gemcitabine, dexamethasone, and cisplatin), DHAP, and ICE.Drugs that inhibit ALK activity such as crizotinib and alectinib have been successful in establishing complete and partial remissions in a limited number of patients with advanced, refractory ALK-positive ALCL. These and other drugs are undergoing clinical trials to determine there safety and effectiveness in treating ALK-positive ALCL. (Also see clinical trials that use ALK inhibitors in ALK-positive ALCL and clinical trials that use ALK inhibitors in ALK-positive cancers.) ALK-negative anaplastic large cell lymphoma
Signs and symptoms
Unlike ALK-positive ALCL, ALK-negative ALCL tends to occur in older adults (median age at diagnosis: 55–60 years) and presents primarily with lymph node involvement; only 20% of patients with ALK-ALCL present with extra-nodal disease in sites such as the skin, bone, and soft tissues. Nonetheless, most individuals (~67%) present with advanced stage grade III or IV disease in which neoplastic infiltrates occur in multiple lymph node locations and/or extra-nodal sites. ALK autoantibodies are not found in this type of ALCL. The prognosis of ALK-negative ALCL is often quoted as being worse than that for ALK-positive ALCL but this may reflect the older age and advanced stage at which ALK-negative disease presents: studies comparing age- and grade-matched ALK-positive to ALK-negative ALCL patients show little differences in prognoses. Diagnosis
The histology of ALK-negative ALCL, similar to ALK-positive ALCL, consist of "hallmark" cells that strongly express CD30. Unlike ALK-positive ALCL, however, ALK-negative ALC does not fall into different morphological patterns.
As the disease progresses, mental deterioration and personality changes occur. Typical symptoms include loss of social inhibitions, asocial behavior, gradual impairment of judgment, concentration and short-term memory, euphoria, mania, depression, or apathy. Subtle shivering, minor defects in speech and Argyll Robertson pupil may become noticeable. Delusions, common as the illness progresses, tend to be poorly systematized and absurd. They can be grandiose, melancholic, or paranoid. These delusions include ideas of great wealth, immortality, thousands of lovers, unfathomable power, apocalypsis, nihilism, self-guilt, self-blame, or bizarre hypochondriacal complaints. Later, the patient experiences dysarthria, intention tremors, hyperreflexia, myoclonic jerks, confusion, seizures and severe muscular deterioration. Eventually, the paretic dies bedridden, cachectic and completely disoriented, frequently in a state of status epilepticus. Diagnosis
The diagnosis could be differentiated from other known psychoses and dementias by a characteristic abnormality in eye pupil reflexes (Argyll Robertson pupil), and, eventually, the development of muscular reflex abnormalities, seizures, memory impairment (dementia) and other signs of relatively pervasive neurocerebral deterioration. Definitive diagnosis is based on the analysis of cerebrospinal fluid and tests for syphilis. Prognosis
Although there were recorded cases of remission of the symptoms, especially if they had not passed beyond the stage of psychosis, these individuals almost invariably experienced relapse within a few months to a few years. Otherwise, the patient was seldom able to return home because of the complexity, severity and unmanageability of the evolving symptom picture. Eventually, the patient would become completely incapacitated, bed ridden, and would die, the process taking about three to five years on average.