OBJECTIVE: To evaluate hematological, cytogenetic and molecular responses as well as the overall, progression-free and event-free survivals of chronic myeloid leukemia patients treated with a third tyrosine kinase inhibitor after failing to respond to imatinib and nilotinib/dasatinib. METHODS: Bone marrow karyotyping and real-time quantitative polymerase chain reaction were performed at baseline and at 3, 6, 12 and 18 months after the initiation of treatment with a third tyrosine kinase inhibitor. Hematologic, cytogenetic and molecular responses were defined according to the European LeukemiaNet recommendations. BCR-ABL1 mutations were analyzed by Sanger sequencing. RESULTS: We evaluated 25 chronic myeloid leukemia patients who had been previously treated with imatinib and a second tyrosine kinase inhibitor. Nine patients were switched to dasatinib, and 16 patients were switched to nilotinib as a third-line therapy. Of the chronic phase patients (n=18), 89% achieved a complete hematologic response, 13% achieved a complete cytogenetic response and 24% achieved a major molecular response. The following BCR-ABL1 mutations were detected in 6/14 (43%) chronic phase patients: E255V, Y253H, M244V, F317L (2) and F359V. M351T mutation was found in one patient in the accelerated phase of the disease. The five-year overall, progression-free and event-free survivals were 86, 54 and 22% (p<0.0001), respectively, for chronic phase patients and 66%, 66% and 0% (p<0.0001), respectively, for accelerated phase patients. All blast crisis patients died within 6 months of treatment. Fifty-six percent of the chronic phase patients lost their hematologic response within a median of 23 months. CONCLUSIONS: Although the responses achieved by the third tyrosine kinase inhibitor were not sustainable, a third tyrosine kinase inhibitor may be an option for improving patient status until a donor becomes available for transplant. Because the long-term outcome for these patients is poor, the development of new therapies for resistant chronic myeloid leukemia patients is necessary.

Imunodeficiência humoral é uma característica intrínseca da leucemia linfocítica crônica B. A quimioterapia, principalmente quando o paciente é politratado, e em especial os análogos da purina, ampliam o espectro de susceptibilidade destes pacientes a agentes infecciosos oportunistas devido ao efeito imunossupressor celular destas drogas. Relatamos um paciente com leucemia linfocítica crônica submetido a várias linhas de quimioterapia, inclusive o 2-CdA, que apresentou múltiplas complicações infecciosas associadas a grave imunodeficiência celular.

Hypogamaglobulinemia is frequently associated with B-CLL rendering the patients prone to bacterial infections. The use of purine analogs that cause depletion of T lymphocytes in the treatment of this disease, increases the spectrum of susceptibility of these patients to oportunistic agents. We report a case of a young B-CLL patient treated with 2-CdA, who presented multiple infectious complications during the course of his disease associated with a severe cellular immune deficiency.