RESUMO
The outcome of 55 children with severe aplastic anemia (SAA) who received a second hematopoietic stem cell transplantation (HSCT) was retrospectively analyzed using the registration data of the Japanese Society for Hematopoietic Cell Transplantation. The 5-year overall survival (OS) and failure-free survival (FFS) after the second transplantation were 82.9% (95% confidence interval (CI), 69.7-90.8)) and 81.2% (95% CI, 67.8-89.4), respectively. FFS was significantly better when the interval between the first and second transplantation was >60 days (88.9%; 95% CI, 73.0-95.7) than when it was ⩽60 days (61.4%; 95% CI, 33.3-80.5; P=0.026). All 12 patients who were conditioned with regimens containing fludarabine and melphalan were alive with hematopoietic recovery. These findings justify the recommendation of a second HSCT for children with SAA who have experienced graft failure after first HSCT.
Assuntos
Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Adolescente , Anemia Aplástica/mortalidade , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Análise de SobrevidaRESUMO
This prospective study aimed to investigate the influence of pretransplant serum ferritin levels on the outcomes of allogeneic hematopoietic SCT (HSCT). In total, 190 patients with acute leukemia or myelodysplastic syndrome were consecutively enrolled. The patients were divided into two groups: low-ferritin group (<1000 ng/mL) and high-ferritin group (⩾1000 ng/mL). The primary end point was the cumulative incidence of infection within 100 days after HSCT, which was similar between the two groups: bloodstream infection, 35 vs 38%, P=0.65; bacterial infection, 44 vs 41%, P=0.68; and fungal infection, 6 vs 8%, P=0.71. The 1-year adjusted probability of OS of the high-ferritin group was significantly lower than that of the low-ferritin group (76 vs 63%, P=0.017). Using receiver operating characteristic curve, the threshold of pretransplant serum ferritin levels for bloodstream infection was 1400 ng/mL; the threshold for OS, EFS and non-relapse mortality was 1349 ng/mL. In conclusion, pretransplant serum ferritin levels of ⩾1000 ng/mL did not influence the incidence of infection but adversely affected OS after HSCT. A higher threshold of pretransplant serum ferritin levels may predict HSCT outcomes.
Assuntos
Infecções Bacterianas , Ferritinas/sangue , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Micoses , Período Pré-Operatório , Adulto , Idoso , Aloenxertos , Infecções Bacterianas/sangue , Infecções Bacterianas/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Micoses/sangue , Micoses/mortalidade , Estudos Prospectivos , Taxa de SobrevidaRESUMO
Diabetes mellitus (DM) is a factor in the hematopoietic cell transplantation-comorbidity index. However, the impact of pre-transplant DM on morbidity and cause-specific non-relapse mortality (NRM) remains unclear. We performed a retrospective study with registry data that included a total of 7626 patients who underwent their first allogeneic hematopoietic SCT (HSCT) between 2007 and 2010. The median age was 44 years (range 0-88). Compared with patients without pre-transplant DM (non-DM group, n=7248), patients with pre-transplant DM (DM group, n=378) were older and were more likely to have high-risk disease, a reduced-intensity conditioning regimen and GVHD prophylaxis using tacrolimus. Multivariate analyses showed that pre-transplant DM was associated with increased risks of NRM (hazard ratio (HR)1.46, 95% confidence interval (CI) 1.21-1.76, P<0.01) and infection-related NRM (HR 2.08, 95% CI 1.58-2.73, P<0.01). The presence of pre-transplant DM was associated with an increased risk of overall mortality in a multivariate analysis (HR 1.55, 95% CI 1.35-1.78, P<0.01). In conclusion, pre-transplant DM was a risk factor for NRM, particularly infection-related mortality, after allogeneic HSCT. To improve the clinical outcome in patients with DM, the benefits of strict infection control and appropriate glycemic control should be explored in future trials.
