RESUMO
OBJECTIVE: A post hoc analysis of two phase III trials was carried out to explore the influence of age and treatment factors on the effect of bortezomib consolidation on progression-free survival (PFS) post autologous stem cell transplantation (ASCT). METHODS: Patients with newly diagnosed multiple myeloma were assigned to one of two trials (ClinicalTrials.gov IDs: NCT00416273, NCT00416208), which were conducted in parallel, based on age (18-60 or 61-75 years, respectively). Following induction and ASCT, patients were randomized 1:1 to four 35-day cycles of bortezomib consolidation (1.6 mg/m2 IV on days 1, 8, 15, 22) or observation only. RESULTS: Median PFS with bortezomib consolidation vs observation was 33.6 vs 29.0 months (P = 0.3599) in patients aged 18-60 years (n = 202), and 33.4 vs 26.4 months (P = 0.0073) in patients aged 61-75 years (n = 155), respectively. Bortezomib consolidation post-ASCT appeared to equalize outcomes between older and younger patients who received prior treatment of differing intensity. This suggests that the effect of consolidation may be relative and may depend on the composition and intensity of induction and high-dose therapy. CONCLUSION: Older patients receiving less intensive prior treatment could experience a larger PFS benefit from bortezomib consolidation.
Assuntos
Antineoplásicos/uso terapêutico , Bortezomib/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Bortezomib/administração & dosagem , Bortezomib/efeitos adversos , Terapia Combinada , Quimioterapia de Consolidação , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento , Adulto JovemRESUMO
Patients with follicular lymphoma (FL) and progression of disease (POD) within 24 months after frontline treatment (POD24) have poor overall survival (OS). The optimal salvage treatment for these patients is unknown. We assessed the role of high-dose therapy and autologous stem cell transplantation (ASCT) in transplant-eligible patients. We analyzed 162 patients with advanced-stage FL who had received frontline treatment within the GLSG1996 or GLSG2000 trials. All patients had POD at age ≤ 65 years and had not received a prior transplant. Second-line treatment was not specified by study protocols. Survival was calculated from time of second-line treatment. Eighteen patients (11%) progressed (n = 16) or died (n = 2) during cytoreductive second-line treatment (considered "cytoreduction failure"); none received ASCT, and their median second-line OS was <1 year. A total of 113 patients had POD24 (70%), whereas 49 had POD after 24 months (30%). Sixty-three patients without cytoreduction failure received ASCT (39%), and 81 received no transplant (50%). In patients with POD24, a significant survival benefit was associated with ASCT with a 5-year second-line progression-free survival for ASCT versus no transplant of 51% versus 19% (hazard ratio, .38; 95% confidence interval, .24 to .62; P < .0001) and a 5-year second-line OS of 77% versus 59% (hazard ratio, .54, 95% confidence interval, .30 to .95; P= .031). Thus, ASCT is an effective treatment option for transplant-eligible patients with high-risk FL as identified by POD24 and should be evaluated in prospective clinical trials.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma Folicular/terapia , Transplante Autólogo/mortalidade , Adulto , Idoso , Progressão da Doença , Feminino , Seguimentos , Alemanha , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Terapia de Salvação/métodos , Análise de Sobrevida , Transplante Autólogo/normasRESUMO
Autologous transplantation is controversial for older patients with multiple myeloma. The role of age-adjusted high-dose melphalan and the impact of induction chemotherapy cycles is still unclear. A total of 434 patients aged 60-70 years were randomly assigned to 4 cycles of standard anthracycline-based induction chemotherapy or no induction. For all patients, double autologous transplantation after melphalan 140 mg/m2 (MEL140) was planned. The primary end point was progression-free survival. Of 420 eligible patients, 85% received a first transplant and 69% completed double transplantation. Treatment duration was short with a median of 7.7 months with induction chemotherapy cycles and 4.6 months without induction. On an intention-to-treat basis, median progression-free survival with induction chemotherapy cycles (207 patients) was 21.4 months versus 20.0 months with no induction cycles (213 patients) (hazard ratio 1.04, 95% confidence interval 0.84-1.28; P=0.36). Per protocol, progression-free survival was 23.7 months versus 23.0 months (P=0.28). Patients aged 65 years or over (55%) did not have an inferior outcome. Patients with low-risk cytogenetics [absence of del17p13, t(4;14) and 1q21 gains] showed a favorable overall survival and included the patients with sustained first remission. MEL140 was associated with a low rate of severe mucositis (10%) and treatment-related deaths (1%). Based on hazard ratio, the short treatment arm consisting of mobilization chemotherapy and tandem MEL140 achieved 96% of the progression-free survival, demonstrating its value as an independent component of therapy in older patients with multiple myeloma who are considered fit for autologous transplantation. (clinicaltrials.gov identifier: 02288741).
