RESUMEN
We hypothesized that the compatibility of each HLA loci between donor and patient induced divergent transplant-related immunologic responses, which attributed to the individualized manifestation of clinical outcomes. Here, we analyzed 7898 Japanese pairs transplanted with T-cell-replete marrow from an unrelated donor with complete HLA allele typing data. Multivariable competing risk regression analyses were conducted to evaluate the relative risk (RR) of clinical outcomes after transplantation. A significant RR of HLA allele mismatch compared with match was seen with HLA-A, -B, -C, and -DPB1 for grade III-IV acute graft-versus-host disease (GVHD), and HLA-C for chronic GVHD. Of note, only HLA-C and HLA-DPB1 mismatch reduced leukemia relapse, and this graft-versus-leukemia effect of HLA-DPB1 was independent of chronic GVHD. HLA-DRB1 and HLA-DQB1 double (DRB1_DQB1) mismatch was revealed to be a significant RR for acute GVHD and mortality, whereas single mismatch was not. Thus, the number of HLA-A, -B, -C, -DPB1, and DRB1_DQB1 mismatches showed a clear-cut risk difference for acute GVHD, whereas the number of mismatches for HLA-A, -B, -C, and DRB1_DQB1 showed the same for mortality. In conclusion, we determined the biological response to HLA locus mismatch in transplant-related immunologic events, and provide a rationale for use of a personalized algorithm for unrelated donor selection.
Asunto(s)
Trasplante de Médula Ósea , Prueba de Histocompatibilidad , Histocompatibilidad/fisiología , Leucemia/terapia , Donante no Emparentado , Adolescente , Adulto , Anciano , Alelos , Trasplante de Médula Ósea/efectos adversos , Trasplante de Médula Ósea/estadística & datos numéricos , Niño , Preescolar , Femenino , Sitios Genéticos/inmunología , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/genética , Enfermedad Injerto contra Huésped/inmunología , Antígenos HLA-A/genética , Antígenos HLA-A/inmunología , Antígenos HLA-B/genética , Antígenos HLA-B/inmunología , Antígenos HLA-C/genética , Antígenos HLA-C/inmunología , Cadenas beta de HLA-DP/genética , Cadenas beta de HLA-DP/inmunología , Cadenas beta de HLA-DQ/genética , Cadenas beta de HLA-DQ/inmunología , Cadenas HLA-DRB1/genética , Cadenas HLA-DRB1/inmunología , Humanos , Lactante , Recién Nacido , Leucemia/epidemiología , Leucemia/genética , Leucemia/inmunología , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Several high-risk HLA allele mismatch combinations (HR-MMs) for severe acute graft-versus-host disease (GVHD) have been identified by analyzing transplantation outcomes in Japanese unrelated hematopoietic stem cell transplant recipients. In this study, we analyzed the effects of HR-MMs in 3 transplantation time periods. We confirmed that the incidence of grade III to IV acute GVHD in the HR-MM group was significantly higher than that in the low-risk (LR) MM group (hazard ratio [HR], 2.74; P < .0001) in the early time period (1993 to 2001). However, the difference in the incidence of grade III to IV acute GVHD between the HR-MM and LR-MM groups was not statistically significant (HR, 1.06; P = .85 and HR, .40; P = .21, respectively) in the mid (2002 to 2007) and late (2008 to 2011) time periods. Similarly, survival in the HR-MM group was significantly inferior to that in the LR-MM group (HR, 1.46; P = .019) in the early time period, whereas the difference in survival between the 2 groups was not statistically significant in the mid and late time periods (HR, 1.06; P = .75 and HR, .82; P = .58, respectively). In conclusion, the adverse impact of HR-MM has become less significant over time. Unrelated transplantation with a single HR-MM could be a viable option in the absence of a matched unrelated donor or an unrelated donor with a single LR-MM.
