Anaplastic Lymphoma Research Articles

Diagnostic and management challenges in primary cutaneous anaplastic large cell lymphoma with necrosis, inflammation, and surgical intervention: A case report

Diagnostic and management challenges in primary cutaneous anaplastic large cell lymphoma with necrosis, inflammation, and surgical intervention: A case report

Primary anaplastic T-cell lymphoma of the omentum presenting as small bowel obstruction and complicated with Massilia timonae infection: a case report

BackgroundAnaplastic large-cell lymphoma primarily involving the omentum is an extremely rare entity with variable clinical presentation. Owing to its rarity and nonspecific clinical manifestation, omental T-cell lymphoma is often diagnosed at a later stage, riddled with complications. While imaging modalities such as computed tomography scan can help a physician reach a diagnosis, cases that present with complications may require a multidisciplinary approach that combines surgical exploration along with consultation from Oncology.Case presentationWe hereby report a rare case of a 66-year-old African American male patient who presented to the emergency department with complaints of acute gastrointestinal obstruction. A computed tomography scan of the abdomen and pelvis revealed evidence of an internal hernia and surgical exploration revealed a hemorrhagic and infarcted omentum. Biopsies along with immunophenotypic studies confirmed the diagnosis of anaplastic T-cell lymphoma of the omentum complicated by Massilia timonae infection.ConclusionThe case highlights the significance of considering lymphoma, although rare, as a differential in a patient who presents with small bowel obstruction and the importance of investigating for malignancy for early diagnosis and treatment of primary omental lymphomas, before complications develop.

GATA3 Immunohistochemical Staining in Classical Hodgkin Lymphoma and its Diagnostic Utility in Differential Diagnosis.

Classical Hodgkin lymphoma (CHL) is a common lymphoid neoplasm with a wide range of differential diagnosis. Although it has a specific immunophenotype, aberrant expression of antigens can cause problems at its diagnosis. In this study we evaluated the usefulness of GATA3 in differential diagnosis of classical Hodgkin lymphoma. One hundred CHL cases and a control group of 106 lymphoma cases, which include anaplastic large cell lymphoma (ALK (+) and (-)), EBV (+) large B cell lymphoma, T-cell/ histiocyte rich B cell lymphoma, primary mediastinal large B cell lymphoma, nodular lymphocyte predominant Hodgkin lymphoma and mediastinal grey zone lymphoma, were included in the study. GATA3 immunohistochemistry were applied to all cases and its nuclear expression was accepted as positive. Expression status of GATA3 was compared in between the CHL and the control group, as well as among each lymphoma subtype. In addition, whether the biopsy type effects its diagnostic performance is assessed. In CHLs relationship with EBV status and GATA3 expression is evaluated. GATA3 expression was significantly higher in CHL cases compared to the control group (p<0,001). When compared with the individual subgroups GATA3 is still found to be useful in differential diagnosis except for ALK (-) ALCL (p=0,678) and mediastinal gray zone lymphomas (p=0,327). GATA3 expression is significantly higher in EBV (-) CHLs (p=0,02). In core needle biopsies its diagnostic performance is limited (p=0,178). GATA3 is a useful marker for differentiating CHL from B-cell non-Hodgkin lymphomas but its efficiency is limited in ALK (-) ALCL and mediastinal grey zone lymphomas. Due to the heterogeneous reaction diagnostic value is limited in core needle biopsies.

Recurrent somatic mutations of FAT family cadherins induce an aggressive phenotype and poor prognosis in anaplastic large cell lymphoma.

