RESUMEN
Current studies describing younger children with Hodgkin lymphoma are limited by geographical region, small sample sizes and variable age groups. Although published data is lacking, there appears to be a trend toward a higher male to female ratio and a higher proportion of mixed cellularity subtype when compared to older cohorts. We performed a retrospective multicenter study utilizing the Pediatric Health Information System® database to evaluate patients aged 0-39 years with Hodgkin lymphoma. We identified 3,034 unique patients who met inclusion criteria. Younger age groups had a larger proportion of males, Hispanic/Latino ethnicity, and mixed cellularity subtype. Treatment-related complications, including mucositis, pain, bacterial infections, and thrombosis, were documented more frequently in older cohorts. We also found significant age-related differences in medical management. This study is the largest study evaluating age-related differences in patients with Hodgkin lymphomaand the first study to evaluate for differences in complicationsand supportive care management.
Asunto(s)
Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/epidemiología , Adolescente , Masculino , Femenino , Niño , Preescolar , Estudios Retrospectivos , Lactante , Adulto , Factores de Edad , Adulto Joven , Recién NacidoRESUMEN
OBJECTIVES: The objective of this study was to translate a deep learning (DL) approach for semiautomated analysis of body composition (BC) measures from standard of care CT images to investigate the prognostic value of BC in pediatric, adolescent, and young adult (AYA) patients with lymphoma. METHODS: This 10-year retrospective, single-site study of 110 pediatric and AYA patients with lymphoma involved manual segmentation of fat and muscle tissue from 260 CT imaging datasets obtained as part of routine imaging at initial staging and first therapeutic follow-up. A DL model was trained to perform semiautomated image segmentation of adipose and muscle tissue. The association between BC measures and the occurrence of 3-year late effects was evaluated using Cox proportional hazards regression analyses. RESULTS: DL-guided measures of BC were in close agreement with those obtained by a human rater, as demonstrated by high Dice scores (≥ 0.95) and correlations (r > 0.99) for each tissue of interest. Cox proportional hazards regression analyses revealed that patients with elevated subcutaneous adipose tissue at baseline and first follow-up, along with patients who possessed lower volumes of skeletal muscle at first follow-up, have increased risk of late effects compared to their peers. CONCLUSIONS: DL provides rapid and accurate quantification of image-derived measures of BC that are associated with risk for treatment-related late effects in pediatric and AYA patients with lymphoma. Image-based monitoring of BC measures may enhance future opportunities for personalized medicine for children with lymphoma by identifying patients at the highest risk for late effects of treatment. KEY POINTS: ⢠Deep learning-guided CT image analysis of body composition measures achieved high agreement level with manual image analysis. ⢠Pediatric patients with more fat and less muscle during the course of cancer treatment were more likely to experience a serious adverse event compared to their clinical counterparts. ⢠Deep learning of body composition may add value to routine CT imaging by offering real-time monitoring of pediatric, adolescent, and young adults at high risk for late effects of cancer treatment.
Asunto(s)
Composición Corporal , Aprendizaje Profundo , Linfoma , Adolescente , Niño , Humanos , Progresión de la Enfermedad , Linfoma/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Masculino , Femenino , Modelos de Riesgos Proporcionales , Valor Predictivo de las PruebasRESUMEN
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Aggressive Mature B-Cell Lymphomas include recommendations for the diagnosis and management of pediatric patients with primary mediastinal large B-cell lymphoma (PMBL) and sporadic variants of Burkitt lymphoma and diffuse large B-cell lymphoma. PMBL is now considered as a distinct entity arising from mature thymic B-cells accounting for 2% of mature B-cell lymphomas in children and adolescents. This discussion section includes the recommendations outlined in the NCCN Guidelines for the diagnosis and management of pediatric patients with PMBL.
