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1.
Bull Cancer ; 2019 Oct 02.
Artigo em Francês | MEDLINE | ID: mdl-31586527

RESUMO

Haploidentical hematopoietic stem cell transplantation has been growing steadily since 2012. The SFGM-TC has twice published guidelines concerning T-cell repleted haploidentical grafts with high dose cyclophosphamide post-transplantation. The 2013 workshop recommended using the non-myeloablative Baltimore protocol with bone marrow and developed prospective protocols to evaluate these transplantations. The 2015 workshop reported improved results of reduced conditioning regimens in Hodgkin's lymphoma and intensive conditioning in myeloid hemopathies, and a similar outcome with 10/10 HLA matched donor with the same disease-risk score thus raising the question of the qualifier "alternative" for haploidentical transplants. The current work concerns the criteria for selecting the donor. The main criterion remains the absence of anti-HLA antibodies directed against the donor present in the recipient sera (DSA - Donor Specific Antibodies). In case of DSA and in the absence of an alternative donor, desensitization protocols exist. The other criteria are impossible to prioritize: age, sex, CMV, and blood type. The degree of relatedness and the number of HLA incompatibilities do not seem to be a criterion of choice. The 'ideal' donor would be a young man, CMV-matched, without major ABO incompatibility with a marrow transplant. There is insufficient data for the KIR-ligand and NIMA/NIPA mismatch. Peripheral stem cell grafts appear to yield more acute GVHD than bone marrow grafts after intensive conditioning, but with comparable survival rates. Based on the literature review, the comparison of haploidentical with unrelated donors encourages inclusion in existing national protocols randomizing these different donors.

2.
Bull Cancer ; 106(1S): S52-S58, 2019 Jan.
Artigo em Francês | MEDLINE | ID: mdl-30665669

RESUMO

The recommendations of the French Health and Drug Safety Authorities (HAS/ANSM-Haute Autorité de santé/Agence nationale de sécurité du médicament) are known, but there are always new developments underway. With regards to CMV suppression, there is the introduction of platelet glycoprotein Ia and the Intercept (Amotosalem+UVA) inactivation method which addresses bacterial risk. The irradiation of platelets is included in the recommendations to ensure HEV-negative plasma post allograft. In terms of blood transfusion safety, these measures as well as the broader spectrum of Ia, particularly for arboviruses, are a real breakthrough. The survey conducted in clinical services and the services providing blood products for transfusion along with a literature review have shown that several improvements need to be made. The first is a reduction of transfusions of concentrated red blood cells with introduction at a threshold of 7g/dL during hospitalization of patients without a fragile clinical status. The second improvement would address transfusion of refractory thrombocytopenia, encouraging an increase in discussion between clinicians and those conducting the transfusion in order to consider different etiologies and to identify appropriate care protocols. Third would be the need for the transmission of information between the transplantation doctors and blood transfusion specialists in order to define an approach to transfusion care adapted to the patient's situation. It is important to inform and educate patients about transfusion protocols post allotransplant or autotransplant. It must be clearly communicated to patients that they should always have on their person their blood group documentation. This is especially true when receiving care for a hemopathy or an autologous transplant. If undergoing an allogeneic transplant, patients should also carry transfusion guidelines post autotransplant or post allotransplant along with the phone numbers for the stem cell transplantation department and the blood transfusion center responsible for their care.


Assuntos
Autoenxertos , Transfusão de Eritrócitos/normas , Transplante de Células-Tronco Hematopoéticas/normas , Registros Médicos , Transfusão de Plaquetas/normas , Trombocitopenia/terapia , Adulto , Antígenos de Grupos Sanguíneos , Criança , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Comunicação Interdisciplinar , Educação de Pacientes como Assunto , Trombocitopenia/etiologia , Transplante Homólogo
3.
BMC Pharmacol Toxicol ; 19(1): 81, 2018 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-30522521

