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Journal of Medical Case Reports May 2024All-trans retinoic acid (ATRA) is an indispensable part of the treatment of acute promyelocytic leukemia (APL). Although, mild cutaneous toxicities like mucocutaneous... (Review)
Review
A rare incidence of severe dermatological toxicities triggered by concomitant administration of all-trans retinoic acid and triazole antifungal in patients with acute promyelocytic leukemia: a case series and review of the literature.
BACKGROUND
All-trans retinoic acid (ATRA) is an indispensable part of the treatment of acute promyelocytic leukemia (APL). Although, mild cutaneous toxicities like mucocutaneous xerosis, rash, and pruritus are well reported, ATRA associated severe dermatological toxicities are extremely rare. ATRA is primary metabolized by cytochrome P450 (CYP450) enzyme system, and triazole antifungals are notorious for their strong inhibitory effect on CYP450.
CASE PRESENTATION
Three Asian APL patients experienced rare ATRA-induced severe dermatological toxicities: exfoliative dermatitis (ED) in cases 1 and 2, and necrotic scrotal ulceration in case 3. Both case 1 (33-year-old female), and case 2 (28-year-old male) landed in emergency department with dehydration, generalized skin erythema and xerosis during their induction chemotherapy. Both of these patients also developed invasive aspergillosis and required concomitant triazole antifungals during their chemotherapy. For ED, intravenous fluids and broad-spectrum antibiotics were started along with application of local emollients to prevent transdermal water loss. Although their general condition improved but skin exfoliation continued with complete desquamation of palms and soles. Dermatology was consulted, and clinical diagnosis of ED was established. Discontinuation of ATRA resulted in complete resolution of ED. Case 3 (15-year-old boy) reported two blackish mildly tender scrotal lesions during induction chemotherapy. He also had mucocutaneous candidiasis at presentation and was kept on triazole antifungal. Local bacterial & fungal cultures, and serological testing for herpes simplex virus were reported negative. Despite adequate local care and optimal antibiotic support, his lesions persisted, and improved only after temporary discontinuation of ATRA. After a thorough literature review and considering the temporal association of cutaneous toxicities with triazole antifungals, we speculate that the concomitant use of triazole antifungals inhibited the hepatic metabolism of ATRA, resulting in higher serum ATRA concentration, and markedly accentuated cutaneous toxicities in our patients.
CONCLUSION
By highlighting this crucial pharmacokinetic interaction, we want to caution the fellow oncologists to be mindful of the inhibitory effect of triazole antifungals on CYP450. We propose using a non-myelosuppressive combination of ATRA and arsenic trioxide for management of APL hence, obliterating the need of prophylactic antifungals. However, in the event of invasive fungal infection (IFI), we suggest using alternative class of antifungals.
Topics: Humans; Leukemia, Promyelocytic, Acute; Male; Antifungal Agents; Female; Tretinoin; Adult; Triazoles; Antineoplastic Agents; Aspergillosis; Drug Eruptions
PubMed: 38797854
DOI: 10.1186/s13256-024-04577-1 -
PloS One 2024Iron deficiency anemia (IDA) is a prevalent hematological complication associated with gastrointestinal (GI) cancers due to an increased loss of iron and decreased iron...
BACKGROUND
Iron deficiency anemia (IDA) is a prevalent hematological complication associated with gastrointestinal (GI) cancers due to an increased loss of iron and decreased iron absorption. The purpose of this systematic review is to evaluate the use of parenteral iron to treat IDA in patients with GI cancer.
METHODS
PubMed, Cochrane, EMBASE, CINHAL and Scopus were searched from January 1, 2010 to September 29, 2023 with no language restrictions. We excluded editorials, case reports, abstracts, conference papers, and poster presentations. Studies were included if they discussed IDA, GI neoplasms, use of iron supplementation (with or without erythropoietin-stimulating agents [ESAs]), defined anemia and had an adult patient population. We assessed the efficacy of parenteral iron in comparison to other iron supplementation methods when treating IDA in patients with GI cancer. The Cochrane Risk of Bias Tool 2 (RoB 2) and the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) assessment tools were used to assess the quality of the included studies. Moreover, the Cochrane Effective Practice and Organization data collection form was used to collect pertinent study information.
RESULTS
Our search yielded 3,969 studies across all databases. Twenty-one studies were included (6 randomized control trials; 15 non-randomized studies). Of the 15 studies evaluating hemoglobin (Hb) response, seven studies found an increase in Hb levels when patients were treated with IV iron. The 14 studies evaluating red blood cell (RBC) transfusion rates found conflicting differences in RBC transfusion needs when treated with IV iron. Studies analyzing health related outcomes typically found an increase in quality of life and decreased post-operative complications.
