Monosomy 7 in donor cell-derived leukemia after bone marrow transplantation for severe aplastic anemia: Report of a new case and review of the literature.

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.

Myeloproliferative syndrome of monosomy 7: a brief report

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.(AU)

Karyotype abnormalities and theirclinical signifi cance in a group ofchronic myeloid leukemia patientstreated with hematopoietic stemcell transplantation

CONTEXT AND OBJECTIVE: Following hematopoietic stem cell transplantation (HSCT), karyotypingis a valuable tool for monitoring engraftment and disease status. Few studies have examined the prognostic signifi cance of karyotypes in patientswho underwent HSCT for chronic myeloid leukemia (CML). The objective of this study was to evaluate the signifi cance of pretransplantationcytogenetic status in relation to outcomes following HSCT in CML patients.DESIGN AND SETTING: Case series study at Instituto Nacional do Cƒncer (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 abnormalitieson the Philadelphia (Ph) chromosomewere 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 hadadditional abnormalities. Only one case did not present any cytogenetic response. Five patients presented cytogenetic relapse associated withclinical 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, nodifferences in survival rates were observed. Our study supports the view that classical cytogenetic analysis remains an important tool regardingHSCT outcome.(AU)

CONTEXTO E OBJETIVO: Ap¢s o transplante de c‚lulas tronco-hematopo‚ticas (TCTH), o cari¢tipo ‚uma ferramenta valiosa para monitorar o status do enxerto e da doen‡a. Poucos estudos investigaram osignifi cado progn¢stico do cari¢tipo nos pacientes que se submeteram ao TCTH para leucemia miel¢idecr“nica (LMC). O objetivo desse estudo foi verifi car o signifi cado dos achados citogen‚ticos pr‚-TCTH empacientes portadores de LMC.TIPO DE ESTUDO E LOCAL: S‚rie de casos. Instituto Nacional do Cƒncer (INCA), Rio de Janeiro, Brasil.METODOLOGIA: Foram realizados estudos citogen‚ticos por bandeamento G em 39 pacientes submetidos ao TCTH.RESULTADOS: Trinta e um pacientes estavam em fase cr“nica e oito em fase acelerada. Pr‚-TCTH, altera‡äescromoss“micas adicionais ao cromossomo Philadelphia (Ph) foram observadas em 11 pacientes. A maisfreqente foi o duplo Ph observado em quatro casos. Ap¢s o TCTH, quimerismo total foi observado em31 pacientes (79,5%). Desses, 23 (82,3%) apresentavam somente o cromossomo Ph. Quimerismo mistofoi observado em sete pacientes, sendo trˆs com altera‡äes adicionais ao Ph. Um caso nÆo apresentouresposta ao TCTH. Reca¡da citogen‚tica associada com reca¡da cl¡nica foi observada em cinco pacientes. Ap¢s o TCTH, 27 pacientes permanecem vivos e com remissÆo cl¡nica e citogen‚tica.CONCLUSÇO: Em nosso estudo a presen‡a de altera‡äes cromoss“micas adicionais ao Ph, pr‚vias ao TCTH, nÆo foi associada com pior evolu‡Æo, com risco de reca¡da, bem como nÆo foi observada diferen‡a entre as taxas de sobrevida. Nosso estudo sugere que a citogen‚tica cl ssica permanece uma grande ferramenta no monitoramento do TCTH.(AU)

Chromosome 17 abnormalities and mutation of the TP53 gene: Correlationbetween cytogenetics, flow cytometry and molecular analysis in three casesof chronic myeloid leukemia

Alterations involving the short arm of chromosome 17 (17p) during the progression of chronic myeloid leukemia(CML) have been described. This chromosomal region contains the tumor suppressor gene TP53 that may be animportant factor in the evolution of this disease. In this study, we used flow cytometry and western blotting to assessp53 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 (AU)

Karyotype abnormalities and their clinical significance in a group of chronic myeloid leukemia patients treated with hematopoietic stem cell transplantation.

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.

Translocation (11;11)(p13- p15;q23) in a child with therapy-related acute myeloid leukemia following chemotherapy with DNA-topoisomerase II inhibitors for Langerhans cell histiocytosis.

