RESUMO
Melanoma is the most common skin cancer in children. While the current literature establishes treatment protocols for adult-type melanoma, very few pediatric-specific studies exist, and children are often excluded from melanoma clinical trials2. We report a case series of 23 pediatric patients aged 2-20 years old diagnosed with melanoma at the University of Rochester Medical Center between 1/1/2011 and 1/1/2022. 9/23 patients were Stage III; all patients underwent wide local excision and 9 received adjuvant therapies. 2/23 (8.7%) patients had recurrence of their malignancy after therapy while 21/23 (91.3%) remained without disease progression; 1 patient died from unknown cause, but the rest are alive and currently without disease. All patients whose initial therapy included nivolumab in addition to wide local excision did not have recurrence or progression of their disease. This case series highlights trends in the presentation, treatment, and outcomes of pediatric melanoma; however, additional multi-center studies are needed to establish the clinical utility of such features in pediatric melanoma.
Assuntos
Inibidores de Checkpoint Imunológico , Melanoma , Humanos , Melanoma/tratamento farmacológico , Melanoma/patologia , Criança , Adolescente , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Feminino , Pré-Escolar , Linfonodo Sentinela/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Estadiamento de Neoplasias , Adulto Jovem , Nivolumabe/uso terapêutico , Adulto , Quimioterapia AdjuvanteRESUMO
BACKGROUND: Severe combined immunodeficiency (SCID) is fatal unless durable adaptive immunity is established, most commonly through allogeneic haematopoietic cell transplantation (HCT). The Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades, focusing on the effects of population-based newborn screening for SCID that was initiated in 2008 and expanded during 2010-18. METHODS: We analysed transplantation-related data from children with SCID treated at 34 PIDTC sites in the USA and Canada, using the calendar time intervals 1982-89, 1990-99, 2000-09, and 2010-18. Categorical variables were compared by χ2 test and continuous outcomes by the Kruskal-Wallis test. Overall survival was estimated by the Kaplan-Meier method. A multivariable analysis using Cox proportional hazards regression models examined risk factors for HCT outcomes, including the variables of time interval of HCT, infection status and age at HCT, trigger for diagnosis, SCID type and genotype, race and ethnicity of the patient, non-HLA-matched sibling donor type, graft type, GVHD prophylaxis, and conditioning intensity. FINDINGS: For 902 children with confirmed SCID, 5-year overall survival remained unchanged at 72%-73% for 28 years until 2010-18, when it increased to 87% (95% CI 82·1-90·6; n=268; p=0·0005). For children identified as having SCID by newborn screening since 2010, 5-year overall survival was 92·5% (95% CI 85·8-96·1), better than that of children identified by clinical illness or family history in the same interval (79·9% [69·5-87·0] and 85·4% [71·8-92·8], respectively [p=0·043]). Multivariable analysis demonstrated that the factors of active infection (hazard ratio [HR] 2·41, 95% CI 1·56-3·72; p<0·0001), age 3·5 months or older at HCT (2·12, 1·38-3·24; p=0·001), Black or African-American race (2·33, 1·56-3·46; p<0·0001), and certain SCID genotypes to be associated with lower overall survival during all time intervals. Moreover, after adjusting for several factors in this multivariable analysis, HCT after 2010 no longer conveyed a survival advantage over earlier time intervals studied (HR 0·73, 95% CI 0·43-1·26; p=0·097). This indicated that younger age and freedom from infections at HCT, both directly driven by newborn screening, were the main drivers for recent improvement in overall survival. INTERPRETATION: Population-based newborn screening has facilitated the identification of infants with SCID early in life, in turn leading to prompt HCT while avoiding infections. Public health programmes worldwide can benefit from this definitive demonstration of the value of newborn screening for SCID. FUNDING: National Institute of Allergy and Infectious Diseases, Office of Rare Diseases Research, and National Center for Advancing Translational Sciences.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Imunodeficiência Combinada Severa , Humanos , Recém-Nascido , Transplante de Células-Tronco Hematopoéticas/métodos , Estudos Longitudinais , Triagem Neonatal , Modelos de Riscos Proporcionais , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/terapia , Imunodeficiência Combinada Severa/genéticaRESUMO
