RESUMEN
Acute myeloid leukemia (AML) is a severe condition with a high mortality. When making decisions about the optimal tailor-made therapy, numerous prognostic factors are considered. The study represents a detailed analysis of the role of these factors and treatment outcomes based on a long-term follow-up of patients treated in 5 hematology intensive care centers in the Czech Republic.The studied group comprised 1,188 patients with de novo AML and 328 patients with secondary AML. The latter were significantly older, had more unfavorable cytogenetic changes and less frequently received curative therapy. Curatively treated patients achieved fewer complete remissions and relapsed more often than those with de novo AML. Patients with secondary AML had lower rates of allogeneic transplantation as part of consolidation therapy and a significantly shorter median overall survival. A lower proportion of the patients were alive at the time of analysis. However, the treatment outcome of de novo AML patients is not satisfactory, the only exception being those with acute promyelocytic leukemia. The analysis, which did not evaluate the intention-to-treat criteria and was without randomization, found allogeneic stem cell transplantation to be the most effective modality of consolidation therapy in both groups of patients. .
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Leucemia Mieloide Aguda/mortalidad , Neoplasias Primarias Secundarias/mortalidad , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Aberraciones Cromosómicas , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucemia Mieloide Aguda/etiología , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/terapia , Pronóstico , Factores de Tiempo , Resultado del TratamientoRESUMEN
INTRODUCTION: We present two years' experience in the treatment of adult acute lymphoblastic leukemia (ALL) according to the German GMALL 07/2003 study protocol at CELL (Czech leukemia study group--for life) hematological centers in the Czech Republic. METHODS: A total number of 37 patients were included in this analysis. We evaluated complete remission and molecular remission rate, incidence of relapse, patients' status at the end of the follow-up period, incidence of chemotherapy-related adverse events and causes of death. A statistical analysis of risk factors affecting survival was carried out. RESULTS: Complete remission was achieved in 36 (97%) patients and molecular remission in 16 (62%) of 26 evaluable patients. Disease relapse occurred in 5 (14%) patients. At the end of the follow-up period with a median of 261 days, 28 (76%) patients were alive in complete remission, one (3%) with relapsed disease and 8 (22%) dead. Treatment toxicity resulted in death in 5 cases, relapse or progression of ALL in 3 patients. Adverse events most often followed consolidation I, induction phase I, consolidation II and induction phase II. Infectious complications in the context of febrile neutropenia, GIT mucositis and side effects of PEG-asparaginase were the most common adverse events observed. The toxicity of allogeneic transplantation was not unexpected, four (25%) patients died after transplantation. Two-year progression-free and overall survival were 66% and 70%, respectively. High risk ALL, age over 35 years, CNS infiltration, disease relapse and permanent minimal residual disease were identified as the major adverse prognostic risk factors. Practical experiences and possible pitfalls of the protocol are described in the discussion. CONCLUSION: Our initial impression is promising. The treatment is feasible, the results very good and the toxicity acceptable. Patients at high risk should be headed to allogeneic transplantation, since the results ofconsolidation chemotherapy alone are very poor in this group. We believe that this study protocol could become a standard adult acute lymphoblastic leukemia treatment in the Czech Republic.
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Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Humanos , Persona de Mediana Edad , Inducción de Remisión , Adulto JovenRESUMEN
BACKGROUND: Despite a considerable effort, the majority of acute myeloid leukaemia (AML) patients do not have a suitable specific molecular marker for monitoring minimal residual disease (MRD). The results of some studies suggest the Wilms tumour gene (WT1) as a possible molecular marker of MRD. METHODS AND RESULTS: We measured the expression of WT1 at diagnosis and during treatment of the acute myeloid leukaemia (AML) patients. The expression of WT1 was measured by the quantitative real-time RT-PCR in peripheral leukocytes from 56 AML at diagnosis and 7 patients with AML transformed from myelodysplastic syndromes (MDS). The WT1 expression was significantly elevated (up to 3 orders of magnitude) in peripheral blood samples (PB) of AML patients at diagnosis compared to PB samples of healthy donors (P < 0.0001). The level of WT1 expression depends particularly on FAB AML subtype, with the highest being found in AML patients with subtypes M4, M1, M3 and AML transformed from MDS. Conversely, AML patients with M2 and with the presence of AML1/ET0 at presentation showed a significantly lower expression of the WT1 gene compared to the remaining AML patients at presentation (P = 0,005). Further, sequence samples of 12 AML patients under long-term surveillance were tested for the WT1 expression in parallel with the expression of specific MRD markers--fusion genes: AMLI/ETO, PML/RARalpha and CBFB/MYH11. The levels of WT1 gene expression and the above specific fusion genes significantly correlated. Moreover, 14 patients without the specific MRD marker were tested for the WT1 expression. The results show that haematological relapses were associated with the rise of expression of the specific fusion genes and with the WT1 gene expression. The rise of WT1 expression above the level seen in leucocytes from peripheral blood and/or bone marrow of healthy donors--in four patients under long-term surveillance the "molecular relapse" predicted ongoing haematological relapses as early as 2 months in advance. CONCLUSIONS: Our results, in accordance with some of the previously published ones, show that WT1 expression seems to be a suitable marker of minimal residual disease in AML patients.
