not-yet-known not-yet-known not-yet-known unknown TITLE: A Successful Haploidentical Hematopoietic Stem Cell Transplant in a Rare Case of Bloom Syndrome Associated with Monosomy 7/MDS – Uncharted Territory!

Background: Higher doses of anthracyclines and heart-relevant radiotherapy increase cardiovascular disease (CVD) risk. This study assessed CVD and CVD risk factors among adult childhood cancer survivors (CCSs) across cardiotoxic treatment risk groups and examined associations between lifestyle behaviors and treatment risks. Methods: We invited CCSs aged ≥18 years at study, diagnosed at ages 0-20, who survived ≥5 years for an assessment of anthropometry, CVD, CVD risk factors, lifestyle, and cancer history. We classified participants into three cardiotoxic treatment risk groups (no/low-risk, moderate-risk, high-risk) based on anthracyclines and heart-relevant radiotherapy. Multinomial logistic regression assessed lifestyle differences across groups. Results: With median age at study of 33 years (IQR: 26-39; 53% male), 356 CCSs participated in this study devided into the no/low-risk (25%), moderate-risk (40%), or high-risk (35%) cardiotoxic treatment groups. Overall CVD prevalence was 6% and similar across the three risk groups. Heart valve problems were rare though more common in the high-risk group (no/low-risk, 0%; moderate-risk, 1%; vs. high-risk, 4%; p=0.037). CVD risk factors were present in 44% of CCSs—including dyslipidemia, obesity, hypertension, and diabetes—without variation across risk groups. Overall adherence to health behavior recommendations was low, with no differences in diet adherence, physical activity (PA), sedentary behavior, smoking, or alcohol consumption across cardiotoxic risk groups. Conclusion: We found no differences in CVD, CVD risk factors, or lifestyle behaviors across cardiotoxic treatment risk groups. Health promotion that engages diet, PA, smoking cessation, and alcohol reduction should be prioritized for all CCSs regardless of cardiotoxic treatment risk levels.

