RESUMEN
AIM: Paediatric recipients of haematopoietic stem cell transplants (HSCT) are at increased risk of developing post-traumatic stress disorder (PTSD), and there is a need to identify interventions that can alleviate stress in this group. The aim of this study was to examine the previously unexplored effect of music therapy on children undergoing HSCT, by analysing physiological parameters and comparing them with a control group. METHODS: We performed a randomised clinical pilot study of 24 patients up to the age of 16 undergoing HSCT at Karolinska University Hospital, Huddinge, Sweden. Music therapy, including expressive and receptive elements, was performed twice a week in the treatment group and compared to standard care in the control group. Physiological parameters were evaluated according to the hospital's protocols. RESULTS: The music therapy group had significantly reduced evening heart rates compared to the control group (p < 0.001), and the effect was sustainable for four to eight hours after the intervention. There were no significant differences in saturation or blood pressure observed between the groups. CONCLUSION: Music therapy significantly lowered the heart rate of children undergoing HSCT for at least four to eight hours, indicating reduced stress levels and potentially lowering the risk of developing PTSD.
Asunto(s)
Frecuencia Cardíaca , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Musicoterapia , Trastornos por Estrés Postraumático/prevención & control , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Trastornos por Estrés Postraumático/etiologíaRESUMEN
BACKGROUND: Type 1 narcolepsy is a neurological disorder characterized by excessive daytime sleepiness and cataplexy associated with the HLA allele DQB1*06:02. Genetic predisposition along with external triggering factors may drive autoimmune responses, ultimately leading to the selective loss of hypocretin-positive neurons. OBJECTIVE: The aim of this study was to investigate potential aetiological factors in Swedish cases of postvaccination (Pandemrix) narcolepsy defined by interferon-gamma (IFNγ) production from immune cells in response to molecularly defined targets. METHODS: Cellular reactivity defined by IFNγ production was examined in blood from 38 (HLA-DQB1*06:02(+) ) Pandemrix-vaccinated narcolepsy cases and 76 (23 HLA-DQB1*06:02(+) and 53 HLA-DQB1*06:02(-) ) control subjects, matched for age, sex and exposure, using a variety of different antigens: ß-haemolytic group A streptococcal (GAS) antigens (M5, M6 and streptodornase B), influenza (the pandemic A/H1N1/California/7/09 NYMC X-179A and A/H1N1/California/7/09 NYMC X-181 vaccine antigens, previous Flu-A and -B vaccine targets, A/H1N1/Brisbane/59/2007, A/H1N1/Solomon Islands/3/2006, A/H3N2/Uruguay/716/2007, A/H3N2/Wisconsin/67/2005, A/H5N1/Vietnam/1203/2004 and B/Malaysia/2506/2004), noninfluenza viral targets (CMVpp65, EBNA-1 and EBNA-3) and auto-antigens (hypocretin peptide, Tribbles homolog 2 peptide cocktail and extract from rat hypothalamus tissue). RESULTS: IFN-γ production was significantly increased in whole blood from narcolepsy cases in response to streptococcus serotype M6 (P = 0.0065) and streptodornase B protein (P = 0.0050). T-cell recognition of M6 and streptodornase B was confirmed at the single-cell level by intracellular cytokine (IL-2, IFNγ, tumour necrosis factor-alpha and IL-17) production after stimulation with synthetic M6 or streptodornase B peptides. Significantly, higher (P = 0.02) titres of serum antistreptolysin O were observed in narcolepsy cases, compared to vaccinated controls. CONCLUSION: ß-haemolytic GAS may be involved in triggering autoimmune responses in patients who developed narcolepsy symptoms after vaccination with Pandemrix in Sweden, characterized by a Streptococcus pyogenes M-type-specific IFN-γ cellular immune response.