Assuntos
Mieloma Múltiplo/terapia , Transplante de Células-Tronco/métodos , Idoso , Citogenética , Intervalo Livre de Doença , Feminino , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Quimioterapia de Indução/métodos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Mucosite/induzido quimicamente , Mieloma Múltiplo/complicações , Mieloma Múltiplo/mortalidade , Transplante de Células-Tronco/mortalidade , Transplante Autólogo , Resultado do TratamentoRESUMO
BACKGROUND: Routine prophylactic platelet transfusion is the standard of care for patients with severe thrombocytopenia. We assessed the effect of a new strategy of therapeutic platelet transfusion on the number of transfusions and safety in patients with hypoproliferative thrombocytopenia. METHODS: We did a multicentre, open-label, randomised parallel-group trial at eight haematology centres in Germany. Patients aged 16-80 years, who were undergoing intensive chemotherapy for acute myeloid leukaemia or autologous haemopoietic stem-cell transplantation for haematological cancers, were randomly assigned via a computer-generated randomisation sequence to receive either platelet transfusion when bleeding occurred (therapeutic strategy) or when morning platelet counts were 10×10(9) per L or lower (prophylactic strategy). Investigators undertaking interventions were not masked to group assignment. The primary endpoint was the number of platelet transfusions. Analysis was by intention to treat. This trial is registered, NCT00521664. FINDINGS: 197 patients were assigned the prophylactic strategy and 199 the therapeutic strategy. Of 391 patients analysed, the therapeutic strategy reduced the mean number of platelet transfusions by 33·5% (95% CI 22·2-43·1; p<0·0001) in all patients (2·44 [2·22-2·67] in prophylactic group vs 1·63 [1·42-1·83] in therapeutic group), 31·6% (18·6-42·6; p<0·0001) in those with acute myeloid leukaemia (2·68 [2·35-3·01] vs 1·83 [1·58-2·10]), and 34·2% (6·6-53·7; p=0·0193) in those who had had autologous transplantation (1·80 [1·45-2·15] vs 1·18 [0·82-1·55]. We noted no increased risk of major haemorrhage in patients who had undergone autologous transplantation. In those with acute myeloid leukaemia, risk of non-fatal grade 4 (mostly CNS) bleeding was increased. We recorded 15 cases of non-fatal haemorrhage: four retinal in each transfusion group, and one vaginal and six cerebral in the therapeutic group. 12 patients died in the study: two from fatal cerebral haemorrhages in the therapeutic group, and ten (five in each treatment group) unrelated to major bleeding. INTERPRETATION: The therapeutic strategy could become a new standard of care after autologous stem-cell transplantation; however, prophylactic platelet transfusion should remain the standard for patients with acute myeloid leukaemia. The new strategy should be used by some haematology centres only if the staff are well educated and experienced in the new approach and can react in a timely way to first signs of CNS bleeding. FUNDING: Deutsche Krebshilfe eV (German Cancer Aid).