Overall survival after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) using alemtuzumab, fludarabine, and melphalan is associated with high rates of mixed chimerism (MC) and secondary graft failure (GF). We hypothesized that peritransplantation alemtuzumab levels or specific patterns of inflammation would predict these risks. We assessed samples from the Bone Marrow Transplant Clinical Trials Network 1204 (NCT01998633) to study the impact of alemtuzumab levels and cytokine patterns on MC and impending or established secondary GF (defined as donor chimerism <5% after initial engraftment and/or requirement of cellular intervention). Thirty-three patients with hemophagocytic lymphohistiocytosis (n = 25) and other IEIs (n = 8) who underwent HCTs with T-cell-replete grafts were included. Patients with day 0 alemtuzumab levels ≤0.32 µg/mL had a markedly lower incidence of MC, 14.3%, vs 90.9% in patients with levels >0.32 µg/mL (P = .008). Impending or established secondary GF was only observed in patients with day 0 alemtuzumab levels >0.32 µg/mL (P = .08). Unexpectedly, patients with impending or established secondary GF had lower CXCL9 levels. The cumulative incidence of impending or established secondary GF in patients with a day 14+ CXCL9 level ≤2394 pg/mL (day 14+ median) was 73.6% vs 0% in patients with a level >2394 pg/mL (P = .002). CXCL9 levels inversely correlated with alemtuzumab levels. These data suggest a model in which higher levels of alemtuzumab at day 0 deplete donor T cells, inhibit the graft-versus-marrow reaction (thereby suppressing CXCL9 levels), and adversely affect sustained engraftment in the nonmyeloablative HCT setting. This trial was registered at www.clinicaltrials.gov as #NCT01998633.
Assuntos
Anticorpos Monoclonais Humanizados , Transplante de Células-Tronco Hematopoéticas , Humanos , Alemtuzumab/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Melfalan/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doadores de Tecidos , Quimiocina CXCL9RESUMO
BACKGROUND: Pediatric central nervous system (CNS) tumors are the leading cause of pediatric cancer mortality. Research addressing genomic biomarkers and clinical outcomes is needed to inform therapeutic decision-making. METHODS: We conducted a retrospective analysis of pediatric patients (age <21) diagnosed with a primary CNS tumor at four upstate New York hospitals from 2008 to 2021. Clinical and histopathologic data were identified from each patient, including genomic analysis of somatic mutations and tumor mutational burden (TMB) where available. These variables were each compared with overall survival using Cox regression analyses. Multivariable analysis was conducted to identify patient characteristics that may independently predict survival. RESULTS: We identified 119 patients. Common tumor types included low-grade glioma (N = 51), high-grade glioma (N = 29), and medulloblastoma (N = 11). Common driver mutations included TP53 inactivation (N = 16), BRAF-KIAA1549 fusion (N = 16), FGFR1 amplification (N = 12), BRAF V600E mutation (N = 12), NF1 loss (N = 12), and H3F3A K28M mutation (N = 6). Median TMB was one mutation/megabase (mut/Mb, range = 0-132). Overall survival was 79.9%. Variables associated with poorer survival on univariable analysis were higher TMB (p = .002, HR 4.97), high-grade tumors (p = .009, HR 84.3), and high-grade glioma histology (p = .021, HR 3.14). Multivariable analyses further identified TMB (p = .011, HR 4.46) and high-grade histology (p = .015, HR 5.28) as independently predictive of worse survival. Tumor progression was more common in high-TMB (N = 15, 44%) than in low-TMB tumors (N = 19, 35%). CONCLUSIONS: High TMB is correlated with higher rates of progression and death as compared to low-TMB tumors. These findings may help identify patients who may benefit from alternative treatments, such as immunotherapies.
