All of these fusion proteins are considered to act like NPMI-ALK in possessing high ALK activity that promotes the development and progression ALK-positive ALCL by activating the cell signaling pathways cited in the Introduction. 15% Of individuals with ALK-positive ALCL also have point mutations in the NOTCH1 gene. While most of these abnormalities are thought to be detrimental not all are. For example, DUSP22 gene rearrangements are associated with favorable outcomes in ALK-positive (as well as ALK-negative) ALCL. Treatment and prognosis
A recommended induction therapy for ALK-positive ALCL in individuals with lesions containing more than 10 percent CD30-positive cells consists of brentuximab vedotin (a drug consisting of an anti-CD30 antibody attached to a cell-killing agent, monomethyl auristatin E); two chemotherapy drugs, cyclophosphamide and the anthracycline, doxorubicin; and the  corticosteroid, prednisone. This regimen gave a progression-free survival rate of 48.2 months in one study and overall survival rates of 70–90% at five years in other studies. For >60 year old and medically unfit individuals of any age, the standard CHOP regimen (cyclophosphamide, doxorubicin, prednisone, and the chemotherapeutic agent, vincristine) is used. For younger, medically fit individuals, the chemotherapeutic agent etoposide is added to the CHOP regimen (CHOP plus etoposide is termed the "CHOEP" regimen). For patients with lesions that contain <10% CD30-positive neoplastic cells, brentuximab vedotin, which targets these cells, is not used. Rather, patients are treated with an anthracycline-based chemotherapy regimen.
Several systemic illnesses have been associated with plastic bronchitis:
Cardiac: constrictive pericarditis, congenital heart disease
Pulmonary: asthma, allergic bronchopulmonary aspergillosis, aspergillosis, bronchiectasis, cystic fibrosis, tuberculosis, pneumonia, and bronchocentric granulomatosis
Disorders of lymphatic drainage: lymphangiectasia, lymphangiomatosis
Miscellaneous: acute chest syndrome/sickle cell disease, amyloidosis, rheumatoid arthritis, membranous colitis, inhaled irritants, neoplastic (lymphoma)The most common form of plastic bronchitis follows cardiac surgery for congenital heart disease, especially the Fontan procedure. Systemic blood flow is diverted to pulmonary flow, elevating pressures in the pulmonary venous system, and promoting leaks of proteinaceous and lipid-rich fluids from the lymphatics into the bronchial tree. Diagnosis
The diagnosis of plastic bronchitis is confirmed by recovery of casts that have been coughed up or visualized during a bronchoscopy. There is no specific cytologic, pathologic or laboratory test that is diagnostic for casts due to lymphatic PB. Imaging
Simple chest X-rays may reveal collapse due to airway obstruction. The contralateral lung may be hyperinflated. Casts can be visualized within the major airways using computerized axial tomography scans.Heavy T2-weighted MRI, and, as appropriate, intranodal lymphangiogram and/or dynamic contrast-enhanced MR lymphangiography may be useful for identifying pathological lymphatic tissue or lymphatic flow. Management
Acute therapy for PB is often focused on removal or facilitated expectoration of the casts. This is followed by short and long term efforts to identify and remediate the underlying condition resulting in the excessive airway leakage or inflammation that is causing the casts to form.PB can present as a life threatening emergency when the casts obstruct the major airways resulting in acute respiratory distress.