RESUMO

BACKGROUND: The use of isavuconazole is approved for the management of invasive aspergillosis and mucormycosis, only in adults, as no paediatric pharmacology studies have been reported to date. Very few paediatric cases have been published concerning the use of isavuconazole. Amphotericin B is the only antifungal agent recommended in paediatric mucormycosis, but adverse effects and especially nephrotoxicity, even with the liposomal formulation, could be problematic. In this context, the use of other antifungal molecules active on Mucorales becomes needful. CASE PRESENTATION: We describe a case of mucormycosis with rapid onset dissemination in a 3-year-old girl recently diagnosed with acute lymphocytic leukaemia. She was successfully treated with isavuconazole alone and then in combination with liposomal amphotericin B. Isavuconazole therapy was guided by therapeutic drug monitoring. CONCLUSIONS: This case offers new perspectives on the potential use of isavuconazole in children with mucormycosis, as an alternative or adjunct to liposomal amphotericin B.

4.
Artigo em Inglês | MEDLINE | ID: mdl-30385256

RESUMO

We previously reported in a French prospective randomized study that transplantation of 2 unrelated cord blood (UCB) units instead of 1 unit does not decrease the risk of transplantation failure but may enhance alloreactivity. Here we evaluated the influence of pretransplantation minimal residual disease (MRD) on leukemia relapse and survival after single- versus double-UCB transplantation (UCBT). Among 137 children and young adults who underwent UCBT in this randomized study, 115 had available data on MRD assessment done immediately before initiation of the pretransplantation conditioning regimen. MRD was considered positive at a level of ≥10-4, which was the case of 43 out of 115 patients. Overall, the mean 3-year survival probability was 69.1 ± 4.4%, and it was not significantly influenced by the MRD level: 70.7 ± 5.4% in MRD-negative (<10-4) patients (n = 72), 71.1 ± 9.4% in MRD-positive patients with 10-4 ≤ MRD <10-3 (n = 26) and 58.8 ± 11.9% in MRD-positive patients with ≥10-3 (n = 17). In the MRD-positive group, the mean risk of relapse was significantly lower in the double-UCBT arm compared with the single-UCBT arm (10.5 ± 7.2% versus 41.7 ± 10.4%; P = .025) leading to a higher mean 3-year survival rate (82.6 ± 9.3% versus 53.6 ± 10.3%; P = .031). This difference was observed only in patients who had not received antithymocyte globulin during their conditioning regimen. In the MRD-negative group, there was no difference between the single- and the double-UCBT arms. We conclude that even in cases of positive pretransplantation MRD, UCBT in children and young adults with acute leukemia yields a high cure rate, and that a double-unit strategy may enhance the graft-versus-leukemia effect and survival in these patients.

5.
Blood ; 132(7): 750-754, 2018 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-29760162

RESUMO

Outcomes remain poor for refractory severe aplastic anemia (SAA) patients. Alternative donor transplantation may be considered, but results from previous studies are not encouraging. We conducted a prospective nationwide phase 2 study to assess unrelated cord blood (CB) transplantation (CBT) efficacy and safety in refractory SAA patients (Aplastic Anemia and Cord Blood Transplantation protocol). To demonstrate a significant difference in 1-year survival from 20% (null hypothesis) to 50% (alternative hypothesis), we needed to include 25 transplanted patients and therefore included 26 (median age, 16 years). Eligibility criteria required 1 or 2 unrelated CB units, containing separately or together >4 × 107 frozen nucleated cells (NCs) per kilogram of recipient body weight. Conditioning regimen comprised fludarabine (FLU), cyclophosphamide (CY), antithymocyte globulin (ATG), and 2-Gy total body irradiation (TBI). With a median follow-up of 38.8 months, engraftment occurred in 23 patients (88%); cumulative incidences of grade II-IV acute and chronic graft-versus-host disease were 45.8% and 36%, respectively. Twenty-three patients were alive at 1 year, with an 88.5% overall survival (OS) rate, differing significantly from the expected 20% (P < .0001; 84% OS at 2 years). CBT with units containing ≥4 × 107 frozen NCs per kilogram is therefore a valuable curative option for young adults with refractory SAA and no available matched unrelated donors. This trial was registered at www.clinicaltrials.gov as #NCT01343953.