Anything to HelpHarmony Farner, MA, CCRP11Research Division of Quality of Life and Palliative Care, Department of Oncology, St. Jude Children’s Research Hospital, USACorrespondence to:Harmony Farner, MA, CCRP /St. Jude Children’s Research Hospital / 262 Danny Thomas Pl, MS 1121, Memphis, TN 38105 / 901-595-7457 / Email: harmony.farner@stjude.orgText word count: 1236Brief running title: Anything to HelpKey words: pediatric oncology, quality of life, palliative careTables: 0Figures: 0I typed the patient’s phone number into my phone multiple times and immediately deleted it, too nervous to make the recruitment call. After several aborted attempts, suddenly the phone was ringing. I remember thinking to myself, “don’t pick up, don’t pick up - please go to voicemail.” And then, a young man answered. Immediately a knot formed in my throat.I had spent the better part of a day leaving voicemails for adolescent and young adult patients and parents eligible for a research study about prognostic communication preferences in the setting of advanced pediatric cancer. When C answered the phone, I stumbled over my words, shocked that someone had answered. Faltering, I explained that I was calling to ask if he might be interested in participating in a research study that sought to understand how patients with cancer want to hear information about prognosis. I felt like my body was collapsing in on itself, trying to make myself as small as possible in an attempt to avoid the tongue lashing that was surely coming for bothering a cancer patient. But to my surprise, C immediately replied yes, even before I had a chance to fully describe what the study entailed. He told me, “Anything to help.”When I started my job as a researcher within the palliative care division, I felt squarely outside of my comfort zone. Who was I to ask childhood cancer patients for their time, especially when they may have little time left in this world? Even worse, how could I ask them to talk about their poor prognosis? As an anthropologist, I’ve approached and interviewed participants living in abject poverty in Baltimore, women serving time in a correctional facility in Memphis, and members of the Makah Tribe in Washington state, just to name a few. Walking into a pod of inmates at a correctional facility didn’t scare me, but this sure did. My training taught me to be respectful of participants’ time, their words, their feelings, and their story. We were to cause them no harm. I worried that asking patients to talk about their illness could cause distress, and I couldn’t bear the thought of adding another stressor in their lives.I remember waiting for C at the clinic, nervously watching the clock and reviewing the interview guide for the umpteenth time.  He had suggested that we meet at 7am, before his full day of appointments. He bounded in, leading the nurse to the room instead of the other way around. He was dressed in comfortable jeans, sneakers, and a hoodie. His sparkling eyes, broad smile, and positive energy filled the room – it was the kind of energy that was infectious, lifting your mood just by being in his presence. This was a young man who was living and eager to enjoy every moment of it.I remember asking C to take me back to the beginning, and he started by recounting, “Well, the first time they cracked my skull open…” knocking twice on his head with his fist and a mischievous smile on his face. I must have looked shocked, because he reassured me, explaining, “I was really excited about [the craniotomy] because they were going to keep me awake, and I was like, ‘Cool, I want to be awake while people are cracking open my head!’ ” As we laughed together, any nervousness I had quickly dissipated.At the end of the interview, I thanked C profusely for his time and his candor. I was taken aback when C thanked me in return for asking his questions that he had never been asked before and for encouraging him to speak about his cancer journey unfiltered. He noted that, despite the excellent medical care that he had received, no one had ever asked him to reflect on his cancer journey, his poor prognosis, and his preferences for talking about how cancer would affect his future life. He was genuinely grateful to have been given this opportunity to speak his mind, and he apologized for talking too much. I assured him that there was no such thing.I left the interview both relieved and elated to know that the experience had been so beneficial for C. I found myself wondering if he was a rare example, or was there a chance that other patients might feel similarly? I would later discover that while C was an exceptional human being, he wasn’t the only one excited to tell their story.Many months later, I had the chance to reach back out to study participants to ask if they might be interested in joining a focus group to review the study findings and collaborate to create an intervention to improve prognostic communication. This time, I was excited to call C, and once again he agreed to participate with enthusiasm and no hesitation. He shared with me that he was working full-time, had enrolled in college courses, and had recently married the love of his life – and yet he still wanted to prioritize being a part of this research study despite his busy schedule. Over the next few months, C participated in all four focus groups, offering valuable insights into his cancer journey. He was never shy about speaking his mind, and he frequently helped encourage other more timid patients to share their perspectives. At times, he appeared tired, but he was always actively present and committed to the research process. After each focus group, part of my job entailed emailing participants to thank them for attending the session. Each time, I was deeply moved when C emailed me, expressing his sincere thanks to our research team for including him in this important work.Since meeting C, my perspective as a researcher has profoundly evolved. I no longer view recruitment and data collection as a burden imposed on cancer patients, but rather as a potential opportunity to enable those who are interested to tell their story, in their own words. I no longer fret over the process of describing our research study, as C taught me that just because a topic is emotionally charged does not mean that it’s disrespectful to invite people to share their thoughts about it. Rather, I’ve learned that I can show the utmost respect by creating space for patients to speak their mind. Not asking the hard questions doesn’t mean that people aren’t thinking about them – conversely, asking these questions can be a gift, empowering them to reflect aloud on this very real, very hard experience that otherwise is rarely addressed.Even as C approached the end of his life, he continued to express enthusiasm and gratitude for the opportunity to participate in research. He was thrilled to receive a copy of a recently published manuscript that reported on findings from the study, and as they encircled his bedside, his family reflected together with him on the powerful legacy that his research contributions would make on the world.I now know that, by speaking with patients about difficult topics related to their cancer, we can learn how to better treat the whole individual. Perhaps even more importantly, we can honor their personhood by centering their voices and elevating their stories. Our research participants, like all of us, contain multitudes – and we will never see the whole story unless we ask.Acknowledgement: I would like to thank Dr. Trisha Paul for her guidance and support in drafting and revising this essay.

Background: Pediatric patients with pelvic solid tumors often receive multi-modal treatment but the long-term effects of this treatment on lower urinary tract (LUT) function are not well-described. This prospective cohort study (NCT05818462) investigates the effect of EBRT on LUT function by comparing patient-reported outcome measures, non-invasive urodynamic studies, and post-void residuals (PVRs) amongst childhood cancer survivors (CCS). Methods: All subjects were CCS >1 year off-therapy for a pediatric solid tumor. Subjects were divided into two cohorts: a study cohort of patients who received pelvic EBRT and a control cohort who received only chemotherapy. Research subjects completed the Dysfunctional Voiding Scoring system (DVSS) survey, uroflow testing, and PVR bladder scan. Results: Thirty-two patients enrolled. Sixteen patients received pelvic EBRT. There were an equal number of patients exposed to alkylators (69%) in each cohort. The study cohort was more likely to have abnormal uroflow patterns (81% vs 56%, p=0.12). The flow pattern distribution differed between groups (p=0.03); the study cohort was more likely to have a “plateau” shaped curve (44% vs 6%) and abnormal PVR (OR 9.0, p=0.002). Exploratory conditional likelihood ratio models yielded potential associations between pelvic EBRT and LUTD, as well as a potential dose-response. There was no difference in DVSS scores between cohorts. Conclusion: EBRT appears to affect LUT function in CCS who received pelvic EBRT. DVSS does not appear useful as a screening tool in this population. Further study is needed to better appreciate the impact of EBRT on LUT function and develop more accurate screening tools.