Asunto(s)
Narcolepsia/inmunología , Streptococcus agalactiae/inmunología , Estreptodornasa y Estreptoquinasa/inmunología , Adolescente , Adulto , Anciano , Antiestreptolisina/sangre , Niño , Femenino , Humanos , Interferón gamma/biosíntesis , Interferón gamma/sangre , Masculino , Persona de Mediana Edad , Narcolepsia/epidemiología , Fragmentos de Péptidos/biosíntesis , Fragmentos de Péptidos/sangre , Serotipificación , Streptococcus agalactiae/enzimología , Suecia/epidemiologíaRESUMEN
Allogeneic hematopoietic stem cell transplantation (ASCT) and its conditioning with chemoradiotherapy often results in liver toxicity, the most severe form being veno-occlusive liver disease (VOD). N-acetyl-L-cysteine (NAC), an antioxidant glutathione precursor, may provide protection from liver toxicity. Patients with elevated bilirubin (>26 mmol/l) and/or elevated (ALT) (>1.4 microkat/l) and/or aspartate aminotransferase (AST) (>1.4 microkat/l) levels were randomized to treatment with NAC or no treatment. Among 522 transplanted patients, 160 were included in the trial. NAC was given, 100 mg/kg per day, as a 6-h i.v. infusion until normalization of bilirubin, ALT and AST values. Maximum bilirubin level was the same in patients randomized to NAC (n=72) or controls (n=88). Increase and recovery of ALT and AST were the same in patients randomized to NAC or controls. There were two patients in the NAC group who developed VOD, as compared to three of the controls. To conclude, NAC does not improve liver toxicity after ASCT.
Asunto(s)
Acetilcisteína/administración & dosificación , Depuradores de Radicales Libres/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Enfermedad Veno-Oclusiva Hepática/prevención & control , Neoplasias/terapia , Adolescente , Adulto , Anciano , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Estudios Prospectivos , Factores de Tiempo , Trasplante HomólogoRESUMEN
The influence of conditioning regimen, donor background and HLA matching on development of BK virus (BKV)-associated haemorrhagic cystitis (HC) was examined in 175 allogeneic haematopoietic stem cell transplant (HSCT) patients, undergoing 179 HSCT events. Twenty-seven patients presented late-onset HC, and BK viruria was verified in 23/27 HC events. Seventy-one (40%) HSCTs were performed with myeloablative conditioning (MC), 108 (60%) were performed with reduced intensity conditioning (RIC), 66 (37%) were performed with a related donor (RD) grafts and 113 (63%) with an unrelated donor (URD) graft. BK viruria was more common during HC, than non-HC events, after MC as compared to RIC (both P<0.001), and with an HLA-mismatched donor (P<0.01). By multivariate logistical regression analysis, independent risk factors for HC were BKV (OR 6.7; 95% CI 2.0-21.7; P=0.001), MC (OR 6.0; 95% CI 2.1-17.3; P<0.001) and URD (OR 3.4; 95% CI 1.1-10.6; P=0.03). However, when analysing HSCT performed with URD or RD grafts separately, BKV (OR 8.5; 95% CI 1.8-19.3; P=0.004) and MC (OR 5.9; 95% CI 1.3-11.3; P=0.009) increased the risk for HC only with a URD, but not with an RD graft.
Asunto(s)
Cistitis/virología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones por Polyomavirus , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/efectos adversos , Infecciones Tumorales por Virus , Adolescente , Adulto , Anciano , Virus BK/patogenicidad , Niño , Preescolar , Cistitis/fisiopatología , Femenino , Prueba de Histocompatibilidad , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Infecciones por Polyomavirus/fisiopatología , Infecciones por Polyomavirus/orina , Estudios Retrospectivos , Factores de Riesgo , Trasplante Homólogo/métodos , Infecciones Tumorales por Virus/fisiopatología , Infecciones Tumorales por Virus/orinaRESUMEN
Fludarabine-based conditioning (FBC) was given to 24 patients and conventional myeloablative conditioning (MC) to 33 patients, most children, before hematopoietic stem cell transplantation (HSCT) for non-malignant diseases. The donors were human leukocyte antigen (HLA)-A, -B, -DRbeta1-identical related (33%) or unrelated (67%). In the FBC group, two grafts failed versus three in the MC group; all were successfully regrafted. Fever was more common in the MC patients (P=0.003). Bacteremia occurred in 25% of the FBC group and 50% in the MC group (P=0.1). In the FBC group, platelet engraftment was faster and transfusions were fewer (P<0.05). Mucositis and renal function were similar in the two groups. The MC group had higher maximum bilirubin (P=0.03) and less often normal spirometry (P=0.04) after HSCT. A 7-year-old girl in the MC group had permanent alopecia. No patients had severe acute graft-versus-host disease (GVHD). Chronic GVHD was rare. Complete donor CD3+ chimerism was more common in the MC group (P=0.01), but CD33+ engraftment was better with FBS (P=0.03). Treatment-related mortality was 4 and 15%, and 5-year survival was 89 and 85% in the FBC and MC groups. Although survival was similar, FBC is a promising alternative to MC in non-malignant disorders.