6.
Haematologica ; 103(8): 1278-1287, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29724903

RESUMO

Heterozygous germline GATA2 mutations strongly predispose to leukemia, immunodeficiency, and/or lymphoedema. We describe a series of 79 patients (53 families) diagnosed since 2011, made up of all patients in France and Belgium, with a follow up of 2249 patients/years. Median age at first clinical symptoms was 18.6 years (range, 0-61 years). Severe infectious diseases (mycobacteria, fungus, and human papilloma virus) and hematologic malignancies were the most common first manifestations. The probability of remaining symptom-free was 8% at 40 years old. Among the 53 probands, 24 had missense mutations including 4 recurrent alleles, 21 had nonsense or frameshift mutations, 4 had a whole-gene deletion, 2 had splice defects, and 2 patients had complex mutations. There were significantly more cases of leukemia in patients with missense mutations (n=14 of 34) than in patients with nonsense or frameshift mutations (n=2 of 28). We also identify new features of the disease: acute lymphoblastic leukemia, juvenile myelomonocytic leukemia, fatal progressive multifocal leukoencephalopathy related to the JC virus, and immune/inflammatory diseases. A revised International Prognostic Scoring System (IPSS) score allowed a distinction to be made between a stable disease and hematologic transformation. Chemotherapy is of limited efficacy, and has a high toxicity with severe infectious complications. As the mortality rate is high in our cohort (up to 35% at the age of 40), hematopoietic stem cell transplantation (HSCT) remains the best choice of treatment to avoid severe infectious and/or hematologic complications. The timing of HSCT remains difficult to determine, but the earlier it is performed, the better the outcome.

7.
Pediatr Blood Cancer ; 65(7): e27038, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29528179

RESUMO

BACKGROUND: Etoposide phosphate (EP; single injection, 60 mg/kg) followed by total body irradiation (TBI) at 12 Gy has been used as an allogeneic stem cell transplantation (allo-SCT) conditioning regimen for children since 2010. In our institution, EP has been suspected of leading to acute nephrotoxicity. The aim of this study was to assess the potential renal toxicity of EP in this context. MATERIALS AND METHODS: A retrospective study was carried out on children hospitalized between 2007 and 2015 for allo-SCT with TBI-based myeloablative conditioning associated with cyclophosphamide (CY, 60 mg/kg/day × 2 days) or EP. The primary endpoint of the study was the occurrence of acute kidney injury (AKI). Additional endpoints were time to recovery for children with AKI, survival, and treatment-related mortality. RESULTS: Thirty-five patients were analyzed (CY: 22 vs. EP: 13). AKI occurred more frequently in the EP group than in the CY one (69% vs. 27%, adjusted odds ratio 6.0, 95% confidence interval [CI] [1.145; 31.445], P = 0.03). The median time to recovery was estimated at 3 days, 95% CI (2; 17), with CY and 11 days 95% CI (5; 18) with EP (adjusted hazard ratio of recovery for EP vs. CY 0.262, 95% CI [0.071; 0.969], P = 0.04). No significant difference was highlighted between the two treatments for survival or for treatment-related mortality. DISCUSSION: This study shows that EP at high dosage or one of its excipients is probably responsible for AKI, as compared to CY. Further studies are required to explore the origin of this adverse effect.

9.
Blood ; 131(7): 717-732, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29146883

RESUMO

Bone marrow (BM) failure (BMF) in children and young adults is often suspected to be inherited, but in many cases diagnosis remains uncertain. We studied a cohort of 179 patients (from 173 families) with BMF of suspected inherited origin but unresolved diagnosis after medical evaluation and Fanconi anemia exclusion. All patients had cytopenias, and 12.0% presented ≥5% BM blast cells. Median age at genetic evaluation was 11 years; 20.7% of patients were aged ≤2 years and 36.9% were ≥18 years. We analyzed genomic DNA from skin fibroblasts using whole-exome sequencing, and were able to assign a causal or likely causal germ line mutation in 86 patients (48.0%), involving a total of 28 genes. These included genes in familial hematopoietic disorders (GATA2, RUNX1), telomeropathies (TERC, TERT, RTEL1), ribosome disorders (SBDS, DNAJC21, RPL5), and DNA repair deficiency (LIG4). Many patients had an atypical presentation, and the mutated gene was often not clinically suspected. We also found mutations in genes seldom reported in inherited BMF (IBMF), such as SAMD9 and SAMD9L (N = 16 of the 86 patients, 18.6%), MECOM/EVI1 (N = 6, 7.0%), and ERCC6L2 (N = 7, 8.1%), each of which was associated with a distinct natural history; SAMD9 and SAMD9L patients often experienced transient aplasia and monosomy 7, whereas MECOM patients presented early-onset severe aplastic anemia, and ERCC6L2 patients, mild pancytopenia with myelodysplasia. This study broadens the molecular and clinical portrait of IBMF syndromes and sheds light on newly recognized disease entities. Using a high-throughput sequencing screen to implement precision medicine at diagnosis can improve patient management and family counseling.