DISCUSSION
This review demonstrates improved outcomes of IDA in patients with GI cancer treated with IV iron instead of other iron supplementation methods. Timely diagnosis and appropriate IDA management can greatly improve quality of life in this patient population, especially if myelosuppressive chemotherapy is required.
Topics: Humans; Anemia, Iron-Deficiency; Gastrointestinal Neoplasms; Iron; Administration, Intravenous
PubMed: 38776289
DOI: 10.1371/journal.pone.0302964 -
Frontiers in Oncology 2024Ovarian cancer is a prevalent malignant tumor of the female reproductive system, often remaining concealed until it reaches an advanced stage. The standard treatment...
Ovarian cancer is a prevalent malignant tumor of the female reproductive system, often remaining concealed until it reaches an advanced stage. The standard treatment protocol includes cytoreductive surgery for ovarian cancer plus postoperative consolidation chemotherapy and maintenance therapy, although it carries a high recurrence rate. During the treatment period, chemotherapy can lead to bone marrow suppression, a condition known as Chemotherapy-Induced Myelosuppression (CIM). This suppression may necessitate dose reduction or chemotherapy treatment cycle delay. In severe cases, CIM can result in infection, fever, and potential harm to the patient's life. Here, we report a case of a female patient with ovarian malignant tumor of biochemical recurrence who treated with chemotherapy combined with Trilaciclib, following previous perioperative chemotherapy with occurrence of severe CIM. It involves an intravenous injection of Trilaciclib before chemotherapy, which significantly abates the side effects of chemotherapy, reduces the occurrence of severe CIM, improves the patients' quality of life, and decreases the economic burden of hospitalization. We hope that this retrospective analysis of the case may serve as a reference in preventing and treating severe CIM during chemotherapy in some patients with malignant tumors, ultimately benefiting more patients with tumors.
PubMed: 38764584
DOI: 10.3389/fonc.2024.1343239 -
Frontiers in Neurology 2024The efficacy and safety of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with whole-brain radiotherapy (WBRT) for treating brain...
BACKGROUND
The efficacy and safety of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with whole-brain radiotherapy (WBRT) for treating brain metastases in non-small cell lung cancer patients remains to be determined.
METHODS
A systematic search was conducted using databases including PubMed, Embase, Web of Science, Cochrane, Wanfang, and China National Knowledge Infrastructure (CNKI), aiming to identify relevant clinical studies on the treatment of brain metastases originating from non-small cell lung cancer through the combination of EGFR-TKI and WBRT. Statistical analysis was performed utilizing Stata 17.0 software, covering clinical studies published until March 1, 2023.
RESULTS
This analysis incorporated 23 randomized controlled trials (RCTs), involving a total of 2,025 patients. Of these, 1,011 were allocated to the group receiving both EGFR-TKI and WBRT, while 1,014 were assigned to the WBRT alone group. The findings reveal that the combination of EGFR-TKI and WBRT significantly improves the intracranial objective remission rate (RR = 1.57, 95% CI: 1.42-1.74, < 0.001), increases the intracranial disease control rate (RR = 1.30, 95% CI: 1.23-1.37, < 0.001), and enhances the 1-year survival rate (RR = 1.48, 95% CI: 1.26-1.73, < 0.001). Additionally, this combined treatment was associated with a significant survival advantage (RR = 1.48, 95% CI: 1.26-1.73, < 0.001) and a reduced incidence of adverse effects (RR = 0.65, 95% CI: 0.51-0.83, < 0.001), particularly with respect to nausea and vomiting (RR = 0.54, 95% CI: 0.37-0.81, = 0.002) and myelosuppression (RR = 0.59, 95% CI: 0.40-0.87, = 0.008). However, no statistically significant differences were observed for diarrhea (RR = 1.15, 95% CI: 0.82-1.62, = 0.418), and skin rash (RR = 1.35, 95% CI: 0.88-2.07, = 0.164).
CONCLUSION
In contrast to WBRT alone, the combination of EGFR-TKI and WBRT significantly improves intracranial response, enhancing the objective response rate, disease control rate, and 1-year survival rate in NSCLC patients with brain metastases. Moreover, aside from mild cases of rash and diarrhea, there is no statistically significant increase in the incidence of additional adverse effects. Based on the comprehensive evidence collected, the use of third-generation EGFR-TKI combined with WBRT is recommended as the preferred treatment for NSCLC patients with brain metastases, offering superior management of metastatic brain lesions.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/#, CRD42023415566.
