RESUMO
BACKGROUND: Serious chronic medical conditions occur in childhood cancer survivors. We aimed to investigate incidence of and risk factors for end-organ damage resulting in registration on a waiting list for or receiving a solid organ transplantation and 5-year survival following these procedures. METHODS: The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort of individuals who survived at least 5 years after childhood cancer diagnosed at younger than 21 years of age, between Jan 1, 1970, and Dec 31, 1986, at one of 25 institutions in the USA. We linked data from CCSS participants treated in the USA diagnosed between Jan 1, 1970, and Dec 31, 1986 (without solid organ transplantation before cohort entry) to the Organ Procurement and Transplantation Network-a database of all US organ transplants. Eligible participants had been diagnosed with leukaemia, lymphoma, malignant CNS tumours, neuroblastoma, Wilms' tumours, and bone and soft tissue sarcomas. The two primary endpoints for each type of organ transplant were date of first registration of a transplant candidate on the waiting list for an organ and the date of the first transplant received. We also calculated the cumulative incidence of being placed on a waiting list or receiving a solid organ transplantation, hazard ratios (HRs) for identified risk factors, and 5-year survival following transplantation. FINDINGS: Of 13â318 eligible survivors, 100 had 103 solid organ transplantations (50 kidney, 37 heart, nine liver, seven lung) and 67 were registered on a waiting list without receiving a transplant (21 kidney, 25 heart, 15 liver, six lung). At 35 years after cancer diagnosis, the cumulative incidence of transplantation or being on a waiting list was 0·54% (95% CI 0·40-0·67) for kidney transplantation, 0·49% (0·36-0·62) for heart, 0·19% (0·10-0·27) for liver, and 0·10% (0·04-0·16) for lung. Risk factors for kidney transplantation were unilateral nephrectomy (HR 4·2, 95% CI 2·3-7·7), ifosfamide (24·9, 7·4-83·5), total body irradiation (6·9, 2·3-21·1), and mean kidney radiation of greater than 15 Gy (>15-20 Gy, 3·6 [1·5-8·5]; >20 Gy 4·6 [1·1-19·6]); for heart transplantation, anthracycline and mean heart radiation of greater than 20 Gy (dose-dependent, both p<0·0001); for liver transplantation, dactinomycin (3·8, 1·3-11·3) and methotrexate (3·3, 1·0-10·2); for lung transplantation, carmustine (12·3, 3·1-48·9) and mean lung radiation of greater than 10 Gy (15·6, 2·6-92·7). 5-year overall survival after solid organ transplantation was 93·5% (95% CI 81·0-97·9) for kidney transplantation, 80·6% (63·6-90·3) for heart, 27·8% (4·4-59·1) for liver, and 34·3% (4·8-68·6) for lung. INTERPRETATION: Solid organ transplantation is uncommon in ageing childhood cancer survivors. Organ-specific exposures were associated with increased solid organ transplantation incidence. Survival outcomes showed that solid organ transplantation should be considered for 5-year childhood cancer survivors with severe end-organ failure. FUNDING: US National Institute of Health, American Lebanese Syrian Associated Charities, US Health Resources and Services Administration.
Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Neoplasias/terapia , Transplante de Órgãos/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Doença Hepática Terminal/cirurgia , Feminino , Insuficiência Cardíaca/cirurgia , Transplante de Coração/estatística & dados numéricos , Humanos , Incidência , Lactente , Recém-Nascido , Falência Renal Crônica/cirurgia , Transplante de Rim/estatística & dados numéricos , Transplante de Fígado/estatística & dados numéricos , Lesão Pulmonar/cirurgia , Transplante de Pulmão/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Listas de Espera , Adulto JovemRESUMO
BACKGROUND: The ELIANA trial showed that 61 (81%) of 75 paediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia achieved overall remission after treatment with tisagenlecleucel, a chimeric antigen receptor targeted against the CD19 antigen. We aimed to evaluate patient-reported quality of life in these patients before and after tisagenlecleucel infusion. METHODS: ELIANA, a global, single-arm, open-label, phase 2 trial, was done in 25 hospitals across Australia, Austria, Belgium, Canada, France, Germany, Italy, Japan, Norway, Spain, and the USA. Patients with B-cell acute lymphoblastic leukaemia aged at least 3 years at the time of screening and 21 years or younger at the time of initial diagnosis who were in second or greater bone marrow relapse, chemorefractory, relapsed after allogeneic stem-cell transplantation, or were otherwise ineligible for allogeneic stem-cell transplantation were enrolled. Patients