Anaplastic Large Cell Lymphoma (ALCL) is a rare and aggressive T-cell lymphoma, classified into ALK-positive and ALK-negative subtypes, based on the presence of chromosomal translocations involving the ALK gene. The current standard of treatment for ALCL is polychemotherapy, with a high overall survival rate. However, a subset of patients does not respond to or develops resistance to these therapies, posing a serious challenge for clinicians. Recent targeted treatments such as ALK kinase inhibitors and anti-CD30 antibody-drug conjugates have shown promise but, for a fraction of patients, the prognosis is still unsatisfactory. We investigated the genetic landscape of ALK + ALCL by whole-exome sequencing; recurring mutations were characterized in vitro and in vivo using transduced ALCL cellular models. Recurrent mutations in FAT family genes and the transcription factor RUNX1T1 were found. These mutations induced changes in ALCL cells morphology, growth, and migration, shedding light on potential factors contributing to treatment resistance. In particular, FAT4 silencing in ALCL cells activated the β-catenin and YAP1 pathways, which play crucial roles in tumor growth, and conferred resistance to chemotherapy. Furthermore, STAT1 and STAT3 were hyper-activated in these cells. Gene expression profiling showed global changes in pathways related to cell adhesion, cytoskeletal organization, and oncogenic signaling. Notably, FAT mutations associated with poor outcome in patients. These findings provide novel insights into the molecular portrait of ALCL, that could help improve treatment strategies and the prognosis for ALCL patients.

Clinical characteristics and prognostic factors of epidermal growth factor receptor-mutated non-small cell lung cancer transformed into small-cell lung cancer after treatment

Objective: To analyze the clinical characteristics and prognostic factors of non-small cell lung cancer (NSCLC) patients with sensitive epidermal growth factor receptor (EGFR) mutations who developed small cell lung cancer (SCLC) transformation after treatment with EGFR tyrosine kinase inhibitors (TKI). Methods: We conducted a retrospective collection of clinical data for 21 patients with advanced EGFR mutant NSCLC who developed SCLC transformation after EGFR-TKI treatment at Beijing Chest Hospital, Capital Medical University from January 2015 to December 2021. The clinical characteristics were summarized and the prognosis analysis was conducted. Patients were followed up until February 2024. The efficacy was evaluated using Solid Tumor Response Evaluation Criteria, and survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences in survival time (OS) between limited stage and extensive stage in transformed SCLC patients. Cox proportional hazards model was used to analyze the influencing factors of survival after SCLC transformation. Results: Among the 21 patients, there were 5 males and 16 females, with an age range of 33-74 years old [(58.9±2.6) years old]. All 21 patients were adenocarcinoma with sensitive EGFR mutations. There were 18 cases (85.7%) with EGFR gene 19del mutation, including 1 case of 19del+anaplastic lymphoma kinase (ALK) mutation, and 3 cases of L858R mutation. Among the transformed SCLC, there were 11 cases of pure SCLC and 10 cases of mixed SCLC (coexisting of adenocarcinoma and small cell carcinoma components). The median time from diagnosis of NSCLC to SCLC transformation was 12.0 months (95%CI: 7.6-16.3 months). Among the 21 cases of SCLC transformation, there were 13 cases with the extensive stage and 8 cases with the limited stage. Among them, 16 patients received systemic chemotherapy based on etoposide, of which 13 cases could be evaluated for efficacy, 11 cases could be calculated for PFS. Five cases had partial remission, 5 cases were stable, 3 cases had disease progression, and 3 cases cloud not be evaluated. The median progression free survival time (PFS) was 4.8 months (95%CI: 2.8-6.8 months). The median survival time (OS) after SCLC transformation in 21 patients was 10.6 months (95%CI: 7.0-14.2 months), with a median OS of 8.8 months (95%CI: 6.3-11.4 months) for patients with the extensive stage and 27.5 months (95%CI: 9.6-34.4 months) for patients with the limited stage, with statistically significant differences (P=0.002). Cox proportional hazards model analysis showed that the limited stage after SCLC transformation was a protective factor for OS (HR=0.32, 95%CI: 0.12-0.73, P=0.010). The median OS of 21 patients from the diagnosis of lung cancer was 24.9 months (95%CI: 13.0-36.7 months). Conclusions: NSCLC patients with SCLC transformation are all adenocarcinomas, and the proportion of EGFR19del mutations is relatively high. After SCLC transformation, the standard chemotherapy regimen for SCLC is generally used for treatment. The OS after SCLC transformation is related to the stage, and the prognosis is better in the limited stage.

