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.

Diretrizes para o diagnóstico, classificação, profilaxia e tratamento da doença enxerto contra hospedeiro crônica / Guidelines for the diagnosis, classification, prophylaxis and treatment of chronic graft-versus-host disease

A falta de critérios diagnósticos padronizados, amplamente utilizados, pode comprometer tanto a avaliação real da incidência da doença contra hospedeiro crônica bem como a correlação de sua gravidade com a taxa de mortalidade pós-transplante. Na I Reunião de Diretrizes da Sociedade Brasileira de Transplante de Medula Óssea, realizada em junho de 2009, o Grupo de Estudos de DECH Brasil - Seattle (GEDECH), baseado na realidade dos Centros brasileiros, apresentou as recomendações para diagnóstico, classificação, profilaxia e tratamento da doença enxerto contra hospedeiro crônica propostas pelo National Institutes of Health. Estas propostas incluíram padronização das características utilizadas no diagnóstico e ferramentas para a pontuação dos órgãos envolvidos e avaliação global da gravidade a serem utilizados em estudos clínicos da doença enxerto contra hospedeiro crônica. Estes critérios são úteis para uma melhor análise da incidência desta doença, além de poder avaliar a gravidade do comprometimento de um órgão ou sítio envolvido e a influência na mortalidade tardia do transplante. A profilaxia e os tratamentos propostos para esta importante complicação dos transplantes de células-tronco hematopoéticas foram discutidos e graduados de acordo com níveis de evidência estabelecidos pelo National Institutes of Health.

The lack of widely-used standardized diagnostic criteria may impair both the true evaluation of chronic graft-versus-host disease and the correlation of its severity with transplant-related mortality. At the I Consensus of the Brazilian Society of Bone Marrow Transplantation - SBTMO that took place in June 2009, the Group of GVHD Studies Brazil-Seattle (GEDECH), presented the guidelines for diagnosis, classification, prophylaxis and treatment of chronic GVHD as proposed by the National Institutes of Health and based on the reality in Brazilian Centers. These proposals, including standardization of features used in diagnosis and tools to score involved organs and to assess the overall severity, should be used in clinical studies of chronic graft-versus-host disease. These criteria are useful to better analyze the incidence of this disease, in addition to evaluate the extension of the involvement of organs or the site affected and its influence on late transplantation mortality. Prophylaxis and treatment proposed for this important complication of hematopoietic stem cell transplantations were discussed and graded according to the levels of evidence established by the National Institutes of Health.

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.

Cytogenetic biclonality in a child with hypocellular primary myelodysplastic syndrome.

A 13-year-old boy with hypocellular primary myelodysplastic syndrome, classified as refractory cytopenia, underwent umbilical cord blood transplantation. Cytogenetic analysis revealed two rare biclonal chromosomal aberrations, del(17)(p12) and del(11)(q23). Cytogenetic analysis was a valuable tool in diagnosis, in clinical decision-making, and in treatment and follow-up. To our knowledge, this is the first reported case of cytogenetic biclonality involving chromosomes 17 and 11.

Low-power laser in the prevention of induced oral mucositis in bone marrow transplantation patients: a randomized trial.

We investigated the clinical effects of low-power laser therapy (LPLT) on prevention and reduction of severity of conditioning-induced oral mucositis (OM) for hematopoietic stem cell transplantation (HSCT). We randomized 38 patients who underwent autologous (AT) or allogeneic (AL) HSCT. A diode InGaAlP was used, emitting light at 660 nm, 50 mW, and 4 J/cm2, measured at the fiberoptic end with 0.196 cm2 of section area. The evaluation of OM was done using the Oral Mucositis Assessment Scale (OMAS) and the World Health Organization (WHO) scale. In the LPLT group, 94.7% of patients had an OM grade (WHO) lower than or equal to grade 2, including 63.2% with grade 0 and 1, whereas in the controls group, 31.5% of patients had an OM grade lower than or equal to grade 2 (P < .001). Remarkably, the hazard ratio (HR) for grades 2, 3, and 4 OM was 0.41 (range, 0.22-0.75; P = .002) and for grades 3 and 4 it was 0.07 (range, 0.11-0.53; P < .001). Using OMAS by the calculation of ulcerous area, 5.3% of the laser group presented with ulcers of 9.1 cm2 to 18 cm2, whereas 73.6% of the control group presented with ulcers from 9.1 cm2 to 18 cm2 (P = .003). Our results indicate that the use of upfront LPLT in patients who have undergone HSCT is a powerful instrument in reducing the incidence of OM and is now standard in our center.

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.

Altas doses de VP-16, ciclofosfamida e irradiaçäo corpórea total hiperfracionada seguida de transplante alogeneico de medula óssea: um regime agressivo e bem tolerado no tratamento de neoplasias hematológicas de mau prognóstico

No período de agosto/86 a fevereiro/87, três pacientes foram tratados com VP-16-1800 mg/m2, em infusäo única em 26 horas no dia -6, seguida por Ciclofosfamida (EDX) 50 mg/Kg/d nos dias -5 -4 e -3. Irradiaçäo corpórea total (ICT) - 1000 cGy em 5 fracçöes de 200cGy nos dias -2, -1 e 0. O transplante de medula óssea (TMO) foi realizado no dia 0 utilizando doadores HLA compatíveis. O estudo incluiu três pacientes: um paciente portador de Leucemia Linfoblástica Aguda (LLA) em 1ª recaída medular; um paciente portador de Leucemia Mielóide Crônica (LMC) em 2ª fase crônica e um paciente portador de LLA em 2ª remissäo. a idade variou entre quatro e 29 anos. A principal toxicidade apresentada por este regime foi mucosite severa que ocorreu nos três pacientes. Todos os três pacientes apresentaram ulceraçöes orais e um deles apresentou diarréia hemorrágica com volume superior a dois litros. Em todos os pacientes o quadro se resolveu nas três semanas que se seguiram ao TMO Um paciente apresentou alteraçöes eletrocardiográficas significativas sem, entretanto, ocorreram manifestaçöes clínicas de cardiotoxicidade. A eficácia do regime pode ser testada no paciente em recaída que permanece em remissäo 210 dias pós-TMO. No paciente portador de LMC houve eliminaçäo do cromossomo Ph1. Concluímos que VP-16/EDX/CT é um regime eficaz e bem tolerado no tratamento de neoplasias hematológicas