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2.
Transplant Cell Ther ; 29(8): 531.e1-531.e4, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37169288

RESUMO

Curative therapy for sickle cell disease (SCD) through hematopoietic cell transplantation (HCT) is associated with a high level of risk for treatment-related gonadal dysfunction and future infertility. Both the myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) regimens used for SCD HCT are considered to carry a high risk for ovarian damage. Cyclophosphamide equivalent doses (CEDs) are thought to correlate with the degree of gonadal damage in pediatric oncology patients. We aimed to evaluate ovarian outcomes previously reported from our center, characterize the conditioning regimens as MAC or RIC, and calculate the CED for each regimen. The ovarian outcomes diminished ovarian reserve (DOR), as determined by an anti-Müllerian hormone (AMH) below the normal limits for age and assay or <5%, and premature ovarian insufficiency (POI), defined as a follicle-stimulating hormone (FSH) level >40 mIU/ML, are presented by conditioning regimen from 3 clinical studies from our center (2 published and 1 presented as an abstract in 2022). The studies were not mutually exclusive of patients. CEDs were calculated for each regimen. The CED ranged from 3388 to 9705 mg/m2 for MAC regimens and from 5600 to 18,750 mg/m2 for RIC regimens. DOR was observed in all regimens; however, in one study 2 patients had normal AMH levels after a fludarabine/melphalan regimen, and 1 patient had a normal AMH level after a fludarabine/melphalan/thiotepa regimen. Rates of POI were more variable and ranged from 40% to 100% after MAC regimens and from 0 to 100% after RIC regimens. Female patients with SCD who undergo HCT have very high rates of DOR after both MAC HCT and RIC HCT. Two of the 3 RIC regimens evaluated had higher CEDs than were seen in any of the MAC regimens evaluated. Rates of POI were more variable but may increase with time from transplantation. All SCD patients need to be counseled about the risk of infertility and provided information about fertility preservation.


Assuntos
Anemia Falciforme , Transplante de Células-Tronco Hematopoéticas , Infertilidade , Insuficiência Ovariana Primária , Criança , Humanos , Feminino , Melfalan , Saúde Reprodutiva , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Insuficiência Ovariana Primária/etiologia , Infertilidade/etiologia , Anemia Falciforme/terapia
3.
Transplant Cell Ther ; 28(11): 770.e1-770.e6, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35995392

RESUMO

Allogeneic hematopoietic cell therapy (HCT) is an established cure for sickle cell disease (SCD); however, HCT conditioning regimens are known to be gonadotoxic. Anti-mullerian hormone (AMH) measures ovarian reserve, and follicle-stimulating hormone (FSH) defines premature ovarian insufficiency (POI) at values >40 mIU/mL in pubertal females. The present study was conducted to assess ovarian reserve and function before and after transplantation in pediatric and adolescent females with SCD treated with allogeneic HCT between January 2015 and June 2020 at Children's Healthcare of Atlanta. In this retrospective review of 17 females age <21 years with SCD who had AMH levels measured at baseline and at 2 years post-HCT, AMH levels were categorized as normal, low, or undetectable, and FSH levels were measured and used to identify pubertal females who had developed POI. Demographic and treatment data were abstracted from the institutional database and medical records, and a descriptive statistical analysis was conducted. Of the 17 patients in the study cohort, 14 had been treated with hydroxyurea and 3 had chronic transfusions but with no significant iron overload. AMH levels were normal in 15 patients (88%) and low in 2 patients (12%) at baseline. The median age at HCT was 7.5 years (range, 3.7 to 20.3 years), and 14 patients (82%) underwent matched related donor HCT. After HCT, 15 patients (88%) had undetectable AMH and 2 (12%) had low AMH, with no apparent differences by HCT conditioning regimen. No pubertal patients had POI at baseline, whereas 55% of pubertal patients had progressed to POI by 2 years post-HCT. In this cohort, the majority of females had normal AMH levels at baseline but undetectable levels after HCT. Females with SCD considering HCT should be counseled about the treatment-related risk of gonadal dysfunction. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.