Asunto(s)
Anemia Aplásica/terapia , Antineoplásicos/farmacología , Trasplante de Células Madre Hematopoyéticas/métodos , Hemoglobinopatías/terapia , Síndromes de Inmunodeficiencia/terapia , Acondicionamiento Pretrasplante , Vidarabina/análogos & derivados , Adolescente , Adulto , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped , Humanos , Lactante , Masculino , Persona de Mediana Edad , Vidarabina/farmacologíaRESUMEN
To prevent neutropenic infections, patients are kept in isolation rooms after allogeneic haematopoietic stem cell transplantation (ASCT). Patients living within one hours' driving distance from our unit were given the opportunity of treatment at home after ASCT during the pancytopenic phase. We compared 36 patients treated at home during March 1998 until December 2000, with 54 controls treated in the hospital during September 1995 and September 2001. The incidence of grades II-IV acute graft-versus-host disease (GVHD) was lower in the home care group compared to the controls, that is, 17 vs 44% (P < 0.01). The cumulative incidence of chronic GVHD was 52% in the home care group, compared to 57% in the controls. Transplant-related mortality (TRM) was 13% in the home care patients vs 44% in the controls (P = 0.002). The probability of relapse was similar in the two groups. The 4-year survival was 63% in the home care patients compared to 44% in the controls (P = 0.04). Home care after ASCT is a novel approach that resulted in less TRM, similar incidence of chronic GVHD and relapse, and improved long-term survival compared to controls treated in the hospital.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Servicios de Atención de Salud a Domicilio , Pancitopenia/terapia , Adolescente , Adulto , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/patología , Trasplante de Células Madre Hematopoyéticas/mortalidad , Hospitalización , Humanos , Incidencia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pancitopenia/etiología , Pancitopenia/mortalidad , Recurrencia , Análisis de Supervivencia , Trasplante HomólogoRESUMEN
BACKGROUND: Using unrelated bone marrow, there is an increased risk of graft-versus-host disease (GVHD). METHODS: HLA-A-, HLA-B-, and HLA-DR-compatible unrelated bone marrow was given to 132 patients. The diagnoses included chronic myeloid leukemia (n=43), acute lymphoblastic leukemia (n=29), acute myeloid leukemia (n=27), myelodysplastic syndrome (n=4), lymphoma (n=3), myeloma (n=1), myelofibrosis (n=1), severe aplastic anemia (n=12), and metabolic disorders (n=12). The median age was 25 years (range 1-55 years). HLA class I was typed serologically, and class II was typed by polymerase chain reaction using sequence-specific primer pairs. Immunosuppression consisted of antithymocyte globulin or OKT3 for 5 days before transplantation and methotrexate combined with cyclosporine. RESULTS: Engraftment was seen in 127 of 132 patients (96%). Bacteremia occurred in 47%, cytomegalovirus (CMV) infection in 49%, and CMV disease in 8%. The cumulative incidences of acute GVHD > or = grade II and of chronic GVHD were 23% and 50%, respectively. The 5-year transplant-related mortality rate was 39%. The overall 5-year patient survival rate was 49%; in patients with metabolic disorders and severe aplastic anemia, it was 61% and 48%, respectively. The disease-free survival rate was 47% in patients with hematological malignancies in first remission or first chronic phase and 38% in patients with more advanced disease (P=0.04). Acute GVHD was associated with early engraftment of white blood count (P=0.02). Poor outcome in multivariate analysis was associated with acute myeloid leukemia (P=0.01) and CMV disease (P=0.04). CONCLUSION: Using HLA-A-, HLA-B-, and HLA-DR-compatible unrelated bone marrow and immunosuppression with antithymocyte globulin, methotrexate, and cyclosporine, the probability of GVHD was low and survival was favorable.