received a single intravenous administration of a target dose of 0·2-5â×â106 transduced viable T cells per kg for patients weighing 50 kg or less or 0·1-2·5â×â108 transduced viable T cells for patients weighing more than 50 kg. The primary outcome, reported previously, was the proportion of patients who achieved remission. A prespecified secondary endpoint, reported here, was patient-reported quality of life measured with the Pediatric Quality of Life Inventory (PedsQL) and European Quality of Life-5 Dimensions questionnaire (EQ-5D). Patients completed the questionnaires at baseline, day 28, and months 3, 6, 9, and 12 after treatment. The data collected were summarised using descriptive statistics and post-hoc mixed models for repeated measures. Change from baseline response profiles were illustrated with cumulative distribution function plots. The proportion of patients achieving the minimal clinically important difference and normative mean value were reported. Analysis was per protocol. This study is registered with ClinicalTrials.gov, NCT02435849. FINDINGS: Between April 8, 2015, and April 25, 2017, 107 patients were screened, 92 were enrolled, and 75 received tisagenlecleucel. 58 patients aged 8-23 years were included in the analysis of quality of life. At baseline, 50 (86%) patients had completed the PedsQL questionnaire and 48 (83%) had completed the EQ-5D VAS. Improvements in patient-reported quality-of-life scores were observed for all measures at month 3 after tisagenlecleucel infusion (mean change from baseline to month 3 was 13·3 [95% CI 8·9-17·6] for the PedsQL total score and 16·8 [9·4-24·3] for the EQ-5D visual analogue scale). 30 (81%) of 37 patients achieved the minimal clinically important difference at month 3 for the PedsQL total score and 24 (67%) of 36 patients achieved this for the EQ-5D visual analogue scale. INTERPRETATION: These findings, along with the activity and safety results of ELIANA, suggest a favourable benefit-risk profile of tisagenlecleucel in the treatment of paediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia. FUNDING: Novartis.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Recidiva Local de Neoplasia/terapia , Medidas de Resultados Relatados pelo Paciente , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Qualidade de Vida , Receptores de Antígenos de Linfócitos T/administração & dosagem , Terapia de Salvação , Adolescente , Adulto , Terapia Baseada em Transplante de Células e Tecidos/métodos , Criança , Feminino , Seguimentos , Humanos , Imunoterapia/métodos , Infusões Intravenosas , Masculino , Recidiva Local de Neoplasia/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
We analyzed late fatal infections (LFIs) in allogeneic stem cell transplantation (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research. We analyzed the incidence, infection types, and risk factors contributing to LFI in 10,336 adult and 5088 pediatric subjects surviving for ≥2 years after first HCT without relapse. Among 2245 adult and 377 pediatric patients who died, infections were a primary or contributory cause of death in 687 (31%) and 110 (29%), respectively. At 12 years post-HCT, the cumulative incidence of LFIs was 6.4% (95% confidence interval [CI], 5.8% to 7.0%) in adults, compared with 1.8% (95% CI, 1.4% to 2.3%) in pediatric subjects; P < .001). In adults, the 2 most significant risks for developing LFI were increasing age (20 to 39, 40 to 54, and ≥55 years versus 18 to 19 years) with hazard ratios (HRs) of 3.12 (95% CI, 1.33 to 7.32), 3.86 (95% CI, 1.66 to 8.95), and 5.49 (95% CI, 2.32 to 12.99) and a history of chronic graft-versus-host disease GVHD (cGVHD) with ongoing immunosuppression at 2 years post-HCT compared with no history of GVHD with (HR, 3.87; 95% CI, 2.59 to 5.78). In pediatric subjects, the 3 most significant risks for developing LFI were a history of cGVHD with ongoing immunosuppression (HR, 9.49; 95% CI, 4.39 to 20.51) or without ongoing immunosuppression (HR, 2.7; 95% CI, 1.05 to 7.43) at 2 years post-HCT compared with no history of GVHD, diagnosis of inherited abnormalities of erythrocyte function compared with diagnosis of acute myelogenous leukemia (HR, 2.30; 95% CI, 1.19 to 4.42), and age >10 years (HR, 1.92; 95% CI, 1.15 to 3.2). This study emphasizes the importance of continued vigilance for late infections after HCT and institution of support strategies aimed at decreasing the risk of cGVHD.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Terapia de Imunossupressão/efeitos adversos , Infecções/mortalidade , Leucemia Mieloide Aguda , Adolescente , Adulto , Fatores Etários , Idoso , Aloenxertos , Criança , Pré-Escolar , Doença Crônica , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
