Acute lymphoblastic leukemia (ALL) is an uncommon and rapidly progressing blood cancer originating in the bone marrow, characterized by the abnormal proliferation of immature lymphocytes. Although most cases of ALL are observed in children, the disease pattern shows two peaks: one in early childhood and another around the age of 50. Approximately a fifth to a third of adults diagnosed with ALL exhibit cytogenetic abnormalities involving the Philadelphia chromosome. Despite the existence of several studies on Philadelphia chromosome-positive ALL (Ph+ ALL), our case accentuates the use of a multi-disciplinary approach to treatment and involves a patient from a unique demographic.

The use of tyrosine kinase inhibitors (TKIs) has become the mainstay of treatment in patients suffering from chronic myeloid leukemia (CML), an adult leukemia caused by a reciprocal translocation between chromosomes 9 and 22, which creates an oncogene resulting in a myeloproliferative neoplasm. These drugs function by inhibiting the ATP-binding site on the fusion oncoprotein and subsequently halting proliferative activity. The goal of this work is to investigate the current state of research into genetic factors that influence the efficacy of four FDA-approved TKIs used to treat CML. This overview attempts to identify genetic criteria that could be considered when choosing one drug over the others and to identify where more research is needed. Our results suggest that the usual liver enzymes impacting patient response may not be a major factor affecting the efficacy of imatinib, nilotinib, and bosutinib, and yet, that is where most of the past research has focused. More research is warranted on the impact that human polymorphisms of the CYP enzymes have on dasatinib. The impact of polymorphisms in UGT1A1 should be investigated thoroughly in other TKIs, not only nilotinib. The role of influx and efflux transporters has been inconsistent thus far, possibly due to failures to account for the multiple proteins that can transport TKIs and the impact that tumors have on transporter expression. Because physicians cannot currently use a patient\'s genetic profile to better target their treatment with TKIs, it is critical that more research be conducted on auxiliary pathways or off-target binding effects to generate new leads for further study. Hopefully, new avenues of research will help explain treatment failures and improve patient outcomes.

This case report presents the clinical details of a 42-year-old female without previous medical issues who presented with upper gastrointestinal bleeding (UGIB) characterized by melanotic stools. Initial examination revealed mild anemia and subsequent endoscopy identified a 4 cm submucosal gastric mass displaying recent bleeding indicators. Subsequent surgical pathology confirmed a high-grade gastrointestinal stromal tumor (GIST) of grade 2 with a heightened risk of recurrence. The significance of this case lies in underscoring the necessity of considering GIST in the differential diagnosis of UGIB, particularly among middle-aged individuals with no identifiable risk factors such as recent or chronic non-steroidal anti-inflammatory drug (NSAID) use, peptic ulcer disease, or alarm symptoms. Early detection and prompt surgical intervention assume paramount importance in enhancing patient outcomes. While complete resection stands as the cornerstone of treatment, adjuvant imatinib therapy is recommended for high-risk patients to mitigate the risk of recurrence.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tract and is most commonly seen in the stomach. The standard treatment for patients with advanced GISTs include both surgical resection and imatinib therapy. There have been cases that document the alterations of patients\' GIST histomorphology both with primary GIST prior to imatinib therapy and with recurrent GIST after imatinib therapy. However, there has been no documented case of a patient who has recurrent GIST with chondroid differentiation at the primary site after imatinib therapy. In this article, we report an incidental finding of a 58-year-old patient who had two treatments of imatinib therapy prior to surgical resection of her recurrent GIST in her stomach. We also explore through a mini-literature review the various cases of GIST with chondroid differentiation that have been reported to compare the histomorphology, immunophenotype, and patient demographic of these cases. This article is significant for reporting a rare finding of GIST after imatinib therapy and highlights the various presentations that GIST could acquire after imatinib therapy that exclude another malignant process, such as chondrosarcoma.

A 50-year-old female presented with symptomatic anemia and hematemesis due to a 3.3 cm gastric gastrointestinal stromal tumor (GIST), which was located in the fundus. Adequate endoscopic views were only achieved in the retroflexed position and attempts at hemostasis via endoscopic clips were unsuccessful. Subsequently, TC-325 hemostatic powder was sprayed on the bleeding lesion and given retroflexed positioning, the powder also coated the esophagogastroduodenoscopy (EGD) scope where it abutted the gastroesophageal junction (GEJ). Hemostasis was successful, but the scope was unable to be withdrawn due to adherence to the surrounding mucosa. With torque maneuvering and a moderate amount of withdrawal force, the scope was successfully freed. The patient was started on imatinib mesylate and did not experience further bleeding episodes. This case highlights the challenge of achieving hemostasis in a bleeding GIST, the beneficial role of hemostatic powder spray, and the need for caution when utilizing it in a retroflexed manner.

