Overt failure is defined as a loss of hematologic remission or progression to accelerated-phase or blast-crisis phase chronic myelogenous leukemia (CML) as previously defined. A consistently rising quantitative reverse–transcription polymerase chain reaction BCR/ABL level suggests relapsing disease. For initial use of imatinib mesylate, the designation of relative failure or suboptimal response has been proposed for lack of complete hematologic remission by 3 months, no cytogenetic response by 6 months, or no major cytogenetic response by 12 months.[1,2] Nilotinib and dasatinib induce such high rates of complete cytogenetic responses and major molecular responses within several months that new benchmarks are required for responsiveness. These investigators propose that a complete cytogenetic response by 3 months should define an optimal response.[3,4]
In case of treatment failure or suboptimal response, patients should undergo BCR/ABL kinase domain mutation analysis to help guide therapy with the newer tyrosine kinase inhibitors or with allogeneic transplantation.[5,6] Mutations in the tyrosine kinase domain can confer resistance to imatinib mesylate; alternative inhibitors such as dasatinib, nilotinib, or bosutinib, higher doses of imatinib mesylate, and allogeneic stem cell transplantation (SCT) have been studied in this setting.[7,8,9,10,11,12,13,14,15,16,17,18,19] In particular, the T315I mutation marks resistance to imatinib, dasatinib, nilotinib, and bosutinib. In a phase I escalation study with 81 patients, patients with the T315I mutation responded to ponatinib, an oral tyrosine kinase inhibitor.[Level of evidence: 3iiiDiv] Ponatinib also has activity in heavily pretreated-resistant CML and in a third of the patients with accelerated-phase or blast-crisis phase CML. Clinical trial participation should help establish the optimal sequence of these options.
A link to a list of current clinical trials is included at the end of this section. For some types or stages of cancer, there may not be any trials listed. Check with your doctor for clinical trials that are not listed here but may be right for you.
Resectable Gastrointestinal Stromal Tumors
Resectable gastrointestinal stromal tumors (GISTs) can be completely or almost completely removed by surgery. Treatment may include the following:
Surgery to remove tumors that are 2 centimeters...
Infusions of buffy-coat leukocytes or isolated T cells obtained by pheresis from the bone marrow transplant donor have induced long-term remissions in more than 50% of patients who relapse following allogeneic transplant.[21,22] The efficacy of this treatment is thought to be the result of an immunologic graft-versus-leukemia effect. This treatment is most effective for patients whose relapse is detectable only by cytogenetics or molecular studies and is associated with significant graft-versus-host disease. After relapse from allogeneic SCT, some patients will also respond to interferon alpha. Most patients will respond to imatinib mesylate with durable (>1 year) cytogenetic and molecular responses. (These patients had not previously received imatinib.)[24,25,26]