Assuntos
Anemia Falciforme , Transplante de Células-Tronco Hematopoéticas , Menopausa Precoce , Reserva Ovariana , Hormônios Peptídicos , Insuficiência Ovariana Primária , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Adulto Jovem , Anemia Falciforme/terapia , Hormônio Antimülleriano , Hormônio Foliculoestimulante , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Insuficiência Ovariana Primária/etiologia
4.
Transplant Cell Ther ; 27(4): 352.e1-352.e5, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33836890

RESUMO

The incidence and risk factors for severe adverse events (SAEs) in related donors (RD) of hematopoietic cell transplants is unknown. The Related Donor Safe study is a prospective observational cohort of 1680 RDs and represents an opportunity to examine characteristics of SAEs in RDs. In this cohort, we found that SAEs were reported in a total 12 (0.71%) RDs. Of these, 5 SAEs occurred in bone marrow donors (5/404, 1.24%), and 7 (7/1276, 0.55%) were in donors of peripheral blood stem cells. All of the SAEs were considered to be related (definite, probable, or possible) to the donation process. There were no donor fatalities. Of the 12 RDs who experienced an SAE, 10 were either overweight or obese. Five of the 12 RDs had predonation medical conditions that would have resulted in either possible or definite ineligibility for donation were they being assessed as unrelated donors. These SAE data will be useful in the counseling of prospective RDs before planned donation and may be helpful in identifying donors who should be considered medically unsuitable for donation.


Assuntos
Células-Tronco de Sangue Periférico , Estudos de Coortes , Humanos , Estudos Prospectivos , Fatores de Risco , Doadores não Relacionados
5.
J Pediatr Hematol Oncol ; 42(7): e575-e582, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32205784

RESUMO

OBJECTIVES: This study describes the hormone profiles for gonadal late effects after alkylator-based hematopoietic stem cell transplant (HSCT) regimens used for sickle-cell disease (SCD). METHODS: This is a retrospective chart review of subjects followed in the post-HSCT clinic for sickle-cell disease. Patient demographics, pubertal development, characteristics of pre-HSCT disease severity, treatment before HSCT, conditioning regimens, presence of graft versus host disease and follicle-stimulating hormone, anti-Müllerian hormone (AMH), luteinizing hormone and testosterone were abstracted from the medical record. RESULTS: Forty subjects (24 female individuals) with SCD were 9 (±4.3) years old at HSCT and 7.9 years (±5.6) from HSCT. At the time of transplant, 8% of female individuals and no male individuals were pubertal and 58% of female individuals and 38% of male individuals had been treated with hydroxyurea. Post-HSCT, all of the female individuals had diminished ovarian reserve on the basis of low AMH values and 10 of the pubertal female individuals (71%) had premature ovarian insufficiency defined as follicle-stimulating hormone >40 mIU/mL ×2. There was no ovarian recovery and AMH remained very low or undetectable up to 13 years post-HSCT. In male individuals, luteinizing hormone and testosterone levels were normal for age. CONCLUSIONS: Post-HSCT for SCD, all female individuals had diminished ovarian reserve and most female individuals had POI, whereas male individuals had normal testosterone hormone production.


Assuntos
Anemia Falciforme/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Hipogonadismo/epidemiologia , Hipogonadismo/etiologia , Condicionamento Pré-Transplante/efeitos adversos , Alquilantes/efeitos adversos , Hormônio Antimülleriano/sangue , Criança , Feminino , Humanos , Estudos Longitudinais , Hormônio Luteinizante/sangue , Masculino , Reserva Ovariana/efeitos dos fármacos , Insuficiência Ovariana Primária/induzido quimicamente , Estudos Retrospectivos , Testosterona/sangue , Condicionamento Pré-Transplante/métodos
6.
Biol Blood Marrow Transplant ; 25(5): 955-964, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30605731

RESUMO

Although donation of bone marrow (BM) or peripheral blood stem cells (PBSCs) from children to family members undergoing allogeneic transplantation are well-established procedures, studies detailing levels of pain, symptoms, and long-term recovery are lacking. To address this lack, we prospectively enrolled 294 donors age <18 years at 25 pediatric transplantation centers in North America, assessing them predonation, peridonation, and at 1 month, 6 months, and 1 year postdonation. We noted that 71% of children reported pain and 59% reported other symptoms peridonation, with resolution to 14% and 12% at 1 month postdonation. Both older age (age 13 to 17 years versus younger) and female sex were associated with higher levels of pain peridonation, with the highest rates in older females (57% with grade 2-4 pain and 17% with grade 3-4 pain). Multivariate analyses showed a 4-fold increase in risk for older females compared with males age <13 years (P <.001). At 1 year, 11% of 13- to 17-year-old females reported grade 2-4 pain, compared with 3% of males age 13 to 17 years, 0% of females age <13 years, and 1% of males age <13 years (P = .01). Males and females age 13 to 17 years failed to return to predonation pain levels at 1 year 22% and 23% of the time, respectively, compared with 3% and 10% in males and females age <13 years (P = .002). Our data show that females age 13 to 17 years are at increased risk of grade 2-4 pain at 1 year and >20% of females and males age 13 to 17 years do not return to baseline pain levels by 1 year after BM donation. Studies aimed at decreasing symptoms and improving recovery in older children are warranted.


