RESUMO
Haploidentical hematopoietic-cell transplantation using post-transplant cyclophosphamide(Haplo-PTCy) is a feasible procedure in children with haematologic malignancies. However, data of a large series of children with acute leukaemia(AL) in this setting is missing. We analysed 144 AL Haplo-PTCy paediatric recipients; median age was 10 years. Patients had acute lymphoblastic(ALL; n = 86) or myeloblastic leukaemia(AML; n = 58) and were transplanted in remission(CR1: n = 40; CR2: n = 57; CR3+: n = 27) or relapse (n = 20). Bone marrow was the graft source in 57%; donors were father (54%), mother (35%), or sibling (11%). Myeloablative conditioning was used in 87%. Median follow-up was 31 months. At day +100, cumulative incidence (CI) of neutrophil recovery and acute GVHD (II-IV) were 94% and 40%, respectively. At 2-years, CI of chronic GVHD and relapse, were 31%, 40%, and estimated 2-year overall survival (OS), leukaemia-free survival (LFS) and graft-versus-host-relapse-free survival (GRFS) were 52%, 44% and 34% respectively. For patients transplanted in remission, positive measurable residual disease (MRD) prior to transplant was associated with decreased LFS (p = 0.05) and GRFS (p = 0.003) and increased risk of relapse (p = 0.02). Mother donor was associated with increased risk of chronic GVHD (p = 0.001), decreased OS (p = 0.03) and GRFS (p = 0.004). Use of PBSC was associated with increased risk of chronic GVHD (p = 0.04). In conclusion, achieving MRD negativity pre-transplant, avoiding use of mother donors and PBSC as graft source may improve outcomes of Haplo-PTCy in children with AL.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Células-Tronco de Sangue Periférico , Criança , Ciclofosfamida/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Leucemia Mieloide Aguda/complicações , Mães , Recidiva Local de Neoplasia , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/efeitos adversosRESUMO
Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus and all cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with the estimated prevalence of MetS being 31-49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal of reviewing literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors.
Assuntos
Doenças Cardiovasculares , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Síndrome Metabólica , Aloenxertos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Humanos , Síndrome Metabólica/etiologia , Síndrome Metabólica/prevenção & controle , Guias de Prática Clínica como AssuntoAssuntos
Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas , Doadores não Relacionados , Adolescente , Adulto , Fatores Etários , Aloenxertos , Criança , Pré-Escolar , Doença Crônica , Feminino , Seguimentos , Humanos , Incidência , Lactente , Masculino , Fatores de RiscoRESUMO
A total of 21 patients with severe aplastic anemia (SAA) underwent marrow transplantation from HLA-identical siblings following a standard conditioning regimen with cyclophosphamide (50 mg/kg/day × 4 days) and horse antithymocyte globulin (30 mg/kg/day × 3 days). Post-grafting immunosuppression consisted of a short course of methotrexate (MTX) combined with cyclosporine (CSP). The transplant protocol tested the hypothesis that the incidence of chronic GvHD could be reduced by limiting the marrow grafts to ⩽2.5 × 108 nucleated marrow cells/kg. None of the patients rejected the graft, all had sustained engraftment and all are surviving at a median of 4 (range 1-8) years after transplantation. Chronic GvHD developed in 16% of patients given ⩽2.5 × 108 nucleated marrow cells/kg. Post-grafting immunosuppression has been discontinued in 20 of the 21 patients. In conclusion, limiting the number of transplanted marrow cells may have resulted in minimal improvement in the incidence and severity of chronic GvHD.
Assuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea/métodos , Contagem de Células , Doença Enxerto-Hospedeiro/prevenção & controle , Adolescente , Adulto , Anemia Aplástica/complicações , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Teste de Histocompatibilidade , Humanos , Terapia de Imunossupressão/métodos , Masculino , Pessoa de Meia-Idade , Irmãos , Resultado do Tratamento , Adulto JovemAssuntos
Transplante de Medula Óssea , Transplante de Células-Tronco de Sangue Periférico , Células-Tronco/citologia , Condicionamento Pré-Transplante , Adolescente , Adulto , Fatores Etários , Idoso , Ensaios Clínicos Fase II como Assunto , Estudos de Coortes , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia/terapia , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Síndromes Mielodisplásicas/terapia , Fatores de Tempo , Transplante Homólogo , Resultado do TratamentoRESUMO
Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Programas de Rastreamento , Segunda Neoplasia Primária/diagnóstico , Feminino , Humanos , Masculino , Segunda Neoplasia Primária/epidemiologia , Especificidade de Órgãos , Fatores de RiscoRESUMO
The 2005 National Institutes of Health (NIH) consensus criteria for chronic GVHD have set standards for reporting. Many questions, however, have arisen regarding their implementation and utilization. To identify perceived areas of controversy, we conducted an international survey on diagnosis and scoring of chronic GVHD. Agreement was observed for 50-83% of the 72 questions in 7 topic areas. There was agreement on the need for modifying criteria in six situations: two or more distinctive manifestations should be enough to diagnose chronic GVHD; symptoms that are not due to chronic GVHD should be scored differently; active disease and fixed deficits should be distinguished; a minimum threshold body surface area of hidebound skin involvement should be required for a skin score of 3; asymptomatic oral lichenoid changes should be considered a score 1; and lung biopsy should be unnecessary to diagnose chronic GVHD in a patient with bronchiolitis obliterans as the only manifestation. The survey also identified 26 points of controversy. Whenever possible, studies should be conducted to confirm the appropriateness of any revisions. In cases where data are not available, clarification of the NIH recommendations by consensus is necessary. This survey should inform future research in the field and revisions of the current consensus criteria.
Assuntos
Doença Enxerto-Hospedeiro/diagnóstico , Doença Crônica , Coleta de Dados , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Índice de Gravidade de Doença , Inquéritos e Questionários , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Estados UnidosRESUMO
Most reports of chronic GVHD after cord blood transplantation (CBT) have utilized traditional diagnostic criteria. We used traditional criteria and National Institutes of Health (NIH) criteria prospectively to evaluate chronic GVHD in a cohort of 87 adult and pediatric recipients of single or double unrelated CBT for treatment of hematologic malignancies. Fifty-four patients developed traditionally defined chronic GVHD, for an estimated 2-year probability of 64%. Among 54 patients, 25 (46%) met the NIH criteria for persistent, recurrent or late acute GVHD at onset. Twenty-four (44%) had overlap chronic GVHD, including one who presented initially with late acute GVHD, and only seven (13%) had classic chronic GVHD, including one who also presented initially with late acute GVHD. Among patients who successfully discontinued all systemic immunosuppression (SI), the median time to discontinuation of corticosteroid treatment was 315 days (range 28-977), and the median time to discontinuation of all SI was 353 days (range 67-977). Chronic GVHD diagnosed by traditional criteria after CBT had a predominance of acute GVHD clinical features.
Assuntos
Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/terapia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Imunologia de Transplantes , Transplante Homólogo , Adulto JovemRESUMO
Allogeneic hematopoietic cell transplantation (HCT) is the only known cure for patients with Fanconi anemia (FA) who develop aplasia or leukemia. However, transplant regimens typically contain high-dose alkylators, which are poorly tolerated in FA patients. Furthermore, as many patients lack human leukocyte antigen (HLA)-matched family donors, alternative donors are used, which can increase the risk of both graft rejection and graft-versus-host disease (GVHD). To improve on these three concerns, we developed a multi-institutional clinical trial using a fludarabine (FLU)-based conditioning regimen with limited alkylators/low-dose radiation, HLA-haploidentical marrow, followed by reduced-dose cyclophosphamide (CY) to treat three FA patients with aplasia. All three patients engrafted with 100% donor CD3 chimerism at 1 month. One patient died early from disseminated toxoplasmosis infection. Of the two survivors, one had significant pretransplant co-morbidities and inadequate immunosuppression, and developed severe acute GVHD. The other patient had only mild acute and no chronic GVHD. With a follow-up of 2 and 3 years, respectively, both patients are doing well, are transfusion-independent, and maintain full donor chimerism. The patient with severe GVHD has resolving oral GVHD and good quality of life. We conclude that using low-intensity conditioning, HLA-haploidentical marrow, and reduced-dose CY for in vivo T-cell depletion can correct life-threatening aplasia in FA patients.
Assuntos
Anemia de Fanconi/terapia , Rejeição de Enxerto/prevenção & controle , Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos HLA/imunologia , Transplante de Células-Tronco Hematopoéticas , Depleção Linfocítica , Linfócitos T/imunologia , Vidarabina/análogos & derivados , Adolescente , Antineoplásicos/uso terapêutico , Criança , Terapia Combinada , Anemia de Fanconi/imunologia , Feminino , Seguimentos , Humanos , Quimeras de Transplante/imunologia , Condicionamento Pré-Transplante , Transplante Homólogo , Vidarabina/uso terapêuticoRESUMO
A nonmyeloablative conditioning regimen consisting of fludarabine (FLU) and 2 Gy TBI has been used extensively and with substantial engraftment success without promoting excessive nonrelapse mortality in medically infirm patients requiring hematopoietic cell transplantation. In this paper, we studied this same low-toxicity regimen as a means of promoting engraftment of unrelated donor hematopoietic cell transplantation in patients with Fanconi anemia (FA). All patients tolerated the regimen well with no mucositis or other severe toxicities. Of six patients transplanted, five achieved stable mixed or full donor chimerism. Acute and chronic GVHD occurred in four and three patients, respectively. Three patients are alive and well at a median of 45.9 (range, 20.9-68.1) months after transplant. In summary, this FLU-based regimen facilitates stable engraftment of unrelated PBSCs, but is associated with significant chronic GVHD.