Background: Sarcopenia (SP) is described as a prognostic factor in adult and pediatric cancer patients. However, there is no data regarding Wilms Tumor (WT). Our aim was to study the association between sarcopenia and oncological outcomes in WT. Methods: A retrospective study of patients diagnosed with WT at our institution between 2010-2022 was performed. SP at diagnosis was assessed by measuring the psoas muscle area (PMA) at the L4-L5 level on CT/MRI, and was defined as z-score values <-2. Demographics, complications and outcomes were analyzed. Results: Forty-eight patients (50% male) were included, with a mean age of 44.91±31.12 months. Twelve patients (25%) had SP at diagnosis vs. 36 (75%) who did not. Forty-one patients (85.4%) underwent total nephrectomy and 7 (14.6%) nephron-sparing surgery (NSS). No statistical differences were found in demographics, risk group or treatment between the SP and non-sarcopenic (NSP) groups. SP was associated with a higher rate of postsurgical complications (33.3% for the SP-group vs. 5.6% for the NSP-group; p=0.023) and with a higher rate of relapse (33.3% vs. 13.8% respectively; p=0.09). With a median follow-up of 57.75 (1.87-150.8) months, event-free survival (EFS) was lower for the SP-group (84.20±17.45 vs. 135.40±8.65 months respectively; p=0,08). One patient in the SP-group died. The 5-years overall survival (OS) was 89% for the SP-group vs. 100% for the NSP-group. Conclusions: Among our patients, SP can be considered as a risk factor for complications in patients with WT and could be associated with poor outcomes, increasing the risk of relapse and decreasing EFS.

Objective: To evaluate current clinical practices, identify perceived barriers, and explore healthcare professionals’ perspectives on the use of autologous umbilical cord blood (AUCB) in neonatal cardiac surgery across Europe. Methods: A descriptive, cross-sectional online survey was distributed to healthcare professionals involved in neonatal cardiac surgery. The questionnaire, developed ad hoc by a multidisciplinary expert team, assessed institutional AUCB use, perceived benefits and barriers, and professionals’ interest in further information. The survey was disseminated through European scientific societies and professional social media platforms. Data were collected anonymously and analyzed using descriptive statistics. Results: A total of 42 responses were analyzed. The majority of respondents were neonatologists (50%), followed by perfusionists and neonatal nurses; 78% were based in Spain. Only 10% of participants reported institutional use of AUCB, primarily for selected patients in the postoperative setting. Reported benefits included reduced transfusion requirements and decreased exposure to allogeneic blood products. Among non-users, key barriers included logistical challenges (18%), insufficient scientific evidence (15%), and limited training (10%). The most frequently cited overall obstacle was lack of education and training (78%), followed by regulatory restrictions. Only 8% considered the current evidence sufficient to support routine AUCB use. Despite limited implementation, overall interest was high (mean rating 4.6/5), with many respondents expressing interest in future collaboration. Conclusions: AUCB use in neonatal cardiac surgery remains limited and institution-dependent across Europe. Significant barriers—including insufficient training, logistical challenges, and perceived evidence gaps—hinder broader adoption. These findings highlight the need for standardized protocols, targeted educational strategies, and further clinical evidence to facilitate safe and effective integration of AUCB into neonatal cardiac care.

Background Pediatric hematopoietic stem cell transplantation (HSCT) is a life-saving therapy for malignant and non-malignant hematologic diseases. However, access to this high-complexity treatment remains limited and uneven across the Andean subregion. This study aimed to evaluate the current status, capacity, and equity of pediatric HSCT programs in six Andean countries (Bolivia, Chile, Colombia, Ecuador, Peru, and Venezuela) within the framework of WHO Global Initiative of Childhood Cancer. Methods A mixed-methods, cross-sectional situational assessment was conducted between November 2024 and January 2025 under the coordination of the Andean Health Organization (ORAS-CONHU) and the Pan American Health Organization (PAHO). Standardized national and center-level surveys (34 and 150 items, respectively) were applied to Ministries of Health and HSCT centers to collect data on infrastructure, workforce, financing, quality management, and barriers to access. Quantitative data were analyzed descriptively and validated by national committees, complemented by qualitative interviews with key stakeholders. Results Twenty-seven HSCT centers were identified across the subregion, revealing major disparities in access and capacity. Chile reached 100% coverage of estimated transplant needs, while Colombia, Peru, and Venezuela achieved 80%, 29%, and 42.5%, respectively. Bolivia and Ecuador had the lowest coverage (1.6% and 24%). Only 28% of units were pediatric-exclusive, and less than two-thirds met full quality and training standards. High-cost medicines, limited infrastructure, and shortages of specialized personnel were identified as critical barriers, while regional collaboration and national policies emerged as key facilitators. Conclusion The study highlights significant inequities in pediatric HSCT access and capacity across the Andean subregion. Strengthening infrastructure, workforce training, financing mechanisms, and data systems, supported by sustained regional cooperation, is essential to achieve equitable, high-quality transplant care for all children.