10.
Bull Cancer ; 104(12S): S99-S105, 2017 Dec.
Artigo em Francês | MEDLINE | ID: mdl-29173979

RESUMO

In September 2016 in Lille, France, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 7th Allogeneic Stem Cell Transplantation Clinical Practices Harmonization Workshop Series. Our work group focused on chemotherapy drug dose adaptation for hematopoietic stem cell transplantation patients presenting a comorbidity. The purpose of this workshop was to provide recommendations on chemotherapy drug dose adaptation for patient populations receiving hematopoietic stem cell transplantation who also had the following comorbidities: obesity, chronic kidney disease and hepatopathy.


Assuntos
Transplante de Células-Tronco Hematopoéticas/normas , Imunossupressores/administração & dosagem , Hepatopatias , Obesidade , Insuficiência Renal Crônica , Condicionamento Pré-Transplante/normas , Adulto , Fatores Etários , Bussulfano/administração & dosagem , Criança , Comorbidade , Ciclofosfamida/administração & dosagem , Etoposídeo/administração & dosagem , França , Humanos , Hepatopatias/epidemiologia , Melfalan/administração & dosagem , Obesidade/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Sociedades Médicas , Inquéritos e Questionários , Tiotepa/administração & dosagem , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Irradiação Corporal Total
11.
J Hematol Oncol ; 10(1): 102, 2017 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-28482908

RESUMO

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB). METHODS: Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN)-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9%) or a third party haploidentical donor (57.1%). One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. RESULTS: One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg) up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%). Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. CONCLUSIONS: Adoptive transfer of rapidly isolated ADV-VST is an effective therapeutic option for achieving in vivo expansion of specific T cells and clearance of viral load, even as a pre-emptive treatment. Our study highlights that third party haploidentical donors are of great interest for ADV-VST generation in the context of UCB transplantation. (N° Clinical trial.gov: NCT02851576, retrospectively registered).


Assuntos
Infecções por Adenovirus Humanos/terapia , Adenovírus Humanos/imunologia , Imunoterapia Adotiva/métodos , Subpopulações de Linfócitos T/transplante , Viremia/terapia , Infecções por Adenovirus Humanos/sangue , Infecções por Adenovirus Humanos/prevenção & controle , Adolescente , Adulto , Aloenxertos , Criança , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Humanos , Separação Imunomagnética , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Interferon gama/metabolismo , Leucaférese , Masculino , Especificidade do Receptor de Antígeno de Linfócitos T , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Doadores de Tecidos , Transplante Haploidêntico , Resultado do Tratamento , Carga Viral , Ativação Viral , Adulto Jovem
12.
Bull Cancer ; 103(11S): S198-S200, 2016 Nov.
Artigo em Francês | MEDLINE | ID: mdl-27842861

RESUMO

Within the context of the SFGM-TC's 6th workshop series on the harmonization of clinical practices, our workshop proposes a standardization of the informed consent process for hematopoietic stem cell donors and recipients leading up to an autologous or allogenic transplantation. All informed consent was for bone marrow or peripheral stem cell donors, and mononuclear/lymphocyte donors according to usual procedures. The informed consent for autologous and allogenic related or unrelated adults and pediatric transplantation patients have been included. A first step has been conducted for collecting in advance the informed consent forms used routinely in all francophone transplantation centers. In a second step, a comprehensive version has been re-written by a multidisciplinary team. For the purposes of understanding the risks and advantages, language has been carefully considered and streamlined. In the third step, texts were sent to stem cell transplantation experts, experts at the French biomedical agency (agence de la biomédecine [ABM]), law specialists, members of the ethical committee of the French society of hematology and several transplant recipients to be edited and proofread.


