-
ENeurologicalSci Sep 2023Langerhans cell histiocytosis (LCH) is a rare disease that usually occurs in children <15 years of age. Adult-onset LCH is extremely rare. Previous published guidelines...
INTRODUCTION
Langerhans cell histiocytosis (LCH) is a rare disease that usually occurs in children <15 years of age. Adult-onset LCH is extremely rare. Previous published guidelines and studies mainly focused on pediatric patients. The rarity and also insufficient knowledge of LCH in adults, especially central neuvous system (CNS) involvement of LCH, often resulted in missed and delayed diagnosis.
CASE PRESENTATION
A 35-year-old woman presented with cognitive impairment, anxietydepression, decreased eyesight, skin rash, hypernatremia, gonadal hormone deficiency and hypothyroidism. She had experienced menstrual disturbance and infertility since 10 years ago. MRI examination showed a mass lesion in the hypothalamic-pituitary region. Sighs of radiologic neurodegeneration were not found on brain MRI scans, however. Biopsy of skin rash confirmed the the diagnosis of multisystem LCH. BRAF V600E mutation was detected in the peripheral blood mononuclear cells. She accepted combination chemotherapy of vindesine and prednisone and accquired partial remission. The patient died of severe pneumonia during the second course of chemotherapy.
CONCLUSION
Given the complicated differential diagnoses of neuroendocrine disorders, it was essential to be aware of CNS involvement of LCH at first, especially in adults. BRAF V600E mutation may participated in disease progression.
PubMed: 37435445
DOI: 10.1016/j.ensci.2023.100471 -
Cancer Medicine Mar 2024Blinatumomab early-line treatment in B-cell precursor acute lymphoblastic leukemia (B-ALL) might improve clinical outcomes.
BACKGROUND
Blinatumomab early-line treatment in B-cell precursor acute lymphoblastic leukemia (B-ALL) might improve clinical outcomes.
METHODS
We conducted a retrospective real-world cohort analysis in 20 newly diagnosed B-ALL patients who received reduced-dose chemotherapy (idarubicin, vindesine, and dexamethasone) for 1-3 weeks, followed by blinatumomab for 1-4 weeks as an induction therapy.
RESULTS
At the end of the induction therapy, a complete remission rate of 100% was achieved; 17 (85%) patients were minimal residual disease (MRD) negative (<1 × 10 ). Adverse events (AEs) were reported in 12 (60%) patients-43.8% were grade 1-2 and 56.2% were grade 3-4. No incidence of neurotoxicity or grade ≥3 cytokine release syndrome was reported.
CONCLUSIONS
Blinatumomab demonstrated a significant improvement in clinical outcomes in patients with newly diagnosed B-ALL irrespective of their poor-risk factor status and the pretreatment blast burden.
Topics: Humans; Retrospective Studies; Induction Chemotherapy; Antibodies, Bispecific; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Burkitt Lymphoma
PubMed: 38491815
DOI: 10.1002/cam4.7062 -
Frontiers in Oncology 2023SSBP2-CSF1R is an important biomarker for clinical diagnosis and prognosis of Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL). This case report...
SSBP2-CSF1R is an important biomarker for clinical diagnosis and prognosis of Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL). This case report presents a pediatric Ph-like ALL patient carrying the SSBP2-CSF1R fusion gene. The patient was resistant to most conventional chemotherapy regimens and to dasatinib, an inhibitor that has been reported to have a therapeutic effect on SSBP2-CSF1R fusion Ph-like ALL, as she remained minimal residual disease (MRD) positive (detection by flow cytometry) and SSBP2-CSF1R fusion gene (detection by RT-PCR) positive after five rounds of such regimens. We thus conducted a large-scale screening to assess the sensitivity of the patient's leukemic cells to anti-cancer drugs. Based on the susceptibility results, we chose to combine cytarabine, homoharringtonine, dexamethasone, fludarabine, vindesine, and epirubicin for treatment. Clinical results showed that after a course of treatment, both MRD and SSBP2-CSF1R fusion gene turned negative, and there was no recurrence during an 18-month follow-up. In conclusion, our study suggests that the SSBP2-CSF1R fusion gene may be an important biomarker of primary drug resistance in Ph-like ALL, and indicate that the combination of cytarabine, homoharringtonine, dexamethasone, fludarabine, vindesine, and epirubicin can achieve optimal therapeutic results in this category of patients.