Assuntos
Diabetes Mellitus/mortalidade , Transplante de Células-Tronco Hematopoéticas , Infecções/mortalidade , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Lactente , Infecções/etiologia , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Risk of relapse during the unrelated donor coordination period biases comparisons between allogeneic hematopoietic stem cell transplantation from an HLA 8 of 8 allele-matched unrelated donor (8/8 MUD) and that from a related donor with an HLA-1 antigen mismatch in the graft-versus-host (GVH) direction (RD/1AGMM-GVH). To reduce this bias, we performed a decision analysis focusing on acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in first complete remission (CR1). The primary outcome measure was 5-year survival probability with or without quality-of-life (QOL) adjustment. A baseline analysis showed that the decision to perform MUD transplantation was superior to that to perform RD/1AGMM-GVH transplantation for patients with AML or ALL. However, in the ALL cohort, the direction of superiority was reversed when the interval between CR1 and 8/8 MUD transplantation was >5.5 months (without QOL adjustment) or >6 months (after QOL adjustment) or when overall survival of RD/1AGMM-GVH transplantation improved by 1.3% without QOL adjustment and 2.1% after QOL adjustment. In conclusion, 8/8 MUD should be prioritized in transplantation for AML and ALL in CR1. However, the MUD coordination period and improvements in RD/1AGMM-GVH transplantation might change the donor selection priority in transplantation for ALL in CR1.
Assuntos
Técnicas de Apoio para a Decisão , Seleção do Doador/métodos , Antígenos HLA , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Doadores não Relacionados , Adolescente , Adulto , Idoso , Aloenxertos , Feminino , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
To elucidate the impact of pretransplant body mass index (BMI) on the clinical outcome, we performed a retrospective study with registry data including a total of 12 050 patients (age ⩾18 years) who received allogeneic hematopoietic SCT (HSCT) between 2000 and 2010. Patients were stratified as follows: BMI<18.5 kg/m(2), Underweight, n=1791; 18.5⩽BMI<25, Normal, n=8444; 25⩽BMI<30, Overweight, n=1591; BMI⩾30, Obese, n=224. The median age was 45 years (range, 18-77). A multivariate analysis showed that the risk of relapse was significantly higher in the underweight group and lower in the overweight and obese groups compared with the normal group (hazard ratio (HR), 1.16, 0.86, and 0.74, respectively). The risk of GVHD was significantly higher in the overweight group compared with the normal group. The risk of non-relapse mortality (NRM) was significantly higher in the overweight and obese group compared with the normal group (HR 1.19 and HR 1.43, respectively). The probability of OS was lower in the underweight group compared with the normal group (HR 1.10, P=0.018). In conclusion, pretransplant BMI affected the risk of relapse and NRM after allogeneic HSCT. Underweight was a risk factor for poor OS because of an increased risk of relapse. Obesity was a risk factor for NRM.
Assuntos
Índice de Massa Corporal , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/complicações , Sobrepeso , Probabilidade , Recidiva , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Magreza , Transplante Homólogo , Resultado do Tratamento , Adulto JovemAssuntos
Cardiopatias/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/efeitos adversos , Adolescente , Adulto , Idoso , Pressão Sanguínea , Cardiopatias/fisiopatologia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: We retrospectively analyzed 80 instances of varicella zoster virus (VZV) disease in 72 patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) and examined the clinical differences between localized and disseminated disease. Risk factors for developing VZV dissemination were also evaluated. RESULTS: Of the 80 instances, 54 instances were localized diseases and 26 were disseminated diseases. Patient characteristics did not differ significantly between the 2 groups, except for the first-line therapy and the duration from symptom onset to treatment. In the disseminated group, intravenous acyclovir was used as the first-line therapy more frequently, and more time elapsed before beginning antiviral therapy compared with the localized group. In multivariate analyses, the duration from symptom onset to treatment was identified as an independent risk factor that significantly affected the development of VZV dissemination. Gender, total body irradiation, and chronic graft-versus-host disease, of which the latter 2 factors were reported as risk factors for the development of VZV disease after HSCT, did not affect the development of VZV dissemination. CONCLUSION: Our results suggest that VZV infection or reactivation may easily progress to viremia with delayed use of antiviral agents and may result in VZV dissemination in immunocompromised patients.
