Monosomy 7 arises as a recurrent chromosome aberration in donor cell leukemia after hematopoietic stem cell transplantation. We report a new case of donor cell leukemia with monosomy 7 following HLA-identical allogenic bone marrow transplantation for severe aplastic anemia (SAA). The male patient received a bone marrow graft from his sister, and monosomy 7 was detected only in the XX donor cells, 34 months after transplantation. The patient's bone marrow microenvironment may have played a role in the leukemic transformation of the donor hematopoietic cells.

A leucemia mieloide crônica (LMC) é uma doença mieloproliferativa clonal caracterizada citogeneticamente pelo cromossomo Philadelphia. Dentre as opções terapêuticas estão a hidroxiureia, o interferon-a, o transplante alogeneico de células-tronco hematopoéticas e o imatinibe. Esta última terapia tem demonstrado eficácia, principalmente na fase crônica da doença. Entretanto, alguns estudos têm demonstrado que alterações cromossômicas adicionais levam resistência à terapia, enquanto outros relatam aparecimento de manifestações clínicas indesejáveis, como cefaleia, náuseas e vômitos. Devido à importância desta terapia alvo-molecular, torna-se necessário analisar a resposta deste tratamento considerando a qualidade de vida dos pacientes. O objetivo deste trabalho foi analisar as manifestações clínicas indesejáveis e a resposta citogenética durante o tratamento com imatinibe em pacientes com LMC após uso prévio de interferon-a. O estudo clínico foi feito através de prontuários de 51 pacientes. A análise citogenética foi feita em células de medula óssea através da técnica de bandeamento GTG. As manifestações clínicas mais frequentes foram: cefaleia (37%), náusea (37%), vômito (33%) e edema periférico (33%). Esses sintomas foram considerados leves a moderados. Os pacientes que alcançaram resposta citogenética completa tiveram uma sobrevida significativamente maior que os pacientes que não apresentaram resposta citogenética ao tratamento (p=0.007). Oito pacientes sem resposta citogenética faleceram. Nossos resultados mostraram a importância do acompanhamento clínico (analisando o grau de tolerância medicamentosa) e citogenético, onde a presença de alterações cromossômicas adicionais mostrou um comportamento biológico distinto que não pode ser avaliado pelas técnicas moleculares. Desta forma, a análise citogenética representa uma importante ferramenta para o diagnóstico e monitoramento destes pacientes.

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized cytogenetically by the Philadelphia chromosome (Ph). Therapeutic options of this disease are: hydroxyurea, interferon-a, allogeneic HSCT and more recently imatinib. This latter therapy demonstrated efficacy in the treatment of CML, particularly in the chronic phase. However some studies have demonstrated that there are additional chromosomal alterations related to resistance while others have reported undesirable clinical manifestations during imatinib therapy such as headache, nausea and vomiting. Because of the importance of this new molecular target therapy, it may be necessary to analyze the response of this treatment in respect to the quality of life of patients. The aim of this study was to analyze the clinical manifestations and the cytogenetic response during imatinib therapy in fifty-one patients with CML who had previously been treated using interferon-a. Cytogenetic analysis was performed in bone marrow cells using GTG-banding. The commonest clinical manifestations were mild to moderate: headache (37%), nausea (37%), vomiting (33%) and edema (33%). Patients that achieved major cytogenetic response had a significantly longer median survival than patients without response (p=0.007). Eight patients evolved to death; none of them exhibited cytogenetic responses to imatinib. Our results show the importance of the clinical (analyzing the degree of tolerance to the drug) and cytogenetic follow-up, where the presence of additional chromosomal alterations showed a distinct biological pattern that is not identifiable by molecular techniques, and so cytogenetic analysis is an important tool for the diagnosis and monitoring of this group of patientss.

We report the case of a five-month-old black male infant who had recurrent episodes of respiratory infections and also presented anemia and enlargements of the spleen, liver and lymphnodes. Hematological analysis revealed morphological abnormalities with megaloblastic dyserythropoiesis, while fetal hemoglobin assaying showed normal levels. Conventional and molecular cytogenetic analysis revealed monosomy of chromosome 7. Despite all therapeutic efforts during allogenic bone marrow transplantation, the child died due to generalized infection. The clinical and genetic distinctions between monosomy 7 syndrome and myelodysplastic disorders in childhood are discussed.