Assuntos
Neoplasias Hematológicas/terapia , Hemorragia/prevenção & controle , Transfusão de Plaquetas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas , Feminino , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/complicações , Transplante de Células-Tronco Hematopoéticas , Hemorragia/etiologia , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Trombocitopenia/terapia , Adulto JovemRESUMO
The individual risk of infection and requirements for medical treatment after high-dose chemotherapy have been unpredictable. In this prospective, multicenter, open-label study we investigated the potential of granulocyte colony-stimulating factor (G-CSF) responsiveness as a predictor. A total of 168 patients with multiple myeloma or lymphoma received a single dose of subcutaneous G-CSF (lenograstim, 263 µg) after high-dose chemotherapy. Highly variable leukocyte peaks were measured and grouped as low (quartile 1; leukocytes 100-10 100/µL), medium (quartile 2; leukocytes > 10 100-18 300/µL), and high (quartiles 3/4; leukocytes > 18 300-44 800/µL). G-CSF responsiveness (low vs medium vs high) was inversely correlated with febrile neutropenia (77% vs 60% vs 48%; P = .0037); the rate of infection, including fever of unknown origin (91% vs 67% vs 54%; P < .0001); days with intravenous antibiotics (9 vs 6 vs 5; P < .0001); and antifungal therapy (P = .042). In multivariate analysis, G-CSF responsiveness remained the only factor significantly associated with infection (P = .016). In addition, G-CSF responsiveness was inversely correlated with grade 3/4 oral mucositis (67% vs 33% vs 23%; P < .0001). G-CSF responsiveness appears as a signature of the myeloid marrow reserve predicting defense against neutropenic infection after intensive chemotherapy. This study is registered at http://www.clinicaltrials.gov as NCT01085058.
Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos , Infecções/etiologia , Linfoma/complicações , Linfoma/tratamento farmacológico , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Adolescente , Adulto , Idoso , Feminino , Humanos , Infecções/sangue , Lenograstim , Linfoma/sangue , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Análise Multivariada , Neutropenia/sangue , Neutropenia/etiologia , Transplante de Células-Tronco de Sangue Periférico , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Proteínas Recombinantes , Fatores de Risco , Adulto JovemRESUMO
We present an analysis of prognostic factors derived from a trial in patients with acute myeloid leukemia older than 60 years. The AML96 trial included 909 patients with a median age of 67 years (range, 61-87 years). Treatment included cytarabine-based induction therapy followed by 1 consolidation. The median follow-up time for all patients is 68 months (5.7 years). A total of 454 of all 909 patients reached a complete remission (50%). Five-year overall survival (OS) and disease-free survival were 9.7% and 14%, respectively. Multivariate analyses revealed that karyotype, age, NPM1 mutation status, white blood cell count, lactate dehydrogenase, and CD34 expression were of independent prognostic significance for OS. On the basis of the multivariate Cox model, an additive risk score was developed that allowed the subdivision of the largest group of patients with an intermediate-risk karyotype into 2 groups. We are, therefore, able to distinguish 4 prognostic groups: favorable risk, good intermediate risk, adverse intermediate risk, and high risk. The corresponding 3-year OS rates were 39.5%, 30%, 10.6%, and 3.3%, respectively. The risk model allows further stratification of patients with intermediate-risk karyotype into 2 prognostic groups with implications for the therapeutic strategy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Estudos de Coortes , Citarabina/uso terapêutico , Daunorrubicina/uso terapêutico , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Proteínas Nucleares/genética , Nucleofosmina , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Indução de Remissão , Fatores de Risco , Tirosina Quinase 3 Semelhante a fms/genéticaRESUMO
From 2002 to 2007, 103 patients with primary myelofibrosis or postessential thrombocythemia and polycythemia vera myelofibrosis and a median age of 55 years (range, 32-68 years) were included in a prospective multicenter phase 2 trial to determine efficacy of a busulfan (10 mg/kg)/fludarabine (180 mg/m(2))-based reduced-intensity conditioning regimen followed by allogeneic stem cell transplantation from related (n = 33) or unrelated donors (n = 70). All but 2 patients (2%) showed leukocyte and platelet engraftment after a median of 18 and 22 days, respectively. Acute graft-versus-host disease grade 2 to 4 occurred in 27% and chronic graft-versus-host disease in 43% of the patients. Cumulative incidence of nonrelapse mortality at 1 year was 16% (95% confidence interval, 9%-23%) and significantly lower for patients with a completely matched donor (12% vs 38%; P = .003). The cumulative incidence of relapse at 3 years was 22% (95% confidence interval, 13%-31%) and was influenced by Lille risk profile (low, 14%; intermediate, 22%; and high, 34%; P = .02). The estimated 5-year event-free and overall survival was 51% and 67%, respectively. In a multivariate analysis, age older than 55 years (hazard ratio = 2.70; P = .02) and human leukocyte antigen-mismatched donor (hazard ratio = 3.04; P = .006) remained significant factors for survival. The study was registered at www.clinicaltrials.gov as #NCT 00599547.