Assuntos
Conferências de Consenso como Assunto , Termos de Consentimento/normas , Transplante de Células-Tronco Hematopoéticas/normas , Sociedades Médicas/normas , Doadores de Tecidos , Adulto , Criança , Família , França , Células-Tronco Hematopoéticas , Humanos , Linfócitos , Projetos Piloto , Estudos de Validação como Assunto
13.
Blood ; 127(26): 3450-7, 2016 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-27099151

RESUMO

Transplantation of 2 unrelated cord blood (UCB) units instead of 1 has been proposed to increase the cell dose. We report a prospective randomized study, designed to compare single- vs double-UCB transplantation in children and young adults with acute leukemia in remission or myelodysplasia. Eligible patients had at least two 4-6 HLA-identical UCBs with >3 × 10(7) nucleated cells/kg for the first and >1.5 × 10(7) for the second. The primary end point was the 2-year cumulative incidence of transplantation strategy failure, a composite end point including transplant-related mortality (TRM), engraftment failure, and autologous recovery. Randomized patients who did not proceed to transplantation due to refractory disease were considered transplantation failures. A total of 151 patients were randomized and included in the intent-to-treat analysis; 137 were transplanted. Double-UCB transplantation did not decrease transplantation strategy failure (23.4% ± 4.9% vs 14.9% ± 4.2%). Two-year posttransplant survival, disease-free survival, and TRM were 68.8% ± 6.0%, 67.6% ± 6.0%, and 5.9% ± 2.9% after single-unit transplantation compared with 74.8% ± 5.5%, 68.1% ± 6.0%, and 11.6% ± 3.9% after double-unit transplantation. The final relapse risk did not significantly differ, but relapses were delayed after double-unit transplantation. Overall incidences of graft-versus-host disease (GVHD) were similar, but chronic GVHD was more frequently extensive after double-UCB transplantation (31.9% ± 5.7% vs 14.7% ± 4.3%, P = .02). In an exploratory subgroup analysis, we found a significantly lower relapse risk after double-unit transplantation in patients receiving total body irradiation without antithymocyte globulin (ATG), whereas the relapse risk was similar in the group treated with busulfan, cyclophosphamide, and ATG. Single-UCB transplantation with adequate cell dose remains the standard of care and leads to low TRM. Double-unit transplantation should be reserved for patients who lack such units. This trial was registered at www.clinicaltrials.gov as #NCT01067300.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Leucemia/terapia , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante/métodos , Doença Aguda , Adolescente , Adulto , Soro Antilinfocitário/administração & dosagem , Criança , Pré-Escolar , Doença Crônica , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Leucemia/mortalidade , Masculino , Síndromes Mielodisplásicas/mortalidade , Taxa de Sobrevida , Irradiação Corporal Total , Adulto Jovem
15.
J Immunother ; 37(3): 170-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24598452

RESUMO

We report herein the results we obtained and the limitations we experienced during the production and use of a bank of Epstein-Barr virus (EBV)-transformed human cytotoxic T lymphocytes (EBV-CTLs). To assess the feasibility and toxicity of this strategy, we selected and stored, in liquid nitrogen, 4 billion EBV-CTLs from each of the 13 selected donors. Subsequently, in a multicenter phase I/II study, 11 patients with EBV-associated lymphoma resistant to conventional treatments received 1-3 doses of 5 million EBV-CTLs/kg with 1-3 and 0-4 compatibilities for human leukocyte antigen (HLA)-I and HLA-II, respectively. Except for one event of fever after injection, no immediate or delayed toxicity, no graft versus host disease, and no graft rejection attributable to CTL infusion were observed. Three patients presented complete remission and 1 partial remission after treatment. Considering the clinical options currently available, and the constrains associated with CTL preparation and implementation, we conclude that CTL banks should consist of a reasonably small number of cell lines with documented specificities. This objective could be more easily achieved if the few homozygous donors for the most frequent HLA alleles of the targeted population could be made available for such a project.