Impact of select actionable genomic alterations on efficacy of neoadjuvant immunotherapy in resectable non-small cell lung cancer

BackgroundNeoadjuvant immune checkpoint inhibitors (ICIs) have improved survival outcomes compared with chemotherapy in resectable non-small cell lung cancer (NSCLC). However, the impact of actionable genomic alterations (AGAs) on the efficacy...

Outcome of childhood ALK-positive anaplastic large cell lymphoma relapses: Real-life experience of the French Society of Pediatric Oncology (SFCE) cohort of 75 French children.

To describe treatments and outcomes of French children treated for relapsed/refractory anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK+ ALCL). We conducted the analysis of a series of 75 French children treated for a first relapsed/refractory ALK+ ALCL between 1999 and 2017. The median time to first relapse was 8.1months from initial diagnosis (2.9 after end of treatment), with 12 relapses during frontline treatment or within 1month of the end of treatment. Treatment of the first relapse varied according to the period of time and risk factors: 48 received multiagent chemotherapy, including 21 and 19 consolidated with allogeneic stem cell transplantation (SCT) and autologous-SCT, respectively. Twenty-one patients received weekly vinblastine, and six received ALK inhibitors (ALKi). Overall, 64/75 patients reached a second complete remission (CR2). Eight out of 11 patients who did not reach CR2 died and the other three were rescued with ALKi, vinblastine, and nivolumab. With a median follow-up of 8.2years, 60 patients are alive, 43 in CR2, 15 in CR3, two in CR4; and 15 patients died, six from toxicity and nine from disease progression. The 5-year event-free survival and overall survival after first relapse were 51.7% (95% confidence interval [CI]: 39.6%-62.6%) and 80.7% (95% CI: 69.6%-88.1%), respectively. Time to relapse greater than 12months from initial diagnosis was proven to be a prognostic factor in relapsed/refractory ALK+ ALCL. In relapsed ALK+ ALCL, high survival rate can be reached with various therapeutic strategies. The main challenge remains to prevent subsequent relapses, and to lower long-term morbidity.

Establishment of potential reference measurement procedure and reference materials for EML4-ALK fusion variants measurement

Echinoderm microtubule-associated protein 4 (EML4) - anaplastic lymphoma kinase (ALK) fusion gene detection is of great significance in personalized tumor treatment. With the development of EML4-ALK fusion variants detection, it is necessary to establish traceability to ensure the consistency and comparability of its detection results in clinical practice. The establishment of traceability relies on SI traceable reference materials (RMs) and potential reference measurement procedures (RMPs). In this study, a potential RMP for the quantitative detection of V1 and V3 fusion mutations and the reference type (ALK-ref, including wild type, V1 and V3 mutant type) based on reverse transcription dPCR (RT-dPCR) and EML4-ALK fusion gene RMs were established. The proposed potential RMP has high specificity, good inter-laboratory reproducibility (CV < 7.3%) and good linear relationship (0.92 < slope < 1.06, R2 ≧ 0.99). The limit of detection (LoD) of V1, V3, and ALK-ref are 2 copies/reaction, 2 copies/reaction, and 1 copy/reaction, respectively. Interlaboratory studies using the EML4-ALK RMs and potential RMP showed that participating laboratories can produce consistent copy concentrations of fusion variant and ALK-ref as well as the ratio of EML4-ALK/ALK-ref. The established potential RMP with high specificity and accuracy can be used to characterize the EML4-ALK RMs, and the potential RMP and RM are useful to establish the traceability of EML4-ALK fusion measurement to improve the comparability and consistency in clinical tests.