Assuntos
Dor/etiologia , Doadores de Tecidos , Coleta de Tecidos e Órgãos/efeitos adversos , Adolescente , Fatores Etários , Transplante de Medula Óssea , Feminino , Humanos , Masculino , Fatores Sexuais , Fatores de Tempo , Transplante Homólogo
7.
Haematologica ; 104(4): 844-854, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30381298

RESUMO

Unlike unrelated donor registries, transplant centers lack uniform approaches to related donor assessment and deferral. To test whether related donors are at increased risk for donation-related toxicities, we conducted a prospective observational trial of 11,942 related and unrelated donors aged 18-60 years. Bone marrow (BM) was collected at 37 transplant and 78 National Marrow Donor Program centers, and peripheral blood stem cells (PBSC) were collected at 42 transplant and 87 unrelated donor centers in North America. Possible presence of medical comorbidities was verified prior to donation, and standardized pain and toxicity measures were assessed pre-donation, peri-donation, and one year following. Multivariate analyses showed similar experiences for BM collection in related and unrelated donors; however, related stem cell donors had increased risk of moderate [odds ratios (ORs) 1.42; P<0.001] and severe (OR 8.91; P<0.001) pain and toxicities (OR 1.84; P<0.001) with collection. Related stem cell donors were at increased risk of persistent toxicities (OR 1.56; P=0.021) and non-recovery from pain (OR 1.42; P=0.001) at one year. Related donors with more significant comorbidities were at especially high risk for grade 2-4 pain (OR 3.43; P<0.001) and non-recovery from toxicities (OR 3.71; P<0.001) at one year. Related donors with more significant comorbidities were at especially high risk for grade 2-4 pain (OR 3.43; P<0.001) and non-recovery from toxicities (OR 3.71; P<0.001) at one year. Related donors reporting grade ≥2 pain had significant decreases in Health-Related Quality of Life (HR-QoL) scores at one month and one year post donation (P=0.004). In conclusion, related PBSC donors with comorbidities are at increased risk for pain, toxicity, and non-recovery at one year after donation. Risk profiles described in this study should be used for donor education, planning studies to improve the related donor experience, and decisions regarding donor deferral. Registered at clinicaltrials.gov identifier:00948636.


Assuntos
Doadores Vivos , Transplante de Células-Tronco de Sangue Periférico , Células-Tronco de Sangue Periférico , Qualidade de Vida , Doadores não Relacionados , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
8.
Biol Blood Marrow Transplant ; 25(4): 699-711, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30423480

RESUMO

The development of reduced-intensity approaches for allogeneic hematopoietic cell transplantation has resulted in growing numbers of older related donors (RDs) of peripheral blood stem cells (PBSCs). The effects of age on donation efficacy, toxicity, and long-term recovery in RDs are poorly understood. To address this we analyzed hematologic variables, pain, donation-related symptoms, and recovery in 1211 PBSC RDs aged 18 to 79 enrolled in the Related Donor Safety Study. RDs aged > 60 had a lower median CD34+ level before apheresis compared with younger RDs (age > 60, 59 × 106/L; age 41 to 60, 81 × 106/L; age 18 to 40, 121 × 106/L; P < .001). This resulted in older donors undergoing more apheresis procedures (49% versus 30% ≥ 2 collections, P < .001) and higher collection volumes (52% versus 32% > 24 L, P < .001), leading to high percentages of donors aged > 60 with postcollection thrombocytopenia <50 × 109/L (26% and 57% after 2 and 3days of collection, respectively). RDs aged 18 to 40 had a higher risk of grades 2 to 4 pain and symptoms pericollection, but donors over age 40 had more persistent pain at 1, 6, and 12 months (odds ratio [OR], 1.7; P = 0.02) and a higher rate of nonrecovery to predonation levels (OR, 1.7; P = .01). Donors reporting comorbidities increased significantly with age, and those with comorbidities that would have led to deferral by National Marrow Donor Program unrelated donor standards had an increased risk for persistent grades 2 to 4 pain (OR, 2.41; P < .001) and failure to recover to predonation baseline for other symptoms (OR, 2.34; P = .004). This information should be used in counseling RDs regarding risk and can assist in developing practice approaches aimed at improving the RD experience for high-risk individuals.