Assuntos
Neoplasias do Sistema Nervoso Central , Neoplasias Cerebelares , Glioma , Humanos , Criança , Estudos Retrospectivos , Proteínas Proto-Oncogênicas B-raf/genética , Biomarcadores Tumorais/genética , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/terapia , Glioma/genética , Glioma/terapia , Glioma/patologia , MutaçãoRESUMO
T-cell large granular lymphocytic (T-LGL) leukemia is a rare, typically indolent neoplasm with a median age of onset above 60 years. Pathogenesis involves clonal T-cell expansion, and nearly all reported pediatric cases have been associated with concurrent autoimmune disease. Immunosuppressive therapy often mitigates sequelae, but definitive cure is not routinely achieved. Here we present an otherwise healthy 13-year-old with T-LGL leukemia refractory to all standard treatments. Our patient ultimately underwent allogeneic bone marrow transplant (BMT) and is now stable in remission 3 years post-BMT. BMT may offer a viable definitive cure for refractory T-LGL leukemia in very young patients.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Linfocítica Granular Grande , Adolescente , Transplante de Medula Óssea/efeitos adversos , Criança , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Linfocítica Granular Grande/terapia , Pessoa de Meia-Idade , Linfócitos T/patologiaRESUMO
Adolescent and young adult (AYA) patients with acute leukemia (AL) have inferior outcomes in comparison to younger patients, and are more likely to develop acute and chronic GVHD than younger children following HLA matched sibling donor stem cell transplant (SCT). We compared the incidence of grade II-IV acute GVHD, chronic GVHD, and survival in AYA (age 13-21 years) to younger children (age 2-12 years) who received an unrelated donor SCT for acute leukemia on Children's Oncology Group trials between 2004-2017. One hundred and eighty-eight children and young adults ages 2-21 years underwent URD SCT. Sixty-three percent were aged 2-12 and 37% were age 13-21. Older age was a risk factor for grade II-IV acute GVHD in multivariate analysis with a hazard ratio (HR) of 1.95 [95% confidence interval (CI) 1.23-3.10], but not for chronic GVHD, HR 1.25 [95% CI 0.57-2.71]. Younger patients relapsed more often (34.5 ± 4.4% vs. 22.8 ± 4.0%, p = 0.032), but their Event-Free Survival (42.6 ± 4.7% vs. 51.8 ± 6.1%, p = 0.18) and Overall Survival at 5 years (48.5 ± 4.9% vs. 51.5 ± 6.4%, p = 0.56) were not different than AYA patients. AYA patients who receive an URD SCT for acute leukemia are significantly more likely to develop grade II-IV acute GVHD, though survival is similar.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Doença Aguda , Adolescente , Criança , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Transplante de Células-Tronco/efeitos adversos , Doadores não Relacionados , Adulto JovemAssuntos
Artralgia , Artralgia/diagnóstico , Artralgia/etiologia , Pré-Escolar , Diagnóstico Diferencial , Feminino , HumanosRESUMO
Chronic myeloid leukemia (CML) is effectively treated with long-term tyrosine kinase inhibitor (TKI) therapy, yet little is known about risks of prolonged TKI exposure in young patients, and long-term effect monitoring is not standardized. We surveyed North American pediatric oncologists (n = 119) to evaluate perceived risk of and surveillance practices for potential toxicities associated with prolonged TKI exposure in children and adolescents/young adults (AYAs) with CML. Survey domains included general and specific risk perceptions and surveillance practices for asymptomatic patients on chronic TKI therapy. We analyzed data descriptively and explored relationships between risk perceptions and surveillance. Risk perceptions varied among oncologists but were similar across six categories (thyroid, cardiac, vascular, metabolic, fertility, psychologic), with less than one-third rating each risk as moderate or high in pediatric and AYA patients. More oncologists perceived moderate or high risk of growth abnormalities in children (62% pediatric, 14% AYA) and financial toxicity in all patients (60% pediatric, 64% AYA). A greater proportion of oncologists with moderate or high perceived risk of thyroid abnormalities reported testing thyroid function compared to those with lower perceived risk; patterns for metabolic risk/lipid tests and cardiac risk/tests were similar. In summary, we found that pediatric oncologists had variable risk perceptions and surveillance practices for potential toxicities associated with prolonged TKI exposure. Standardizing surveillance would help quantify risks and refine recommendations.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.2017085 .