ALK-positive Anaplastic Large Cell Lymphoma Involving the Spinal Cord

Abstract Introduction/Objective ALK-positive anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that accounts for approximately 3% of non-Hodgkin lymphoma cases in the adult population. Lymph node involvement is most commonly seen, followed by extra-nodal involvement of the skin, soft tissue, and bone. Central nervous system involvement is rare at the time of diagnosis. This case study features a patient with systemic ALK-positive ALCL involving multiple nodal and extra-nodal sites, most notably the spinal cord. Methods/Case Report A 22-year-old female presented to the hospital with worsening back pain accompanied by neurological symptoms. MRI scans of her spine revealed extensive patchy abnormal marrow signal with enhancement of the thoracolumbar vertebrae (T1-L2) and adjacent extension into the spinal canal (T3-T7, T10-L1, L3-S1) and paraspinal soft tissues. A laminectomy of the T5-T7 and T11-T12 levels was performed for surgical decompression, and epidural and paraspinal resection specimens were submitted. These specimens, along with an excisional axillary lymph node biopsy, demonstrated ALK-positive ALCL after comprehensive immunohistochemical studies. In-situ hybridization for EBV was negative. CHOP therapy was initiated, but treatment was complicated by Candidemia and disseminated intravascular coagulation. The patient rapidly declined and passed away less than a month after hospital admission. At autopsy, enlargement of lymph nodes, the left ovary (17.8 g), and spleen (383.6 g) were noted on gross examination. A solid, white-tan lesion (2.1 x 0.9 x 0.8 cm) was found in the left ovary. Necrosis and infiltrates of large, pleomorphic lymphoid cells with irregular nuclear contours and prominent nucleoli were seen on microscopic examination of the spinal cord and leptomeninges, vertebral bone marrow, mediastinal lymph nodes, spleen, and left ovary. Consistent with previously submitted surgical specimens, the viable neoplastic cells stained strongly positive for ALK-1, CD4, and CD30. Results (if a Case Study enter NA) NA Conclusion This case study highlights an atypical presentation of ALCL with a fatal outcome. Given the availability of effective treatment options, prompt diagnosis is crucial to improving survival outcomes. Additional research is necessary to elucidate the clinical and pathological features of ALCL. The differential for back pain is broad, but including this entity for patients with similarly insidious clinical presentations can prevent a delay in diagnosis that allows for rapid progression of disease.

A Case Report of Inflammatory Myofibroblastic Tumor Mimicking Leiomyosarcoma of the Uterus

Abstract Introduction/Objective Inflammatory myofibroblastic tumor (IMT) of the uterus is a rare entity that presents significant diagnostic challenges due to its infrequency and has the potential for being misdiagnosed as a leiomyoma, endometrial stromal tumor, or myxoid leiomyosarcoma, resulting in undertreatment or overtreatment. Methods/Case Report We present a case report of a 50-year-old woman with a history of anemia due to heavy menstruation caused by fibroids, who underwent hysterectomy. The concurrent pelvic wash cytology raised suspicious for myxoid leiomyosarcoma. Results (if a Case Study enter NA) Macroscopic examination revealed both well and poorly circumscribed nodules, ranging upto 4.7 cm in maximum dimension. Cut surfaces exhibited a spectrum of appearances, including tan-pink, whorled and rubbery, as well as soft, hemorrhagic, edematous, and mucinous areas with necrosis. Microscopically, the tumor exhibited myxoid spindle cell proliferation, in the background of lymphoplasmacytic inflammatory infiltrates. She was diagnosed with IMT metastasis to left fallopian tube, ovary, and omentum. Immunohistochemical (IHC) analysis further confirmed the diagnosis, showing strong and diffuse cytoplasmic positivity for ALK (anaplastic lymphoma kinase), caldesmon, and smooth muscle actin. This case underscores the critical importance of accurate diagnosis in guiding appropriate treatment strategies. Moreover, given the morphological overlap with other uterine tumors, the identification of ALK rearrangement emerges as a pivotal diagnostic marker, distinguishing IMT from its mimics such as leiomyoma, leiomyosarcoma and smooth muscle tumor of uncertain malignant potential (STUMP). Enhancing our understanding of the histomorphological features and ALK immunostaining of uterine IMT is essential for optimizing patient management and outcomes. Conclusion IMT in the female genital tract can mimic other more common benign and malignant tumors like leiomyoma, leiomyosarcoma, and endometrial stromal sarcoma. Familiarity with clinical and histologic features and the use of ALK immunostaining can be critical for correct diagnosis.