Asunto(s)
Alelos , Enfermedad Injerto contra Huésped/terapia , Antígenos HLA/inmunología , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Factores de Edad , Femenino , Expresión Génica , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/patología , Antígenos HLA/genética , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/patología , Prueba de Histocompatibilidad , Humanos , Masculino , Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Factores de Tiempo , Trasplante Homólogo , Resultado del Tratamiento , Donante no EmparentadoRESUMEN
Efficacy, safety and pharmacokinetics of meropenem (MEPM) were assessed when 1 g (40 mg/kg for some of the pediatric patients) t.i.d. was administered every 8hours to 101 adult and 6 pediatric patients with febrile neutropenia (FN) as diagnosed based on the Japanese guideline for FN treatment. The efficacy rate evaluated as antifebrile effect up to Day 4 of treatment was 40.0% (40/100) in adult and 66.7% (4/6) in pediatric patients. The antifebrile effect in adult patients was analyzed after stratifying them according to their neutrophil counts up to Day 4. Treatment with MEPM produced an antifebrile effect not only in patients with higher neutrophil counts (> or = 500/mm3) but also in those with lower counts (< 100/mm3), and the efficacy rate was comparable between the two groups: 38.2% in the < 100/mm3 group and 29.4 to 55.6% in the > or = 500/mm3 group. The bacteriological efficacy of MEPM evaluated as disappearance rate on Days 3 to 5 and Day 7 was both 100% (8/8 and 4/4, respectively). The time above minimal inhibitory concentration (% T > MIC) in the treatment interval was greater than 90% in 9 out of 10 patients for whom likely causative organism was isolated and identified after MEPM treatment or for whom causative organism emerging after treatment was isolated and identified. The incidence of adverse events was 93.1% in adult and 83.3% in pediatric patients. There were three deaths and one serious adverse event reported among the adult patients; however, all these cases were assessed as not related to the study medication. The incidence of adverse drug reactions was 45.5% and 66.7%, respectively. All the observed adverse drug reactions were mild or moderate in severity and none of them was severe. Adverse drug reactions which were unknown from the previous MEPM clinical studies and investigation of the results of clinical experience include 'chest discomfort', 'blood uric acid decreased', 'lymphocyte deformation', 'blood uric acid increased', 'abnormal funduscopy', 'hypesthesia' and 'hemorrhagic cystitis'. All these events were mild or moderate in severity and resolved without requiring any action or after providing symptomatic treatment. There was no unknown adverse drug reaction that resulted in treatment discontinuation. No nervous system disorders such as convulsion and impaired consciousness were reported. The results show that monotherapy of MEPM 1 g (or 40 mg/kg for some of the pediatric patients) t.i.d. every 8 hours was effective, and was also safe and well tolerated in adult and pediatric patients with FN. Therefore, MEPM monotherapy is expected to be useful as the initial treatment for Japanese patients with FN.
Asunto(s)
Antibacterianos/uso terapéutico , Fiebre/tratamiento farmacológico , Neutropenia/tratamiento farmacológico , Tienamicinas/uso terapéutico , Adulto , Anciano , Femenino , Humanos , Masculino , Meropenem , Persona de Mediana Edad , Tienamicinas/efectos adversosRESUMEN
Both obesity and malnutrition are considered risk factors for complications after bone marrow transplantation (BMT). To elucidate the impact of pretransplantation body mass index (BMI) on clinical outcome, we performed a retrospective cohort study with registration data from the Japan Marrow Donor Program (JMDP). Between January 1998 and December 2005, a total of 3935 patients received unrelated BMT through the JMDP; of these, 3827 patients for whom pretransplantation height and weight data were available were included in the study. Patients were stratified according to pretransplantation BMI values (low BMI: BMI < 18 kg/m(2), n = 295; normal BMI: 18 < or = BMI < 25 kg/m(2), n = 2906; overweight: 25 < or = BMI <30 kg/m(2), n = 565; obese: 30 kg/m(2) < or = BMI, n = 61). In a univariate analysis, pretransplantation BMI was associated with a significantly greater risk of grade II-IV acute graft-versus-host disease (GVHD; P = .03). Multivariate analysis showed that pretransplantation BMI tended to be associated with an increased risk of grade II-IV acute GVHD (P = .07). Obesity was associated with an increased risk of infection compared with normal BMI (odds ratio = 1.9; 95% confidence interval = 1.1 to 3.2; P = .02). Our findings demonstrate a correlation between pretransplantation BMI and posttransplantation complications. Although BMI depends strongly on multiple factors, the effect of obesity on clinical outcome should be evaluated in a prospective study.