Assuntos
Anemia de Fanconi/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/efeitos adversos , Vidarabina/análogos & derivados , Irradiação Corporal Total , Criança , Anemia de Fanconi/tratamento farmacológico , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Taxa de Sobrevida , Doadores de Tecidos , Quimeras de Transplante , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/toxicidade , Irradiação Corporal Total/efeitos adversosRESUMO
We conducted a cross-sectional study to estimate the prevalence of metabolic syndrome, a clustering of risk factors associated with cardiovascular disease, among 86 adults who had allogeneic hematopoietic-cell transplant (HCT) as compared with 258 age- and gender-matched US population controls selected from the 2005-2006 National Health and Nutrition Examination Survey database. The median age at study enrollment was 50 years (range, 21-71), and patients were at a median of 3 years (range, 1-21) from HCT. The prevalence of metabolic syndrome was 49% (95% confidence intervals (CI), 38-60%) among HCT recipients, a 2.2-fold (95% CI, 1.3-3.6, P=0.002) increase compared with controls. The prevalence rates of elevated blood pressure and hypertriglyceridemia were significantly higher among HCT recipients than among controls, but the prevalence rates of abdominal obesity, elevated blood glucose and low high-density lipoprotein cholesterol were not. HCT survivors with metabolic syndrome were more likely to have microalbuminuria (43 vs 10%) and elevated creatinine (31 vs 11%). No patient, donor or transplant characteristics were associated with the diagnosis of metabolic syndrome. We conclude that metabolic syndrome occurs frequently among allogeneic HCT survivors who are seen by transplant physicians. Approaches to screening, prevention and management of metabolic syndrome should be developed for HCT recipients.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndrome Metabólica/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Condicionamento Pré-Transplante , Transplante Homólogo , Adulto JovemRESUMO
We previously reported a 25% incidence of serious graft-versus-host disease (GVHD) (that is, acute or chronic GVHD that caused death, lengthy hospitalization or disability, or resulted in recurrent major infections) among 171 hematopoietic cell transplantation (HCT) recipients after nonmyeloablative (NMA) regimen. Here we present a retrospective study applying the same criteria to 264 recipients of peripheral blood HCT after myeloablative (MA) regimen, and compare the results with the previous study after additional follow-up. The MA group was younger and had lower comorbidity scores at HCT than those in the NMA group. The overall incidence of serious GVHD was 17% (44/264) in the MA group versus 28% (48/171) in the NMA group. The adjusted hazard ratio (HR) of serious GVHD in the MA group compared to the NMA group was 0.65 (95% CI, 0.4-1.1); P=0.13, and if follow-up was censored at the onset of recurrent or progressive malignancy, HR was 0.67 (95% CI, 0.4-1.3), P=0.22. We conclude that the choice between MA and NMA regimens does not greatly affect the risk of serious GVHD as an overall indicator of outcomes related to either acute or chronic GVHD. Serious GVHD may be considered as an endpoint in clinical trials with GVHD-related outcomes.