Assuntos
Infecções por Vírus Epstein-Barr/terapia , Herpesvirus Humano 4/imunologia , Imunoterapia Adotiva , Linfoma/terapia , Linfócitos T Citotóxicos/imunologia , Adolescente , Adulto , Idoso , Linhagem Celular , Criança , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Estudos de Viabilidade , Feminino , Humanos , Linfoma/imunologia , Linfoma/virologia , Masculino , Pessoa de Meia-Idade , Carga Viral , Adulto Jovem
16.
Transplantation ; 94(3): 287-94, 2012 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-22785249

RESUMO

BACKGROUND: Parenteral nutrition (PN) is still widely preferred to enteral nutrition (EN) in malnourished patients undergoing allogeneic stem-cell transplantation (allo-SCT) after myeloablative conditioning (MAC). The purpose was to determine whether EN improves early outcome after MAC allo-SCT. METHODS: Early outcome was prospectively assessed in patients undergoing MAC allo-SCT. A total of 121 consecutive patients undergoing a first MAC allo-SCT for acute leukemia, myelodysplastic syndrome, or myeloproliferative syndrome were included. Patients who received cord blood were excluded. Enteral nutrition was systematically offered, although PN was provided when EN had been refused or was poorly tolerated. Among the patients, 94 received EN (EN group) and 27 did not (non-EN group). Overall survival (OS), cumulative incidence of engraftment and acute graft-versus-host disease (aGVHD) within the first 100 days after transplantation were studied. Because EN and PN treatment assignments were not random, propensity score adjustments were performed on patient outcomes. RESULTS: Outcome was better in the EN group than in the non-EN group for OS (hazard ratio [HR], 0.12; 95% confidence interval [CI], 0.04-0.42; P=0.0008), neutrophil (HR, 2.07; 95% CI, 1.26-3.39; P=0.004), and platelet (HR, 1.93; 95% CI, 1.004-3.70; P=0.049) engraftments and aGVHD development (HR, 0.12; 95% CI, 0.04-0.39; P=0.0004). In Cox model analysis, EN demonstrated a protective effect (HR, 0.20; 95% CI, 0.05-0.77; P=0.019) on OS, whereas demonstrated a detrimental impact (HR, 4.18; 95% CI, 1.02-17.12; P=0.047). Enteral nutrition was found to be an independent factor in neutrophil engraftment (HR, 2.17; 95% CI, 1.24-3.81; P=0.007), whereas PN delayed platelet engraftment (HR, 0.57; 95% CI, 0.33-0.99; P=0.046). Enteral nutrition was the only factor that was protective against grades 3 to 4 aGVHD development (HR, 0.19; 95% CI, 0.05-0.72; P=0.01). CONCLUSIONS: Routine use of EN is preferable to upfront PN in these patients.


Assuntos
Nutrição Enteral/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Adulto , Plaquetas/metabolismo , Estudos de Coortes , Feminino , Humanos , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Transtornos Mieloproliferativos/terapia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Resultado do Tratamento
18.
Biol Blood Marrow Transplant ; 15(4): 496-504, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19285638

RESUMO

Allogeneic stem cell transplantation has become standard therapy for hematologic malignancies through the positive immunologic graft-versus-leukemia effect. Initial immune recovery relies on peripheral expansion of infused T cells, which switch to a memory-like phenotype. This study prospectively investigated whether changes in subset composition precedes complications after myeloablative HLA-matched transplantation for hematologic malignancies. Of 80 allograft recipients, 18 were still free of clinical complication throughout 395 to 1564 days of follow-up. Compared with this complication-free subgroup, patients who developed chronic graft-versus-host disease (cGVHD) without relapsing recovered similar numbers of circulating T cells with predominance of CD8+ T cells lacking CC-chemokine receptor-7 and CD28 expression throughout the first year after transplantation. Conversely, poor CD8+ T cell recovery with diminished numbers of CD28neg CD8+ T cells (approximately 1/4th of that of relapse-free patients) preceded occurrence of malignant relapse. In multivariate analysis, lower CD28neg CD8+ T cell counts by day 60 postallograft were associated with a greater risk of subsequent relapse (hazard ratio [HR] 0.33; 95% confidence interval [CI]: 0.14-0.76; P = .01). Enumeration of CD28neg CD8+ T cells in patients could assist in predicting risk of relapse and help build an algorithm for accelerating the immune recovery by reducing the immunosuppressive treatment and considering the introduction of preemptive donor lymphocyte infusions.