Asunto(s)
Linfoma de Células B Grandes Difuso , Adolescente , Humanos , Niño , Linfoma de Células B Grandes Difuso/patología , Oncología MédicaRESUMEN
OBJECTIVES: The objective of this study was to use computed tomography (CT) imaging to quantify chemotherapy-induced changes in body composition (BC) in pediatric, adolescent, and young adult (AYA) patients with lymphoma and to compare image-derived changes in BC measures to changes in traditional body mass index (BMI) measures. METHODS: Skeletal muscle (SkM), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) volumes were manually segmented using low-dose CT images acquired from a 10-year retrospective, single-site cohort of 110 patients with lymphoma. CT images and BMI percentiles (BMI%) were acquired from baseline and first therapeutic follow-up. CT image segmentation was performed at vertebral level L3 using 5 consecutive axial CT images. RESULTS: CT imaging detected significant treatment-induced changes in BC measures from baseline to first follow-up time points, with SAT and VAT significantly increasing and SkM significantly decreasing. BMI% measures did not change from baseline to first follow-up and were not significantly correlated with changes in image-derived BC measures. Patients who were male, younger than 12 years old, diagnosed with non-Hodgkin's lymphoma, and presented with stage 3 or 4 disease gained more adipose tissue and lost more SkM in response to the first cycle of treatment compared to their clinical counterparts. CONCLUSIONS: Standard of care CT imaging can quantify treatment-induced changes in BC that are not reflected by traditional BMI assessment. Image-based monitoring of BC parameters may offer personalized approaches to lymphoma treatment for pediatric and AYA patients by guiding cancer treatment recommendations and subsequently enhance clinical outcomes. KEY POINTS: ⢠Standard of care low-dose CT imaging quantifies chemotherapy-induced changes in body composition in pediatric, adolescent, and young adults with lymphoma. ⢠Body mass index could not detect changes in body composition during treatment that were quantified by CT imaging. ⢠Pediatric and AYA patients who were male, younger than 12 years old, and diagnosed with non-Hodgkin's lymphoma, and presented with stage 3 or 4 disease gained more adipose tissue and lost more skeletal muscle tissue in response to the first cycle of treatment compared to their clinical counterparts.
Asunto(s)
Antineoplásicos , Linfoma no Hodgkin , Linfoma , Adolescente , Composición Corporal , Niño , Femenino , Humanos , Linfoma/diagnóstico por imagen , Linfoma/tratamiento farmacológico , Linfoma no Hodgkin/diagnóstico por imagen , Linfoma no Hodgkin/tratamiento farmacológico , Masculino , Estudios Retrospectivos , Nivel de Atención , Tomografía Computarizada por Rayos X/métodos , Adulto JovenRESUMEN
Fertility navigators (FNs) are important in communicating infertility risk and fertility preservation (FP) options to patients receiving gonadotoxic therapies. This retrospective study examined electronic medical records of patients with fertility consults at a large pediatric institution (2017-2019), before and after hiring a full-time FN. Of 738 patient encounters, 173 consults were performed pre-navigator and 565 post-navigator. Fertility consults for long-term follow-up cancer survivors increased most substantially: pre-navigator (n = 7) and post-navigator (n = 387). Across diagnoses, females had a larger increase in consults compared to males (χ2 [3, N = 738] = 8.17, p < .05). Findings highlight FNs' impact on counseling rates, particularly in survivorship.