We report a new case of therapy-related acute myeloid leukemia in a child with Langerhans cell histiocytosis. This patient was previously treated with a protocol of multidrug chemotherapy, containing a relatively low dose of etoposide (total dose of 900/m(2)). Twenty-six months after the end of the therapy, the patient returned to the hospital with fever and anemia. The white blood cell count was 53 x 10(9)/L. The bone marrow examination showed massive infiltration with French-American-British acute myeloid leukemia classification M4 blast cells. The patient did not respond to an intensive treatment with high dose ARA-C and idarubicin. He died 6 months later. The cytogenetic abnormality of the blast cells was a t(11;11)(p13 -15;q23), that has not been described before in a secondary leukemia case.

Cytogenetic analysis of 100 consecutive newly diagnosed cases of acute lymphoblastic leukemia in Rio de Janeiro.

We report the cytogenetic analysis of newly diagnosed Brazilian children with acute lymphocytic leukemia (ALL). We investigated 100 ALL cases from four different institutions in Rio de Janeiro. The frequency of chromosomal abnormalities was 92.3%. The karyotype profile and recurrent abnormalities found in this study do not differ essentially from those described by other groups. Although the Brazilian population is usually the product of different ethnic groups, our results show that the frequency of each recurrent abnormality is similar to that found in populations without our degree of diverse ethnic composition. Hence, our results suggest that childhood ALL in Brazil has the same biological features as that in developed countries, supporting the use of similar treatment protocols. We can therefore expect to reach the same survival rates in the coming years, depending possibly on the efficacy of the support therapy and extent of social assistance.

Cytogenetic analysis of 100 consecutive newly diagnosed cases of acutelymphoblastic leukemia in Rio de Janeiro

We report the cytogenetic analysis of newly diagnosed Brazilian children with acute lymphocytic leukemia(ALL). We investigated 100 ALL cases from four different institutions in Rio de Janeiro. The frequencyof chromosomal abnormalities was 92.3%. The karyotype profile and recurrent abnormalitiesfound in this study do not differ essentially from those described by other groups. Although the Brazilianpopulation is usually the product of different ethnic groups, our results show that the frequency of each recurrentabnormality is similar to that found in populations without our degree of diverse ethnic composition.Hence, our results suggest that childhood ALL in Brazil has the same biological features as that indeveloped countries, supporting the use of similar treatment protocols. We can therefore expect to reachthe same survival rates in the coming years, depending possibly on the efficacy of the support therapy andextent of social assistance.(AU)

The impact of addictional chromosomal abnormalities in response to imatinib mesylate therapy for chronic myeloid leukemia

Imatinib induces a complete cytogenetic response in more than 80% of newly diagnosed patients with chronicmyeloid leukemia (CML) in the chronic phase (CP) and in 41% of patients in the first chronic phase after failureof interferon- treatment. However, some patients do not respond completely. Therefore, according to moststudies, drug resistance in CML patients treated with imatinib is correlated with cytogenetic abnormalities acquiredduring treatment. In this study we analyzed 48 CML patients treated with imatinib mesylate after interferon- resistance in order to elucidate the impact of additional chromosomal abnormalities prior to imatinib in response to therapy. Cytogenetic abnormalities in addition to the Philadelphia chromosome (Ph) were detected in 33.3% of patients. Patients with Ph as the sole cytogenetic abnormality prior to imatinib therapy presented a major cytogeneticresponse and significantly longer median overall survival (p=0.006) than patients with additional chromosomalabnormalities. Therefore, in this group of patients, another choice of treatment should be considered, such as stemcell transplantation or combination regimens as appropriate. The present study indicates the importance of detecting a double Ph chromosome prior to imatinib therapy. Patients showing this abnormality did not respond to imatinib, thus indicating the abnormality's association with resistance. Our study suggests that classical cytogenetic analysisis still an important tool prior to and during follow-up of CML patients treated with imatinib.(AU)