Assuntos
Antígenos CD28/imunologia , Linfócitos T CD8-Positivos/imunologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Recuperação de Função Fisiológica/imunologia , Condicionamento Pré-Transplante , Adolescente , Adulto , Criança , Pré-Escolar , Doença Crônica , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/terapia , Neoplasias Hematológicas/mortalidade , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Receptores CCR7/imunologia , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Transplante Homólogo
19.
Br J Haematol ; 143(4): 541-7, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18759760

RESUMO

Gemtuzumab ozogamicin (GO) monotherapy is reported to yield a 20-30% response rate in advanced acute myeloid leukaemia (AML). This study examined the efficacy and tolerability of GO combined with cytarabine (GOCYT) in children with refractory/relapsed CD33(+) AML. Seventeen children received GO 3 mg/m(2) on days 1, 4 and 7 plus cytarabine 100 mg/m(2)/d for 7 d on a compassionate-use basis. Seven patients then received GO-based consolidation. At the outset of GOCYT, two patients were refractory; eight patients were in refractory first relapse; six patients had relapsed after stem cell transplantation (SCT); and one patient [del(5q) therapy-related AML (t-AML)] had not yet been treated. Mean follow-up was 17 months (8-33 months). Ten responses were obtained after GOCYT induction, including complete remission (CR) or CR without complete recovery of platelets (CRp) in six patients (35%). The responses improved in three children who received GOCYT consolidation, increasing the CR + CRp rate to 53%. SCT was subsequently performed in eight responders. Grade 3-4 adverse events consisted of haematological disorders (n = 17, 100%) and documented infections (n = 5, 29%). No cases of sinusoidal obstructive syndrome occurred. Three patients were alive at the cut-off date for this analysis, all of whom had responded to GOCYT. GOCYT combination therapy yielded a high response rate (53%) and showed acceptable toxicity in heavily pretreated children with refractory/relapsed AML. These results warrant a larger prospective study.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Aminoglicosídeos/administração & dosagem , Aminoglicosídeos/efeitos adversos , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Esquema de Medicação , Avaliação de Medicamentos , Métodos Epidemiológicos , Feminino , Humanos , Lactente , Masculino , Recidiva , Resultado do Tratamento
20.
Eur J Pediatr ; 161(7): 390-2, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12111192

RESUMO

UNLABELLED: We report on the development of auto-immune pancytopenia in a child with DiGeorge syndrome carrying the 22q11 microdeletion. She had congenital heart disease, dysmorphic facies, thymic hypoplasia, immunodeficiency, velopharyngeal insufficiency, scoliosis, and a hearing deficit. She had a low T-cell count with a normal CD4/CD8 ratio, IgA deficiency and a normal lymphoblastic response to mitogens. She has presented with pancytopenia since 10 years of age (leucocytes 3,300/mm(3), haemoglobin 107 g/l, platelets 80,000/mm(3)). Platelet-associated antibodies, anti-neutrophil antibodies and Coombs' positive red cells were present. At 14 years of age, she presented with a severe episode of haemolysis with pancytopenia. Steroids were effective in treating the pancytopenia at a dose of 2 mg/kg per day for 6 weeks. Since 15 years of age, she has had episodes of acrocyanosis. At 16 years of age, she still had mild pancytopenia without any treatment. CONCLUSION: the clinical spectrum of the 22q11 microdeletion syndrome is very broad. This case suggests that auto-immune disease such as pancytopenia is part of the 22q11 microdeletion syndrome.


Assuntos
Doenças Autoimunes/diagnóstico , Cromossomos Humanos Par 22 , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/imunologia , Pancitopenia/diagnóstico , Pancitopenia/imunologia , Adolescente , Doenças Autoimunes/complicações , Criança , Síndrome de DiGeorge/complicações , Síndrome de DiGeorge/genética , Feminino , Seguimentos , Deleção de Genes , Humanos , Pancitopenia/complicações , Medição de Risco , Índice de Gravidade de Doença
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