PubMed: 38737351
DOI: 10.3389/fneur.2024.1362061 -
The Lancet. Haematology Jun 2024Genetically engineered chimeric antigen receptor (CAR) T cells have become an effective treatment option for several advanced B-cell malignancies. Haematological... (Review)
Review
Genetically engineered chimeric antigen receptor (CAR) T cells have become an effective treatment option for several advanced B-cell malignancies. Haematological side-effects, classified in 2023 as immune effector cell-associated haematotoxicity (ICAHT), are very common and can predispose for clinically relevant infections. As haematopoietic reconstitution after CAR T-cell therapy differs from chemotherapy-associated myelosuppression, a novel classification system for early and late ICAHT has been introduced. Furthermore, a risk stratification score named CAR-HEMATOTOX has been developed to identify candidates at high risk of ICAHT, thereby enabling risk-based interventional strategies. Therapeutically, growth factor support with granulocyte colony-stimulating factor (G-CSF) is the mainstay of treatment, with haematopoietic stem cell (HSC) boosts available for patients who are refractory to G-CSF (if available). Although the underlying pathophysiology remains poorly understood, translational studies from the past 3 years suggest that CAR T-cell-induced inflammation and baseline haematopoietic function are key contributors to prolonged cytopenia. In this Review, we provide an overview of the spectrum of haematological toxicities after CAR T-cell therapy and offer perspectives on future translational and clinical developments.
Topics: Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Granulocyte Colony-Stimulating Factor; T-Lymphocytes; Hematologic Diseases
PubMed: 38734026
DOI: 10.1016/S2352-3026(24)00077-2 -
Cureus Apr 2024Methotrexate (MTX) is a well-established drug for the use of various neoplastic disorders. Recently, it has been widely used as a disease-modifying antirheumatic drug...
Methotrexate (MTX) is a well-established drug for the use of various neoplastic disorders. Recently, it has been widely used as a disease-modifying antirheumatic drug (DMARD) in low doses, mainly for rheumatoid arthritis (RA) and psoriasis. The drug is known to cause renal damage as well as be excreted via the kidneys, thus causing a higher incidence of adverse effects in patients with impaired renal function. The side effects of MTX toxicity range from mucocutaneous ulcers to nephrotoxicity and bone marrow depression, all of which are seen in this case. Here, we report an elderly male in his late 60s who was prescribed MTX 15 mg once a week along with folic acid 5 mg for RA by a general practitioner. Despite being prescribed once weekly, he continued to take MTX daily without following up with a physician for a span of five months. Following this, he presented to the medicine outpatient department with odynophagia due to oral ulcers for 10 days. He was diagnosed with MTX toxicity, causing nephropathy, myelosuppression, and mucocutaneous ulcerations. He was treated with injectable leucovorin 100 mg thrice a day until the toxicity subsided, leading to his eventual recovery.
PubMed: 38721177
DOI: 10.7759/cureus.57797 -
BMC Pediatrics May 2024Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder in children, and liver involvement in LCH is rare. This retrospective study reported the...
Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder in children, and liver involvement in LCH is rare. This retrospective study reported the clinical features and prognosis of patients with hepatic LCH. Liver involvement was defined by histopathological findings, liver dysfunction or abnormalities, or ultrasound imaging. A total of 130 patients (14.5%) with hepatic LCH out of 899 in the LCH population were enrolled. Patients with liver involvement had greater frequencies of skin, lung, hearing system, and haematologic system involvement, and hemophagocytic lymphohistiocytosis (P<0.001, 0.001, 0.002, 0.009, and <0.001, respectively). Overall survival and progression-free survival were lower in LCH patients with liver involvement than in those without liver involvement (P<0.001 and <0.001). In patients with liver involvement, the overall survival (OS) and progression-free survival (PFS) rates were lower in patients with cholangitis than in those without cholangitis (P<0.020 and 0.030). For the treatment response, the response rate of hepatic LCH patients to initial first-line therapy (n=89) was 22.5%. However, there was no significant difference in the response rate or recurrence rate between patients who shifted from first-line treatment to second-line treatment (n=29) or to targeted therapy (n=13) (P=0.453 and 1.000). The response rate of hepatic LCH patients who received initial second-line therapy (n=13) was 38.5%. Two of these patients subsequently experienced bone recurrence. The response rate of hepatic LCH patients who received initial targeted therapy (n=16) was 75.0%. Three patients subsequently experienced recurrence, including 2 in the bone and 1 in the liver and skin. A total of 39.3% of patients who received second-line treatment had severe myelosuppression (grade III-IV), and 50.8% had varying degrees of gastrointestinal events, whereas there was no severe toxicity in patients who received first-line treatment and targeted therapy. Four patients underwent liver transplantation because of liver cirrhosis. The patients' liver disease improved within a follow-up period of 18-79 months. This study demonstrated that LCH with liver involvement, especially cholangitis, indicates a poor prognosis. Targeted therapy provides a good treatment response and less toxicity. However, it may relapse after withdrawal. Liver transplantation is still a reliable salvage option for patients with end-stage liver disease.