Assuntos
Viroses do Sistema Nervoso Central/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpes Zoster/tratamento farmacológico , Herpesvirus Humano 3/fisiologia , Aciclovir/análogos & derivados , Aciclovir/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Viroses do Sistema Nervoso Central/virologia , Varicela/tratamento farmacológico , Varicela/virologia , Intervalo Livre de Doença , Feminino , Herpes Zoster/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Tempo para o Tratamento , Valaciclovir , Valina/análogos & derivados , Valina/uso terapêutico , Ativação Viral , Adulto JovemRESUMO
BACKGROUND: The number of long-term survivors after hematopoietic stem cell transplantation (HSCT) showed steady increase in the past two decades. Second malignancies after HSCT are a devastating late complication. We analyzed the incidence of, risk compared with that in the general population, and risk factors for secondary solid cancers. PATIENTS AND METHODS: Patients were 17 545 adult recipients of a first allogeneic stem cell transplantation between 1990 and 2007 in Japan. Risks of developing secondary solid tumors were compared with general population by using standard incidence ratios (SIRs). RESULTS: Two-hundred sixty-nine secondary solid cancers were identified. The cumulative incidence was 0.7% [95% confidence interval (CI), 0.6%-0.9%] at 5 years and 1.7% (95% CI, 1.4%-1.9%) at 10 years after transplant. The risk was significantly higher than that in the general population (SIR=1.8, 95% CI, 1.5-2.0). Risk was higher for oral cancer (SIR=15.7, 95% CI, 12.1-20.1), esophageal cancer (SIR=8.5, 95% CI, 6.1-11.5), colon cancer (SIR=1.9, 95% CI, 1.2-2.7), skin cancer (SIR=7.2, 95% CI, 3.9-12.4), and brain/nervous system cancer (SIR=4.1, 95% CI, 1.6-8.4). The risk of developing oral, esophageal, or skin cancer was higher at all times after 1-year post-transplant. Extensive-type chronic graft-versus-host disease (GVHD) was a significant risk factor for the development of all solid tumors (RR=1.8, P<0.001), as well as for oral (RR=2.9, P<0.001) and esophageal (RR=5.3, P<0.001) cancers. Limited-type chronic GVHD was an independent risk factor for skin cancers (RR=5.8, P=0.016). CONCLUSION: Recipients of allogeneic HSCT had a significantly higher â¼2-fold risk of developing secondary solid cancers than the general population. Lifelong screening for high-risk organ sites, especially oral or esophageal cancers, is important for recipients with active, or a history of, chronic GVHD.