BACKGROUND: Fertility counseling before cancer treatment has been advocated by clinical guidelines, though little is known about its long-term impact on the unique reproductive concerns of female adolescent and young adult (AYA) cancer survivors. The goal of this study was to measure the association between fertility counseling by fertility specialists before cancer treatment and subsequent reproductive concerns. METHOD: A cross-sectional analysis was performed among 747 AYA survivors aged 18-40 years who had been recruited from cancer registries and physician and advocacy group referrals between 2015 and 2017. Participants self-reported information on past fertility counseling at cancer diagnosis, cancer type and treatment, and current reproductive concerns, as measured using the multidimensional Reproductive Concerns After Cancer scale. Multivariable log-binomial regression models tested associations between fertility counseling and reproductive concerns. RESULTS: The mean age of the cohort was 33.0 years (standard deviation, 5.1 years), and the mean period since diagnosis was 7.7 years (standard deviation, 5.0 years). Seventy-three percent of participants were white, and 24% were Hispanic. Fertility counseling was reported by 19% of survivors; moderate to high overall reproductive concerns were reported by 44% of participants. In adjusted analysis, fertility counseling was significantly associated with moderate to high reproductive concerns (risk ratio, 1.22; 95% confidence interval, 1.02-1.45) and not modified by exposure to fertility-threatening treatments (Pinteraction = .23). CONCLUSION: A large proportion of AYA cancer survivors across cancer types and treatment exposures reported moderate to high reproductive concerns, suggesting that there is a need to address these cancer-specific reproductive health concerns after treatment. Higher concerns, even with counseling, suggests the need to improve the quality of fertility counseling throughout the cancer continuum.
Assuntos
Sobreviventes de Câncer/psicologia , Aconselhamento/métodos , Fertilidade , Neoplasias/terapia , Adolescente , Adulto , Estudos de Coortes , Estudos Transversais , Feminino , Preservação da Fertilidade/métodos , Humanos , Neoplasias/psicologia , Guias de Prática Clínica como Assunto , Adulto JovemRESUMO
Allogeneic hematopoietic cell transplantation (HCT) can halt organ damage and eliminate symptoms in hemoglobin disorders, including sickle cell disease (SCD) and thalassemia major. Managing the residual manifestations of pre-HCT disease complications and the long-term effects of HCT requires systematic monitoring, follow-up and intervention when indicated. Late complications vary with age and disease status at HCT and with transplant variables such as preparative regimen, donor source and compatibility, and immune reconstitution. An international consensus conference sponsored by the Pediatric Blood and Marrow Transplant Consortium in May 2016 entitled "Late Effects Screening and Recommendations Following HCT for Immune Deficiency and Nonmalignant Hematologic Disorders" focused on follow-up after HCT for hemoglobinopathy. An earlier publication from experts who participated in this session described the pathophysiology and spectrum of complications that HCT recipients experience after HCT for SCD and thalassemia major. This companion publication summarizes the consensus reached by this group of experts about long-term follow-up guidelines after HCT for hemoglobinopathy. In addition, these guidelines might also be included in studies of novel curative therapies such as autologous HCT after hematopoietic progenitor stem cell gene modification.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Hemoglobinopatias/terapia , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Guias como Assunto , Hemoglobinopatias/patologia , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Patients transfused with packed red blood cells (PRBC), including childhood cancer survivors (CCS), experience complications. We describe iron overload (ferritin>500 ng/mL) prevalence and identify risk factors in CCS. OBSERVATIONS: Of 116 participants, 3 (2.6%) had elevated ferritin. All were teenagers at cancer diagnosis and received >8000 mL PRBC. Total PRBC volume correlated best with elevated ferritin (r=0.74; P<0.0001). PRBC (8000 mL) had the best positive and negative predictive value (75% and 100%, respectively) for iron overload. CONCLUSIONS: CCS may have iron overload. Overall prevalence is low. At-risk include teenagers at diagnosis and those receiving higher total PRBC volumes.