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Enfermedades Transmisibles/etiología , Enfermedad Injerto contra Huésped/etiología , Obesidad/complicaciones , Adolescente , Adulto , Anciano , Índice de Masa Corporal , Humanos , Desnutrición/complicaciones , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: NKG2D, an activating and co-stimulatory receptor expressed on natural killer cells and T cells, plays pivotal roles in immunity to microbial infections as well as in cancer immunosurveillance. This study examined the impact of donor and recipient polymorphisms in the NKG2D gene on the clinical outcomes of patients undergoing allogeneic T-cell-replete myeloablative bone marrow transplantation using an HLA-matched unrelated donor. DESIGN AND METHODS: The NKG2D polymorphism was retrospectively analyzed in a total 145 recipients with hematologic malignancies and their unrelated donors. The patients underwent transplantation following myeloablative conditioning; the recipients and donors were matched through the Japan Marrow Donor Program. RESULTS: In patients with standard-risk disease, the donor NKG2D-HNK1 haplotype, a haplotype expected to induce greater natural killer cell activity, was associated with significantly improved overall survival (adjusted hazard ratio, 0.44; 95% confidence interval, 0.23 to 0.85; p=0.01) as well as transplant related mortality (adjusted hazard ratio, 0.42; 95% confidence interval, 0.21 to 0.86; p=0.02), but had no impact on disease relapse or the development of grade II-IV acute graft-versus-host disease or chronic graft-versus-host disease. The NKG2D polymorphism did not significantly influence the transplant outcomes in patients with high-risk disease. CONCLUSIONS: These data suggest an association between the donor HNK1 haplotype and better clinical outcome among recipients, with standard-risk disease, of bone marrow transplants from HLA-matched unrelated donors.
Asunto(s)
Trasplante de Médula Ósea , Antígenos HLA/genética , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/cirugía , Prueba de Histocompatibilidad/métodos , Subfamilia K de Receptores Similares a Lectina de Células NK/genética , Polimorfismo Genético/genética , Adolescente , Adulto , Trasplante de Médula Ósea/métodos , Trasplante de Médula Ósea/mortalidad , Niño , Preescolar , Femenino , Estudios de Seguimiento , Haplotipos , Neoplasias Hematológicas/mortalidad , Humanos , Lactante , Donadores Vivos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Although the AB0 blood group is one of two major antigen systems of relevance for transplantation in humans, there are still conflicting data concerning the influence of AB0 incompatibility on transplant outcome. This study investigated the effect of AB0 incompatibility in recipients of bone marrow transplants from unrelated donors. DESIGN AND METHODS: We retrospectively analyzed data from 5,549 patients who underwent bone marrow transplantation from unrelated donors in the Japan Marrow Donor Program. RESULTS: Overall survival rates in the group with major and minor mismatches were significantly lower than the rate in the AB0-identical group (AB0-identical 63.0%; major mismatch, 56.9%; minor mismatch, 57.1% at 1 year). Treatment-related mortality was higher in the major and minor mismatch groups, but there was no significant difference in the rate of relapse. Cox proportional hazards modeling showed that both major and minor AB0 incompatibility were significant risk factors for transplant-related mortality, independently of disease, patients' age, and HLA incompatibility. Delayed engraftment of neutrophils, platelets, and erythrocytes was observed in transplants with major incompatibility. There was a high incidence of grade 3 and 4 acute graft-versus-host disease in the groups with major and minor mismatches, which was caused by a high incidence of stage 2 to 4 liver graft-versus-host disease. Interestingly, the risk of grade 2 to 4 graft-versus-host disease in the major mismatch group was higher in patients with early engraftment of erythrocytes. Among the patients receiving reduced-intensity conditioning, the transplant-related mortality was also increased in AB0-incompatible transplants. CONCLUSIONS: Major and minor AB0 incompatibility have specific effects on transplant-related mortality and acute graft-versus-host disease in recipients of bone marrow transplants from unrelated donors.