Assuntos
Mielofibrose Primária/cirurgia , Transplante de Células-Tronco/métodos , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Bussulfano/uso terapêutico , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Mielofibrose Primária/mortalidade , Recidiva , Transplante de Células-Tronco/efeitos adversos , Transplante Homólogo , Vidarabina/análogos & derivados , Vidarabina/uso terapêuticoRESUMO
We report long-term results after a median follow-up of 105 months in 18 patients with multiple myeloma who received an intensified myeloablative conditioning regimen regimen consisting of modified total body irradiation, busulfan, cyclophosphamide, and antithymocyte globulin, followed by allogeneic stem cell transplantation (SCT). Grade II-IV acute graft-versus-host disease occurred in 7 patients (44%), and treatment-related mortality was 17%. Complete remission (CR) with negative immunofixation after allogeneic SCT occurred in 53% of the patients. For all patients, the estimated overall survival at 12 years was 50% (95% confidence interval [CI], 26%-74%), and the estimated event-free survival (EFS) was 35% (95% CI, 23%-57%). Those patients who achieved CR after SCT had a 12-year estimated PFS of 60%, whereas none of the patients without CR remained progression-free. Our data indicate that an intensified myeloablative conditioning regimen followed by allogeneic SCT can produce long-term survival and freedom from disease in patients with multiple myeloma who achieve CR.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Depleção Linfocítica/métodos , Mieloma Múltiplo/cirurgia , Linfócitos T/citologia , Condicionamento Pré-Transplante/métodos , Adulto , Soro Antilinfocitário/uso terapêutico , Bussulfano/uso terapêutico , Ciclofosfamida/uso terapêutico , Progressão da Doença , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Transfusão de Linfócitos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Recidiva , Indução de Remissão , Análise de Sobrevida , Sobreviventes/estatística & dados numéricos , Transplante Homólogo , Resultado do Tratamento , Irradiação Corporal TotalAssuntos
Leucemia/classificação , Transtornos Mieloproliferativos/classificação , Organização Mundial da Saúde , Neoplasias da Medula Óssea/classificação , Neoplasias da Medula Óssea/diagnóstico , Neoplasias da Medula Óssea/genética , Neoplasias da Medula Óssea/patologia , Análise Citogenética , Humanos , Leucemia/diagnóstico , Leucemia/genética , Leucemia/patologia , Mutação/fisiologia , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/patologia , Proteínas Nucleares/genética , Nucleofosmina , Terminologia como Assunto , Tirosina Quinase 3 Semelhante a fms/genéticaRESUMO
PURPOSE: Mantle cell lymphoma (MCL) is characterized by a poor prognosis with a low to moderate sensitivity to chemotherapy and a median survival of only 3 to 4 years. In an attempt to improve outcome, the German Low Grade Lymphoma Study Group (GLSG) initiated a randomized trial comparing the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and rituximab (R-CHOP) with CHOP alone as first-line therapy for advanced-stage MCL. PATIENTS AND METHODS: One hundred twenty-two previously untreated patients with advanced-stage MCL were randomly assigned to six cycles of CHOP (n = 60) or R-CHOP (n = 62). Patients up to 65 years of age achieving a partial or complete remission underwent a second randomization to either myeloablative radiochemotherapy followed by autologous stem-cell transplantation or interferon alfa maintenance (IFNalpha). All patients older than 65 years received IFNalpha maintenance. RESULTS: R-CHOP was significantly superior to CHOP in terms of overall response rate (94% v 75%; P = .0054), complete remission rate (34% v 7%; P = .00024), and time to treatment failure (TTF; median, 21 v 14 months; P = .0131). No differences were observed for progression-free survival. Toxicity was acceptable, with no major differences between the two therapeutic groups. CONCLUSION: The combined immunochemotherapy with R-CHOP resulted in a significantly higher response rate and a prolongation of the TTF as compared with chemotherapy alone. Hence, R-CHOP may serve as a new baseline regimen for advanced stage MCL, but needs to be further improved by novel strategies in remission.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Interferon-alfa/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Prednisona/uso terapêutico , Vincristina/uso terapêutico , Idoso , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Feminino , Alemanha , Humanos , Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/radioterapia , Masculino , Pessoa de Meia-Idade , Prednisona/efeitos adversos , Rituximab , Transplante de Células-Tronco , Falha de Tratamento , Vincristina/efeitos adversosRESUMO