Topics: Humans; Histiocytosis, Langerhans-Cell; Male; Female; Retrospective Studies; Child, Preschool; Infant; Child; Liver Diseases; Treatment Outcome; Adolescent; Prognosis
PubMed: 38714959
DOI: 10.1186/s12887-024-04764-5 -
The American Journal of Managed Care May 2024Numerous advances in the standard of care for metastatic colorectal cancer (mCRC), including the approval of several new treatments indicated for treatment in the third...
Numerous advances in the standard of care for metastatic colorectal cancer (mCRC), including the approval of several new treatments indicated for treatment in the third line or later (3L+), have been made, yet data and appropriate guidance on the optimal sequencing and treatment strategies for these lines of therapy are lacking. Four treatments-regorafenib, trifluridine/tipiracil alone or with bevacizumab, and fruquintinib-are FDA-approved and recommended by the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for the treatment of mCRC in the 3L+. When considering sequencing of treatment options for patients in the 3L+, the goal of treatment is to improve survival, but also maintain quality of life, a goal that requires consideration of relative efficacy and cumulative toxicity such as persistent myelosuppression.
Topics: Humans; Colorectal Neoplasms; Trifluridine; Antineoplastic Combined Chemotherapy Protocols; Thymine; Bevacizumab; Pyridines; Phenylurea Compounds; Pyrrolidines; Drug Combinations; Neoplasm Metastasis; Quality of Life
PubMed: 38701364
DOI: 10.37765/ajmc.2024.89546 -
Frontiers in Medicine 2024is a gram-negative bacterium. In recent years, has gradually attracted increasing attention due to its strong virulence and poor prognosis. Clinical reports of...
BACKGROUND
is a gram-negative bacterium. In recent years, has gradually attracted increasing attention due to its strong virulence and poor prognosis. Clinical reports of pulmonary infection caused by are rare.
CASE PRESENTATION
A patient with acute T lymphoblastic leukemia experienced myelosuppression after chemotherapy, developed a secondary pulmonary infection with and was hospitalized due to fever. The patient underwent testing for inflammatory markers, chest imaging, blood culture, bronchoalveolar lavage, pleural drainage, and metagenomic next-generation sequencing of alveolar lavage fluid and pleural fluid to obtain evidence of infection, and was treated with four generations of cephalosporin combined with fluoroquinolone antibiotics. The patient's condition significantly improved.
DISCUSSION
Among pulmonary infectious pathogens, is relatively rare. Once an strain is cultured in the clinical work, pathogenic sequencing should be performed on the detected samples for early accurate diagnosis and effective anti-infection treatment.
PubMed: 38698785
DOI: 10.3389/fmed.2024.1357714 -
In Vivo (Athens, Greece) 2024Immune checkpoint inhibitors can induce immune-related adverse events in various organs, thus careful observation is required.
BACKGROUND/AIM
Immune checkpoint inhibitors can induce immune-related adverse events in various organs, thus careful observation is required.
CASE REPORT
A 69-year-old man was diagnosed with advanced lung adenocarcinoma and treated with combined therapy of carboplatin plus pemetrexed plus pembrolizumab. After two cycles of treatment, anemia was noted. Myelosuppression due to cytotoxic anticancer agents was suspected and the cytotoxic agents were discontinued, followed by three courses of pembrolizumab monotherapy. However, the anemia persisted, requiring red blood cell transfusions. A bone marrow biopsy revealed erythroblast hypoplasia and chromosomal abnormalities, resulting in a diagnosis of pure red cell aplasia. These adverse events were considered immune-related because of the treatment history with an immune checkpoint inhibitor, and 60 mg/day (1 mg/kg/day) of prednisolone was initiated. Anemia improved, and it did not recur during the tapering of prednisolone.
CONCLUSION
Immune-related pure red cell aplasia should be considered for patients presenting anemia during treatment with immune checkpoint inhibitors.
Topics: Humans; Red-Cell Aplasia, Pure; Male; Aged; Adenocarcinoma of Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Chromosome Aberrations; Antineoplastic Combined Chemotherapy Protocols; Antibodies, Monoclonal, Humanized
PubMed: 38688637
DOI: 10.21873/invivo.13599