Assuntos
Transfusão de Eritrócitos/efeitos adversos , Ferritinas/sangue , Sobrecarga de Ferro/sangue , Neoplasias/sangue , Neoplasias/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Sobrecarga de Ferro/epidemiologia , Sobrecarga de Ferro/etiologia , Masculino , Neoplasias/epidemiologia , Prevalência , Fatores de RiscoRESUMO
Current screening guidelines are available for anthracycline-induced cardiotoxicity. However, the utility of echocardiogram screening for late-onset anthracycline cardiotoxicity especially in the decade immediately after end of therapy is debatable. A retrospective chart review of patients seen in the Thriving after Cancer Clinic at Rady Children's Hospital January 2006 to December 2013 was performed. Treatment data, echocardiogram results, cardiology referral notes and cardiac medication data were abstracted from anthracycline-exposed survivors. Descriptive and univariate comparative statistics were performed. Of 368 patients (45% female, median 5.3 y old at diagnosis [range 0 to 18.3], median 5.0 y from end of therapy [EOT] [range 0 to 18.2]), a total of 4 patients (10-year cumulative incidence after EOT 1.3%; 95% confidence interval, 0.1%-19.7%) required cardiac medication for late-onset cardiotoxicity (>1 y after EOT). Those requiring medication for late-onset cardiotoxicity were exposed to more anthracyclines than survivors without cardiotoxicity (median, 360 mg/m [range, 300 to 375 mg/m] vs. 182 mg/m [range, 26 to 515 mg/m], P=0.009). None had neck or chest radiation. In this population, medication initiation for late-onset anthracycline cardiotoxicity was limited predominantly to the first 3 years after EOT, with the next >13 years after EOT. These findings add to the growing body of literature assessing current guidelines to inform improvements in screening practices of survivorship providers.
Assuntos
Antraciclinas/efeitos adversos , Sobreviventes de Câncer , Cardiotoxicidade/diagnóstico por imagem , Ecocardiografia , Neoplasias/tratamento farmacológico , Adolescente , Adulto , Antraciclinas/administração & dosagem , Cardiotoxicidade/patologia , Cardiotoxicidade/fisiopatologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias/patologia , Neoplasias/fisiopatologiaRESUMO
An international consensus conference sponsored by the Pediatric Blood and Marrow Transplant consortium entitled "Late Effects Screening and Recommendations Following Allogeneic Hematopoietic Cell Transplant for Immune Deficiency and Nonmalignant Hematologic Disease" was held in Minneapolis, Minnesota on May 10, 2016 and May 11, 2016. The purpose of the conference was to address the unmet need for greater understanding of and the screening for long-term complications in the growing population of survivors of transplantation for nonmalignant disorders. The conference focused on transplantation for hemoglobinopathy, immune deficiency, and inherited bone marrow syndromes. A multidisciplinary group of experts in the disease areas and transplantation late effects presented the current state of understanding of how the underlying disease, pretransplantation therapies, and transplantation-related factors uniquely interact to influence the development of late toxicities. Recommendations were put forth by the group for the late effects screening of survivors of transplantation for these nonmalignant disorders. The findings and recommendations that came from this conference will be presented in a series of 6 additional manuscripts in the upcoming months. In this manuscript, we explore the need for screening practices specific to the survivors of transplantation for nonmalignant diseases and the methodologic challenges associated with the study of these patients.
Assuntos
Doenças da Medula Óssea/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemoglobinopatias/terapia , Síndromes de Imunodeficiência/terapia , Efeitos Adversos de Longa Duração/diagnóstico , Efeitos Adversos de Longa Duração/etiologia , Doenças da Medula Óssea/genética , Criança , Diretrizes para o Planejamento em Saúde , Humanos , Programas de Rastreamento/métodos , SobreviventesRESUMO
Severe combined immunodeficiency (SCID) is 1 of the most common indications for pediatric hematopoietic cell transplantation (HCT) in patients with primary immunodeficiency. Historically, SCID was diagnosed in infants who presented with opportunistic infections within the first year of life. With newborn screening (NBS) for SCID in most of the United States, the majority of infants with SCID are now diagnosed and treated in the first 3.5 months of life; however, in the rest of the world, the lack of NBS means that most infants with SCID still present with infections. The average survival for SCID patients who have undergone transplantation currently is >70% at 3 years after transplantation, although this can vary significantly based on multiple factors, including age and infection status at the time of transplantation, type of donor source utilized, manipulation of graft before transplantation, graft-versus-host disease prophylaxis, type of conditioning (if any) utilized, and underlying genotype of SCID. In at least 1 study of SCID patients who received no conditioning, long-term survival was 77% at 8.7 years (range out to 26 years) after transplantation. Although a majority of patients with SCID will engraft T cells without any conditioning therapy, depending on genotype, donor source, HLA match, and presence of circulating maternal cells, a sizable percentage of these will fail to achieve full immune reconstitution. Without conditioning, T cell reconstitution typically occurs, although not always fully, whereas B cell engraftment does not, leaving some molecular types of SCID patients with intrinsically defective B cells, in most cases, dependent on regular infusions of immunoglobulin. Because of this, many centers have used conditioning with alkylating agents including busulfan or melphalan known to open marrow niches in attempts to achieve B cell reconstitution. Thus, it is imperative that we understand the potential late effects of these agents in this patient population. There are also nonimmunologic risks associated with HCT for SCID that appear to be dependent upon the genotype of the patient. In this report, we have evaluated the published data on late effects and attempted to summarize the known risks associated with conditioning and alternative donor sources. These data, while informative, are also a clear demonstration that there is still much to be learned from the SCID population in terms of their post-HCT outcomes. This paper will summarize current findings and recommend further research in areas considered high priority. Specific guidelines regarding a recommended approach to long-term follow-up, including laboratory and clinical monitoring, will be forthcoming in a subsequent paper.