Assuntos
Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Agonistas Mieloablativos/uso terapêutico , Condicionamento Pré-Transplante/métodos , Doença Aguda , Adolescente , Adulto , Idoso , Doença Crônica , Estudos de Coortes , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversosRESUMO
Allogeneic hematopoietic cell transplantation (HCT) represents a potentially curative approach for patients with myelodysplastic syndromes (MDSs). While a large proportion of HCT recipients become long-term disease-free survivors, recurrence of MDS remains the leading cause of mortality after HCT. The role of donor lymphocyte infusion (DLI) in patients with relapsed MDS after HCT is unclear. We report results among 16 patients treated with DLI for relapsed MDS after HCT at a single institution between March 1993 and February 2004. The cohort contained 10 men and 6 women with a median age of 49 (range, 22-67) years. CR with resolution of cytopenias and prior disease markers occurred in 3 of 14 patients who could be evaluated. Two patients survived without MDS for 68 and 65 months after DLI, respectively, but died with pneumonia. Grades II-IV acute GVHD and chronic GVHD occurred after DLI in 6 (43%) and 5 (36%) patients, respectively. All three responders developed grades III-IV acute GVHD and extensive chronic GVHD after DLI. Our results confirm prior reports that DLI can result in CR in some patients with recurrent MDS after transplant, but long-term survival is infrequent.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transfusão de Linfócitos , Síndromes Mielodisplásicas/terapia , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Transfusão de Linfócitos/efeitos adversos , Masculino , Pessoa de Meia-Idade , RecidivaRESUMO
Allogeneic hematopoietic transplantation is the only currently available therapy that has the potential to cure agnogenic myeloid metaplasia (AMM) or primary myelofibrosis (PMF). Amelioration of fibrosis and eradication of the abnormal clone is thought to occur through the repopulation of marrow by donor-derived hematopoiesis and graft-vs.-host reaction leading to graft vs. tumor effect. We report here a 50-year-old female with AMM/PMF, conditioned with busulfan and cyclophosphamide, who rejected a single locus (HLA-B) mismatched bone marrow transplant from her daughter, but recovered normal autologous hematopoiesis with disappearance of marrow fibrosis and extramedullary hematopoiesis. Variable number tandem repeats (VNTR) analysis showed a gradual loss of donor-derived hematopoietic cells with recovery of autologous hematopoiesis. This case therefore illustrates that eradication of AMM/PMF in this patient with myeloablative chemotherapy combined with a transient allogeneic effect was sufficient to suppress the abnormal stem cell clone associated with AMM/PMF with subsequent cure.
Assuntos
Transplante de Medula Óssea/imunologia , Rejeição de Enxerto , Mielopoese/fisiologia , Mielofibrose Primária/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Transplante HomólogoRESUMO
Low-dose methotrexate (MTX) is widely used in autoimmune diseases because of its anti-inflammatory activity. We report here the results of a retrospective study to review the outcomes of low-dose MTX used for treatment of refractory chronic graft-versus-host disease GVHD, with the goal of reducing the amount of prednisone needed to control the disease. In all, 14 patients with refractory chronic GVHD received MTX at a dose of 7.5 mg/m(2)/weekly for 3--0 weeks. Also, 11 patients had skin involvement, often with scleroderma or fasciitis. The median duration of chronic GVHD at the start of MTX was 38 (range 1--35) months. In this retrospective review, we found no grade 3-- toxicities, and none of the patients needed blood transfusion or growth factors. In 10 patients (71%), GVHD could be adequately controlled with prednisone at doses below 1 mg/kg every other day without the addition of other agents. Four patients decreased the amount of concomitant immunosuppressive treatment, five continued with the same regimen, four required an increase in immunosuppressive treatment, and one decided to discontinue all treatment. From this preliminary analysis, MTX appears to be a well-tolerated, inexpensive and possibly steroid-sparing agent that is worthy of further evaluation in prospective trials for treatment of chronic GVHD.
Assuntos
Doença Enxerto-Hospedeiro/tratamento farmacológico , Metotrexato/administração & dosagem , Adulto , Idoso , Doença Crônica , Avaliação de Medicamentos , Quimioterapia Combinada , Feminino , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Metotrexato/toxicidade , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Estudos Retrospectivos , Terapia de Salvação , Resultado do TratamentoRESUMO
Allogeneic haematopoietic cell transplantation (HCT) is effective therapy for Fanconi anaemia (FA). FA patients do not tolerate conditioning with 200 mg/kg of cyclophosphamide (Cy), typically used in aplastic anaemia. We previously published results of studies in which Cy doses were gradually reduced from 200 to 100 mg/kg. Here we update results of the initial studies and report data on 30 new patients conditioned with Cy either at 80 mg/kg (n = 7) or at 60 mg/kg (n = 23), given over 4 days before HCT from human leucocyte antigen-matched related donors. Methotrexate and cyclosporine were given for graft-versus-host disease (GVHD) prophylaxis. All seven patients given Cy at 80 mg/kg and 21 of 23 given Cy at 60 mg/kg had sustained engraftment, while two patients, both with clonal cytogenetics abnormalities, experienced graft failure. Grades 2-3 acute GVHD rates were 57% and 14% for patients given the higher and lower Cy doses, respectively (P = 0.001). Four patients given Cy at 80 mg/kg and 22 given Cy at 60 mg/kg were alive at a median of 47 (44-58) months and 16 (3-52) months, respectively. Cy at 60 mg/kg has acceptable toxicities, low rates of GVHD, and is sufficient for engraftment of related grafts in most FA patients.