Assuntos
Neoplasias Esofágicas/etiologia , Doença Enxerto-Hospedeiro/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neoplasias Bucais/etiologia , Segunda Neoplasia Primária/etiologia , Adolescente , Adulto , Distribuição por Idade , Neoplasias Esofágicas/epidemiologia , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Incidência , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Fatores de Risco , Transplante Homólogo , Adulto JovemRESUMO
Few studies have evaluated the risk factors for chronic GVHD and organ involvement associated with different graft types, including unrelated cord blood (U-CB). We retrospectively studied 4818 adult patients who received their first allogeneic transplantation and survived for at least 100 days. The incidence of chronic GVHD at 2 years was 37%. The following factors were associated with the development of chronic GVHD: female donor/male recipient, CMV-Ab seropositivity, matched related peripheral blood grafts vs matched related BM grafts, no in vivo T-cell depletion and the occurrence of grade II-IV acute GVHD. Among these factors, the association with acute GVHD occurrence was consistently significant across donor subtypes. The use of U-CB was not associated with chronic GVHD, but was associated with a low incidence of extensive chronic GVHD. Chronic GVHD patients who had received U-CB transplants showed less frequent involvement of the oral cavity (28% vs 55%), eye (12% vs 26%), liver (20% vs 44%), lung (11% vs 25%) and joint (0% vs 6%) than those with matched related BM grafts. In conclusion, we found that U-CB transplants were associated with a low incidence of extensive chronic GVHD and less frequent involvement of the oral cavity, eye, liver, lung and joints.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Doença Enxerto-Hospedeiro/complicações , Transplante Homólogo/efeitos adversos , Adolescente , Adulto , Idoso , Doença Crônica , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Transplante Homólogo/métodos , Doadores não Relacionados , Adulto JovemRESUMO
To determine whether a difference in donor source affects the outcome of transplantation for patients with primary myelofibrosis (PMF), a retrospective study was conducted using the national registry data on patients who received first allogeneic hematopoietic cell transplantation (HCT) with related BM (n=19), related PBSCs (n=25), unrelated BM (n=28) or unrelated umbilical cord blood (UCB; n=11). The 5-year OS rates after related BM, related PBSC and unrelated BM transplantation were 63%, 43% and 41%, respectively, and the 2-year OS rate after UCB transplantation was 36%. On multivariate analysis, the donor source was not a significant factor for predicting the OS rate. Instead, performance status (PS) ≥2 (vs PS 0-1) predicted a lower OS (P=0.044), and RBC transfusion ≥20 times before transplantation (vs transfusion ≤9 times) showed a trend toward a lower OS (P=0.053). No advantage of nonmyeloablative preconditioning regimens in terms of decreasing nonrelapse mortality or increasing OS was found. Allogeneic HCT, and even unrelated BM and UCB transplantation, provides a curative treatment for PMF patients.
Assuntos
Transfusão de Sangue , Transplante de Medula Óssea , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Mielofibrose Primária/terapia , Adulto , Idoso , Causas de Morte , Feminino , Sangue Fetal , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mutação , Mielofibrose Primária/mortalidade , Modelos de Riscos Proporcionais , Recidiva , Sistema de Registros , Estudos Retrospectivos , Sociedades Médicas , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
We retrospectively assessed the outcome and pretransplantation predictors of the outcome in 118 patients aged ≥ 50 years who received fludarabine-containing reduced-intensity allo-SCT (RIST) for B-cell ALL in the first or second CR. Eighty patients received transplants from unrelated donors. Seventy-eight patients were positive for the Ph chromosome. The median follow-up period was 18 months and the 2-year OS rate was 56%. The 2-year cumulative incidence of relapse and non-relapse mortality was 28% and 26%, respectively. The incidence of grades II-IV and III-IV acute GVHD was 46% and 24%, respectively. After 2 years, the incidence of chronic GVHD was 37%. Multivariate analysis of pretransplant factors showed that a higher white blood cell count (≥ 30 × 10(9)/L) at diagnosis (hazard ratio (HR)=2.19, P=0.007) and second CR (HR=2.02, P=0.036) were significantly associated with worse OS, whereas second CR (HR=3.83, P<0.001) and related donor (HR=2.34, P=0.039) were associated with a higher incidence of relapse. Fludarabine-containing RIST may be a promising strategy for older patients with B-cell ALL in their first remission.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Condicionamento Pré-Transplante/métodos , Fatores Etários , Idoso , Linfócitos B/imunologia , Estudos de Coortes , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Indução de Remissão , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivadosRESUMO
Cryptogenic organizing pneumonia (COP), previously known as bronchiolitis obliterans organizing pneumonia (BOOP), is a significant complication after allogeneic hematopoietic SCT (HCT). However, the pathogenesis of this complication has not yet been elucidated. Therefore, we identified the pre-transplant risk factors for the development of COP/BOOP using the Japan transplant registry database between 2005 and 2009. Among 9550 eligible recipients, 193 experienced COP/BOOP (2%). HLA disparity (odds ratio (OR) 1.51, P=0.05), female-to-male HCT (OR 1.53, P=0.023), and PBSC transplant (OR 1.84, P=0.0076) were significantly associated with an increased risk of COP/BOOP. On the other hand, BU-based myeloablative conditioning (OR 0.52, P=0.033), or fludarabine-based reduced-intensity conditioning (OR 0.50, P=0.0011) in comparison with a TBI-based regimen and in vivo T-cell depletion (OR 0.46, P=0.055) were associated with a lower risk. Of the 193 patients with COP/BOOP, 77 died, including non-relapse death in 46 (59%). Pulmonary failure and fatal infection accounted for 41% (n=19) and 26% (n=12) of the non-relapse death. Allogeneic immunity and conditioning toxicity could be associated with COP/BOOP. Prospective studies are required to elucidate the true risk factors for COP/BOOP and to develop a prophylactic approach.