Assuntos
Transplante de Células-Tronco de Sangue Periférico/métodos , Células-Tronco de Sangue Periférico/metabolismo , Adolescente , Adulto , Idoso , Doadores de Sangue , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Blood ; 132(17): 1737-1749, 2018 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-30154114

RESUMO

The Primary Immune Deficiency Treatment Consortium (PIDTC) performed a retrospective analysis of 662 patients with severe combined immunodeficiency (SCID) who received a hematopoietic cell transplantation (HCT) as first-line treatment between 1982 and 2012 in 33 North American institutions. Overall survival was higher after HCT from matched-sibling donors (MSDs). Among recipients of non-MSD HCT, multivariate analysis showed that the SCID genotype strongly influenced survival and immune reconstitution. Overall survival was similar for patients with RAG, IL2RG, or JAK3 defects and was significantly better compared with patients with ADA or DCLRE1C mutations. Patients with RAG or DCLRE1C mutations had poorer immune reconstitution than other genotypes. Although survival did not correlate with the type of conditioning regimen, recipients of reduced-intensity or myeloablative conditioning had a lower incidence of treatment failure and better T- and B-cell reconstitution, but a higher risk for graft-versus-host disease, compared with those receiving no conditioning or immunosuppression only. Infection-free status and younger age at HCT were associated with improved survival. Typical SCID, leaky SCID, and Omenn syndrome had similar outcomes. Landmark analysis identified CD4+ and CD4+CD45RA+ cell counts at 6 and 12 months post-HCT as biomarkers predictive of overall survival and long-term T-cell reconstitution. Our data emphasize the need for patient-tailored treatment strategies depending upon the underlying SCID genotype. The prognostic significance of CD4+ cell counts as early as 6 months after HCT emphasizes the importance of close follow-up of immune reconstitution to identify patients who may need additional intervention to prevent poor long-term outcome.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Transplante de Células-Tronco Hematopoéticas , Reconstituição Imune/imunologia , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/mortalidade , Imunodeficiência Combinada Severa/terapia , Genótipo , Humanos , Contagem de Linfócitos , Estudos Retrospectivos
10.
Biol Blood Marrow Transplant ; 24(10): 2040-2046, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29933069

RESUMO

We enrolled 150 patients in a prospective multicenter study of children with acute myeloid leukemia undergoing hematopoietic stem cell transplantation (HSCT) to compare the detection of measurable residual disease (MRD) by a "difference from normal" flow cytometry (ΔN) approach with assessment of Wilms tumor 1 (WT1) gene expression without access to the diagnostic specimen. Prospective analysis of the specimens using this approach showed that 23% of patients screened for HSCT had detectable residual disease by ΔN (.04% to 53%). Of those patients who proceeded to transplant as being in morphologic remission, 10 had detectable disease (.04% to 14%) by ΔN. The disease-free survival of this group was 10% (0 to 35%) compared with 55% (46% to 64%, P < .001) for those without disease. The ΔN assay was validated using the post-HSCT specimen by sorting abnormal or suspicious cells to confirm recipient or donor origin by chimerism studies. All 15 patients who had confirmation of tumor detection relapsed, whereas the 2 patients with suspicious phenotype cells lacking this confirmation did not. The phenotype of the relapse specimen was then used retrospectively to assess the pre-HSCT specimen, allowing identification of additional samples with low levels of MRD involvement that were previously undetected. Quantitative assessment of WT1 gene expression was not predictive of relapse or other outcomes in either pre- or post-transplant specimens. MRD detected by ΔN was highly specific, but did not identify most relapsing patients. The application of the assay was limited by poor quality among one-third of the specimens and lack of a diagnostic phenotype for comparison.


Assuntos
Citometria de Fluxo , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Condicionamento Pré-Transplante , Doadores não Relacionados , Proteínas WT1/sangue , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Recém-Nascido , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Neoplasia Residual , Transplante Homólogo
11.
Blood ; 128(21): 2561-2567, 2016 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-27625358

RESUMO

Children with sickle cell disease experience organ damage, impaired quality of life, and premature mortality. Allogeneic bone marrow transplant from an HLA-matched sibling can halt disease progression but is limited by donor availability. A Blood and Marrow Transplant Clinical Trials Network (BMT CTN) phase 2 trial conducted from 2008 to 2014 enrolled 30 children aged 4 to 19 years; 29 were eligible for evaluation. The primary objective was 1-year event-free survival (EFS) after HLA allele-matched (at HLA-A, -B, -C, and -DRB1 loci) unrelated donor transplant. The conditioning regimen included alemtuzumab, fludarabine, and melphalan. Graft-versus-host disease (GVHD) prophylaxis included calcineurin inhibitor, short-course methotrexate, and methylprednisolone. Transplant indications included stroke (n = 12), transcranial Doppler velocity >200 cm/s (n = 2), ≥3 vaso-occlusive pain crises per year (n = 12), or ≥2 acute chest syndrome episodes (n = 4) in the 2 years preceding enrollment. Median follow-up was 26 months (range, 12-62 months); graft rejection was 10%. The 1- and 2-year EFS rates were 76% and 69%, respectively. The corresponding rates for overall survival were 86% and 79%. The day 100 incidence rate of grade II-IV acute GVHD was 28%, and the 1-year incidence rate of chronic GVHD was 62%; 38% classified as extensive. There were 7 GVHD-related deaths. A 34% incidence of posterior reversible encephalopathy syndrome was noted in the first 6 months. Although the 1-year EFS met the prespecified target of ≥75%, this regimen cannot be considered sufficiently safe for widespread adoption without modifications to achieve more effective GVHD prophylaxis. The BMT CTN #0601 trial was registered at www.clinicaltrials.gov as #NCT00745420.