Assuntos
Sobrevivência de Enxerto/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Pesquisa/tendências , Imunodeficiência Combinada Severa/terapia , Adolescente , Adulto , Linfócitos B , Criança , Pré-Escolar , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Lactente , Linfócitos T/patologia , Fatores de Tempo , Condicionamento Pré-Transplante/métodos , Adulto JovemRESUMO
Sustained donor engraftment after allogeneic hematopoietic cell transplantation (HCT) converts to healthy donor hemoglobin synthesis and halts disease symptoms in patients with sickle cell disease and thalassemia major. A disease-free survival probability that exceeds 90% has been reported when HCT using an HLA-matched sibling donor is performed in young patients with low-risk disease or treatment-related risk factors. Alternate donor HCT and HCT in adults is performed infrequently because of a higher risk profile. Transplant-specific risks include conditioning regimen-related toxicity, graft-versus-host disease, graft rejection with marrow aplasia or disease recurrence, and infections associated with immunosuppression and delayed immune reconstitution. The magnitude of risk depends on patient age, clinical status of the underlying disease (eg, organ injury from vasculopathy and iron overload), donor source, and intensity of the conditioning regimen. These risks are commonly monitored and reported in the short term. Documenting very late outcomes is important, but these data are rarely reported because of challenges imposed by patient drop-out and insufficient resources. This report summarizes long-term follow-up results after HCT for hemoglobin disorders, identifies gaps in knowledge, and discusses opportunities for future investigations. This consensus summary will be followed by a second article detailing comprehensive long-term follow-up recommendations to aid in maintaining health in these individuals and identifying late complication risks that could facilitate interventions to improve outcomes.
Assuntos
Anemia Falciforme/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Talassemia/terapia , Criança , Seguimentos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Fatores de Risco , Fatores de Tempo , Doadores de Tecidos/provisão & distribuição , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante HomólogoRESUMO
Fanconi anemia (FA), dyskeratosis congenita (DC), and Diamond Blackfan anemia (DBA) are 3 of the most common inherited bone marrow failure syndromes (IBMFS), in which the hematologic manifestations can be cured with hematopoietic cell transplantation (HCT). Later in life, these patients face a variety of medical conditions, which may be a manifestation of underlying disease or due to pre-HCT therapy, the HCT, or a combination of all these elements. Very limited long-term follow-up data exist in these populations, with FA the only IBMFS that has specific published data. During the international consensus conference sponsored by the Pediatric Blood and Marrow Transplant Consortium entitled "Late Effects Screening and Recommendations following Allogeneic Hematopoietic Cell Transplant (HCT) for Immune Deficiency and Nonmalignant Hematologic Disease" held in Minneapolis, Minnesota in May of 2016, a half-day session was focused specifically on the unmet needs for these patients with IBMFS. A multidisciplinary group of experts discussed what is currently known, outlined an agenda for future research, and laid out long-term follow-up guidelines based on a combination of evidence in the literature as well as expert opinion. This article addresses the state of science in that area as well as consensus regarding the agenda for future research, with specific screening guidelines to follow in the next article from this group.