Asunto(s)
Anticuerpos Antiidiotipos/inmunología , Trasplante de Médula Ósea/inmunología , Enfermedad Injerto contra Huésped/etiología , Antígenos HLA-A/análisis , Antígenos HLA-B/análisis , Antígenos HLA-DR/análisis , Linfocitos T/inmunología , Acondicionamiento Pretrasplante , Adolescente , Adulto , Anticuerpos Monoclonales/uso terapéutico , Bacteriemia/complicaciones , Niño , Preescolar , Infecciones por Citomegalovirus/complicaciones , Supervivencia sin Enfermedad , Femenino , Supervivencia de Injerto/inmunología , Prueba de Histocompatibilidad , Humanos , Terapia de Inmunosupresión/métodos , Lactante , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
The safety of AmBisome was evaluated in 187 transplant recipients treated for 197 episodes. Patients included 89 bone marrow transplant recipients, 64 liver transplant recipients, 20 renal transplant recipients and 14 recipients of combined organs. AmBisome was instituted for verified invasive fungal infection in 34 cases, suspected invasive fungal infections in 80 cases and as prophylaxis in 83 cases. AmBisome was given for a median of 11 days (range 1-112 days) with a maximum daily dose of 1.49 +/- 0.70 mg/kg/day (mean +/- SD). The total cumulative dose of AmBisome was 1.11 +/- 1.78 g (mean +/- SD). Side-effects definitely attributed to AmBisome therapy included low potassium (n = 3), low back pain (n = 3), dyspnoea (n = 2), allergic rash (n = 1), nausea and vomiting (n = 1), confusion (n = 1), rise in alkaline phosphatase (n = 1) and cholecystitis (n = 1) with an overall incidence of 13 of 197 (7%). AmBisome was discontinued due to side-effects in 6 (3%) of the cases. During AmBisome treatment the mean cyclosporin dose was 9.6 +/- 28.8 mg/kg/day. Compared to pre- and post-AmBisome therapy there was a significantly increased cyclosporin concentration in blood during AmBisome therapy. Side-effects with possible association to AmBisome therapy included low serum potassium (36%), increase in serum creatinine (31%), rise in alkaline phosphatases (26%) and fever (3%). The overall mean increase in serum creatinine was 20%. Other possible side-effects like headache, abdominal pain, rash, rise in bilirubin, cramps and pancreatitis was seen in single patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Anfotericina B/efectos adversos , Ciclosporina/uso terapéutico , Micosis/tratamiento farmacológico , Adolescente , Adulto , Anciano , Trasplante de Médula Ósea/efectos adversos , Niño , Preescolar , Femenino , Humanos , Lactante , Trasplante de Riñón/efectos adversos , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana EdadRESUMEN
Three different types of anti-T cell antibody were used in patients undergoing haematopoietic stem cell transplantation (HSCT) with an HLA-A, -B and -DR compatible unrelated donor: ATG-Fresenius (ATG-F) (n = 26), Thymoglobuline (TMG) (n = 61) and OKT-3 (n = 45). The groups were comparable regarding diagnosis, stage, age, conditioning and GVHD prophylaxis, Adverse events were less frequent after ATG-F treatment. Levels of IL-2, IL-6, IFN-gamma, TNF-alpha and GM-CSF were increased after OKT-3 infusion. In multivariate analysis OKT-3 treatment (P = 0.01), G-CSF treatment (P = 0.02) and a cell dose >/=2.7 x 108/kg (P = 0.03) gave a faster engraftment. Acute GVHD grades II-IV occurred in 25% of the ATG-F patients, 12% of the TMG-patients and 43% (P < 0.001 vs TMG) of the OKT-3 patients. OKT-3 was associated with acute GVHD in multivariate analysis. TRM was 26% using TMG as compared to 43% in the OKT-3 group (P = 0.03). Patient survival at 4 years was 63%, 50% and 45% in the ATG-F, TMG and OKT-3-treated patients, respectively (NS). Relapses were 8%, 49% and 34%, respectively (ATG-F vs TMG, P = 0.03). Relapse-free survivals were 61%, 40% and 37% (NS). Among CML patients the probability of relapse was 61% in TMG-treated patients, while no patients relapsed in the other two groups. To conclude, the type of anti-T cell antibody affects GVHD and relapse after HSCT using unrelated donors.