Assuntos
Anemia Falciforme/mortalidade , Anemia Falciforme/terapia , Transplante de Medula Óssea , Doadores não Relacionados , Adolescente , Aloenxertos , Anemia Falciforme/fisiopatologia , Inibidores de Calcineurina/administração & dosagem , Criança , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , Taxa de Sobrevida
12.
J Pediatr Hematol Oncol ; 38(8): e310-e314, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27403771

RESUMO

Monomorphic plasmacytoma-type posttransplant lymphoproliferative disorder (PTLD) has not been reported after pediatric hematopoietic stem cell transplantation. We present a child with hepatitis-associated severe aplastic anemia who underwent an unrelated allogeneic hematopoietic stem cell transplantation and subsequently developed graft failure and an Epstein-Barr virus-positive monomorphic plasmacytoma-type PTLD of recipient origin. Despite broad-spectrum antimicrobials, weaning immunosuppression, rituximab administration, and a stem cell boost she died from complications of PTLD and a fungal pulmonary infection on day +78.


Assuntos
Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Linfoproliferativos/etiologia , Plasmocitoma/etiologia , Anemia Aplástica/complicações , Criança , Infecções por Vírus Epstein-Barr , Evolução Fatal , Feminino , Rejeição de Enxerto , Humanos , Pneumopatias/etiologia , Pneumopatias/microbiologia , Transtornos Linfoproliferativos/virologia , Plasmocitoma/virologia , Transplante Homólogo
13.
Int J Radiat Oncol Biol Phys ; 94(2): 349-59, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26853343

RESUMO

PURPOSE: This study evaluated factors associated with increased risk of pulmonary toxicity (PT) from any cause in pediatric patients after myeloablative conditioning, using total body irradiation (TBI), followed by allogeneic hematopoietic stem cell transplantation (HSCT). METHODS AND MATERIALS: The records of 129 consecutive pediatric patients (range: 1-21 years of age) who underwent TBI-based myeloablative conditioning for hematologic malignancies at our institution between January 2003 and May 2014 were reviewed. Although total TBI doses ranged from 10.5 to 14 Gy, lung doses were limited to 10 Gy with partial transmission blocks. TBI dose rates ranged from 5.6 cGy/min to 20.9 cGy/min. PT was classified using clinical symptoms, radiographic evidence, and ventilatory defects on pulmonary function tests. Noninfectious (idiopathic) pneumonia syndrome (IPS) was characterized by patients exhibiting PT while demonstrating no signs of infection throughout the follow-up period. RESULTS: PT from any cause developed in 70.5% of patients and was significantly associated with increased transplantation-related mortality (TRM) (P=.03) and decreased overall survival (OS) (P=.02). IPS developed in 23.3% of patients but was not associated with increased TRM (P=.6) or decreased OS (P=.5). Acute graft-versus-host disease (GVHD) significantly affected PT (P=.001) but did not significantly influence the development of IPS (P=.4). Infection was a leading cause of PT (75.8%). TBI dose rate significantly affected development of overall PT (P=.02) and was the sole factor to significantly influence the incidence of IPS (P=.002). TBI total dose, dose per fraction, disease type, transplantation chemotherapy, age of patient, sex, and donor type did not significantly impact overall PT or IPS. CONCLUSIONS: A high incidence of PT was noted in this large series of homogeneously treated pediatric patients undergoing TBI for allogeneic HSCT. TBI dose rates affected overall PT and strongly influenced IPS. TBI dose rate is a contributing factor influencing pulmonary toxicity and rates less than 15 cGy/min should be considered to decrease the risk of IPS.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Pulmão/efeitos da radiação , Pneumonia/etiologia , Condicionamento Pré-Transplante/efeitos adversos , Irradiação Corporal Total/efeitos adversos , Doença Aguda , Adolescente , Aloenxertos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Doença Enxerto-Hospedeiro/complicações , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Imunossupressores/uso terapêutico , Incidência , Lactente , Masculino , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Dosagem Radioterapêutica , Condicionamento Pré-Transplante/métodos , Adulto Jovem
14.
Pediatr Blood Cancer ; 63(5): 908-13, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26757445