We successfully performed two allogeneic hematopoietic stem cell transplantations from matched unrelated donors without the use of blood-product support after treosulfan-based conditioning in two women with acute myeloid leukemia who were Jehovah's witnesses and refused transfusions of blood products.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Testemunhas de Jeová , Leucemia Mieloide Aguda/cirurgia , Adulto , Bussulfano/administração & dosagem , Bussulfano/análogos & derivados , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/sangue , Masculino , Pessoa de Meia-Idade , Transplante HomólogoRESUMO
The patient granulocyte-colony stimulating factor (G-CSF) response is represented by the leukocyte peak in the blood induced by a single dose of G-CSF after chemotherapy, and is correlated with subsequent neutropenic infection risk. General patterns for a meaningful risk group stratification, have not yet been determined. Two independent data sets including a total of 306 cases with myeloma or lymphoma and autologous blood stem cell transplant were available. An infection susceptibility curve plotted according to ranked G-CSF responses from a multicenter study reproduced and validated a curve from the previous single center. Two trend changes were seen within these curves at around 11,000 and 22,000 leukocytes/µL, which separated three groups with a high, medium and low risk of infection. While G-CSF response is related to the consecutive duration of neutropenia, it retains additional independent predictive information for infection risk (p<0.0001) and, more important, is a tool available before the onset of the critical period.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma/terapia , Mieloma Múltiplo/terapia , Neutropenia/prevenção & controle , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Infecções Bacterianas/etiologia , Infecções Bacterianas/prevenção & controle , Terapia Combinada , Relação Dose-Resposta a Droga , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Contagem de Leucócitos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Micoses/etiologia , Micoses/prevenção & controle , Neutropenia/etiologia , Fatores de Risco , Fatores de Tempo , Transplante Autólogo , Resultado do TratamentoRESUMO
PURPOSE: The presence of a mutated nucleophosmin-1 gene (NPM1(mut)) in acute myeloid leukemia (AML) is associated with a favorable prognosis. To assess the predictive value with regard to allogeneic stem-cell transplantation (SCT), we compared the clinical course of patients with NPM1(mut) AML eligible for allogeneic SCT in a donor versus no-donor analysis. PATIENTS AND METHODS: Of 1,179 patients with AML (age 18 to 60 years) treated in the Study Alliance Leukemia AML 2003 trial, we identified all NPM1(mut) patients with an intermediate-risk karyotype. According to the trial protocol, patients were intended to receive an allogeneic SCT if an HLA-identical sibling donor was available. Patients with no available donor received consolidation or autologous SCT. We compared relapse-free survival (RFS) and overall survival (OS) depending on the availability of a suitable donor. RESULTS: Of 304 eligible patients, 77 patients had a sibling donor and 227 had no available matched family donor. The 3-year RFS rates in the donor and no-donor groups were 71% and 47%, respectively (P = .005); OS rates were 70% and 60%, respectively (P = .114). In patients with normal karyotype and no FLT3 internal tandem duplication (n = 148), the 3-year RFS rates in the donor and no-donor groups were 83% and 53%, respectively (P = .004); and the 3-year OS rates were 81% and 75%, respectively (P = .300). CONCLUSION: Allogeneic SCT led to a significantly prolonged RFS in patients with NPM1(mut) AML. The absence of a statistically significant difference in OS is most likely a result of the fact that NPM1(mut) patients who experienced relapse responded well to salvage treatment. Allogeneic SCT in first remission has potent antileukemic efficacy and is a valuable treatment option in patients with NPM1(mut) AML with a sibling donor.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/cirurgia , Mutação , Proteínas Nucleares/genética , Doadores de Tecidos , Adulto , Ensaios Clínicos como Assunto , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Nucleofosmina , Estudos Prospectivos , Estudos Retrospectivos , Irmãos , Transplante Autólogo , Transplante Homólogo , Resultado do TratamentoRESUMO