Mediastinal hematomas are thoracic complications often resulting from direct trauma or aortic dissections. Spontaneous non-traumatic mediastinal hematomas are rare. We present a case of spontaneous non-traumatic mediastinal hematoma in a patient on Imatinib therapy for a gastrointestinal stromal tumor (GIST). A 67-year-old female presented to the ER with the chief complaint of constant sharp right shoulder pain that progressed to her chest. The patient was not on any anticoagulants and had not complained of shortness of breath. Under suspicion of a pulmonary embolism, a CT chest scan was performed, and a diagnosis of non-traumatic anterior mediastinal hematoma was confirmed. This case may warrant further investigation into the links between Imatinib use and the formation of mediastinal hematomas.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affecting multiple organ systems. It can cause severe cytokine storms leading to intensive care unit admission requiring mechanical ventilation. However, there have been few studies establishing the outcomes of chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitors who are infected with COVID-19. We present a 69-year-old male with a history of CML on imatinib therapy with COVID-19 who developed acute respiratory distress syndrome needing mechanical ventilatory support, shock requiring vasopressors, and worse outcome secondary to blast crisis.

BACKGROUND: Familial gastrointestinal stromal tumors (GISTs) is a rare autosomal dominant disorder characterized by an array of clinical manifestations. Only 35 kindreds with germline KIT mutations and six with germline PDGFRA mutations have been reported so far. It is often characterized by a series of manifestations, such as multiple lesions and hyperpigmentation. However, the effect of imatinib treatment in these patients is still uncertain.
METHODS: Here, we report two patients (father and daughter) in a Chinese family (for the first time) with germline KIT mutation, and described their pathology, genetics and clinical manifestations. A 25-year-old Chinese woman went to hospital because of abdominal pain, and computed tomography showed multiple tumors in the small intestine. Small pigmented spots appeared on the skin within a few months after birth. Her father also had multiple pigmented spots and a history of multifocal GISTs. Multiple GISTs associated with diffuse interstitial Cajal cells (ICCs) hyperplasia were positive for CD117 and DOG-1. Gene sequencing revealed a germline mutation at codon 560 of exon 11 (p.V560G) of KIT gene in these two patients. Imatinib therapy showed the long-lasting disease stability after resection. Remarkably, the hypopigmentation of the skin could also be observed. Luckily germline KIT mutation has not been identified yet in the 3-year-old daughter of the female patient.
CONCLUSIONS: Diagnosis of familial GISTs depends on combination of diffuse ICCs hyperplasia, germline KIT/PDGFRA mutation, hyperpigmentation and family history.

Xeroderma pigmentosum complementation group C (XPC), a DNA repair protein, plays an important role in the maintenance of genomic integrity and is essential for the nucleotide excision repair pathway. Polymorphisms in the XPC gene may alter DNA repair leading to genetic instability and oncogenesis. The present study aimed to assess the relationship between the XPC Ala499Val (rs2228000 C>T) and Lys939Gln (rs2228001 A>C) non-synonymous polymorphisms and susceptibility to chronic myeloid leukemia (CML) pathogenesis, disease progression and the response to targeted therapeutic regimen, imatinib mesylate.
This case-control study included 212 cases and 212 controls, and the genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism assays.
Our results showed significant association of variant CT (odds ratio = 1.92, 95% confidence interval = 1.21-3.06, p = 0.003) and TT (odds ratio = 2.84, 95% confidence interval = 1.22-6.71, p = 0.007) genotypes in patients with the XPC Ala499Val polymorphism and CML risk. In addition, these genotypes were associated with CML progression to advanced phases (p = 0.006), splenomegaly (p = 0.017) and abnormal lactate dehydrogenase levels (p = 0.03). XPC Lys939Gln was found to correlate with a poor response to therapy, showing borderline significant association with minor cytogenetic response (p = 0.08) and a poor molecular response (p = 0.06). Significant association of the Ala499Val and Lys939Gln polymorphisms with prognosis was observed (Hasford high risk, p = 0.031 and p = 0.019, respectively). Haplotype analysis showed a strong correlation of variant TC haplotype with poor therapy responses (minor cytogenetic response, p = 0.019; poor molecular response, p < 0.0001).
In conclusion, our results suggest that XPC Ala499Val is a high-penetrance CML susceptibility polymorphism. Both polymorphisms studied are considered as genetic markers with respect to assessing disease progression, therapy response and prognosis in CML patients.

Imatinib mesylate is a tyrosine kinase inhibitor with high efficacy in the treatment of chronic myeloid leukemia (CML). Although fluid retention is a common adverse effect of imatinib, it rarely necessitates discontinuation of therapy. Isolated ascites has not been reported as a complication of imatinib therapy in patients with CML. Here, we report the case of a 72-year-old male with CML on imatinib (600 mg daily), who developed ascites two weeks after a laparoscopic hernia repair with intraperitoneal placement of a nylon mesh. The ascites was resistant to diuretic therapy and required repeated large-volume paracentesis. Discontinuation of imatinib resulted in arrest of ascites production, but reintroduction of the drug at the same dose two weeks later was rapidly followed by recurrence of ascites requiring further therapeutic paracenteses. It was postulated that peritoneal inflammation had resulted in increased capillary permeability, which was further augmented by imatinib via inhibition of platelet-derived growth factor receptor (PDGFR), a tyrosine kinase known to play a significant physiological role in the regulation of interstitial fluid pressure and capillary permeability. The possibility of developing ascites after abdominal surgery should be considered in patients receiving imatinib or related PDGFR inhibitors. In such cases, perioperative interruption of tyrosine kinase therapy might be indicated.