RESUMO

BACKGROUND: Splenic dysfunction is a significant complication of sickle cell disease (SCD). Hematopoietic stem cell transplant (HSCT) is a proven cure for SCD; however, its long-term effect on splenic function is not well characterized. PROCEDURE: We conducted a retrospective cohort study of pediatric patients who had HSCT for SCD at two transplant centers. (99m) Tc liver-spleen (LS) scans were blindly reviewed and classified as demonstrating absent, decreased, or normal splenic uptake. RESULTS: Considering all engrafted nonsplenectomized Hb SS and Sß(0) -thalassemia patients with LS scans available, at a median of 2.0 years post-HSCT (range 1.0-9.3 years) eight of 53 (15%) had normal, 40 of 53 (75%) decreased, and five of 53 (9%) absent splenic uptake. More patients had splenic uptake after HSCT: pre-HSCT 14/38 (37%) versus post-HSCT 34/38 (89%), P < 0.0001. Older age at HSCT was associated with worse splenic function post-HSCT (median age at HSCT for absent uptake 16.6 years vs. present uptake 8.0 years, P = 0.030). Extensive chronic GVHD was also more common in patients with absent splenic uptake compared to patients with present uptake (absent 40% vs. present 6%, P = 0.064). CONCLUSIONS: HSCT significantly improves splenic function for most pediatric patients with SCD, but older patient age at time of HSCT and extensive chronic GVHD appear to be risk factors for poor post-HSCT splenic function.


Assuntos
Anemia Falciforme , Transplante de Células-Tronco Hematopoéticas , Recuperação de Função Fisiológica , Baço , Adolescente , Fatores Etários , Aloenxertos , Anemia Falciforme/diagnóstico por imagem , Anemia Falciforme/fisiopatologia , Anemia Falciforme/terapia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Fígado/diagnóstico por imagem , Fígado/fisiopatologia , Masculino , Cintilografia , Estudos Retrospectivos , Baço/diagnóstico por imagem , Baço/fisiopatologia
15.
Blood Cells Mol Dis ; 55(1): 56-61, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25976468

RESUMO

Gonadal hypofunction is described in male and female patients with sickle cell anemia (SCA) after bone marrow transplant (BMT) and in males treated with hydroxyurea (HU). Anti-Müllerian hormone (AMH) is a serum marker of ovarian reserve. This study describes AMH and follicle-stimulating hormone (FSH) levels in female SCA subjects treated with supportive care (SCA-SC), HU (SCA-HU) and BMT (SCA-BMT). SCA (SS/Sß(0)) subjects not on HU, on HU and status-post BMT, ages 10-21 years were recruited. SCA-HU subjects were treated with HU ≥ 20 mg/kg for ≥ 12 consecutive months. SCA-BMT subjects had received busulfan and cyclophosphamide. Serum AMH and random FSH levels were obtained. Diminished ovarian reserve (DOR) was defined as AMH level <5th percentile for age-matched controls. Subjects also with FSH >40 IU/L were classified as having premature ovarian insufficiency (POI). 14 SCA-SC (14.5 ± 2.7 years), 33 SCA-HU (14.4 ± 2.4 years) and 9 SCA-BMT (14.3 ± 2.7 years) females were included. AMH was undetectable in all SCA-BMT subjects and <5th percentile in 24% of SCA-HU subjects. FSH was menopausal (>40 IU/L) in 88.9% of SCA-BMT subjects. All SCA-BMT subjects and 24% of subjects on HU had DOR; 89% of SCA-BMT subjects had POI. AMH and FSH may be useful tools in assessing ovarian reserve and function.


Assuntos
Anemia Falciforme/terapia , Hormônio Antimülleriano/sangue , Antidrepanocíticos/uso terapêutico , Transplante de Medula Óssea , Hidroxiureia/uso terapêutico , Insuficiência Ovariana Primária/terapia , Adolescente , Anemia Falciforme/sangue , Anemia Falciforme/complicações , Anemia Falciforme/diagnóstico , Biomarcadores/sangue , Bussulfano/uso terapêutico , Estudos de Casos e Controles , Criança , Ciclofosfamida/uso terapêutico , Feminino , Hormônio Foliculoestimulante/sangue , Hemoglobina Falciforme/metabolismo , Heterozigoto , Homozigoto , Humanos , Menarca/fisiologia , Agonistas Mieloablativos/uso terapêutico , Reserva Ovariana/efeitos dos fármacos , Insuficiência Ovariana Primária/sangue , Insuficiência Ovariana Primária/complicações , Insuficiência Ovariana Primária/diagnóstico , Adulto Jovem
16.
N Engl J Med ; 371(5): 434-46, 2014 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-25075835