Asunto(s)
Anticuerpos/uso terapéutico , Citocinas/inmunología , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Linfocitos T/inmunología , Adolescente , Adulto , Anticuerpos/inmunología , Niño , Preescolar , Citocinas/metabolismo , Relación Dosis-Respuesta Inmunológica , Femenino , Enfermedad Injerto contra Huésped/inmunología , Neoplasias Hematológicas/inmunología , Prueba de Histocompatibilidad , Humanos , Lactante , Masculino , Enfermedades Metabólicas/terapia , Persona de Mediana Edad , Síndromes Mielodisplásicos/terapia , Trasplante Homólogo , Resultado del TratamientoRESUMEN
After myeloablative treatment and allogeneic stem cell transplantation (ASCT), patients are kept isolated in the hospital to prevent infections during neutropenia. To date, 22 patients have been given the choice of being treated at home. Eleven could not be treated at home, and they served as controls. Most had haematological malignancies. The donors were 12 HLA-compatible unrelated, nine HLA-identical siblings and one twin. In the home care group, three developed bacteraemia, compared to nine in the controls (P < 0.01). Patients in the home care group had fewer days of total parenteral nutrition (median 3 vs 24, P < 0.001), required fewer erythrocyte transfusions (median 4 vs 8, P = 0.01), fewer days on i.v. antibiotics (median 6 vs 13 days), and on analgesics (median 0 vs 15) than the controls (P < 0.05). Days with fever, time to engraftment, days with G-CSF and acute GVHD were the same in the two groups. Seven of 11 patients treated at home were readmitted to the ward for a median of 3 (0-7) days, due to fever or lack of a caregiver at home. Days to discharge to the out-patient clinic were faster in the group treated at home (median 20 vs 35 days, P < 0.01). Patients who were treated at home enjoyed being active and taking a walk when they felt like it. This preliminary report suggests that home care after ASCT is not only safe, but superior to isolation in the hospital.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Servicios de Atención de Salud a Domicilio , Adolescente , Adulto , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Trasplante HomólogoRESUMEN
Thirty-eight patients (> or = 18 years) receiving marrow transplants from HLA-identical or one antigen-mismatched related donors were randomized to intraosseous (i.o.) + intravenous (i.v.) (n = 10), i.o. (n = 8) or i.v. (n = 20) infusions of bone marrow. There were no significant differences in patient characteristics. PMN/l more than 0.5 x 10(9) occurred on days 19 (median), 20 and 18.5 in the i.o. + i.v., i.o. and i.v. groups, respectively. We found a significant reduction in the number of days on total parenteral nutrition (P = 0.03) and a tendency to a reduction in the number of days on antibiotics (P = 0.06) in the i.o. compared to the i.v. group. Bacteraemia did not occur in the i.o. group, but was seen in 30% of the i.v. group (NS). The incidences of acute and chronic graft-versus-host disease, transplantation-related mortality, relapse and patient survival rates were similar in the three groups. Five patients examined with bone marrow scintigraphy showed the same distribution of granulocytes in the bone marrow directly after transplantation and 3 weeks after transplantation, whether the bone marrow was given by the i.o. or by the i.v. route. We conclude that allogeneic bone marrow transplantation can safely be performed by i.o. infusion, but haematopoietic recovery is not improved.