ALK1-negative Epithelioid Histiocytoma

Abstract Introduction/Objective We present a case of epithelioid histiocytoma (EH). The epithelioid nature of this lesion imitates the appearance of neoplastic lesions such as melanocytic, dermatofibroma/histiocytoma, non-Langerhans histiocytosis such as reticulohistiocytoma, atypical fibroxanthoma, and rhabdomyosarcoma. Methods/Case Report Due to the unusual morphology and aberrant immunohistochemical staining pattern of this specific case, the sample was analyzed through Next Generation Sequencing (NGS), which showed the presence of a fusion of genes Sequestosome 1 (SQSTM1) and Anaplastic lymphoma kinas (ALK). SQSTM1 gene produces proteins involved in signal transduction pathways as well as autophagy, while ALK mainly serves the role of cellular communication and development. The most well-known ALK fusion partners include SQSTM and Vinculin (VCL), while there are other fusion partners that were more recently discovered such as Dynactin Subunit 1 (DCTN1) and ETS variant transcription factor 6 (ETV6). The spectrum of neoplasms produced through these fusions is wide as seen in lung adenocarcinoma and renal cell carcinoma (EML4-ALK), epithelioid histiocytoma (SQSTM1-ALK and VCL- ALK), pediatric renal cell carcinoma (VCL-ALK) among others. Results (if a Case Study enter NA) NA Conclusion We hope this case is a helpful addition to the literature to further aid diagnoses of future ALK fusion cases.

Multisystem ALK-Positive Histiocytosis With DCTN1::ALKFusion in an Adult, Responsive to Alectinib: Case Report and Literature Review.

Anaplastic lymphoma kinase (ALK)-positive histiocytosis has emerged as a clinically relevant diagnosis featuring a wide span of clinical presentations, which are unified by the presence of ALK-positive histiocytes on histopathology and molecular drivers involving the ALK kinase gene. This report presents an adult case of multisystem ALK-positive histiocytosis with xanthogranuloma-like features on histopathology that was responsive to ALK inhibition, and includes a review of ALK-positive histiocytoses with cutaneous involvement reported in the literature. A 56-year-old male developed a widespread eruption of red-brown papules on the face, trunk, and upper extremities. Histopathological evaluation revealed a well-circumscribed, nodular dermal infiltrate of epithelioid histiocytes with Touton giant cells, rare bizarre multinucleated cells, and focal emperipolesis. The lesional cells were positive for CD68 and ALK1 immunohistochemical stains, and negative for CD1a. Next-generation sequencing identified a DCTN1::ALK fusion. On imaging, he was found to have bone, lung, soft tissue, and salivary gland involvement. ALK inhibition was initiated with alectinib, resulting in rapid improvement of cutaneous lesions and eventual complete resolution of abnormal imaging findings, which was sustained at 24 months of follow-up. This case adds to the spectrum of ALK-positive histiocytoses and further demonstrates the positive response with targeted therapy.

Breast implant-associated anaplastic large cell lymphoma.

Breast implant-associated anaplastic large cell lymphoma is a subtype of non-Hodgkin's lymphoma that can occur around the surface of textured breast implants or in patients who have previously had textured breast implants. The condition should be suspected in cases of late-onset breast asymmetry and seroma formation around a breast implant. If the implant and surrounding connective tissue capsule is removed, the prognosis is usually very good. The purpose of this clinical review article is to provide a brief overview of the diagnosis and treatment of breast implant-associated anaplastic large cell lymphoma.

Current Knowledge on Breast Implant-Associated Anaplastic Large Cell Lymphoma: Evidence from Italian Ministry of Health Registry Data.