Assuntos
Anemia Aplástica/terapia , Doenças da Medula Óssea/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Hemoglobinúria Paroxística/terapia , Efeitos Adversos de Longa Duração , Anemia Aplástica/complicações , Anemia de Diamond-Blackfan/complicações , Anemia de Diamond-Blackfan/terapia , Pesquisa Biomédica/métodos , Pesquisa Biomédica/tendências , Doenças da Medula Óssea/complicações , Transtornos da Insuficiência da Medula Óssea , Criança , Disceratose Congênita/complicações , Disceratose Congênita/terapia , Anemia de Fanconi/complicações , Anemia de Fanconi/terapia , Previsões , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemoglobinúria Paroxística/complicações , Humanos , Guias de Prática Clínica como Assunto/normasRESUMO
Severe combined immunodeficiency (SCID) is effectively treated with hematopoietic cell transplantation (HCT), with overall survival approaching 90% in contemporary reports. However, survivors are at risk for developing late complications because of the variable durability of high-quality immune function, underlying genotype of SCID, comorbidities due to infections in the pretransplantation and post-transplantation periods, and use of conditioning before transplantation. An international group of transplantation experts was convened in 2016 to review the current knowledge of late effects seen in SCID patients after HCT and to develop recommendations for screening and monitoring for late effects. This report provides recommendations for screening and management of pediatric and adult SCID patients treated with HCT.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Imunodeficiência Combinada Severa/terapia , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Consenso , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Guias de Prática Clínica como Assunto , Imunodeficiência Combinada Severa/imunologiaRESUMO
Patients with inherited bone marrow failure syndromes (IBMFS), such as Fanconi anemia (FA), dyskeratosis congenita (DC), or Diamond Blackfan anemia (DBA), can have hematologic manifestations cured through hematopoietic cell transplantation (HCT). Subsequent late effects seen in these patients arise from a combination of the underlying disease, the pre-HCT therapy, and the HCT process. During the international consensus conference sponsored by the Pediatric Blood and Marrow Transplant Consortium on late effects screening and recommendations following allogeneic hematopoietic cell transplantation for immune deficiency and nonmalignant hematologic diseases held in Minneapolis, Minnesota in May 2016, a half-day session was focused specifically on the unmet needs for these patients with IBMFS. This multidisciplinary group of experts in rare diseases and transplantation late effects has already published on the state of the science in this area, along with discussion of an agenda for future research. This companion article outlines consensus disease-specific long-term follow-up screening guidelines for patients with IMBFS.
Assuntos
Anemia Aplástica/diagnóstico , Anemia de Diamond-Blackfan/diagnóstico , Doenças da Medula Óssea/diagnóstico , Disceratose Congênita/diagnóstico , Anemia de Fanconi/diagnóstico , Transplante de Células-Tronco Hematopoéticas , Hemoglobinúria Paroxística/diagnóstico , Anemia Aplástica/imunologia , Anemia Aplástica/patologia , Anemia Aplástica/terapia , Anemia de Diamond-Blackfan/imunologia , Anemia de Diamond-Blackfan/mortalidade , Anemia de Diamond-Blackfan/terapia , Doenças da Medula Óssea/imunologia , Doenças da Medula Óssea/patologia , Doenças da Medula Óssea/terapia , Transtornos da Insuficiência da Medula Óssea , Criança , Consenso , Conferências de Consenso como Assunto , Disceratose Congênita/imunologia , Disceratose Congênita/mortalidade , Disceratose Congênita/terapia , Anemia de Fanconi/imunologia , Anemia de Fanconi/mortalidade , Anemia de Fanconi/terapia , Hemoglobinúria Paroxística/imunologia , Hemoglobinúria Paroxística/patologia , Hemoglobinúria Paroxística/terapia , Humanos , Cooperação Internacional , Análise de Sobrevida , Transplante HomólogoRESUMO
Very young children undergoing hematopoietic cell transplantation (HCT) are a unique and vulnerable population. We analyzed outcomes of 717 patients from 117 centers who survived relapse free for ≥1 year after allogeneic myeloablative HCT for hematologic malignancy at <3 years of age, between 1987 and 2012. The median follow-up was 8.3 years (range, 1.0 to 26.4 years); median age at follow-up was 9 years (range, 2 to 29 years). Ten-year overall and relapse-free survival were 87% (95% confidence interval [CI], 85% to 90%) and 84% (95% CI, 81% to 87%). Ten-year cumulative incidence of relapse was 11% (95% CI, 9% to 13%). Of 84 deaths, relapse was the leading cause (43%). Chronic graft-versus-host-disease 1 year after HCT was associated with increased risk of mortality (hazard ratio [HR], 2.1; 95% CI, 1.3 to 3.3; P = .0018). Thirty percent of patients experienced ≥1 organ toxicity/late effect >1 year after HCT. The most frequent late effects included growth hormone deficiency/growth disturbance (10-year cumulative incidence, 23%; 95% CI, 19% to 28%), cataracts (18%; 95% CI, 15% to 22%), hypothyroidism (13%; 95% CI, 10% to 16%), gonadal dysfunction/infertility requiring hormone replacement (3%; 95% CI, 2% to 5%), and stroke/seizure (3%; 95% CI, 2% to 5%). Subsequent malignancy was reported in 3.6%. In multivariable analysis, total body irradiation (TBI) was predictive of increased risk of cataracts (HR, 17.2; 95% CI, 7.4 to 39.8; P < .001), growth deficiency (HR, 3.5; 95% CI, 2.2 to 5.5; P < .001), and hypothyroidism (HR, 5.3; 95% CI, 3.0 to 9.4; P < .001). In summary, those who survived relapse free ≥1 year after HCT for hematologic malignancy at <3 years of age had favorable overall survival. Chronic graft-versus-host-disease and TBI were associated with adverse outcomes. Future efforts should focus on reducing the risk of relapse and late effects after HCT at early age.