Asunto(s)
Trasplante de Médula Ósea/métodos , Adulto , Bacteriemia/etiología , Médula Ósea/diagnóstico por imagen , Trasplante de Médula Ósea/efectos adversos , Trasplante de Médula Ósea/diagnóstico por imagen , Femenino , Supervivencia de Injerto , Hematopoyesis , Humanos , Infusiones Intravenosas , Infusiones Parenterales , Masculino , Persona de Mediana Edad , Nutrición Parenteral Total , Estudios Prospectivos , Cintigrafía , SeguridadRESUMEN
Among 551 consecutive recipients of allogeneic bone marrow transplants, 451 survived more than 3 months and were evaluated for chronic graft-versus-host disease (GVHD). Most of the donors were HLA-identical siblings or parents (n = 334). Patients with HLA-mismatched donors (n = 30) and matched unrelated donors (MUD) (n = 87) were also included in the study. In the analysis of all patients, the 5-year cumulative incidence of chronic GVHD was 45%. We analysed 34 risk factors. High recipient age was the single most important risk factor (P < 0.001). Other significant risk factors in multivariate analysis were: acute GVHD grades I-IV (P < 0.001), immune female donor to male recipient (P = 0.006) and chronic myelogenous leukaemia (CML), compared with all other diagnoses (P = 0.014). The cumulative 5-year incidence of chronic GVHD, with no significant risk factors present, was 9%, 29% with one risk factor, 53% with two, 68% with three and 75% with all four risk factors present. In patients with HLA-identical sibling donors and GVHD prophylaxis consisting of a combination of methotrexate (MTX) and cyclosporin A (CsA) (n = 208), increasing recipient age (P < 0.001) and CML (P = 0.007), were found to be significant risk factors for chronic GVHD. Finally, a multivariate analysis in recipients of bone marrow from unrelated donors (n = 89) showed recipient age alone (P = 0.006) to be significantly associated with chronic GVHD.
Asunto(s)
Trasplante de Médula Ósea/inmunología , Enfermedad Injerto contra Huésped/etiología , Neoplasias/terapia , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Enfermedad Crónica , Ciclosporina/uso terapéutico , Femenino , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Inmunosupresores/uso terapéutico , Lactante , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Trasplante HomólogoRESUMEN
BACKGROUND: After myeloablative treatment and allogeneic stem cell transplantation (ASCT), patients are kept isolated in the hospital to prevent infections during neutropenia. METHODS: So far, 22 patients have been given the choice of being treated at home. Eleven could not be treated at home, and they served as controls. Most of them had haematological malignancies. The donors were 12 HLA-compatible unrelated, 9 HLA-identical siblings and one twin. RESULTS: In the home care group, 3 developed bacteraemia, compared to 9 in the controls (p<0.01). The patient in the home care group had fewer days on total parenteral nutrition (median 3 vs. 24, p<0.001), required fewer erythrocyte transfusions (median 4 vs. 8, p=0.01), fewer days on i.v. antibiotics (median 6 vs. 13 days), and on analgesics (median 0 vs. 15) than the controls (p<0.05). Days with fever, time to engraftment, days with G-CSF and acute GVHD were the same in the two groups. 7/11 patients treated at home were readmitted to the ward for median 3 (0-7) days, due to fever or lack of a caregiver at home. Days to discharge to the out-patient clinic was faster in the group treated at home (median 20 vs 35 days, p<0.01). DISCUSSION: Patients who were treated at home enjoyed being active and taking a walk when they felt like it. This preliminary report suggests that home care after ASCT is not only safe, but better than isolation in the hospital.