Asunto(s)
Sistema del Grupo Sanguíneo ABO , Incompatibilidad de Grupos Sanguíneos , Trasplante de Médula Ósea/inmunología , Adolescente , Adulto , Anciano , Suero Antilinfocítico/uso terapéutico , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/prevención & control , Antígenos HLA/inmunología , Prueba de Histocompatibilidad , Humanos , Lactante , Japón , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante de Células Madre , Acondicionamiento Pretrasplante , Resultado del Tratamiento , Irradiación Corporal TotalRESUMEN
Acute promyelocytic leukemia (APL) is the most curable subtype of acute myeloid leukemia. Second complete remission (CR2) can be easily achieved with several therapeutic options even after relapse. However, the optimal strategy to treat APL in CR2 is still controversial. We retrospectively compared the outcome of autologous (auto) and allogeneic (allo) hematopoietic stem cell transplantation (HSCT) for patients with APL in CR2 or CR3. Fifteen patients received auto and 13 received allo HSCT between 1999 and 2004 at eight hospitals belonging to the Nagoya Blood and Marrow Transplantation Group. Four-year disease-free survival (DFS) and overall survival (OS) for autografted patients were 68.9 and 75.8%, whereas those for allografted patients were 46.2 (P = 0.350) and 46.2% (P = 0.185), respectively. Three autografted patients and one allografted patient relapsed, and one autografted patient and five allografted patients died without leukemia relapse. Among 14 autografted patients who were evaluated for MRD with molecular analysis, relapse occurred in one with positive MRD (n = 2) and two with negative MRD (n = 12). These data suggest that auto HSCT is very effective for APL in CR2 or CR3, and may be preferable to allo HSCT for a portion of patients. Prospective studies are required to define the role of auto HSCT in the treatment of relapsed APL.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Promielocítica Aguda/terapia , Recurrencia Local de Neoplasia/terapia , Adolescente , Adulto , Anciano , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Autólogo , Trasplante HomólogoRESUMEN
We describe the clinical outcome of autologous bone marrow transplantation (ABMT) for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL). Between 1985 and 2000, 14 patients in first complete remission underwent transplantation. In all cases, harvested marrow was purged with a cocktail of complement and monoclonal antibodies to common acute lymphoblastic leukemia antigen (CALLA). Eight patients died following BMT: 2 patients from interstitial pneumonia and 6 from disease recurrence. For the 6 surviving patients in continuous remission, the median follow-up period was 96 months. The probability of disease-free survival and the rate of relapse at 5 years were 41.7% and 51.4%, respectively. Minimal residual disease (MRD) was assayed quantitatively with patient-specific D-JH probes in 6 of 14 cases. A higher residual tumor burden at marrow harvest was associated with subsequent relapse. Efforts to reduce the MRD burden before harvesting stem cells should improve the clinical outcome of ABMT.
Asunto(s)
Trasplante de Médula Ósea , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Recurrencia , Inducción de Remisión , Trasplante AutólogoRESUMEN
We hypothesized that reducing the dosage of prophylaxis for graft-versus-host disease (GVHD) would reduce the risk of relapse and toxicity after bone marrow transplantation (BMT) from human leukocyte antigen (HLA)-identical siblings. In a prospective phase II trial, 21 patients with leukemia and myelodysplastic syndrome underwent BMT from HLA-identical siblings and received GVHD prophylaxis consisting of low-dose (1.5 mg/kg per day) cyclosporin A (CSP) with short-term methotrexate (MTX) treatment. This low-dose group was compared with a group of retrospective control patients (n = 22) who received a standard CSP dosage (3.0 mg/kg per day) and MTX. One patient died of transplantation-related causes within 100 days. The regimen-related toxicity was quite tolerable. Although acute GVHD of grades II to III was more frequent in the low-dose group (47.6%) than in the control group (22.7%), the increase in acute GVHD did not significantly contribute to morbidity or mortality. There were no differences between the groups in the incidence and severity of chronic GVHD. The probabilities of relapse and survival of the groups were similar according to the risk for relapse at the time of transplantation. A prospective randomized study is required to determine whether low-dose or standard-dose CSP in combination with MTX is optimal for Japanese patients who undergo allogeneic BMT from HLA-identical siblings.