Assuntos
Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/terapia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Fatores Etários , Aloenxertos , Pré-Escolar , Doença Crônica , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lactente , Masculino , Taxa de SobrevidaRESUMO
BACKGROUND: Pulmonary complications after cancer therapy are varied. This study describes pulmonary outcomes among childhood cancer survivors and evaluates their impact on daily activities. METHODS: The incidence of pulmonary outcomes (asthma, chronic cough, emphysema, lung fibrosis, oxygen need, and recurrent pneumonia) reported among 5-year cancer survivors (n = 14,316) and the incidence of death due to pulmonary causes among all eligible survivors (n = 20,690) in the Childhood Cancer Survivor Study were compared with those for sibling controls (n = 4027) with cumulative incidence, standardized mortality ratio (SMR), and piecewise exponential models. Logistic regression with random effects was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for activity limitations with pulmonary complications. RESULTS: By the age of 45 years, the cumulative incidence of any pulmonary condition was 29.6% (95% CI, 29.1%-30.0%) for cancer survivors and 26.5% (95% CI, 24.9%-28.0%) for siblings. Fewer survivors reported ever smoking (23.6% vs 36.4%, P < .001), but survivors were more likely to report chronic cough (rate ratio [RR], 1.6; 95% CI, 1.4-1.9), oxygen need (RR, 1.8; 95% CI, 1.5-2.2), lung fibrosis (RR, 3.5; 95% CI, 2.3-5.4), and recurrent pneumonia (RR, 2.0; 95% CI, 1.4-3.0). The SMR for death due to pulmonary causes was 5.9 (95% CI, 4.2-8.1), and it was associated with platinum exposure and lung radiation (P < .01). The impact of chronic cough on daily activities for survivors (OR vs survivors without chronic cough, 2.7) was greater than that for siblings (OR, 2.0; P = .04). CONCLUSIONS: Pulmonary complications are substantial among adult survivors of childhood cancer and can affect daily activities. Cancer 2016;122:3687-96. © 2016 American Cancer Society.
Assuntos
Pneumopatias/etiologia , Neoplasias/terapia , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Razão de Chances , Avaliação de Resultados em Cuidados de Saúde/métodos , Estudos Retrospectivos , Fatores de Risco , Irmãos , Sobreviventes , Adulto JovemRESUMO
PURPOSE OF REVIEW: Significant improvements in unrelated donor hematopoietic stem cell transplantation (HSCT) in recent years have solidified its therapeutic role in severe aplastic anemia (SAA) and led to the evolution of treatment algorithms, particularly for children. RECENT FINDINGS: Advances in understanding the genetics of inherited bone marrow failure syndromes (IBMFS) have allowed more confidence in accurately diagnosing SAA and avoiding treatments that could be dangerous and ineffective in individuals with IBMFS, which can be diagnosed in 10-20% of children presenting with a picture of SAA. Additionally long-term survival after matched sibling donor and matched unrelated donor HSCT now exceed 90% in children. Late effects after HSCT for SAA are minimal with current strategies, and compare favorably to late effects after upfront immunosuppressive therapy, except for patients with chronic graft versus host disease. SUMMARY: Careful assessment for signs or symptoms of IBMFS, along with genetic screening for these disorders, is of major importance. Matched sibling donor HSCT is already considered the standard of care for upfront therapy and some groups are evaluating matched unrelated donor HSCT as primary therapy. Ongoing studies will continue to challenge treatment algorithms and may lead to an even more expanded role for HSCT in SAA.
