and 10 months in the TACE-camrelizumab group, with no significant difference between the two groups (P = 0.348). The TACE-regorafenib group had a median PFS of 7 months, which was significantly longer than that of the TACE-camrelizumab group (4 months, P = 0.004). There was no significant difference in the incidence of AEs between the two groups (P = 0.544).
CONCLUSIONS: TACE-regorafenib was safe, well-tolerated, and showed promising efficacy in patients with sorafenib-refractory advanced HCC, whereas TACE-camrelizumab demonstrated similar survival benefits.

Posterior quadrant epilepsy surgery, involving the occipital lobe, parietal lobe, or the posterior border of the temporal lobe, accounts for a small percentage of focal resections for medically refractory epilepsy. Prior studies investigating seizure control from posterior quadrant epilepsy surgery are limited. In this study, a retrospective database of patients undergoing surgery for left sided posterior cortex epilepsy at a single large level 4 epilepsy center was analyzed between August 2008 to April 2021 in order to characterize seizure control outcomes. Nine patients presented with epileptogenic foci in the left posterior cortex with a malformation of cortical development deemed as the etiology of seizures for all but one patient. Absolute seizure freedom (Engel I) was achieved in 4 of 9 patients, with the remaining 5 patients achieving an improvement in the frequency of seizures (Engel II/III). Complete resection of the anatomic and physiologic abnormalities was performed in 3 of 4 patients with Engel 1 outcomes and 1 of 5 patients with Class II/III outcomes. Five patients developed new right sided visual field defects, all of which were expected based on the sub-lobar, occipital localization and were viewed as acceptable by the patients and did not interfere with activities of daily living. Overall, our study demonstrates the potential for surgical resection to yield excellent seizure-control outcomes with anticipated, tolerable neurological deficits. This information is important for patients with disabling seizures who may not benefit sufficiently from palliative procedures.

UNASSIGNED: Refractory Mycoplasma pneumoniae pneumonia (RMPP) has a serious, rapid progression that can easily cause a variety of extra-pulmonary complications. Therefore, the early identification of RMPP is crucial. This study aimed to construct and validate a risk prediction model based on clinical manifestations, laboratory blood indicators, and radiological findings to help clinicians identify patients who are at high risk of RMPP.
UNASSIGNED: We retrospectively analyzed the medical records of 369 children with Mycoplasma pneumoniae pneumonia (MPP) admitted to Xi\'an Children\'s Hospital, China. The demographics, clinical features, laboratory data, and radiological findings between the RMPP group and the general Mycoplasma pneumoniae pneumonia (GMPP) group were compared and subjected to univariate and multivariate logistic regression analyses.
UNASSIGNED: The fever peak and duration of the children in the RMPP group (n=86) were higher and longer compared with those in the GMPP group (n=283) (P<0.05). There was a significant difference in the incidence of lobar pneumonia and pleural effusion in pulmonary imaging between the two groups (P<0.05). Laboratory tests showed that the children with RMPP had lower serum uric acid (SUA) and albumin (ALB) as compared with the GMPP group (P<0.05). White blood cells (WBCs), neutrophil count (NEP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), C-reactive protein (CRP), and neutrophil-to-lymphocyte ratio (NLR) were higher in the RMPP group (P<0.05). Binary logistic regression analysis showed that the fever duration, pleural effusion, WBC, NEP, lactate dehydrogenase (LDH), CRP, NLR, and SUA levels were independent predictors of RMPP (P<0.05). The receiver operator characteristic (ROC) curve results showed fever duration, WBC, NEP, CRP, LDH, SUA, and NLR had good predictive value. The areas under the curve (AUCs) were 0.861, 0.730, 0.758, 0.837, 0.868, 0.744, and 0.713 and the best cutoff values were 10.50, 10.13, 6.43, 29.45, 370.50, 170.50, and 3.47, respectively. Finally, fever duration of more than 10.5 days, pleural effusion, WBC >10.13×109/L, NEP >6.43×109/L, CRP >29.45 mg/L, LDH >370.50 U/L, NLR >3.47, and SUA <170.5 µmol/mL constructed a prediction model of RMPP. According to internal validation, the mean AUC of the nomogram based on the development dataset was 0.956 [95% confidence interval (CI): 0.937-0.974] with good discrimination ability for predicting RMPP patients. The calibration plot and Hosmer-Lemeshow test (P=0.70) of the prediction model showed good consistency between the predicted probability and actual probability. Decision curve analysis (DCA) showed that the nomogram is clinically useful.
UNASSIGNED: The simple and easy-to-use nomogram can help clinicians, especially primary doctors, to make early diagnoses of RMPP.

UNASSIGNED: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous but treatable immune-mediated neuropathy. Ofatumumab (OFA) is a fully human anti-CD20 monoclonal antibody that has shown promising efficacy in central demyelinating diseases, such as multiple sclerosis (MS). However, there is a lack of studies on the usage of OFA in peripheral demyelinating diseases, particularly CIDP. A case of relapsed and refractory CIDP with an ineffective response to conventional immunotherapy and intolerance to rituximab (RTX) but a positive response to subcutaneous injections of OFA is presented.
UNASSIGNED: The patient, a 46-year-old man diagnosed with CIDP, received high-dose intravenous methylprednisolone, intravenous immunoglobulin (IVIG), and plasma exchange(PE) during the acute phase of the disease, and long-term oral administration of prednisone, azathioprine (AZA), and mycophenolate mofetil (MMF) during the remission phase. However, the patient suffered six relapses over a five-year period, and because of these, along with an ineffective response to conventional immunotherapy, and intolerance to RTX, subcutaneous injections of OFA were selected as a prophylactic treatment against relapses. After a total of six injections of OFA, CD19+B cells were substantially depleted. The patient has been followed for more than 23 months without relapse.
UNASSIGNED: This case demonstrates the effectiveness and good tolerability of OFA in the treatment of relapsed and refractory CIDP. Further studies are needed to investigate the efficacy and safety of OFA in patients with relapsed and refractory CIDP, especially in those who have shown an ineffective response to conventional immunotherapy and are intolerant to RTX.

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