Asunto(s)
Trasplante de Médula Ósea , Ciclosporina/administración & dosificación , Enfermedad Injerto contra Huésped/prevención & control , Inmunosupresores/administración & dosificación , Metotrexato/administración & dosificación , Adolescente , Adulto , Pueblo Asiatico , Trasplante de Médula Ósea/efectos adversos , Trasplante de Médula Ósea/mortalidad , Ciclosporina/efectos adversos , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Antígenos HLA , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Humanos , Japón , Masculino , Metotrexato/efectos adversos , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Hermanos , Trasplante HomólogoRESUMEN
Pulmonary complications are frequent and sometimes lethal in allogeneic hematopoietic stem cell transplantation recipients. In our hospital, 16 transplanted patients had pulmonary complications at post-mortem examination. We review the patients' clinical courses and histopathological findings of their lungs, and discuss the factors related to the onset of the pulmonary complications. In 16 patients, 10 had infectious lung diseases and the other 6 were non-infectious. Five of the patients with infectious diseases had fungal infections: 2 aspergillosis, 2 candidiasis and 1 mucormycosis. In the other 5, 2 had cytomegalovirus pneumonia, 1 had herpes simplex virus pneumonia and 2 had bacterial pneumonia. These ten patients were highly immunocompromised because of steroid therapy or neutropenia. The histopathological diagnosis of all 6 patients with non-infectious disease was diffuse alveolar damage (DAD). Most of the DAD patients were also complicated with other organ damage due to regimen-related toxicity (RRT), and their respiratory symptoms had appeared during the rapid tapering off of their immunosuppressant drugs. These results revealed that prevention of fungal infection was still important for highly immunocompromised patients. Efforts to reduce RRT such as using a reduced intensity regimen and careful tapering off of immunosupressants are expected to lead to a decrease in non-infectious pulmonary complications.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Enfermedades Pulmonares Fúngicas/etiología , Adulto , Antineoplásicos/efectos adversos , Femenino , Neoplasias Hematológicas/terapia , Humanos , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Pulmón/patología , Enfermedades Pulmonares Fúngicas/patología , Enfermedades Pulmonares Fúngicas/prevención & control , Masculino , Persona de Mediana Edad , Neumonía Bacteriana/etiología , Neumonía Bacteriana/patología , Neumonía Viral/etiología , Neumonía Viral/patología , Trasplante HomólogoRESUMEN
In this symposium, we saw new horizons in allogeneic transplantation. Are these truly revolutionary? We do not yet know the answer. However, there is no question about the importance of allogeneic T cells. T cells are much more powerful than any pharmacological drug man has ever generated. The question is, how do we take the most advantage of their potential. Every participant was encouraged to search for good answers to this question until the next meeting.
Asunto(s)
Trasplante de Células Madre/tendencias , Animales , Células Sanguíneas/trasplante , Trasplante de Médula Ósea/tendencias , Humanos , Trasplante de Células Madre/métodos , Inmunología del Trasplante , Trasplante Homólogo/inmunología , Trasplante Homólogo/métodos , Trasplante Homólogo/tendenciasRESUMEN
Between October 1981 and December 2000, 46 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) underwent allogeneic hematopoietic stem cell transplantation (HSCT) in the Nagoya Blood and Marrow Transplantation Group. The median age was 28.5 years (range, 4-51 years). All but one patient achieved engraftment. Grade II-to-IV acute graft-versus-host disease (GVHD) developed in 32.5% of patients, and chronic GVHD developed in 40.5%. The incidences of relapse and treatment-related mortality (TRM) at 5 years were 65% and 26%, respectively. The estimated overall survival rate at 5 years was 23%. Univariate analysis showed that improved disease-free survival (DFS) was independently associated with complete remission (CR) at transplantation (39%), compared with non-CR (8%) (P = .023). Non-CR at transplantation was associated with a higher risk of relapse. Donor type, acute GVHD, and time from diagnosis to HSCT all had a significant effect on TRM. In a multivariate analysis, 9 months or more from diagnosis to HSCT was the only variable statistically significant for DFS (relative risk, 3.22; P = .01). This study demonstrates that allogeneic HSCT cures a significant population of patients with Ph+ ALL. Relapse is the major obstacle limiting the success of HSCT. Early transplantation during CR from donors, including unrelated persons or mismatched relatives, may offer improved long-term DFS.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/mortalidad , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Recurrencia , Análisis de Supervivencia , Tasa de Supervivencia , Donantes de Tejidos , Trasplante Homólogo/estadística & datos numéricos , Resultado del TratamientoRESUMEN
On the basis of transplantation data from the Japan Society for Hematopoietic Cell Transplantation, we retrospectively analyzed the impact of cytogenetics at diagnosis on the outcome of transplantation in 628 patients with acute myeloid leukemia who underwent autologous (n = 200), allogeneic related (n = 363), or allogenic unrelated (n = 65) stem cell transplantation (SCT) at first complete remission. For autologous SCT, patients at good cytogenetic risk had a significantly lower relapse rate (P = .017) and a significantly higher event-free survival (EFS) (P = .013) compared with those at intermediate risk. For allogeneic SCT, patients at good cytogenetic risk had a significantly lower relapse rate (P = .019) and insignificantly higher EFS (P = .093) than those at poor risk. For unrelated SCT, there was no significant difference in relapse rate or EFS between patients at good risk and those at intermediate risk. Comparison of the 3 transplantation modalities revealed that autologous SCT patients had a significantly higher incidence of relapse compared with related or unrelated SCT patients in the intermediate-risk group but not in the good-risk group. However, there were no significant differences in EFS among the 3 transplant modalities in either of these 2 risk groups. In multivariate analysis, cytogenetics was found to be an independent predictor of relapse as well as of treatment failure.