Assuntos
Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas/tendências , Algoritmos , Anemia Aplástica/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Histocompatibilidade , Humanos , Doadores de Tecidos , Condicionamento Pré-Transplante/métodosRESUMO
BACKGROUND: Long-term survivors of pediatric cancer are at risk of life-threatening late effects of their cancer. Previous studies have shown excesses in long-term mortality within high-risk groups defined by demographic and treatment characteristics. METHODS: To investigate conditional survival in a pediatric cancer population, the authors performed an analysis of conditional survival in the original Childhood Cancer Survivor Study (CCSS) cohort and the Surveillance, Epidemiology, and End Results (SEER) database registry. The overall probability of death for patients at 5 years and 10 years after they survived 5, 10, 15, and 20 years since cancer diagnosis and cause-specific death in 10 years for 5-year survivors were estimated using the cumulative incidence method. RESULTS: Among patients in the CCSS and SEER cohorts who were alive 5 years after their cancer diagnosis, within each diagnosis group at least 92% were alive in the subsequent 5 years, except for patients with leukemia, of whom only 88% of 5-year survivors remained alive in the subsequent 5 years. The probability of all-cause mortality in the next 10 years among patients who survived at least 5 years after diagnosis was 8.8% in CCSS and 10.6% in SEER, approximately 75% of which was due to neoplasms as the cause of death. CONCLUSIONS: The risk of death among survivors of pediatric cancer in 10 years can vary between diagnosis groups by at most 12%, even up to 20 years after diagnosis. This information is clinically significant when counseling patients regarding their conditional survival, particularly when survivors are seen in long-term follow-up.
Assuntos
Modificador do Efeito Epidemiológico , Mortalidade/tendências , Neoplasias/mortalidade , Sobreviventes/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias/diagnóstico , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Programa de SEER , Taxa de Sobrevida , Fatores de Tempo , Adulto JovemRESUMO
Donor-derived myelodysplastic syndrome/acute leukaemia (DD-MDS/AL) is a rare life-threatening complication of allogeneic haematopoietic stem cell (HSC) transplantation. However, it is unknown whether the risk differs by HSC source. Therefore, we evaluated the incidence of DD-MDS/AL in 2390 engrafted patients. With a median follow-up of 7·1 years (1-20·8), the incidence of DD-MDS/AL was 0·53% (95% confidence interval (CI), 0·01-1·41%], 0·56% (95%CI, 0·01-1·36%) and 0·56% (95%CI, 0·01-1·10%) in recipients of bone marrow (n = 1117), peripheral blood (n = 489) and umbilical cord blood (UCB, n = 784), respectively. While follow-up is shorter in recipients of UCB and peripheral blood, incidence of DD-MDS/AL is, thus far, similar between HSC sources.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia/etiologia , Síndromes Mielodisplásicas/etiologia , Doadores de Tecidos , Doença Aguda , Adolescente , Adulto , Idoso , Criança , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Incidência , Leucemia/epidemiologia , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Síndromes Mielodisplásicas/epidemiologia , Síndromes Mielodisplásicas/terapia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Adult survivors of childhood central nervous system (CNS) tumors may be at risk for pulmonary dysfunction. This study enumerates the incidence of pulmonary dysfunction and explores associations between craniospinal irradiation (CSI) and pulmonary dysfunction among survivors of childhood CNS tumors. METHODS: Participants included Childhood Cancer Survivor Study (CCSS) cohort members treated for CNS malignancies when
Assuntos
Neoplasias do Sistema Nervoso Central/complicações , Pneumopatias/etiologia , Avaliação de Resultados em Cuidados de Saúde , Sobreviventes/estatística & dados numéricos , Adolescente , Adulto , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/terapia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Pneumopatias/epidemiologia , Pneumopatias/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Testes de Função Respiratória , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários , Taxa de Sobrevida , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Childhood, adolescent, and young adult (CAYA) cancer survivors are at risk of pulmonary dysfunction. Current follow-up care guidelines are discordant. Therefore, the International Late Effects of Childhood Cancer Guideline Harmonization Group established and convened a panel of 33 experts to develop evidence-based surveillance guidelines. We critically reviewed available evidence regarding risk factors for pulmonary dysfunction, types of pulmonary function testing, and timings of surveillance, then we formulated our recommendations. We recommend that CAYA cancer survivors and healthcare providers are aware of reduced pulmonary function risks and pay vigilant attention to potential symptoms of pulmonary dysfunction, especially among survivors treated with allogeneic haematopoietic stem cell transplantation, thoracic radiotherapy, and thoracic surgery. Based on existing limited evidence and current lack of interventions, our panel recommends pulmonary function testing only for symptomatic survivors. Since scarce existing evidence informs our recommendation, we highlight the need for prospective collaborative studies to address pulmonary function knowledge gaps among CAYA cancer survivors.