Assuntos
Doença Enxerto-Hospedeiro , Leucemia Mielogênica Crônica BCR-ABL Positiva , Médicos , Adolescente , Criança , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Adulto JovemRESUMO
Adolescents and young adults (AYAs; age 15-39 years) with cancer are under-represented in cancer clinical trials because of patient, provider, and institutional barriers. Health care technology is increasingly available to and highly used among AYAs and has the potential to improve cancer care delivery. The COVID-19 pandemic forced institutions to rapidly adopt novel approaches for enrollment and monitoring of patients on cancer clinical trials, many of which have the potential for improving AYA trial participation overall. This consensus statement from the Children's Oncology Group AYA Oncology Discipline Committee reviews opportunities to use technology to optimize AYA trial enrollment and study conduct, as well as considerations for widespread implementation of these practices. The use of remote patient eligibility screening, electronic informed consent, virtual tumor boards, remote study visits, and remote patient monitoring are recommended to increase AYA access to trials and decrease the burden of participation. Widespread adoption of these strategies will require new policies focusing on reimbursement for telehealth, license portability, facile communication between electronic health record systems and advanced safeguards to maintain patient privacy and security. Studies are needed to determine optimal approaches to further incorporate technology at every stage of the clinical trial process, from enrollment through study completion.
Assuntos
COVID-19 , Neoplasias , Adolescente , Adulto , COVID-19/epidemiologia , Criança , Comunicação , Humanos , Neoplasias/terapia , Pandemias , SARS-CoV-2 , Tecnologia , Adulto JovemRESUMO
Due to the evolving use of haploidentical donor grafts in hematopoietic cell transplantation, there is increased need to better understand the risks and benefits of using bone marrow versus peripheral blood grafts, as well as how specific pre-transplantation conditioning regimens impact patient safety and treatment outcomes. We performed a retrospective analysis of 38 patients at two centers who underwent haploidentical hematopoietic cell transplantation using fludarabine plus melphalan-based conditioning regimens with post-transplant cyclophosphamide and peripheral blood donor grafts. We observed an unexpectedly high rate of early non-relapse mortality and severe cytokine release syndrome. The poor outcomes with 1-year overall survival of 34%, disease-free survival of 29%, and non-relapse mortality of 34% motivate us to reconsider the appropriateness of the combination of fludarabine and melphalan conditioning with T-cell replete peripheral blood grafts in the setting of haploidentical hematopoietic cell transplant with post-transplant cyclophosphamide.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Melfalan/efeitos adversos , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversos , Vidarabina/efeitos adversos , Vidarabina/análogos & derivadosRESUMO
BACKGROUND: Infant acute myeloid leukemia is a rare but aggressive form of leukemia. OBSERVATION: We report 2 children who presented with hyperleukocytosis, subsequently diagnosed with infant acute myeloid leukemia, and both developed isolated central nervous system relapse while on chemotherapy. Both infants underwent successful bone marrow transplantation with myeloablative conditioning (thiotepa, busulfan, and cyclophosphamide) without radiation, followed by 12 empiric post-transplant lumbar punctures with intrathecal cytarabine. Both patients tolerated these therapies well, and are without infections, chronic graft-versus-host disease, or any post-transplant sequelae. CONCLUSION: Nonradiation-based conditioning followed by empiric central nervous system-directed intrathecal chemotherapy may be considered for high-risk infants with leukemia.