Assuntos
Bronquiolite Obliterante/etiologia , Pneumonia em Organização Criptogênica/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fatores de Risco , Análise de Sobrevida , Adulto JovemRESUMO
In this study, outcomes for 575 adult ALL patients aged ≥45 years who underwent first allo-SCT in CR were analyzed according to the type of conditioning regimen (myeloablative conditioning (MAC) for 369 patients vs reduced-intensity conditioning (RIC) for 206 patients). Patients in the RIC group were older (median age, 58 vs 51 years, P<0.0001). There were no statistically significant differences in 3-year OS, disease-free survival (DFS) and non-relapse mortality (NRM): 51% vs 53%, 47% vs 39% and 38% vs 36%, respectively. Multivariate analysis showed that CR2 and HLA mismatching were associated with poor OS (P=0.002 and P=0.019, respectively). HLA mismatching was associated with lower rate of relapse (P=0.016), but was associated with higher rate of NRM (P=0.001). RIC was associated with good OS and DFS in patients who received HLA-mismatch transplantation and were aged ≥55 years compared with MAC by multivariate analysis for each event with interaction (hazard ratio (HR) and 95% confidence interval 0.35 and 0.15-0.81, P=0.014 for OS and 0.36 and 0.16-0.81, P=0.013 for DFS). Therefore, patients ≥55 years of age with HLA-mismatch transplantation should be candidates for RIC rather than MAC.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Condicionamento Pré-Transplante/métodos , Idoso , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Recidiva , Estudos Retrospectivos , Transplante HomólogoRESUMO
INTRODUCTION: Varicella zoster virus (VZV) disease is one of the major infectious complications that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Many reports have shown visceral VZV infection, a special type of VZV disease, to be rare. However, few studies so far have included a large number of patients. FINDINGS: Visceral VZV infection was found in 20 (0.8%) of 2411 patients who underwent allo-HSCT at our hospitals. Seventeen (85%) patients were taking immunosuppressive agents at the time of presentation with zoster. The presenting symptom was abdominal pain in 16 patients (80%), unconsciousness in 3 patients (15%), and no symptoms in 1 patient. The mean time interval from allo-HSCT to symptomatic visceral VZV infection was 273 days (103-800 days). The eruptions appeared within 3 days (0-13) after the first symptoms. Treatment with intravenous acyclovir was initiated before the appearance of eruptions in 3 of 18 patients (all 3 survived) with vesicular eruptions, the same day in 12 patients (11 survived, 1 died), and after the appearance in 3 patients (1 survived, 2 died). The overall mortality was 20%. CONCLUSION: In conclusion, these data confirm that the incidence of visceral VZV infection is infrequent, but this disease is serious. When patients being treated with immunosuppressive agents demonstrate abdominal pain or unconsciousness, the possibility of visceral VZV infection should be considered as well as earlier therapeutic intervention.