RESUMO CONTEXTO E OBJETIVO: Após o transplante de células tronco-hematopoéticas (TCTH), o cariótipo é uma ferramenta valiosa para monitorar o status do enxerto e da doença. Poucos estudos investigaram o significado prognóstico do cariótipo nos pacientes que se submeteram ao TCTH para leucemia mielóide crônica (LMC). O objetivo desse estudo foi verificar o significado dos achados citogenéticos pré-TCTH em pacientes portadores de LMC. TIPO DE ESTUDO E LOCAL: Série de casos. Instituto Nacional do Câncer (INCA), Rio de Janeiro, Brasil. METODOLOGIA: Foram realizados estudos citogenéticos por bandeamento G em 39 pacientes submetidos ao TCTH. RESULTADOS: Trinta e um pacientes estavam em fase crônica e oito em fase acelerada. Pré-TCTH, alterações cromossômicas adicionais ao cromossomo Philadelphia (Ph) foram observadas em 11 pacientes. A mais freqüente foi o duplo Ph observado em quatro casos. Após o TCTH, quimerismo total foi observado em 31 pacientes (79,5%). Desses, 23 (82,3%) apresentavam somente o cromossomo Ph. Quimerismo misto foi observado em sete pacientes, sendo três com alterações adicionais ao Ph. Um caso não apresentou resposta ao TCTH. Recaída citogenética associada com recaída clínica foi observada em cinco pacientes. Após o TCTH, 27 pacientes permanecem vivos e com remissão clínica e citogenética. CONCLUSÃO: Em nosso estudo a presença de alterações cromossômicas adicionais ao Ph, prévias ao TCTH, não foi associada com pior evolução, com risco de recaída, bem como não foi observada diferença entre as taxas de sobrevida. Nosso estudo sugere que a citogenética clássica permanece uma grande ferramenta no monitoramento do TCTH.

CONTEXT AND OBJECTIVE: Following hematopoietic stem cell transplantation (HSCT), karyotyping is a valuable tool for monitoring engraftment and disease status. Few studies have examined the prognostic significance of karyotypes in patients who underwent HSCT for chronic myeloid leukemia (CML). The objective of this study was to evaluate the significance of pretransplantation cytogenetic status in relation to outcomes following HSCT in CML patients. DESIGN AND SETTING: Case series study at Instituto Nacional do Câncer (INCA), Rio de Janeiro, Brazil. METHODS: Cytogenetic analysis was performed by G banding on 39 patients treated with HSCT. RESULTS: Thirty-one patients were in the chronic phase and eight were in the accelerated phase. Prior to HSCT, additional chromosomal abnormalities on the Philadelphia (Ph) chromosome were found in 11 patients. The most frequent additional abnormality was a double Ph, which was observed in four cases. Following HSCT, full chimeras were observed in 31 patients (79.5%). Among these, 23 (82.3%) had presented Ph as the sole abnormality. Mixed chimeras were observed in seven patients, of which three had additional abnormalities. Only one case did not present any cytogenetic response. Five patients presented cytogenetic relapse associated with clinical relapse following HSCT. Twenty-seven patients are still alive and present complete hematological and cytogenetic remission. CONCLUSION: In our study, the presence of additional abnormalities was not associated with worse outcome and relapse risk. Also, no differences in survival rates were observed. Our study supports the view that classical cytogenetic analysis remains an important tool regarding HSCT outcome.

chronic myeloid leukemia (CML) have been described. This chromosomal region contains the tumor suppressor gene TP53 that may be an important factor in the evolution of this disease. In this study, we used flow cytometry and western blotting to assess p53 protein expression and single stranded conformational polymorphism to examine TP53 gene alterations in three patients with CML who showed alterations in 17p. Only the case with del(17)(p11) had p53 expression positive by flow cytometry and an abnormal migration pattern by SSCP analysis. The importance of the correlation between the results obtained with these techniques, as well as the clinical course of the patients, are discussed.

Neste trabalho foram estudados citogeneticamente 50 pacientes de diversas unidades hospitalares do Rio de Janeiro, Brasil, diagnosticados com síndrome mielodisplásica primária. Os dados obtidos mostraram uma freqüência de anomalias cromossômicas de 32% nestes pacientes, sendo as anomalias mais encontradas a del(5q) (10%), -7 (6%) e +8 (4%). Pacientes com anemia refratária ou anemia refratária com sideroblastos em anel apresentaram cariótipos normais ou com deleções simples como del(5q) ou -Y, enquanto pacientes com anemia refratária com excesso de blastos, anemia refratária com excesso de blastos em transformação e leucemia mielomonocítica crônica apresentaram cariótipos complexos ou com anomalias simples do tipo monossomia do 7 ou trissomia do 8, tendo um alto índice de evolução para leucemia mielóide aguda.

In this work we analyzed cytogenetically 50 patients with primary myelodysplastic syndrome from several hospitals of Rio de Janeiro, Brazil. The frequency of cytogenetic abnormalities was 32%. Patients with refractory anemia, or refractory anemia with ringed sideroblasts, presented normal karyotypes or single abnormalities such as del(5q) or -Y, while patients with refractory anemia with an excess of blasts, refractory anemia with an excess of blasts in transformation or chronic myelomonocytic leukemia showed complex karyotypes and single abnormalities involving chromosomes 7 or 8, which are related to a bad prognosis and an elevated risk of evolution to acute myeloid leukemia.