Asunto(s)
Supervivientes de Cáncer , Preservación de la Fertilidad , Neoplasias , Niño , Femenino , Fertilidad , Preservación de la Fertilidad/psicología , Humanos , Masculino , Neoplasias/terapia , Estudios RetrospectivosRESUMEN
Peripheral T-cell lymphoma (PTCL) is an aggressive tumor, rarely seen in pediatrics or adolescent and young adults (AYAs) so there is no upfront or relapsed standard of care. The authors describe a 16-year-old with PTCL, treated with chemotherapy and autologous stem cell transplant. Upon relapse, he received ifosfamide, carboplatin, etoposide, and radiation with durable remission of 4 years. Data in pediatric/AYA PCTL continue to lack an understanding of the biology and microenvironment, the differences to adult patients, and a lack of adequate therapy. Targeted therapy may improve outcomes for children and AYAs with refractory or relapsed PTCL.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Células T Periférico/terapia , Trasplante de Células Madre , Adolescente , Autoinjertos , Carboplatino/administración & dosificación , Etopósido/administración & dosificación , Humanos , Ifosfamida/administración & dosificación , Masculino , RecurrenciaRESUMEN
In the context of an evolving understanding of early T-cell precursor (ETP) lymphoma and leukemia, we present a case of concurrent T-cell lymphoblastic lymphoma and ETP lymphoma in an adolescent female. To our knowledge, this represents the first reported case of both lymphoblastic lymphoma and ETP lymphoma as distinct and conjoined components of the same neoplasm. As an exception to current literature, our patient had a strictly lymphomatous ETP component with no leukemic manifestation. Her ETP component remained viable following induction, supporting ETP resistance to chemotherapy. The patient remains in remission 4 years postallogeneic matched sibling donor bone marrow transplant.
Asunto(s)
Linfoma no Hodgkin , Leucemia-Linfoma Linfoblástico de Células Precursoras , Células Precursoras de Linfocitos T , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Adolescente , Femenino , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológicoRESUMEN
OBJECTIVE: Approximately half of male childhood cancer survivors experience impaired fertility, yet fertility preservation (FP) remains underutilized. Although parent recommendation influences adolescents' decision-making, parents may be uncertain and/or underrate their sons' parenthood goals. This study assessed parent-adolescent and family-level concordance regarding adolescent fertility perspectives (i.e., values, goals) and associations with FP attempts. METHODS: A prospective pilot study examined the impact of a family-centered values clarification tool (FAST) on banking attempts among adolescent males newly diagnosed with cancer at risk for infertility. The FAST assessed adolescent and parent perceptions of adolescents' fertility values and goals (i.e., perceived threat of infertility, perceived benefits/barriers to banking). Parent-adolescent concordance and family-level concordance on fertility perspectives were examined, along with associations with banking attempts and salient demographic factors. RESULTS: Ninety-eight participants (32 adolescents aged 12-20, 37 mothers, 29 fathers) from 32 families completed the FAST before treatment initiation. Parent-adolescent dyads were concordant on approximately one-half of responses. Banking attempts were associated with higher family-level concordance regarding perceived benefits, r(32) = .40, p = .02. Older adolescent age was associated with higher family-level concordance regarding perceived threat, r(31) = .37, p = .04, and benefits, r(32) = .40, p = .03. Fathers' education was associated with higher family-level concordance regarding barriers, r(21) = .53, p = .01. CONCLUSIONS: When parents were concordant with their son's fertility values and goals, particularly perceived benefits, adolescents were more likely to attempt FP. Clinicians should facilitate sharing of fertility perspectives within families before cancer treatment, especially with younger adolescents. Psychosocial support for families facing FP decisions is recommended at diagnosis and across the care continuum.
Asunto(s)
Neoplasias , Padres , Adolescente , Niño , Femenino , Humanos , Masculino , Proyectos Piloto , Estudios Prospectivos , Espermatozoides , Encuestas y CuestionariosRESUMEN
Methotrexate-induced epidermal necrosis (MEN) is an uncommon but potentially fatal complication. We present two pediatric oncology patients, a 5-year-old girl and a 3-year-old boy, who developed MEN from high-dose methotrexate therapy for pre-B-cell acute lymphocytic leukemia. Following administration of systemic methotrexate, the patients developed erythematous lesions with subsequent skin erosions. Pre-medication with systemic corticosteroids and administration of folinic acid rescue following the methotrexate infusion allowed both patients to resume their chemotherapy regimen with methotrexate.
Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras , Enfermedades de la Piel , Niño , Preescolar , Femenino , Humanos , Leucovorina , Masculino , Metotrexato/efectos adversos , NecrosisRESUMEN
PURPOSE: Over half of males experience fertility impairment after childhood cancer therapy, which often causes psychosocial distress. Yet, fertility preservation (FP) remains underutilized. The goals of this study were to determine the feasibility and impact of implementing a family-centered FP values clarification tool on sperm banking attempts among adolescent males newly diagnosed with cancer, and identify key determinants of banking attempts. METHODS: A prospective pilot study was conducted among families of males (12-25 years old), prior to cancer therapy. Thirty-nine of 41 families agreed to participate (95%); 98 participants (32 adolescents, 37 mothers, 29 fathers) completed the Family-centered Adolescent Sperm banking values clarification Tool (FAST). Analyses assessed the impact of the FAST on banking attempts and examined associations between demographic/medical characteristics, FAST subscales (perceived threat, benefits, barriers), and banking attempts. RESULTS: Twenty-three (59%) adolescents attempted to bank, compared to 8 adolescents (33%) during baseline assessment (p=.04). Significant associations were identified between banking attempts and adolescents' report of perceived threat (rpb=.45, p=.01) and benefits (rpb=.57, p=.01). Only mothers' proxy reports of adolescent perceived threat (rpb=.42, p=.01) and benefits (rpb=.47, p=.003) were associated with banking attempts, while fathers' self-reported perceived benefits (rpb=.43, p=.03), self-reported barriers (rpb=.49, p=.01), and proxy reports of adolescent perceived threat (rpb=.38, p=.04) and benefits (rpb=.59, p=.02) were associated with banking attempts. CONCLUSION: Adolescent sperm banking attempt rates significantly increased after implementation of a family-centered FP values clarification tool prior to cancer treatment. Findings underscore the importance of targeting both adolescents and their parents, particularly fathers, in FP efforts.
Asunto(s)
Preservación de la Fertilidad , Fertilidad/genética , Preservación de Semen , Bancos de Esperma , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Madres , Neoplasias/epidemiología , Neoplasias/patología , Estudios Prospectivos , Espermatozoides/crecimiento & desarrollo , Adulto JovenRESUMEN
Ewing sarcoma (EWS) is the second most common and aggressive type of metastatic bone tumor in adolescents and young adults. There is unmet medical need to develop and test novel pharmacological targets and novel therapies to treat EWS. Here, we found that EWS expresses high levels of a p53 isoform, delta133p53. We further determined that aberrant expression of delta133p53 induced HGF secretion resulting in tumor growth and metastasis. Thereafter, we evaluated targeting EWS tumors with HGF receptor neutralizing antibody (AMG102) in preclinical studies. Surprisingly, we found that targeting EWS tumors with HGF receptor neutralizing antibody (AMG102) in combination with GD2-specific, CAR-reengineered T-cell therapy synergistically inhibited primary tumor growth and establishment of metastatic disease in preclinical models. Furthermore, our data suggested that AMG102 treatment alone might increase leukocyte infiltration including efficient CAR-T access into tumor mass and thereby improves its antitumor activity. Together, our findings warrant the development of novel CAR-T-cell therapies that incorporate HGF receptor neutralizing antibody to improve therapeutic potency, not only in EWS but also in tumors with aberrant activation of the HGF/c-MET pathway.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Receptores Quiméricos de Antígenos/inmunología , Sarcoma de Ewing/tratamiento farmacológico , Animales , Neoplasias Óseas/patología , Línea Celular Tumoral , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Inmunoterapia Adoptiva/métodos , Ratones , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-met/inmunología , Sarcoma de Ewing/patología , Transducción de Señal/inmunología , Linfocitos T/inmunología , Microambiente Tumoral/inmunología , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
Pediatric aggressive mature B-cell lymphomas are the most common types of non-Hodgkin lymphoma in children, and they include Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). These diseases are highly aggressive but curable, the treatment is complex, and patients may have many complicated supportive care issues. The NCCN Guidelines for Pediatric Aggressive Mature B-Cell Lymphomas provide guidance regarding pathology and diagnosis, staging, initial treatment, disease reassessment, surveillance, therapy for relapsed/refractory disease, and supportive care for clinicians who treat sporadic pediatric BL and DLBCL.