Assuntos
Dor Abdominal/etiologia , Doença Enxerto-Hospedeiro/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpes Zoster/diagnóstico , Herpes Zoster/patologia , Aciclovir/uso terapêutico , Adulto , Antivirais/uso terapêutico , Doença Crônica , Feminino , Herpes Zoster/tratamento farmacológico , Herpes Zoster/virologia , Herpesvirus Humano 3/isolamento & purificação , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Transplante Homólogo/efeitos adversos , Inconsciência/etiologia , Ativação Viral , Vísceras/patologia , Adulto JovemRESUMO
Although recent improvements have been indicated in the outcome after allogeneic hematopoietic cell transplantation (allo-HCT), little information is available on how changes in transplant modalities have affected the outcomes after allo-HCT in non-remission, based on patient age, donor source and disease type. We compared the incidence and causes of non-relapse mortality (NRM) after allo-HCT in non-remission among three consecutive four-year periods using a nationwide transplant outcome registry database. A total of 3308 patients with acute leukemia in non-remission were analyzed. The risk of NRM decreased over the three periods, and the hazard ratios (HRs) in 2001-2004 and 2005-2008 compared with 1997-2000 were 0.86 (95% CI, 0.70-1.06; P=0.16) and 0.65 (95% CI, 0.53-0.80; P<0.01), respectively. A significant decrease in the HR for overall mortality was also observed in 2005-2008 (HR 0.85; 95% CI, 0.75-0.97; P=0.02). We found that a decrease in the incidences of death due to GVHD and infection contributed to the reduction in NRM, to which high-resolution donor-recipient HLA matching and other improvements may have contributed. As none of the subgroups showed improved survival without a reduction in NRM, the effective prevention of transplant-related complications appears to be necessary for improving outcomes after allo-HCT in non-remission.
Assuntos
Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia/mortalidade , Leucemia/cirurgia , Condicionamento Pré-Transplante/efeitos adversos , Doença Aguda , Adolescente , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Condicionamento Pré-Transplante/mortalidade , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Primary graft failure (pGF) is associated with considerable morbidity and mortality. Salvage hematopoietic SCT (HSCT) can rescue pGF patients; however, the optimal preconditioning regimen and stem cell source are yet to be determined, particularly in children. In this study, we retrospectively analyzed 102 pediatric patients who received salvage allogeneic HSCT for pGF. Salvage HSCT from matched or one-Ag-mismatched related donors (rMM01) provided superior OS compared with that from two- or three-Ags-mismatched related donors (rMM23) or cord blood transplantation (CBT). CBT showed a trend toward a slightly lower engraftment rate and late engraftment achievement compared with rMM23; however, the OS rate was similar between the two groups (47.6±7.7% for rMM23 and 45.7±8.6% for CBT, at 1 year after salvage HSCT). Multivariate analysis showed that preconditioning regimens with fludarabine or irradiation were associated with a higher engraftment rate and those with alkylating agents were associated with better OS. In conclusion, our results showed that rMM01 was the most suitable donor for salvage HSCT for pediatric pGF, and that CBT was an equally important option compared with rMM23 for patients without rMM01.