RESUMO

BACKGROUND: The Primary Immune Deficiency Treatment Consortium was formed to analyze the results of hematopoietic-cell transplantation in children with severe combined immunodeficiency (SCID) and other primary immunodeficiencies. Factors associated with a good transplantation outcome need to be identified in order to design safer and more effective curative therapy, particularly for children with SCID diagnosed at birth. METHODS: We collected data retrospectively from 240 infants with SCID who had received transplants at 25 centers during a 10-year period (2000 through 2009). RESULTS: Survival at 5 years, freedom from immunoglobulin substitution, and CD3+ T-cell and IgA recovery were more likely among recipients of grafts from matched sibling donors than among recipients of grafts from alternative donors. However, the survival rate was high regardless of donor type among infants who received transplants at 3.5 months of age or younger (94%) and among older infants without prior infection (90%) or with infection that had resolved (82%). Among actively infected infants without a matched sibling donor, survival was best among recipients of haploidentical T-cell-depleted transplants in the absence of any pretransplantation conditioning. Among survivors, reduced-intensity or myeloablative pretransplantation conditioning was associated with an increased likelihood of a CD3+ T-cell count of more than 1000 per cubic millimeter, freedom from immunoglobulin substitution, and IgA recovery but did not significantly affect CD4+ T-cell recovery or recovery of phytohemagglutinin-induced T-cell proliferation. The genetic subtype of SCID affected the quality of CD3+ T-cell recovery but not survival. CONCLUSIONS: Transplants from donors other than matched siblings were associated with excellent survival among infants with SCID identified before the onset of infection. All available graft sources are expected to lead to excellent survival among asymptomatic infants. (Funded by the National Institute of Allergy and Infectious Diseases and others.).


Assuntos
Transplante de Células-Tronco Hematopoéticas , Imunodeficiência Combinada Severa/terapia , Complexo CD3/sangue , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Imunoglobulina A/sangue , Incidência , Lactente , Contagem de Linfócitos , Masculino , Retratamento , Estudos Retrospectivos , Imunodeficiência Combinada Severa/imunologia , Imunodeficiência Combinada Severa/mortalidade , Irmãos , Taxa de Sobrevida , Linfócitos T/imunologia , Condicionamento Pré-Transplante , Resultado do Tratamento
17.
Blood ; 124(6): 861-6, 2014 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-24963044

RESUMO

Hematopoietic stem cell transplant (HSCT) is the only cure for sickle cell disease (SCD). HSCT using an HLA-identical sibling donor is currently an acceptable treatment option for children with severe SCD, with expected HSCT survival >95% and event-free survival >85%. HSCT for children with less severe SCD (children who have not yet suffered overt disease complications or only had mild problems) is controversial. It is important to consider the ethical issues of a proposed study comparing HLA-identical sibling HSCT to best supportive care for children with less severe SCD. In evaluating the principles of nonmaleficence, respect for individual autonomy, and justice, we conclude that a study of HLA-identical sibling HSCT for all children with SCD, particularly hemoglobin SS and Sß(0)-thalassemia disease, is ethically sound. Future work should explore the implementation of a large trial to help determine whether HSCT is a beneficial treatment of children with less severe SCD.


Assuntos
Anemia Falciforme/terapia , Transplante de Células-Tronco Hematopoéticas/ética , Anemia Falciforme/complicações , Anemia Falciforme/mortalidade , Criança , Ensaios Clínicos como Assunto/ética , Doença Enxerto-Hospedeiro/etiologia , Antígenos HLA , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Doadores Vivos/ética , Fatores de Risco , Irmãos
18.
Pediatrics ; 133(5): e1156-62, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24777206

RESUMO

BACKGROUND AND OBJECTIVES: In 2010, the Bioethics Committee of the American Academy of Pediatrics issued recommendations that pediatric hematopoietic stem cell donors should have an independent advocate. Formulating appropriate guidelines is hindered by the lack of prospective empirical evidence from families about the experience of siblings during typing and donation. Our aim was to provide these data. METHODS: Families with a child scheduled to undergo hematopoietic stem cell transplant were recruited. All family members, including children aged 9 to 22 years, were eligible. Qualitative interviews were conducted within 3 time periods: pretransplant, 6 to 8, and 9 to 11 months posttransplant. Quantitative scales assessing decision satisfaction and regret were administered at time 2. RESULTS: Thirty-three families were interviewed. Of the 119 family members, 76% perceived there was no choice in the decision to HLA-type siblings; 77% perceived no choice in sibling donation; 86% had no concerns about typing other than needle sticks; and 64% had no concerns about donation. Common concerns raised were dislike of needle sticks (19%), stress before typing results (14%), and fear of donation (15%). Posttransplantation, 33% of donors wished they had been given more information; 56% of donors stated they benefited from donation. Only 1 donor expressed regret posttransplant. CONCLUSIONS: Most family members did not view sibling typing and donation as a choice, were positive about the experience, and did not express regrets. We recommend education for all siblings before typing, comprehensive education for the donor by a health care provider pretransplant, and systematic donor follow-up after transplantation.