We investigated toxicity and efficacy of in vivo T-cell depletion with anti-thymocyte globulin (ATG) as part of an intensified myeloablative conditioning regimen followed by allogeneic stem cell transplantation in patients with advanced multiple myeloma. The conditioning regimen consisted of modified total body irradiation, busulfan and cyclophosphamide (n=15) or in the case of prior dose-limiting radiotherapy of busulfan and cyclophosphamide (n=3). The median age was 44 years (range, 29-53) and the median time from diagnosis to transplant was 12 months (range, 6-144). Grade II-IV acute graft-versus-host disease (GvHD) occurred in six patients (35%). Severe grade III/IV GvHD developed in one patient (6%). Three patients died of therapy-related causes (17%). A complete remission (CR) with negative immunofixation after allogeneic transplantation was seen in eight of the evaluable patients (53%). After a median follow-up of 41 months (range, 8-84), the estimated overall survival at 6 years for all patients is 77% (CI 95%: 58-96%). The estimated progression-free survival at 6 years for all patients is 31% (CI 95%: 2-59%) and 46% (CI 95%: 9-83%) for patients with CR. In vivo T-cell depletion with ATG resulted in a low rate of severe GvHD with low treatment-related mortality, and a substantial number of long-term survivors.
Assuntos
Soro Antilinfocitário/uso terapêutico , Doença Enxerto-Hospedeiro/epidemiologia , Mieloma Múltiplo/terapia , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/efeitos adversos , Doença Aguda , Adulto , Soro Antilinfocitário/efeitos adversos , Bussulfano/uso terapêutico , Doença Crônica , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/classificação , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Depleção Linfocítica , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Estadiamento de Neoplasias , Taxa de Sobrevida , Linfócitos T/imunologia , Fatores de Tempo , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo/mortalidade , Irradiação Corporal TotalRESUMO
A 61-year-old man with Hodgkin lymphoma (mixed type), with lymph node manifestations and extranodal and bone marrow involvement in both supra- and infradiaphragmatic locations (stage 4), had dyspnea and tachycardia on echocardiography. There were pleural and pericardial effusions and thickening of the epicardium and pericardium. These findings and computed tomographic findings were suspicious for manifestations of Hodgkin lymphoma. The pericardial findings were demonstrated on F-18 fluorodeoxyglucose positron emission tomographic imaging.
Assuntos
Fluordesoxiglucose F18 , Neoplasias Cardíacas/diagnóstico por imagem , Doença de Hodgkin/diagnóstico por imagem , Pericárdio , Tomografia Computadorizada de Emissão , Humanos , Masculino , Pessoa de Meia-Idade , Compostos RadiofarmacêuticosRESUMO
BACKGROUND: The standard recommendation to date has been that acute hypoproliferative thrombocytopenia should be treated with a prophylactic platelet transfusion if the morning platelet count is less than 10 000/µL, or less than 20 000/µL if there are additional risk factors. For chronic thrombocytopenia, transfusion has been recommended if the platelet count is less than 5000/µL. In Germany, half a million platelet transfusions are now being given every year, and the number is rising. New studies indicate, however, that a more restrictive transfusion strategy is justified. METHODS: A selective literature search was carried out in PubMed, with additional attention to recommendations from Germany and abroad, and to the guidelines of medical specialty societies. RESULTS: Prophylactic platelet transfusions should be given when clinically indicated in consideration of the individual hemorrhagic risk. To prevent severe hemorrhage, it is more important to respond to the first signs of bleeding than to pay exclusive attention to morning platelet counts below 10 000/µL. This threshold value remains standard for patients with acute leukemia. According to recent studies, however, clinically stable patients who are at low risk for bleeding-e.g., patients who have undergone autologous hematopoietic stem-cell transplantation-may be well served by a therapeutic, rather than prophylactic, platelet transfusion strategy, in which platelets are transfused only when evidence of bleeding has been observed. For cancer patients, intensive-care patients, and patients with other risk factors, a clinically oriented transfusion strategy is recommended, in addition to close attention to threshold platelet values. CONCLUSION: The number of platelet transfusions could be safely lowered by a more restrictive transfusion strategy that takes account of the risk of bleeding, as recommended in the hemotherapy guidelines.