PubMed: 38107066
DOI: 10.3389/fonc.2023.1291570 -
Pharmaceuticals (Basel, Switzerland) Jul 2023Multidrug resistance (MDR) is one of the most problematic issues in chemotherapeutic carcinoma therapy. The ABCB1 transporter, a drug efflux pump overexpressed in cancer...
In-Silico Mining of the Toxins Database (T3DB) towards Hunting Prospective Candidates as ABCB1 Inhibitors: Integrated Molecular Docking and Lipid Bilayer-Enhanced Molecular Dynamics Study.
Multidrug resistance (MDR) is one of the most problematic issues in chemotherapeutic carcinoma therapy. The ABCB1 transporter, a drug efflux pump overexpressed in cancer cells, has been thoroughly investigated for its association with MDR. Thus, discovering ABCB1 inhibitors can reverse the MDR in cancer cells. In the current work, a molecular docking technique was utilized for hunting the most prospective ABCB1 inhibitors from the Toxin and Toxin-Target Database (T3DB). Based on the docking computations, the most promising T3DB compounds complexed with the ABCB1 transporter were subjected to molecular dynamics (MD) simulations over 100 ns. Utilizing the MM-GBSA approach, the corresponding binding affinities were computed. Compared to ZQU (calc. -49.8 kcal/mol), Emamectin B1a (T3D1043), Emamectin B1b (T3D1044), Vincristine (T3D4016), Vinblastine (T3D4017), and Vindesine (T3D2479) complexed with ABCB1 transporter demonstrated outstanding binding affinities with Δ values of -93.0, -92.6, -93.8, -92.2, and -90.8 kcal/mol, respectively. The structural and energetic investigations confirmed the constancy of the identified T3DB compounds complexed with the ABCB1 transporter during the 100 ns MD course. To mimic the physiological conditions, MD simulations were conducted for those identified inhibitors complexed with ABCB1 transporter in the presence of a POPC membrane. These findings revealed that Emamectin B1a, Emamectin B1b, Vincristine, Vinblastine, and Vindesine are promising ABCB1 inhibitors that can reverse the MDR. Therefore, subjecting those compounds to further in-vitro and in-vivo investigations is worthwhile.
PubMed: 37513931
DOI: 10.3390/ph16071019 -
The Oncologist May 2024Pegylated liposomal doxorubicin (PLD) is a liposome-encapsulated form of doxorubicin with equivalent efficacy and less cardiotoxicity. This phase 2 study evaluated the...
BACKGROUND
Pegylated liposomal doxorubicin (PLD) is a liposome-encapsulated form of doxorubicin with equivalent efficacy and less cardiotoxicity. This phase 2 study evaluated the efficacy and safety of the PLD-containing CHOP regimen in newly diagnosed patients with aggressive peripheral T-cell lymphomas (PTCL).
METHODS
Patients received PLD, cyclophosphamide, vincristine/vindesine, plus prednisone every 3 weeks for up to 6 cycles. The primary endpoint was the objective response rate at the end of treatment (EOT).
RESULTS
From September 2015 to January 2017, 40 patients were treated. At the EOT, objective response was achieved by 82.5% of patients, with 62.5% complete response. As of the cutoff date (September 26, 2023), median progression-free survival (mPFS) and overall survival (mOS) were not reached (NR). The 2-year, 5-year, and 8-year PFS rates were 55.1%, 52.0%, and 52.0%. OS rate was 80.0% at 2 years, 62.5% at 5 years, and 54.3% at 8 years. Patients with progression of disease within 24 months (POD24) had worse prognosis than those without POD24, regarding mOS (41.2 months vs NR), 5-year OS (33.3% vs 94.4%), and 8-year OS (13.3% vs 94.4%). Common grade 3-4 adverse events were neutropenia (87.5%), leukopenia (80.0%), anemia (17.5%), and pneumonitis (17.5%).
CONCLUSION
This combination had long-term benefits and manageable tolerability, particularly with less cardiotoxicity, for aggressive PTCL, which might provide a favorable benefit-risk balance.