Assuntos
Necessidades e Demandas de Serviços de Saúde , Transplante de Células-Tronco Hematopoéticas/psicologia , Irmãos/psicologia , Doadores de Tecidos/psicologia , Adaptação Psicológica , Adolescente , Criança , Ética Médica , Medo , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/ética , Teste de Histocompatibilidade/psicologia , Humanos , Consentimento Livre e Esclarecido/ética , Consentimento Livre e Esclarecido/psicologia , Entrevista Psicológica , Masculino , Ferimentos Penetrantes Produzidos por Agulha/psicologia , Defesa do Paciente/ética , Estresse Psicológico/complicações , Doadores de Tecidos/educação , Doadores de Tecidos/ética , Adulto Jovem
19.
Cancer ; 120(6): 909-17, 2014 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-24469862

RESUMO

BACKGROUND: To reduce the risk of adjustment problems associated with hematopoietic stem cell transplant (HSCT) for adolescents/young adults (AYAs), we examined efficacy of a therapeutic music video (TMV) intervention delivered during the acute phase of HSCT to: 1) increase protective factors of spiritual perspective, social integration, family environment, courageous coping, and hope-derived meaning; 2) decrease risk factors of illness-related distress and defensive coping; and 3) increase outcomes of self-transcendence and resilience. METHODS: This was a multisite randomized, controlled trial (COG-ANUR0631) conducted at 8 Children's Oncology Group sites involving 113 AYAs aged 11-24 years undergoing myeloablative HSCT. Participants, randomized to the TMV or low-dose control (audiobooks) group, completed 6 sessions over 3 weeks with a board-certified music therapist. Variables were based on Haase's Resilience in Illness Model (RIM). Participants completed measures related to latent variables of illness-related distress, social integration, spiritual perspective, family environment, coping, hope-derived meaning, and resilience at baseline (T1), postintervention (T2), and 100 days posttransplant (T3). RESULTS: At T2, the TMV group reported significantly better courageous coping (Effect Size [ES], 0.505; P = .030). At T3, the TMV group reported significantly better social integration (ES, 0.543; P = .028) and family environment (ES, 0.663; P = .008), as well as moderate nonsignificant effect sizes for spiritual perspective (ES, 0.450; P = .071) and self-transcendence (ES, 0.424; P = .088). CONCLUSIONS: The TMV intervention improves positive health outcomes of courageous coping, social integration, and family environment during a high-risk cancer treatment. We recommend the TMV be examined in a broader population of AYAs with high-risk cancers.


Assuntos
Transplante de Células-Tronco Hematopoéticas/psicologia , Musicoterapia/métodos , Resiliência Psicológica , Adaptação Psicológica , Adolescente , Adulto , Ansiedade/prevenção & controle , Criança , Relações Familiares , Feminino , Células-Tronco Hematopoéticas , Esperança , Humanos , Masculino , Isolamento Social/psicologia , Apoio Social , Estresse Psicológico/prevenção & controle , Adulto Jovem
20.
J Pediatr Hematol Oncol ; 35(4): 289-98, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23612380

RESUMO

African Americans and Blacks have low participation rates in clinical trials and reduced access to aggressive medical therapies. Hematopoietic cell transplantation (HCT) is a high-risk but potentially curative therapy for sickle cell disease (SCD), a disorder predominantly seen in African Americans. We conducted focus groups to better understand participation barriers to HCT clinical trials for SCD. Nine focus groups of youth with SCD (n=10) and parents (n=41) were conducted at 3 sites representing the Midwest, South Atlantic, and West South Central US. Main barriers to clinical trial participation included gaps in knowledge about SCD, limited access to SCD/HCT trial information, and mistrust of medical professionals. For education about SCD/HCT trials, participants highly preferred one-on-one interactions with medical professionals and electronic media as a supplement. Providers can engage with sickle cell camps to provide information on SCD/HCT clinical trials to youth and local health fairs for parents/families. Youth reported learning about SCD through computer games; investigators may find this medium useful for clinical trial/HCT education. African Americans affected by SCD face unique barriers to clinical trial participation and have unmet HCT clinical studies education needs. Greater recognition of these barriers will allow targeted interventions in this community to increase their access to HCT.


Assuntos
Anemia Falciforme/etnologia , Anemia Falciforme/cirurgia , Negro ou Afro-Americano , Ensaios Clínicos como Assunto , Acessibilidade aos Serviços de Saúde , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Anemia Falciforme/psicologia , Criança , Pré-Escolar , Feminino , Grupos Focais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pais/psicologia
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