Assuntos
Ciclofosfamida/administração & dosagem , Anemia de Fanconi/cirurgia , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/administração & dosagem , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Esquema de Medicação , Anemia de Fanconi/tratamento farmacológico , Anemia de Fanconi/imunologia , Feminino , Doença Enxerto-Hospedeiro , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Análise de Sobrevida , Transplante HomólogoRESUMO
The efficacy of allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning depends on the balance between the desirable antineoplastic effects of donor cells weighed against the undesirable morbidity of graft-versus-host disease (GVHD). Development of serious acute or chronic GVHD was analyzed retrospectively in 171 consecutive patients, who had related or unrelated nonmyeloablative HCT for hematologic malignancies. GVHD was defined as serious when it resulted in (1) death, (2) disability, (3) three or more major infections in 1 year, (4) prolonged hospitalization or (5) suicide or hospitalization for suicidal ideation. According to this definition, 43 of 171 (25%) patients developed serious GVHD with a median follow-up of 30 (range, 12-65) months. The incidence of serious GVHD was similar after related and unrelated HCT. Among the 43 patients with serious GVHD, 20 had grade III-IV acute GVHD, and 30 had extensive chronic GVHD. Among the 171 patients, seven had grade III acute GVHD and 84 had extensive chronic GVHD that did not meet criteria for serious GVHD. Assessment of serious GVHD provides additional useful information to acute GVHD grades and classification of limited and extensive chronic GVHD in describing the overall risk and impact complications caused by donor cells.
Assuntos
Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Atividades Cotidianas , Adolescente , Adulto , Causas de Morte , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Hospitalização , Humanos , Incidência , Infecções , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Suicídio , Condicionamento Pré-Transplante/métodosRESUMO
The clinical significance of early airflow decline after myeloablative allogeneic hematopoietic SCT is uncertain. We performed a retrospective cohort analysis to determine if airflow decline by day 100 is associated with later development of transplant-related airflow obstruction (AFO) and increased mortality risk. Overall, 750 (40%) patients had airflow decline by day 100. Development of airflow decline by day 100 was associated with an increased risk for AFO at 1 year (relative risk 2.6, 95% confidence interval 2.1-3.1) but not with an increase in mortality risk (hazard ratio (HR) 0.86, P=0.05). However, patients with the fastest rate of decline between day 100 and 1 year (12.5% per year +/-24) had the highest mortality risk (HR 3.2, P<0.001). In conclusion, airflow measurements made on day 100 do not predict the rate of airflow decline between day 100 and 1 year, and therefore are not useful as a single measurement for determining mortality risk associated with development of AFO. Closer monitoring of the rate of airflow decline during the first year may facilitate the timely detection and treatment of early airflow decline and prevent the development of fixed AFO and increased mortality risk after hematopoietic stem cell transplant.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Agonistas Mieloablativos/efeitos adversos , Ventilação Pulmonar , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/etiologia , Testes de Função Respiratória , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Condicionamento Pré-Transplante/mortalidade , Transplante HomólogoRESUMO
Allogeneic hematopoietic cell transplantation is followed by humoral immunodeficiency. We evaluated whether antibody levels can be improved by recipient vaccination on day -1 and 50 and whether the levels can be further improved by donor vaccination on day -20. A total of 85 patients were randomized or assigned to one of the following strategies of immunization with Streptococcus pneumoniae polysaccharides, Haemophilus influenzae polysaccharide-protein conjugate, tetanus toxoid (protein recall antigen) and hepatitis B surface antigen (protein neo-antigen): (1) donor on day -20, recipient on days -1, +50 and +365 (D(-20)R(-1,50,365)); (2) donor nil, recipient on days -1, +50 and +365 (D(N)R(-1,50,365)); or (3) donor nil, recipient on day +365 (D(N)R(365)). For H. influenzae and tetanus, IgG levels after grafting were the highest in the D(-20)R(-1,50,365) patients, intermediate in the D(N)R(-1,50,365) patients and the lowest in the D(N)R(365) patients. For S. pneumoniae and hepatitis B, antibody levels appeared to be similar in all three patient groups. The results suggest that for polysaccharide-protein conjugate antigens or protein recall antigens, recipient immunization on days -1 and 50 improves antibody levels and that donor vaccination on day -20 further improves the levels. In contrast, neither recipient immunization on days -1 and 50 nor donor immunization on day -20 appears to be efficacious for polysaccharide antigens and poorly immunogenic protein neo-antigens.