Asunto(s)
Linfoma de Burkitt , Linfoma de Células B Grandes Difuso , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/epidemiología , Linfoma de Burkitt/terapia , Niño , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/terapia , Oncología MédicaRESUMEN
BACKGROUND: Over half of male childhood cancer survivors experience infertility after treatment, which is known to cause distress and impact future quality of life. Sperm banking rates remain low, and little is known about how adolescent and young adult (AYA) males and their families make fertility preservation (FP) decisions. This study examined AYA and parent perceptions of participating in a research study focused on testing a new FP decision tool at the time of cancer diagnosis. METHODS: Forty-four participants (19 mothers, 11 fathers, 14 male AYAs 12-25 years old) from 20 families completed brief assessments at diagnosis and approximately one month later, including a qualitative interview exploring the impact of study participation. Verbatim transcripts were coded through thematic content analysis using the constant comparison method. RESULTS: Two major themes emerged: (1) a positive effect of participating in the study and (2) a neutral effect (no positive/negative effect of participation). Subthemes that emerged for participants who noted a positive effect included (a) participation prompted deeper thinking, (b) participation influenced family conversations, and (c) participation resulted in altruism/helping others. No participant reported a negative effect. CONCLUSIONS: This study demonstrates that participation in family-centered research focused on FP among AYA males, before treatment begins, is perceived as beneficial or neutral at the time of a new cancer diagnosis. These findings provide support for future family-centered FP interventions for this population.
Asunto(s)
Actitud Frente a la Salud , Toma de Decisiones , Familia , Preservación de la Fertilidad/psicología , Neoplasias/psicología , Preservación de Semen/psicología , Adolescente , Adulto , Niño , Padre/psicología , Femenino , Preservación de la Fertilidad/métodos , Humanos , Infertilidad Masculina/etiología , Infertilidad Masculina/prevención & control , Infertilidad Masculina/psicología , Masculino , Madres/psicología , Neoplasias/complicaciones , Proyectos Piloto , Investigación Cualitativa , Calidad de Vida , Factores Socioeconómicos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
PURPOSE: Research among adults shows benefits and low perceived burden of engaging in behavioral research. However, questions remain regarding the ethics of conducting behavioral research in pediatric populations during sensitive situations, including during a new life-threatening diagnosis or at end-of-life. We examined reactions to participating in a behavioral reproductive research study among male adolescents newly diagnosed with cancer and their parents, as a step towards optimizing fertility preservation utilization in a population where future infertility is common. METHODS: Pediatric literature regarding the ethics of behavioral research was reviewed. In our pilot, forty-four participants (19 mothers, 11 fathers, 14 male adolescents newly diagnosed with cancer) from 20 families completed demographic questionnaires and a fertility preservation decision tool developed by the study team. Qualitative interviews exploring the impact of study participation were subsequently conducted. Verbatim transcripts were coded for thematic content using the constant comparison method. RESULTS: Literature review showed positive reactions to research participation among youth/caregivers. In our pilot study, 89% (n = 17) of mothers, 64% (n = 7) of fathers, and 71% (n = 10) of adolescents reported at least one benefit of participating. Eleven percent (n = 2) of mothers, 36% (n = 4) of fathers, and 29% (n = 4) of adolescents said they were not affected; none of the participants reported a negative effect. CONCLUSION: Consistent with prior literature, our study suggests behavioral reproductive research prior to cancer treatment can offer direct benefits to participants and society, without increasing burden. These findings will inform future interventions to improve long-term psychosocial and reproductive outcomes for youth with cancer.