Asunto(s)
Atención Ambulatoria , Antineoplásicos/efectos adversos , Infección Hospitalaria/prevención & control , Neoplasias Hematológicas/tratamiento farmacológico , Servicios de Atención a Domicilio Provisto por Hospital/estadística & datos numéricos , Neutropenia/inducido químicamente , Infecciones Oportunistas/prevención & control , Pancitopenia/inducido químicamente , Trasplante de Células Madre , Adolescente , Adulto , Atención Ambulatoria/estadística & datos numéricos , Antineoplásicos/uso terapéutico , Purgación de la Médula Ósea/efectos adversos , Purgación de la Médula Ósea/estadística & datos numéricos , Infección Hospitalaria/epidemiología , Femenino , Fiebre de Origen Desconocido/epidemiología , Fiebre de Origen Desconocido/etiología , Fiebre de Origen Desconocido/prevención & control , Estudios de Seguimiento , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Neutropenia/complicaciones , Infecciones Oportunistas/epidemiología , Evaluación de Procesos y Resultados en Atención de Salud/estadística & datos numéricos , Pancitopenia/complicaciones , Aislamiento de Pacientes/estadística & datos numéricos , Readmisión del Paciente/estadística & datos numéricos , Proyectos Piloto , Factores de Riesgo , SuizaRESUMEN
Graft failure may contribute to increased morbidity and mortality after allogeneic hematopoietic SCT (allo-HSCT). Here, we present risk factors for graft failure in all first allo-HSCTs performed at our center from 1995 to mid-2010 (n=967). Graft failure was defined as >95% recipient cells any time after engraftment with no signs of relapse, or re-transplantation because of primary or secondary neutropenia (<0.5 × 10(9)/L) and/or thrombocytopenia (<30 × 10(9)/L). Fifty-four patients (5.6%) experienced graft failure. The majority were because of autologous reconstitution (n=43), and only a few patients underwent re-transplantation because of primary (n=6) or secondary (n=5) graft failures. In non-malignant disorders, graft failure had no effect on survival, whereas in malignant disease graft failure was associated with reduced 5-year survival (22 vs 53%, P<0.01). In multivariate analysis, ex vivo T-cell depletion (relative risk (RR) 8.82, P<0.001), HLA-mismatched grafts (RR 7.64, P<0.001), non-malignant disorders (RR 3.32, P<0.01) and reduced-intensity conditioning (RR 2.58, P<0.01) increased the risk for graft failure, whereas graft failures were prevented by total nucleated cell doses of ≥ 2.5 × 10(8)/kg (RR 0.36, P<0.01). In conclusion, graft failure was only associated with inferior survival in malignant disease. Non-malignant disorders, HLA match, conditioning intensity, immunosuppression regimen and cell dose all influenced graft failure risk.
Asunto(s)
Rechazo de Injerto/mortalidad , Trasplante de Células Madre Hematopoyéticas , Inmunodeficiencia Variable Común/mortalidad , Inmunodeficiencia Variable Común/terapia , Supervivencia sin Enfermedad , Rechazo de Injerto/etiología , Enfermedades Metabólicas/mortalidad , Enfermedades Metabólicas/terapia , Neoplasias/mortalidad , Neoplasias/terapia , Neutropenia/etiología , Neutropenia/mortalidad , Mielofibrosis Primaria/mortalidad , Mielofibrosis Primaria/terapia , Factores de Riesgo , Tasa de Supervivencia , Trombocitopenia/etiología , Trombocitopenia/mortalidad , Trasplante HomólogoRESUMEN
We wanted to evaluate factors associated with high costs after allogeneic haematopoietic SCT (HSCT). We collected all in-patient and outpatient costs during the first year after HSCT over 5 years, from 2003 to 2007. Mean 1-year costs per patient were \[euro]141,493 (95% confidence interval (95% CI)=125,019-157,967). Patients treated with non-myeloablative conditioning (NMC) had reduced costs, but patients treated with reduced-intensity or myeloablative conditioning had similar 1-year costs. Multivariate analysis showed that increased 1-year costs were seen in post-transplant complications: rejection (relative hazard (RH) 1.24, P<0.001), acute GVHD of grades III-IV (1.31, P<0.001) and invasive fungal infection (1.15, P=0.02). In addition, increased costs were associated with re-transplantation (1.21, P=0.001), mesenchymal stem-cell therapy (1.26, P<0.001), unrelated donor transplants (1.20, P=0.002) and the need for G-CSF treatment due to poor engraftment (1.12, P=0.047). In patients without any of these risk factors, mean 1-year costs were \[euro]84,773 (95% CI=71,145-98,400) (n=51). With three risk factors, the cost increased to \[euro]249,775 (95% CI=166,824-332,727) (n=14). To conclude, major complications increased the costs of HSCT. Unrelated donor transplants were more expensive than HLA-identical sibling transplants. Costs were reduced in patients treated with NMC.