Assuntos
Rejeição de Enxerto/cirurgia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Terapia de Salvação/métodos , Condicionamento Pré-Transplante/métodos , Adolescente , Criança , Pré-Escolar , Sobrevivência de Enxerto , Humanos , Lactente , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Transplante Homólogo , Resultado do TratamentoRESUMO
The efficacy of unrelated transplantation for patients with ALL who lack an HLA-matched sibling remains unclear. We performed a decision analysis to determine the efficacy of myeloablative transplantation from a genetically HLA-A, -B, -DRB1 allele-matched unrelated donor for patients with Ph chromosome-negative ALL aged 21-54 years. The transition probabilities were estimated from the Japan Adult Leukemia Study Group studies (ALL93; n=80, ALL97; n=82), and the Japan Marrow Donor Program database (transplantation in first CR (CR1): n=177). The primary outcome measure was the 10-year survival probability with or without quality of life (QOL) adjustment. Subgroup analyses were performed according to risk stratification based on the WBC count and cytogenetics, and according to age stratification. In all patients, unrelated transplantation in CR1 was shown to be superior in analyses both with and without QOL adjustment (40.8 vs 28.4% and 43.9 vs 29.0%, respectively). A similar tendency was observed in all subgroups. The decision model was sensitive to the probability of leukemia-free survival following chemotherapy and the probability of survival after transplantation in standard-risk and higher-aged patients. Unrelated transplantation in CR1 improves the long-term survival probability in patients who lack an HLA-matched sibling. However, recent improvements in treatment strategies may change this result.
Assuntos
Técnicas de Apoio para a Decisão , Antígenos HLA-A/imunologia , Antígenos HLA-B/imunologia , Cadeias HLA-DRB1/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Doadores não Relacionados , Adulto , Alelos , Árvores de Decisões , Feminino , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Cadeias HLA-DRB1/genética , Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: We aimed to clarify the impact of the donor source of allogeneic stem cell transplantation (allo-SCT) on Philadelphia chromosome-negative acute lymphoblastic leukemia [Ph(-) ALL] with focus on cord blood (CB). PATIENTS AND METHODS: We retrospectively analyzed data of 1726 patients who underwent myeloablative allo-SCT for adult Ph(-) ALL. The sources of the allo-SCT were related donors (RD; N = 684), unrelated donors (URD; N = 809), and CB (N = 233). RESULTS: Overall survival (OS) in patients after CB allo-SCT in first complete remission (CR1) was comparable with that after RD or URD allo-SCT (RD: 65%, URD: 64% and CB: 57% at 4 years, P = 0.11). CB was not a significant risk factor for relapse or non-relapse mortality as well as for OS in multivariate analyses. Similarly, the donor source was not a significant risk factor for OS in subsequent CR or non-CR (RD: 47%, URD: 39% and CB: 48% in subsequent CR, P = 0.33; RD: 15%, URD: 21% and CB: 18% in non-CR, P = 0.20 at 4 years). CONCLUSION: Allo-SCT using CB led to OS similar to those of RD or URD in any disease status. To avoid missing the appropriate timing, CB is a favorable alternative source for adult Ph(-) ALL patients without a suitable RD or URD.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Sociedades Médicas/normas , Doadores de Tecidos , Adolescente , Adulto , Idoso , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/normas , Feminino , Transplante de Células-Tronco Hematopoéticas/normas , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
The emergence of microalbuminuria following conditioning chemotherapy may predict the development of renal dysfunction. To confirm this, a 1-year retrospective cohort study was conducted in 31 myeloablative allogeneic SCT patients who received five consecutive measurements of albuminuria before conditioning therapy and on days 0, 7, 14 and 28 following SCT. The cohort had neither microalbuminuria nor renal dysfunction at baseline. Microalbuminuria was defined as an albumin-creatinine (Cr) ratio over 30 mg/g, and renal dysfunction was as an estimated glomerular filtration rate <60 mL/min per 1.73 m(2). Cumulative incidence of renal dysfunction over time was analyzed by the Kaplan-Meier method. Multivariate Cox proportional hazards analysis was used to examine an association of de novo microalbuminuria with the incidence of renal dysfunction. In all, 16 patients (52%) developed microalbuminuria that was positive at least two times among the four measurements after SCT. The actuarial occurrence of chronic kidney disease was significantly higher in patients who developed microalbuminuria than in those who did not. Incidence of microalbuminuria had a significant risk of subsequent renal dysfunction (hazard ratio (95% confidence interval), 7.3 (1.2-140)). In conclusion, de novo microalbuminuria following conditioning therapy is a warning of near-term loss of renal function.