Asunto(s)
Investigación Conductal/ética , Preservación de la Fertilidad/ética , Preservación de la Fertilidad/psicología , Neoplasias , Adolescente , Adulto , Niño , Padre , Femenino , Humanos , Infertilidad Masculina , Masculino , Madres , Neoplasias/complicaciones , Neoplasias/terapia , Participación del Paciente/psicología , Proyectos Piloto , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Infertility has a negative impact on quality of life among cancer survivors. Studies show establishing a fertility team results in improved patient satisfaction. A review of electronic medical records was performed to examine predictors of fertility referrals, interventions, and the impact of an opt-out consult mechanism. Findings show many patients, particularly those that are younger, are still not receiving fertility counseling despite the presence of a fertility team. Notably, patients were 3.6 times more likely to receive a consult after the opt-out. Strategies are needed to improve access to fertility related care, particularly in groups where consults are underutilized.
Asunto(s)
Preservación de la Fertilidad , Neoplasias , Derivación y Consulta/estadística & datos numéricos , Adolescente , Adulto , Supervivientes de Cáncer , Niño , Preescolar , Consejo/estadística & datos numéricos , Femenino , Preservación de la Fertilidad/métodos , Preservación de la Fertilidad/estadística & datos numéricos , Humanos , Lactante , Masculino , Estudios Retrospectivos , Adulto JovenAsunto(s)
Enfermedad de Hodgkin , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Adolescente , Diagnóstico Diferencial , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/metabolismo , Enfermedad de Hodgkin/patología , Humanos , Masculino , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , EsclerosisRESUMEN
Soft tissue sarcoma constitutes 8% of all tumors in adolescent and young adults (AYA), with rhabdomyosarcoma (RMS) accounting for 5.2% to 6.5% of the soft tissue sarcoma total within this group. AYAs have a higher propensity for metastasis and inferior outcomes. Metastases to the breast have been reported in â¼3% to 6% of RMS cases. A review of our hospital's tumor registry identified cases of RMS diagnosed between January 1, 2004 and December 31, 2013. A total of 46 patients with RMS were identified, having a mean age of 12.5 years (range, 1 to 49 y). There were 26 males (57%) and 20 females (43%). Eighteen patients (39%) were AYAs, including 10 women. Four patients (8.7%) were identified with breast involvement, all of whom were AYA females. Treatment modalities included chemotherapy, surgical resection, and radiation. One patient is a long-term survivor. Although RMS is uncommon in AYAs, breast involvement occurs almost exclusively in AYA women and is associated with alveolar histology, metastatic disease, and poor outcomes. In total, 4/10 of all AYA females had breast involvement. Routine examination or imaging of the breasts in AYAs with RMS is not currently standard practice at diagnosis or follow-up, but this analysis suggests it should be considered in female AYA patients.
Asunto(s)
Neoplasias de la Mama/secundario , Rabdomiosarcoma/secundario , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , Neoplasias de la Mama Masculina/epidemiología , Neoplasias de la Mama Masculina/secundario , Terapia Combinada , Resultado Fatal , Femenino , Humanos , Masculino , Mastectomía , Estudios Retrospectivos , Rabdomiosarcoma/diagnóstico por imagen , Rabdomiosarcoma/epidemiología , Rabdomiosarcoma/terapia , Terapia Recuperativa , Adulto JovenRESUMEN
Normal hemoglobin is made of a tetramer of 2 α-globin and 2 ß-globin polypeptide chains. Deletions in the ß-globin gene cluster can range from a few hundred base pairs to loss of the entire cluster resulting in rare, but clinically significant, thalassemias. One such entity is εGγAγδß0-thalassemia, a condition that presents within the first few weeks of life as a Coombs-negative hemolytic anemia and is not identified on routine newborn screening or hemoglobin electrophoresis.