Asunto(s)
Aberraciones Cromosómicas , Leucemia Mieloide/genética , Leucemia Mieloide/terapia , Trasplante de Células Madre de Sangre Periférica , Enfermedad Aguda , Adolescente , Adulto , Anciano , Niño , Citogenética , Supervivencia sin Enfermedad , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Trasplante Autólogo , Trasplante Homólogo , Resultado del TratamientoRESUMEN
Prognostic assessment is crucial for the management of AML. Although the use of karyotype analysis for risk-stratification is widely accepted, prognosis of AML remains ambiguous, particularly for patients categorized into the intermediate cytogenetic risk group and additional markers are required for an accurate prediction of outcome. For this study, we used multiplex real-time RT-PCR, which can simultaneously quantify WT1 and 10 distinct fusion gene transcripts, to prospectively evaluate the pre-treatment bone marrow findings of 53 de novo AML patients. Five patients with normal karyotype or insufficient metaphases detected by conventional karyotype analysis proved to have AML1-MTG8, CBFbeta-MYH11 or PML-RARalpha fusion transcripts. WT1 overexpression was observed in 92% of the patients, and the levels were significantly higher in the cytogenetic favorable risk group, especially patients with PML-RARalpha. WT1 levels also correlated with the percentage of blasts in bone marrow, especially in cases of core-binding factor leukemia. There was no association between initial WT1 levels and outcome in terms of event-free survival or overall survival. These results suggest that multiplex real-time RT-PCR is rapid and useful for the precise cytogenetic stratification of AML, and that WT1 levels at presentation correlate with several biologic features of leukemia, but have no prognostic significance.
Asunto(s)
Leucemia Monocítica Aguda/diagnóstico , Leucemia Monocítica Aguda/genética , Proteínas Recombinantes de Fusión/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transcripción Genética/genética , Proteínas WT1/genética , Adolescente , Adulto , Anciano , Médula Ósea/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
A new intensive chemotherapy regimen, DAD, composed of doxorubicin, melphalan and dexamethasone, was given to 17 patients with multiple myeloma. The end point of this regimen was to obtain a deep posttreatment nadir in the M-protein levels so as to increase the chance of plateau attainment which would be associated with prolonged survival in each patient. It was noteworthy that all the 17 evaluable patients achieved a partial response. Nine of the 17 (52.9%) attained a plateau. Ten of the 17 patients (58.8%) obtained a deep posttreatment nadir in their M-protein levels (IgG < 2,000 mg/dl, IgA < 1,000 mg/dl, BJP = 0 g/dl/day), and six of them reached a plateau phase, which was not significantly more frequent than those who did not obtain a deep posttreatment nadir in their M-protein levels (three of seven reached plateau phase). The median survival of the 17 patients (37.6 months) was significantly prolonged compared with that of patients treated with our previous chemotherapy regimens, VMCP (22.5 months) and MMPP (23.5 months), and was comparable to that of MMCP (29.5 months).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Dexametasona/administración & dosificación , Doxorrubicina/administración & dosificación , Esquema de Medicación , Femenino , Humanos , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Inducción de Remisión , Resultado del TratamientoRESUMEN
We present a case of life-threatening Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) with severe hepatitis that was successfully treated by allogeneic stem cell transplantation from an unrelated donor. A 26-year-old woman was admitted to hospital with a high fever and liver dysfunction. Laboratory tests, including bone marrow aspiration, revealed severe HLH that occurred after EBV infection. High-dose methylprednisolone and etoposide therapy did not control the disease. We could control the HLH, but the EBV viremia continued following the CHOPE (cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide) chemotherapy regimen. Therefore, the patient underwent allogeneic bone marrow transplantation from an HLA-matched, unrelated donor. The patient has remained in good condition without disease recurrence for 2 years after bone marrow transplantation. Although there is no consensus regarding allogeneic stem cell transplantation for EBV-HLH, it is the treatment of choice for aggressive EBV-HLH when the patient is refractory to intensive chemotherapy.