Imatinibe induz … resposta citogen‚tica completa em cerca de 80 por cento dos pacientes diagnosticados com leucemia miel¢ide cr“nica (LMC) em fase cr“nica (FC), e em 41 por cento dos pacientes em primeira FC ap¢s falha do tratamento com interferon-alfa. Alguns pacientes, entretanto, nÆo respondem completamente. Em muitos estudos, a resistˆncia … droga em pacientes tratados com imatinibe ‚ correlacionada a altera‡äes cromoss“micas adquiridas durante o tratamento. No presente estudo, foram analisados 48 pacientes tratados com imatinibe ap¢s resistˆncia ao interferon-alfa, com o objetivo de verificar o impacto das altera‡äes cromoss“micas adicionais ao Philadelphia (Ph), pr‚vias … terapia com imatinibe. Altera‡äes adicionais foram detectadas em 33,3 por cento dos pacientes. Pacientes com somente o cromossomo Ph apresentaram melhor taxa de resposta citogen‚tica e sobrevida global significativa maior quando comparados com os pacientes que apresentavam altera‡äes cromoss“micas adicionais antes do in¡cio da terapia com imatinibe. Assim, nesse grupo de pacientes, a escolha de outra conduta terapˆutica, como o transplante de c‚lulas tronco-hematopo‚ticas ou regime de combina‡Æo de drogas, pode ser indicada. O presente estudo indica a importƒncia do duplo Ph antesdo in¡cio da terapia com imatinibe. Todos os pacientes com esta altera‡Æo nÆo responderam ao tratamento, sendo a mesma associada … resistˆncia … droga. Este estudo sugere que a citogen‚tica cl ssica permanece como uma ferramenta importante no monitoramento de pacientes portadores de LMC tratados com imatinibe.(AU)

Myeloproliferative syndrome of monosomy 7: a brief report

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.

The impact of addictional chromosomal abnormalities in response to imatinib mesylate therapy for chronic myeloid leukemia

Imatinib induces a complete cytogenetic response in more than 80% of newly diagnosed patients with chronicmyeloid leukemia (CML) in the chronic phase (CP) and in 41% of patients in the first chronic phase after failureof interferon- treatment. However, some patients do not respond completely. Therefore, according to moststudies, drug resistance in CML patients treated with imatinib is correlated with cytogenetic abnormalities acquiredduring treatment. In this study we analyzed 48 CML patients treated with imatinib mesylate after interferon- resistance in order to elucidate the impact of additional chromosomal abnormalities prior to imatinib in response to therapy. Cytogenetic abnormalities in addition to the Philadelphia chromosome (Ph) were detected in 33.3% of patients. Patients with Ph as the sole cytogenetic abnormality prior to imatinib therapy presented a major cytogeneticresponse and significantly longer median overall survival (p=0.006) than patients with additional chromosomalabnormalities. Therefore, in this group of patients, another choice of treatment should be considered, such as stemcell transplantation or combination regimens as appropriate. The present study indicates the importance of detecting a double Ph chromosome prior to imatinib therapy. Patients showing this abnormality did not respond to imatinib, thus indicating the abnormality's association with resistance. Our study suggests that classical cytogenetic analysisis still an important tool prior to and during follow-up of CML patients treated with imatinib.

Imatinibe induz à resposta citogenética completa em cerca de 80 por cento dos pacientes diagnosticados com leucemia mielóide crônica (LMC) em fase crônica (FC), e em 41 por cento dos pacientes em primeira FC após falha do tratamento com interferon-alfa. Alguns pacientes, entretanto, não respondem completamente. Em muitos estudos, a resistência à droga em pacientes tratados com imatinibe é correlacionada a alterações cromossômicas adquiridas durante o tratamento. No presente estudo, foram analisados 48 pacientes tratados com imatinibe após resistência ao interferon-alfa, com o objetivo de verificar o impacto das alterações cromossômicas adicionais ao Philadelphia (Ph), prévias à terapia com imatinibe. Alterações adicionais foram detectadas em 33,3 por cento dos pacientes. Pacientes com somente o cromossomo Ph apresentaram melhor taxa de resposta citogenética e sobrevida global significativa maior quando comparados com os pacientes que apresentavam alterações cromossômicas adicionais antes do início da terapia com imatinibe. Assim, nesse grupo de pacientes, a escolha de outra conduta terapêutica, como o transplante de células tronco-hematopoéticas ou regime de combinação de drogas, pode ser indicada. O presente estudo indica a importância do duplo Ph antesdo início da terapia com imatinibe. Todos os pacientes com esta alteração não responderam ao tratamento, sendo a mesma associada à resistência à droga. Este estudo sugere que a citogenética clássica permanece como uma ferramenta importante no monitoramento de pacientes portadores de LMC tratados com imatinibe.

Karyotype abnormalities and their clinical significance in a group of chronic myeloid leukemia patients treated with hematopoietic stem cell transplantation

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 percent). Among these, 23 (82.3 percent) 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.

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 por cento). Desses, 23 (82,3 por cento) 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.