Accurate estimation of Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) incidence is crucial for assessing breast-implant-associated risk. However, the size of the implanted population worldwide is unknown, making it challenging to appropriately estimate this figure. This study aims to provide a new reliable and reproducible method to estimate the breast-implanted-population (BIP), reporting a reliable annual BIA-ALCL incidence estimate. Moreover, we discuss all activities performed over the past decade in collecting complete histories, managing, and monitoring outcomes of each Italian case. Data from the National Breast Implant Registry and from manufacturers have been used to define a new formula to estimate the BIP at risk of developing a breast-implant-related event. From the BIA-ALCL registry, complete information on Italian cases has been collected and analysed. Overall survival is estimated by the Kaplan-Meier curve. From 2010 to June 2024, 111 BIA-ALCL cases were recorded in Italy. The estimated incidence rate showed an upward trend, ranging from 2.68 to 6.35 cases per 100,000 patient-years. Thanks to newly promoted disease awareness, most patients had a complete response to treatment, resulting in a three-year overall survival rate estimate of 98.2%. The BIP formula showed to be an innovative, effective and reproducible tool to make a reliable estimation of the implanted population, confirming that BIA-ALCL is a rare disease with an incidence rate estimate varying from 2.7 to 6.3 cases/100.000 patient-years in the last five years. Eleven-year experience in this field also confirmed that this disease has a favorable prognosis if properly treated. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The prognostic value of the morhological types of ALK-positive anaplastic large cell lymphoma in children

The prognostic value of the morhological types of ALK-positive anaplastic large cell lymphoma in children

Anaplastic Large B-Cell Lymphoma: Cutaneous Presentations

Anaplastic Large B-Cell Lymphoma: Cutaneous Presentations

Cardiovascular toxicity of anaplastic lymphoma kinase inhibitors for patients with non-small cell lung cancer: a network meta-analysis.

Aim: We conducted network meta-analysis to assess cardiovascular toxicity of anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs).Materials & methods: Eleven articles involving 2855 patients and six interventions including crizotinib, alectinib, ceritinib, lorlatinib, brigatinib and chemotherapy were analyzed.Results: No significant difference was observed in overall cardiovascular risk among ALK-TKIs. Subgroup analysis showed that for cardiac toxicity, crizotinib and alectinib were more likely to cause myocardial rhythm abnormalities. Crizotinib and ceritinib had a higher risk of Q-T prolongation than chemotherapy. For vascular toxicity, crizotinib and ceritinib had a higher risk of thrombotic events than brigatinib. Crizotinib and lorlatinib were more likely to cause blood pressure abnormalities.Conclusion: Clinicians should carefully monitoring cardiovascular events when ALK-TKIs used in NSCLCs patients with baseline cardiovascular diseases.

Taiwan Nationwide Study of First-Line ALK-TKI Therapy in ALK-Positive Lung Adenocarcinoma.