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/economía , Acondicionamiento Pretrasplante/economía , Costos y Análisis de Costo , Rechazo de Injerto/economía , Enfermedad Injerto contra Huésped/economía , Factor Estimulante de Colonias de Granulocitos/economía , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Antígenos HLA/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Veno-Oclusiva Hepática/economía , Humanos , Análisis Multivariante , Reoperación/economía , Suecia , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/economía , Donante no EmparentadoRESUMEN
Sixty-one children with a median age of 6 years (range 1-16) were given prophylaxis/therapy for 78 courses of treatment with liposomal amphotericin (AmBisome) and were reviewed retrospectively. Thirty-six received allogeneic bone marrow, 22 a liver transplant, 2 kidneys and 1 a liver and kidney. AmBisome was given as prophylaxis in 30 episodes, as treatment for suspected invasive fungal infections (IFI) in 33 and for a verified IFI in 15. AmBisome prophylaxis was given for a median of 14 days in a dose of 1 mg/kg/day. The median dose of AmBisome was 2.1 mg/kg/day (range 0.9-5.0). The median duration of therapy was 10 days in children with suspected IFI and 20 days in children with verified IFI. The total dose ranged from 0.025 g up to a maximum of 3.95 g. Proven and probable side effects of AmBisome were a decrease in the level of serum potassium (30/78 cases), renal toxicity (22), an increase in the alkaline phosphatases (24), back pain (2), fever and abdominal pain (2), anaphylactic reaction (1), an increase in the bilirubin level (1), nausea (1), chest pain (1) and fever (1). Of 31 children with suspected IFI, fever disappeared in 21 (68%). In 14 verified or suspected IFI cases treated for 5 days or more, the clinical cure rate was 12 (86%). Eradication of fungi from a deep site was verified in 8/10 and the survival rate from 1 1/2 years to more than 7 years was 7/12 (58%). We conclude that AmBisome was well tolerated as prophylaxis and therapy in transplanted children, few acute toxic side effects were seen and the cure rate in verified IFI was high.
Asunto(s)
Anfotericina B/uso terapéutico , Profilaxis Antibiótica , Antifúngicos/uso terapéutico , Trasplante de Médula Ósea , Liposomas/uso terapéutico , Complicaciones Posoperatorias/terapia , Adolescente , Anfotericina B/administración & dosificación , Antifúngicos/administración & dosificación , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
In a retrospective analysis, 79 allogeneic bone marrow recipients treated with AmBisome prophylactically or because of proven or suspected invasive fungal infection (IFI) were evaluated in 92 episodes. The median duration of treatment was 14 (range 1-112) days. The mean maximum dose given was 1.64 +/- 0.8 mg kg-1 day-1 and the mean total dose was 1.29 +/- 2.28 g. The overall incidence of reported adverse events was 194, of which none had a serious outcome. In six cases, the drug was withdrawn as a result of toxic or allergic reactions: dyspnoea and flush (3), urticaria (1), cholecystitis (1) and disorientation (one case, probably not related to AmBisome). No anaphylactoid reactions were seen. Laboratory findings, including low serum potassium (48% of the episodes), increased serum creatinine (38%) and increased serum sodium levels (7%), caused no major clinical problems. Thirteen cases of verified IFI were evaluated regarding the efficacy of AmBisome. Survival or cure of the mycotic infection occurred in 5/13 patients (38%). Two patients were treated with AmBisome (3.6 and 3.3 mg kg-1 day-1) because of verified IFI before BMT. One died of IFI. The other died of venoocclusive disease of the liver (VOD) without histological evidence of active IFI. We found a significant (P < 0.05) reduction in autopsy-proven IFI, 12/199 (6%) compared to the period when only conventional doses of amphotericin B were used, 26/227 (11%).