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1.
J Pediatr Hematol Oncol ; 42(8): e788-e790, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32251154

RESUMEN

Chemotherapy-associated cardiotoxicity may delay or impair the ability to administer fully myeloablative chemotherapy for stem cell transplant in those with reduced left ventricular ejection fraction. Studies in adults have been inconsistent regarding the value of ejection fraction in predicting cardiotoxicity in the posttransplant period. Recent publications, however, have demonstrated successful stem cell transplantation in adults despite low ejection fractions. This case series highlights 2 pediatric patients who were successfully treated with stem cell transplantation without posttransplant cardiac complications, despite pretransplant ejection fractions of 38% and 29%.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cardiotoxicidad/terapia , Insuficiencia Cardíaca/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/tratamiento farmacológico , Disfunción Ventricular Izquierda/terapia , Cardiotoxicidad/etiología , Cardiotoxicidad/patología , Niño , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/patología , Humanos , Lactante , Leucemia Mieloide Aguda/patología , Masculino , Pronóstico , Estudios Retrospectivos , Trasplante Homólogo , Disfunción Ventricular Izquierda/patología
2.
Biol Blood Marrow Transplant ; 25(5): 955-964, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30605731

RESUMEN

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.


Asunto(s)
Dolor/etiología , Donantes de Tejidos , Recolección de Tejidos y Órganos/efectos adversos , Adolescente , Factores de Edad , Trasplante de Médula Ósea , Femenino , Humanos , Masculino , Factores Sexuales , Factores de Tiempo , Trasplante Homólogo
3.
Biol Blood Marrow Transplant ; 25(4): 699-711, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30423480

RESUMEN

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.


Asunto(s)
Trasplante de Células Madre de Sangre Periférica/métodos , Células Madre de Sangre Periférica/metabolismo , Adolescente , Adulto , Anciano , Donantes de Sangre , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
4.
Haematologica ; 104(4): 844-854, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30381298

RESUMEN

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.


Asunto(s)
Donadores Vivos , Trasplante de Células Madre de Sangre Periférica , Células Madre de Sangre Periférica , Calidad de Vida , Donante no Emparentado , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven
5.
Biol Blood Marrow Transplant ; 24(10): 2040-2046, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29933069

RESUMEN

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.


Asunto(s)
Citometría de Flujo , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Acondicionamiento Pretrasplante , Donante no Emparentado , Proteínas WT1/sangre , Adolescente , Adulto , Aloinjertos , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Lactante , Recién Nacido , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Neoplasia Residual , Trasplante Homólogo
6.
Cancer Res ; 70(23): 9554-61, 2010 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-20935224

RESUMEN

Response to immunocytokine (IC) therapy is dependent on natural killer cells in murine neuroblastoma (NBL) models. Furthermore, killer immunoglobulin-like receptor (KIR)/KIR-ligand mismatch is associated with improved outcome to autologous stem cell transplant for NBL. Additionally, clinical antitumor response to monoclonal antibodies has been associated with specific polymorphic-FcγR alleles. Relapsed/refractory NBL patients received the hu14.18-IL2 IC (humanized anti-GD2 monoclonal antibody linked to human IL2) in a Children's Oncology Group phase II trial. In this report, these patients were genotyped for KIR, HLA, and FcR alleles to determine whether KIR receptor-ligand mismatch or specific FcγR alleles were associated with antitumor response. DNA samples were available for 38 of 39 patients enrolled: 24 were found to have autologous KIR/KIR-ligand mismatch; 14 were matched. Of the 24 mismatched patients, 7 experienced either complete response or improvement of their disease after IC therapy. There was no response or comparable improvement of disease in patients who were matched. Thus KIR/KIR-ligand mismatch was associated with response/improvement to IC (P = 0.03). There was a trend toward patients with the FcγR2A 131-H/H genotype showing a higher response rate than other FcγR2A genotypes (P = 0.06). These analyses indicate that response or improvement of relapsed/refractory NBL patients after IC treatment is associated with autologous KIR/KIR-ligand mismatch, consistent with a role for natural killer cells in this clinical response.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Interleucina-2/uso terapéutico , Neuroblastoma/tratamiento farmacológico , Receptores de IgG/genética , Receptores KIR/genética , Adolescente , Niño , Preescolar , Genotipo , Antígenos HLA/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Humanos , Lactante , Células Asesinas Naturales/metabolismo , Ligandos , Neuroblastoma/genética , Polimorfismo Genético , Resultado del Tratamiento , Adulto Joven
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