Asunto(s)
Trasplante de Médula Ósea , Infecciones por Virus de Epstein-Barr/cirugía , Trasplante de Células Madre Hematopoyéticas , Linfohistiocitosis Hemofagocítica/cirugía , Adulto , Infecciones por Virus de Epstein-Barr/complicaciones , Femenino , Humanos , Hibridación in Situ , Linfohistiocitosis Hemofagocítica/virología , Reacción en Cadena de la Polimerasa , Viremia/cirugíaRESUMEN
Serine protease granzyme B plays important roles in infections, autoimmunity, transplant rejection, and antitumor immunity. A triple-mutated granzyme B variant that encodes three amino substitutions (Q48R, P88A, and Y245H) has been reported to have altered biological functions. In the polymorphism rs8192917 (2364A>G), the A and G alleles represent wild type QPY and RAH mutant variants, respectively. In this study, we analyzed the impact of granzyme B polymorphisms on transplant outcomes in recipients undergoing unrelated HLA-fully matched T-cell-replete bone marrow transplantation (BMT) through the Japan Donor Marrow Program. The granzyme B genotypes were retrospectively analyzed in a cohort of 613 pairs of recipients with hematological malignancies and their unrelated donors. In patients with myeloid malignancies consisting of acute myeloid leukemia and myelodysplastic syndrome, the donor G/G or A/G genotype was associated with improved overall survival (OS; adjusted hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.41-0.89; Pâ=â0.01) as well as transplant related mortality (TRM; adjusted HR, 0.48; 95% CI, 0.27-0.86, Pâ=â0.01). The recipient G/G or A/G genotype was associated with a better OS (adjusted HR, 0.68; 95% CI, 0.47-0.99; Pâ=â0.05) and a trend toward a reduced TRM (adjusted HR, 0.61; 95% CI, 0.35-1.06; Pâ=â0.08). Granzyme B polymorphism did not have any effect on the transplant outcomes in patients with lymphoid malignancies consisting of acute lymphoid leukemia and malignant lymphoma. These data suggest that there is an association between the granzyme B genotype and better clinical outcomes in patients with myeloid malignancies after unrelated BMT.
Asunto(s)
Trasplante de Médula Ósea/mortalidad , Granzimas/genética , Antígenos HLA/inmunología , Trastornos Mieloproliferativos/terapia , Polimorfismo Genético , Adolescente , Adulto , Anciano , Trasplante de Médula Ósea/inmunología , Niño , Preescolar , Variación Genética , Genotipo , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Humanos , Lactante , Persona de Mediana Edad , Mortalidad , Trastornos Mieloproliferativos/mortalidad , Pronóstico , Donantes de Tejidos , Trasplante Homólogo/inmunología , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Patients treated in a protective isolation unit (PIU) often experience loneliness and increased feelings of seclusion, leading to elevated levels of distress, but the relationship between psychiatric distress and environmental factors is unclear. Therefore, we retrospectively compared the impact of environmental factors on insomnia and depression between patients in the PIU and those in a standard ward (SW). METHODS: Subjects were 246 patients with hematological disorders hospitalized in Meitetsu Hospital between April 1, 2007 and July 31, 2008 (62 PIU patients and 184 SW patients). We assessed insomnia and depression, as well as concomitant corticosteroid (CS) administration, stem cell transplantation (SCT) therapy, and complications resulting from these therapies. Details of medical history and patient information were retrospectively extracted from patients' charts, medical records and the electronic laboratory database at the hospital. RESULTS: Patients in the PIU tended to be complicated by insomnia or depression more than those in the SW, but the stay in the PIU was not significantly related to the incidence of insomnia or depression. Our findings indicated that use of CS was a risk factor for insomnia. The prevalence of depression was higher in patients with therapeutic complications. All PIU patients with depression also received SCT. CONCLUSION: Our findings suggest an increased potential for insomnia after administration of CS and depression in cases with complications after SCT, which is important to keep in mind for patients with hematological disorders.