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Genes del Tumor de Wilms , Leucemia Mieloide/diagnóstico , Enfermedad Aguda , Biomarcadores de Tumor/análisis , Subunidad alfa 2 del Factor de Unión al Sitio Principal/análisis , Marcadores Genéticos , Humanos , Leucemia Mieloide/genética , Leucemia Mieloide/terapia , Proteínas de Neoplasias/análisis , Neoplasia Residual , Proteínas de Fusión Oncogénica/análisis , Proteínas de Plantas , Proteína 1 Compañera de Translocación de RUNX1RESUMEN
High-dose immunoablative chemotherapy with autologous haematopoietic cell support might be beneficial in the treatment of intractable forms of MS. We mobilised PBPC in 11 patients with secondary progressive MS and finally eight patients were grafted after high-dose BEAM chemotherapy with either in vitro or in vivo T cell depletion. Median EDSS and SNRS scores at the time of inclusion were 6.5 (6.5-7.5) and 56 (44-65), respectively. PBPC mobilisation was safe with no serious adverse effects, and without significant aggravation of disability. One patient improved significantly (by 1.0 point on EDSS) after the mobilisation. Two mobilisation failures were observed. No life-threatening events occurred during the transplantation. All grafted patients, except one, at least stabilised their disability status. One patient improved significantly (by 1.5 points on EDSS), two patients improved slightly (by 0.5 points on EDSS), one patient worsened by 1.0 point on the EDSS in 10 months. Improvement occurred with a delay of 2-4 months. Median EDSS and SNRS of grafted patients at the last follow up were 6.5 (5.5-8.5) and 64 (39-73), respectively with median follow-up of 8.5 months. Further follow-up is needed to determine the disease course after complete immune reconstitution. Bone Marrow Transplantation (2000) 25, 525-531.
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Trasplante de Células Madre Hematopoyéticas , Inmunosupresores/uso terapéutico , Esclerosis Múltiple/terapia , Adolescente , Adulto , Antígenos CD/análisis , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Relación CD4-CD8 , Carmustina/administración & dosificación , Carmustina/toxicidad , Citarabina/administración & dosificación , Citarabina/toxicidad , Etopósido/administración & dosificación , Etopósido/toxicidad , Femenino , Fiebre , Estudios de Seguimiento , Supervivencia de Injerto , Movilización de Célula Madre Hematopoyética/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Inmunosupresores/toxicidad , Infecciones/inducido químicamente , Leucaféresis , Subgrupos Linfocitarios , Imagen por Resonancia Magnética , Masculino , Melfalán/administración & dosificación , Melfalán/toxicidad , Persona de Mediana Edad , Neutropenia/inducido químicamente , Pronóstico , Índice de Severidad de la EnfermedadRESUMEN
High dose chemotherapy with autologous hematopoietic cell support is a standard approach in the management of selected hematological malignancies. Autoimmune diseases which do not respond to conventional immunosuppression might benefit from high dose immunoablative chemotherapy. The transplantation of hematopoietic cells is necessary after the high dose chemotherapy to restore bone marrow function. The immune system undergoes a new ontogeny which can result in the development of tolerance. Multiple sclerosis (MS) has so far been the most common indication for this kind of treatment. Experience with preclinical studies on murine experimental allergic encephalomyelitis (EAE), as well as the course of MS following bone marrow transplantation for coincidental malignancy in humans formed the basis of the first clinical studies involving high dose chemotherapy and autologous hematopoietic support. Results of the first studies confirm that the method is feasible in patients with MS, and that the effect is very promising. Nonetheless, more consistent results vis a vis the therapeutic effect should emanate from upcoming studies.
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Trasplante de Células Madre Hematopoyéticas , Terapia de Inmunosupresión , Esclerosis Múltiple/terapia , HumanosRESUMEN
Autoimmune diseases (AID) result from the impairment of the effector and/or recognition phase of the immune response. The autoimmune process plays a crucial role in the pathogenesis of the systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), and their treatment is therefore largely based on immunosuppression. However, some patients do not respond to its standard doses. The disease becomes intractable with the survival rate comparable to that of some haematological malignancies, or patients become soon handicapped with very poor quality of life, depending on continual administration of high doses of steroids. The new hope for those patients becomes therapy with high dose myelo- and immuno-ablative chemotherapy with autologous hematopoietic progenitor cell support (PBPC). Tens of patients with intractable forms of AID were transplanted in the pilot clinical studies with promising results. The most frequent indications included: SLE, SSc, and RA. Final conclusion of the therapeutic effects will be drawn from the analysis of larger trails.
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Enfermedades Autoinmunes/terapia , Trasplante de Células Madre Hematopoyéticas , Artritis Reumatoide/terapia , Humanos , Terapia de Inmunosupresión , Lupus Eritematoso Sistémico/terapia , Esclerodermia Sistémica/terapiaRESUMEN
Most patients with Hodgkin's disease (especially early stage disease) are successfully treated using modern treatment modalities. Disease relapse usually occurs within the first three years after initial therapy. Late relapses of Hodgkin's disease, occurring after 10 years or even later, are rare (0.6% of cases only). Their biological behaviour is different from that of early relapses, resembling primary disease. The question whether very late relapses represent a second primary disease in patients with a genetic predisposition to Hodgkin's disease rather than a relapse of the original disease remains the subject of much discussion. We report here two cases of very late relapses of Hodgkin's disease, occurring twenty years after initial treatment. Both patients were now treated by intensified chemotherapy, escalated BEACOPP. In one case, this was followed by radiotherapy of the residual tumor (40 Gy). Both patients are in complete remission.