Assuntos
Transplante de Medula Óssea , Neoplasias do Sistema Nervoso Central/terapia , Citarabina/administração & dosagem , Leucemia Mieloide Aguda/terapia , Agonistas Mieloablativos/administração & dosagem , Condicionamento Pré-Transplante , Aloenxertos , Feminino , Humanos , Lactente , Injeções Espinhais , RecidivaRESUMO
BACKGROUND/AIM: This study explored the mechanisms of the allogeneic graft versus leukemia effect in acute lymphoblastic leukemia (ALL) cells by examining whether they change gene expression in the post-transplant environment containing cytokines and the immunosuppressant cyclosporine, and if such changes affect ALL cell survival. MATERIALS AND METHODS: RNASeq was used to assess leukemia global gene expression and flow cytometry to measure ALL survival in the presence of T cells, NK cells, cytokines, and cyclosporine. RESULTS: A total of 4,805 genes were differentially expressed. Gene set enrichment analysis demonstrated up-regulation of biological processes related to cytokine responses, control of viral infection, and regulation of leukocyte function including proliferation. Down-regulated genes were related to mesenchymal tissue morphogenesis. ALL cells exposed to cytokines and cyclosporine retained susceptibility to T and NK cell killing, and also exhibited increased cell death without exposure to killer cells. CONCLUSION: A significant portion of the graft versus leukemia effect may be mediated by cytokines and cyclosporine.
Assuntos
Sobrevivência Celular/genética , Expressão Gênica , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Criança , Ciclosporina/farmacologia , Citocinas/sangue , Citocinas/fisiologia , Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Transplante HomólogoRESUMO
The compassionate use of available medications with unproven efficacy is often in conflict with their clinical evaluation in placebo-controlled clinical trials. For ultra-rare diseases where no approved treatments exist, such as fibrodysplasia ossificans progressiva (FOP), routine clinical trial enrollment for available medications may be difficult to achieve. Therefore adaptive methods of evaluation are often desirable. Off-on-off-on (O4) approaches offer an opportunity to rapidly assess the potential symptomatic efficacy and tolerability of a medication with a limited number of patients and may aid in the design of more focused clinical trials that are amenable to enrollment. Here we report three children with classic FOP who had recalcitrant flare-ups of the back and who had been treated with an O4 regimen of imatinib. In all three children, fewer flare-ups, decreased swelling and improved function with activities of daily living were reported by the parents and treating physician when the children were "on" imatinib than when they were "off" imatinib. The median time to improvement on imatinib was 2-3 weeks. The anecdotal O4 experience with imatinib reported here in three children with FOP who had recalcitrant flare-ups of the back supports the design of a brief placebo controlled trial to assess the potential efficacy of imatinib in reducing the symptoms in children with refractory flare-ups of FOP. A tool to prospectively measure and quantitate flare-up symptoms is presently being developed and validated and will be used for such a study.
Assuntos
Miosite Ossificante , Ossificação Heterotópica , Receptores de Ativinas Tipo I , Atividades Cotidianas , Criança , Humanos , Mesilato de Imatinib/uso terapêutico , Miosite Ossificante/tratamento farmacológicoRESUMO
Malignant central nervous system (CNS) tumors in young children have a poor prognosis and pose a therapeutic challenge. We describe 11 patients with high-risk CNS tumors (6 atypical teratoid/rhabdoid tumor, 4 nonmedulloblastoma CNS embryonal tumors, and 1 glioblastoma multiforme) who received 32 consolidation cycles of myeloablative carboplatin/thiotepa followed by autologous peripheral blood stem cell rescue. All patients underwent successful stem cell harvest without significant complications. Mean time to absolute neutrophil count ≥0.5×103/µL was 10.2±1.3 days and the mean length of hospital stay was 15.7±3.0 days. There were no regimen-related deaths. Five-year event-free survival and overall survival were 45.5±15.0% and 58.4±16.3%, respectively. Tandem carboplatin/thiotepa consolidation with autologous stem cell rescue is well-tolerated in young children with nonmedulloblastoma CNS tumors.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/terapia , Agonistas Mieloablativos/administração & dosagem , Transplante de Células-Tronco de Sangue Periférico/métodos , Células-Tronco/citologia , Condicionamento Pré-Transplante/métodos , Carboplatina/administração & dosagem , Neoplasias do Sistema Nervoso Central/patologia , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Tiotepa/administração & dosagem , Transplante AutólogoRESUMO
Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Doenças da Imunodeficiência Primária/terapia , Linfócitos T Reguladores/imunologia , Adolescente , Adulto , Animais , Criança , Pré-Escolar , Humanos , Lactente , Pessoa de Meia-Idade , Inquéritos e Questionários , Resultado do Tratamento , Adulto JovemRESUMO
Chronic myeloid leukemia (CML) accounts for 2-3% of leukemias in children under 15 and 9% in adolescents aged 15-19. The diagnosis and management of CML in children, adolescents, and young adults have several differences compared to that in adults. This review outlines the diagnosis and management of the underlying disease as well as challenges that can occur when dealing with CML in this patient population.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Guias de Prática Clínica como AssuntoRESUMO
Chronic myelogenous leukemia (CML) is a rare disease in children for which pediatric evidence-based guidelines are lacking. We designed an anonymous survey for practicing pediatric oncologists and bone marrow transplantation (BMT) physicians to assess their willingness to recommend BMT for a patient with CML based on various clinical scenarios. A total of 274 physicians responded to the survey (13.4% response rate). Nearly all pediatric oncologists and BMT physicians recommended against BMT at time of diagnosis of CML in the chronic phase, with only 8.0% and 1.9% recommending BMT if a matched sibling donor (MSD) and a matched unrelated donor (MUD), respectively, was available. Similarly, after a first poor response to tyrosine kinase inhibitor (TKI) therapy or hematologic relapse, physicians continued to recommend against BMT (39.5% and 23.3% recommended BMT in patients with a matched sibling donor and matched unrelated donor, respectively). However, 81.7% and 69.8% of respondents would recommend BMT after 2 hematologic relapses on TKI therapy, if an MSD and an MUD, respectively, were available. In addition, there was great interest in developing a clinical trial evaluating the safety and efficacy of stopping TKIs in children with CML who achieve and maintain a deep molecular response, with 86.7% of respondents stating they would offer such a trial to their pediatric patients. This survey highlights the need for evidence-based, pediatric-specific guidelines for the management of children and adolescents with CML.
Assuntos
Transplante de Medula Óssea , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Padrões de Prática Médica , Adolescente , Canadá , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Oncologia , Guias de Prática Clínica como Assunto , Irmãos , Transplante Homólogo , Estados Unidos , Doadores não RelacionadosRESUMO
Allogeneic hematopoietic cell transplantation (HCT) with myeloablative conditioning for disorders associated with excessive inflammation such as hemophagocytic lymphohistiocytosis (HLH) is associated with early mortality. A multicenter prospective phase 2 trial of reduced-intensity conditioning with melphalan, fludarabine, and intermediate-timing alemtuzumab was conducted for HLA matched or single HLA locus mismatched related or unrelated donor HCT in a largely pediatric cohort. Graft-versus-host disease (GVHD) prophylaxis was cyclosporine with methylprednisolone. The primary end point was 1-year overall survival (OS). Thirty-four patients with HLH and 12 with other primary immune deficiencies were transplanted. With a median follow-up of 20 months, the 1-year OS for transplanted patients was 80.4% (90% confidence interval [CI], 68.6%-88.2%). Five additional deaths by 16 months yielded an 18-month OS probability of 66.7% (90% CI, 52.9%-77.3%). Two patients experienced primary graft failure, and 18 patients either experienced a secondary graft failure or required a second intervention (mostly donor lymphocyte infusion [DLI]). At 1 year, the proportion of patients alive with sustained engraftment without DLI or second HCT was 39.1% (95% CI, 25.2%-54.6%), and that of being alive and engrafted (with or without DLI) was 60.9% (95% CI, 45.4 %-74.9%). The day 100 incidence of grade II to IV acute GVHD was 17.4% (95% CI, 8.1%-29.7%), and 1-year incidence of chronic GVHD was 26.7% (95% CI, 14.6%-40.4%). Although the trial demonstrated low early mortality, the majority of surviving patients required DLI or second HCT. These results demonstrate a need for future approaches that maintain low early mortality with improved sustained engraftment. The trial was registered at Clinical Trials.gov (NCT 01998633).