CLINICALTRIALS.GOV IDENTIFIER
Chinese Clinical Trial Registry, ChiCTR2100054588; IRB Approved: Ethics committee of Fudan University Shanghai Cancer Center (Date 2015.8.31/No. 1508151-13.
PubMed: 38821519
DOI: 10.1093/oncolo/oyae108 -
Medicine Oct 2023Subcutaneous panniculitis like T-cell lymphoma (SPTCL) is a rare primary cutaneous lymphoma that belongs to peripheral T cell lymphomas, of which the overall prognosis...
RATIONALE
Subcutaneous panniculitis like T-cell lymphoma (SPTCL) is a rare primary cutaneous lymphoma that belongs to peripheral T cell lymphomas, of which the overall prognosis is poor. Chidamide, a deacetylase inhibitor, has been approved for the treatment of peripheral T cell lymphomas. However, due to the rare occurrence of SPTCL, it is currently unknown whether Chidamide is effective for all SPTCL patients and whether there are molecular markers that can predict its therapeutic effect on SPTCL.
PATIENT CONCERNS AND DIAGNOSES
The patient was a sixteen-year-old male and underwent subcutaneous nodule biopsy which showed SPTCL. Next-generation sequencing revealed AT-rich interaction domain 1A (ARID1A) mutation, and positron emission tomography/computed tomography showed scattered subcutaneous fluorodeoxyglucose metabolic lesions throughout the body.
INTERVENTIONS AND OUTCOMES
During the first 3 CHOP (cyclophosphamide, doxorubicin, vindesine, and prednisone) treatment, the patient relapsed again after remission, and the successive addition of methotrexate and cyclosporine did not make the patient relapsing again. Then, after adding Chidamide to the last 3 CHOP treatment, the patient was relieved again. The patient underwent autologous hematopoietic stem cell transplantation (auto-HSCT) after completing a total of 8 cycles of chemotherapy, and continued maintenance therapy with Chidamide after auto-HSCT. Currently, the patient has been in continuous remission for 35 months.
LESSONS SUBSECTIONS
This case is the first report of a refractory/recurrent SPTCL with ARID1A mutation treated with Chidamide. The treatment of Chidamide on the basis of CHOP plus auto-HSCT therapy achieved good results, suggesting that ARID1A may act as a molecular marker to predict the therapeutic effect of Chidamide on SPTCL patients, which helps to improve the precision of SPTCL treatment and the overall prognosis of SPTCL patients.
Topics: Male; Humans; Adolescent; Lymphoma, T-Cell, Peripheral; Neoplasm Recurrence, Local; Lymphoma, T-Cell; Hematopoietic Stem Cell Transplantation; Panniculitis; Mycosis Fungoides; Skin Neoplasms; Antineoplastic Combined Chemotherapy Protocols; DNA-Binding Proteins; Transcription Factors
PubMed: 37800816
DOI: 10.1097/MD.0000000000035413 -
Frontiers in Oncology 2023Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid malignancy and also has an excellent prognosis. Primary thyroid lymphoma (PTL) is rare...
Coexistence of primary thyroid diffuse large B cell lymphoma and papillary thyroid carcinoma in a patient with Hashimoto's thyroiditis: a case report and literature review.
Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid malignancy and also has an excellent prognosis. Primary thyroid lymphoma (PTL) is rare and has a poor prognosis. The co-occurrence of both malignancies is extremely rare, and the preoperative diagnosis is rather difficult. We report the case of a patient with both PTC and PTL in the setting of Hashimoto's thyroiditis (HT). A 59-year-old female patient was referred to our department for progressive enlargement of the thyroid gland over a few months. The imaging results demonstrated an enlarged thyroid and a mass in the thyroid. Total thyroidectomy and bilateral central neck node dissection were conducted. The final diagnosis of the coexistence of thyroid diffuse large B cell lymphoma and PTC was confirmed by histopathology and immunohistochemistry. The patient received radiation therapy and six cycles of chemotherapy combined with targeted therapy, including rituximab, cyclophosphamide, doxorubicin, vindesine, and prednisone (R-CHOP). After 6 months of follow-up, neither tumor has recurred. It is important for physicians to keep PTL in mind for differential diagnosis in HT patients with sudden thyroid enlargement.
PubMed: 37869091
DOI: 10.3389/fonc.2023.1248830