Asunto(s)
Depresión/etiología , Enfermedades Hematológicas/terapia , Aislamiento de Pacientes/psicología , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Adolescente , Corticoesteroides/efectos adversos , Corticoesteroides/uso terapéutico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo , Trasplante de Células Madre/psicología , Adulto JovenRESUMEN
The indication of allogeneic stem cell transplantation (allo-SCT) for Philadelphia chromosome-negative acute lymphocytic leukemia [Ph(-) ALL] from unrelated donors is not established. To assess its potency of unrelated patients in first complete-remission (CR1) transplanted from unrelated donors and the potential prognostic factors affecting the probability of survival, we retrospectively analyzed a total of 41 adult Ph(-) ALL patients in CR1 who underwent unrelated bone marrow transplantation at 6 transplantation centers of the Nagoya Blood and Marrow Transplantation Group between 1993 and 2006. The median age of the 41 patients was 28 years (range, 18-51 years). HLA was matched in 33 transplants, with mismatches in 8 (HLA-A allele mismatch:1, HLA-DR serological mismatch: 2, HLA-DRB1 mismatch: 5). Leukemia-free survival (LFS) at 3 and 6 years from allo-SCT was 60.3 and 47.7%, respectively. LFS at 5 years was 62.1% for those transplanted from HLA-matched donors. LFS was significantly lower with HLA-mismatched donors due to higher transplantation-related mortality. Relapse was observed in 3 patients. Our study suggested that unrelated allo-SCT could improve LFS of patients with a potential graft-versus-leukemia effect. Unrelated allo-SCT for Ph(-) ALL patients in CR1 could be more beneficial by reducing TRM, such as selecting a HLA-matched donor.
Asunto(s)
Trasplante de Médula Ósea/inmunología , Histocompatibilidad/inmunología , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Trasplante de Médula Ósea/efectos adversos , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/mortalidad , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Donantes de Tejidos , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
We retrospectively analyzed the results of 707 adult patients who underwent myeloablative peripheral blood stem cell transplantation (PBSCT) (n = 365) and myeloablative bone marrow transplantation (BMT) (n = 342) for leukemia from HLA-identical sibling donors between 2000 and 2005 using the propensity score method. The results were obtained from the Japan Society for Hematopoietic Cell Transplantation registry. Multivariate Cox analysis showed that PBSCT was associated with lower overall survival (OS) in standard-risk patients [adjusted hazard ratio (aHR) = 1.83; 95% confidence interval (CI) 1.04-3.23; P = 0.036], but not in high-risk patients (aHR = 1.11; 95% CI 0.76-1.61; P = 0.599). Hematopoietic recovery was significantly faster after PBSCT. The risk of acquiring grade III-IV acute graft-versus-host disease (GVHD) (aHR = 2.23; P = 0.040) and extensive chronic GVHD (aHR = 1.93; P = 0.001) were significantly higher after PBSCT. PBSCT was associated with higher non-relapse mortality in standard-risk patients (aHR = 2.30; 95% CI 1.08-4.88; P = 0.030), but not in high-risk patients (aHR = 1.29; 95% CI 0.65-2.54; P = 0.468). Relapse after transplantation did not differ between PBSCT and BMT either in standard-risk group or in high-risk group (aHR = 1.17; 95% CI 0.55-2.52; P = 0.684 and aHR = 0.81; 95% CI 0.52-1.28; P = 0.370, respectively). In this retrospective analysis, OS was significantly lower after PBSCT in standard-risk patients, but not in high-risk patients. PBSCT was associated with significant risks of grade III-IV acute GVHD and extensive chronic GVHD.