The clinical outcomes of patients with anaplastic lymphoma kinase-positive (ALK+) advanced lung adenocarcinoma vary according to real-world data. In this study, we aimed to investigate the treatment discontinuation (TTD) and overall survival (OS) of patients with ALK+ advanced lung adenocarcinoma treated with first-line ALK-TKIs in Taiwan. This retrospective study evaluated all advanced lung adenocarcinoma patients registered in the National Taiwan Cancer Registry from 2017 to 2020 who had ALK rearrangement and received ALK-TKI treatment, using data from Taiwan's National Health Insurance Research Database (NHIRD). The TKI treatment sequences were classified into first generation (G1: crizotinib), second generation (G2: ceritinib, alectinib, brigatinib), and third generation (G3: lorlatinib). A total of 587 patients were analyzed, with a median age of 60.0 years, 91 (15.5%) aged ≥ 74 years, 293 (49.9%) female, 397 (67.6%) never smoked, and 534 (91.0%) with stage IV disease. Patients who received next-generation ALK-TKIs during the treatment course had longer median time to ALK-TKI TTD and OS. The TTD of the G1, G1+2, G1+2+3, G2, and G2+3 groups was 7.5 (5.4-11.1), 40.6 (29.4-not calculated (NC)), 50.3 (41.3-NC), 34.3 (29.2-43.0), and 36.3 (22.4-NC) months, respectively (p < 0.001). The median OS of the patients in the G1, G1+2, G1+2+3, G2, and G2+3 groups was 10.6 (7.5-14.6), not reached (NR) (NC-NC), NR (NC-NC), 43.0 (36.3-NC), and NR (30.3-NC) months, respectively (p < 0.001). Compared with treatment with crizotinib alone, the multivariate analysis revealed that treatment with next-generation TKIs was independently associated with longer TTD (G1+2 (hazard ratio (HR), 0.24; 95% CI 0.17-0.33; p < 0.001), G1+2+3 or G1+3 (HR, 0.17; 95% confidence interval (CI), 0.10-0.28; p < 0.001), G2 (HR, 0.26; 95% CI 0.19-0.36; p < 0.001), and G2+3 (HR, 0.25; 95% CI 0.14-0.44; p < 0.001)) and median OS (G12 (HR, 0.24; 95% CI 0.17-0.35; p < 0.001), G1+2+3 or G1+3 (HR, 0.09; 95% CI 0.04-0.21; p < 0.001), G2 (HR, 0.22; 95% CI 0.15-0.31; p < 0.001), and G2+3 (HR, 0.20; 95% CI 0.10-0.42; p < 0.001)). For patients with ALK+ NSCLC, treatments including next-generation ALK-TKIs were independently associated with longer survival outcomes.

The Use of Anaplastic Lymphoma Kinase Inhibitors in Non-Small-Cell Lung Cancer Treatment-Literature Review.

Lung cancer is the leading cause of cancer-related morbidity and mortality. The median survival time for patients with advanced non-small-cell lung cancer before the era of molecular-based personalized treatment was 7.9 months. The discovery of predictive factors and the introduction of molecular diagnostics into daily practice made a breakthrough, enabling several years of survival in patients with advanced disease. The discovery of rearrangements in the ALK gene and ALK tyrosine kinase inhibitors has resulted in a dramatic improvement in the prognosis of patients with this subtype of cancer. Currently, three generations of ALK inhibitors differing in activity, toxicity and degree of penetration into the central nervous system are available in clinical practice. The current state of knowledge on ALK inhibitors used in clinical practice is summarised in this research paper. Methods of diagnosis of abnormalities in ALK have been shown, and the review of research that contributed to the development of the next generation of ALK inhibitors has been presented.

Anaplastic large cell lymphoma with concomitant Hemophagocytic Lymphohistiocytosis (HLH): hyperinflammation and capillary leakage syndrome

In our 19 years’ experience at King Chulalongkorn Memorial Hospital, we were able to observe 21 pediatric cases with anaplastic large cell lymphoma (ALCL). Of these 21 cases, 4 (19% of ALCL cases) had concurrent hemophagocytic lymphohistiocytosis (HLH). All developed fever, lymphadenopathy and exaggerated signs of capillary leakage syndrome such as generalized edema, pleural effusion or ascites. The hyperinflammation was demonstrated with fever, hypoalbuminemia and elevated inflammatory markers. A high index of suspicion is warranted to recognize concurrent HLH when patients develop cytopenia, splenomegaly, liver dysfunction and pleural or pericardial effusions. For HLH with unknown etiology but with lymphadenopathy, lymph node biopsy should be considered as a part of secondary HLH workup to rule out malignant-associated hemophagocytic syndrome. Treatment with lymphoma-directed therapy should not be contraindicated once a diagnosis of ALCL is made. Instead, one should be cautious whenever a hyperinflammatory state and multi-organ dysfunction exists because HLH-sensitive agents such as corticosteroid, etoposide, cyclosporin A, cyclophosphamide, IVIG and others should be urgently administrated. The mortality was quite high (50%) in our institution. Initial treatment with HLH protocol saved the lives of the other 2 patients (50%), both of whom were cured later with lymphoma-directed protocol.