Assuntos
Antineoplásicos/efeitos adversos , Neoplasias/complicações , Transfusão de Plaquetas/normas , Hemorragia Pós-Operatória/terapia , Trombocitopenia/induzido quimicamente , Trombocitopenia/terapia , Antineoplásicos/uso terapêutico , Medicina Baseada em Evidências , Alemanha , Hematologia/normas , Humanos , Oncologia/normas , Neoplasias/tratamento farmacológico , Guias de Prática Clínica como Assunto , Resultado do TratamentoRESUMO
PURPOSE: The prognosis of elderly patients with acute myeloid leukemia (AML) is still dismal even with intensive chemotherapy. In this trial, we compared the antileukemic activity of standard induction and consolidation therapy with or without the addition of the kinase inhibitor sorafenib in elderly patients with AML. PATIENTS AND METHODS: All patients received standard cytarabine and daunorubicin induction (7+3 regimen) and up to two cycles of intermediate-dose cytarabine consolidation. Two hundred one patients were equally randomly assigned to receive either sorafenib or placebo between the chemotherapy cycles and subsequently for up to 1 year after the beginning of therapy. The primary objective was to test for an improvement in event-free survival (EFS). Overall survival (OS), complete remission (CR) rate, tolerability, and several predefined subgroup analyses were among the secondary objectives. RESULTS: Age, sex, CR and early death (ED) probability, and prognostic factors were balanced between both study arms. Treatment in the sorafenib arm did not result in significant improvement in EFS or OS. This was also true for subgroup analyses, including the subgroup positive for FLT3 internal tandem duplications. Results of induction therapy were worse in the sorafenib arm, with higher treatment-related mortality and lower CR rates. More adverse effects occurred during induction therapy in the sorafenib arm, and patients in this arm received less consolidation chemotherapy as a result of higher induction toxicity. CONCLUSION: In conclusion, combination of standard induction and consolidation therapy with sorafenib in the schedule investigated in our trial is not beneficial for elderly patients with AML.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Niacinamida/administração & dosagem , Sorafenibe , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Tirosina Quinase 3 Semelhante a fms/genéticaRESUMO
PURPOSE: The current European LeukemiaNet (ELN) recommendations for acute myeloid leukemia (AML) propose a new risk reporting system, integrating molecular and cytogenetic factors and subdividing the large heterogenous group of intermediate-risk patients into intermediate-I (IR-I) and intermediate-II (IR-II). We assessed the prognostic value of the new risk classification in a large cohort of patients. PATIENTS AND METHODS: Complete data for classification were available for 1,557 of 1,862 patients treated in the AML96 trial. Patients were assigned to the proposed genetic groups from the ELN recommendations, and survival analyses were performed using the Kaplan-Meier method and log-rank test for significance testing. RESULTS: The median age of all patients was 67 years. With a median follow-up of 8.3 years, significant differences between all risk categories were observed in patients age ≤ 60 years regarding the time to relapse, relapse-free survival, and overall survival (OS). Patients in the IR-II group had a better prognosis than patients in the IR-I group. The median OS times in young patients with favorable risk (FR), IR-I, IR-II, and adverse risk (AR) were 5.3, 1.1, 1.6, and 0.5 years, respectively. Separate analyses in the age group older than 60 years revealed significant differences between FR, AR, and IR as a whole, but not between IR-I and IR-II. CONCLUSION: In younger patients with AML, the ELN classification seems to be the best available framework for prognostic estimations to date. Caution is advised concerning its use for prospective treatment allocation before it has been prospectively validated. In elderly patients, alternative prognostic factors are desirable for further risk stratification of IR.