RESUMO
BACKGROUND: We conducted a phase I clinical immunotherapy trial of CML to evaluate the safety of a clinical-grade leukemic DC product standardized for purity and mature phenotype. METHODS: We injected autologous DC into patients in late chronic or accelerated phases of CML. The patients received mature CD83+ and bcr-abl+ DC prepared from CD14+ cells. Two cohorts of three patients received four injections each of 3 x 10(6) DC and 15 x 10(6) DC/injection, respectively. The first patient was studied before imatinib mesylate (IM) was available, four patients were treated concurrently with IM therapy and one did not tolerate the IM and was off the drug at the time of DC therapy. IM effects on WBC counts precluded DC preparation in numbers sufficient for further dose escalation. The first patient received DC s.c. and all subsequent patients received DC into a cervical lymph node under ultrasound guidance. RESULTS: DC injections were well tolerated. We observed no clinical responses. T cells drawn later in the course of therapy were more sensitive to stimulation by CML DC in vitro. DISCUSSION: The increase in T-cell sensitivity to CML-specific stimulation that accompanied active immunization by CML DC justifies further clinical studies, possibly with modifications such as an increased frequency and number of DC injections.
Assuntos
Células Dendríticas/transplante , Imunoterapia Ativa/métodos , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Idoso , Antígenos CD/análise , Antígeno B7-2/análise , Células da Medula Óssea/citologia , Contagem de Células , Proliferação de Células , Técnicas de Cocultura , Células Dendríticas/citologia , Células Dendríticas/imunologia , Feminino , Proteínas de Fusão bcr-abl/análise , Humanos , Imunoglobulinas/análise , Imunoterapia Ativa/efeitos adversos , Interferon gama/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Leucócitos Mononucleares/citologia , Receptores de Lipopolissacarídeos/análise , Ativação Linfocitária/imunologia , Masculino , Glicoproteínas de Membrana/análise , Pessoa de Meia-Idade , Células Mieloides/citologia , Células Mieloides/imunologia , Células Mieloides/transplante , Linfócitos T/imunologia , Linfócitos T/metabolismo , Transplante Autólogo , Resultado do Tratamento , Antígeno CD83RESUMO
Translocations involving IGH are common in some lymphoid malignancies but are believed to be rare in chronic lymphocytic leukaemia (CLL). To study the clinical utility of fluorescence in situ hybridization (FISH) for IGH translocations, we reviewed 1032 patients with a presumptive diagnosis of CLL. Seventy-six (7%) patients had IGH translocations. Pathology and clinical data were available for the 24 patients evaluated at the Mayo Clinic. Ten (42%) patients had IGH/cyclin D1 fusion and were diagnosed with mantle cell lymphoma (MCL). The immunophenotype was typical of MCL in three of these patients and atypical for MCL in seven patients. One patient had biclonal disease with typical MCL and CLL with IGH/BCL-2. Eleven (46%) patients had IGH/BCL-2 fusion including the patient with biclonal disease. Two of these patients had leukaemic phase follicular lymphoma and nine patients had CLL. The median progression-free survival of patients with CLL and IGH/BCL-2 translocation was 20.6 months. The two patients with IGH/BCL-3 fusion (one of these also had IGH/BCL-11a) had rapid disease progression. The IGH partner gene was not identified in two patients. We conclude that use of an IGH probe in FISH analysis of monoclonal B-cell lymphocytosis improves diagnostic precision and could have prognostic value in patients with CLL.
Assuntos
Genes de Imunoglobulinas , Cadeias Pesadas de Imunoglobulinas/genética , Interfase , Leucemia Linfocítica Crônica de Células B/diagnóstico , Sondas de Oligonucleotídeos , Translocação Genética , Proteína 3 do Linfoma de Células B , Ciclina D1/genética , Diagnóstico Diferencial , Citometria de Fluxo , Genes bcl-2 , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/imunologia , Linfoma de Células B/diagnóstico , Linfoma de Células B/genética , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/genética , Proteínas Proto-Oncogênicas/genética , Fatores de TranscriçãoRESUMO
API2-MALT1 fusion and aneuploidy are common chromosomal abnormalities in MALT lymphoma. In studying their incidence and relationship in primary pulmonary MALT lymphomas, a translocation involving MALT1 and IGH was also identified. In all, 28 primary pulmonary MALT lymphomas were studied by fluorescence in situ hybridization using an API2-MALT1 probe and multiple centromeric probes, as well as IGH-BCL2, IGH-MALT1, and MALT1 breakapart probes in selected cases. Seven (25%) had API2-MALT1 fusion; all seven lacked aneuploidy except for two with trisomy 3 in a small clone. Three (11%) had IGH-MALT1 fusion; two also showed trisomy 3 and 12. A total of 11 (39%) had aneuploidy only, with trisomy 3 and 18 being the most common. Ectopic nuclear bcl-10 expression, which has been previously associated with API2-MALT1, was seen by immunohistochemistry in 86% of API2-MALT1 fusion-positive cases, one IGH-MALT1 fusion-positive case, two aneuploidy-only cases, and two normal cases. In primary pulmonary MALT lymphomas, cytogenetic abnormalities are common (75%) and heterogeneous, encompassing API2-MALT1 and IGH-MALT1, which are mutually exclusive, as well as aneuploidy, which may be present in the latter but is rare in the former. Ectopic nuclear bcl-10 expression is associated with API2-MALT1 but may also be seen in IGH-MALT1 fusion-positive, aneuploidy-only, and normal cases.