This report describes the first successful use of blinatumomab for desensitization against donor-specific antibodies (DSAs) prior to haploidentical hematopoietic stem cell transplantation (haplo-HSCT). A 16-year-old male with aplastic anemia(AA) and high-titer DSA (MFI 5,155) contraindicated conventional plasma exchange due to anaphylaxis history. A reduced-dose blinatumomab regimen (8 μg/day × 8 days) achieved rapid DSA reduction to subthreshold levels (MFI 701) within two weeks. Subsequent paternal haplo-HSCT resulted in neutrophil/platelet engraftment by days +18/+28, with 98.41% donor chimerism. This novel approach demonstrates blinatumomab’s potential as an effective desensitization strategy for highly sensitized haplo-HSCT recipients.

not-yet-known not-yet-known not-yet-known unknown Background : Families of children with cancer often incur substantial nonmedical costs for travel, lodging, and food when accessing specialized care. These costs can contribute to health-related financial strain, yet the relationship between distance to care and unmet nonmedical costs remains poorly understood. Procedure: We conducted a retrospective cohort study of families applying for support from Children’s Cancer Partners of the Carolinas (CCPC) between August 2011 and March 2024. Eligible participants included families of children with cancer from North and South Carolina with complete data on zip code, treatment center, and reimbursed costs. Distance to primary treatment center was calculated in miles and minutes. Outcomes included total unmet nonmedical costs (USD), and the frequency, magnitude, and types of reimbursed costs. Results : Among 1,890 children, the mean age was 10.4 years (SD 5.4), most were male (56%), White (51%), and publicly insured (56%). The most common diagnosis was hematologic malignancy (49%). One-fifth (22%) lived in rural areas. Median unmet nonmedical costs were $1,094/family [IQR $320-2,379] and represent costs of land travel, food, and leisure. Median travel distance was 37.8 miles [IQR 21.3-71.4] or 46.9 minutes [IQR 31.0-81.3] each way. After adjusting for potential confounders, each additional travel minute was associated with $9.14 higher unmet nonmedical costs (95% CI: 6.91, 11.37), and each additional mile was associated with $8.85 higher costs (95% CI: 6.69, 11.00). Conclusions and Relevance : Longer distance to cancer care is associated with increased total unmet nonmedical costs. Additional resources are needed to reduce travel-related cost barriers for families living far from pediatric cancer centers.

Background: To investigate the role of social determinants of health (SDoH) in neurocognitive functioning among children with acute lymphoblastic leukemia (ALL), central nervous system (CNS) tumors, and sickle cell disease (SCD). Procedure: Fifty-eight child-caregiver dyads participated. SDoH included components of socioeconomic status (SES; including family income, caregiver education, and insurance type), race/ethnicity, caregiver marital status, and neighborhood-level deprivation. Neurocognitive functioning was measured using the NIH Toolbox Cognition Battery (NIHTB-CB). Results: Despite expected differences in race/ethnicity (χ 2 (4, n = 51) = 46.1, p < 0.001), there were no differences in SDoH between the three diagnosis groups. Bivariate analyses found a significant association between family income and working memory ( r = 0.31, p < 0.05), processing speed ( r = 0.29, p < 0.05), and fluid cognition composite scores ( r = 0.29, p < 0.05). No other SDoH were associated with neurocognitive functioning. Family income remained significantly associated with performance on working memory ( β = 0.35, p < 0.05), processing speed ( β = 0.33, p < 0.05), and fluid cognition composite scores ( β = 0.29, p < 0.05) after controlling for diagnosis, age, and sex. Conclusions: Lower family income emerged as an important element of SES associated with poorer neurocognitive functioning in children treated for cancer and blood disorders. Further research is needed to determine how family income alters neurocognitive functioning, whether by altering the timing of emergence or magnitude of deficits. Future studies should investigate mechanisms linking low income to neurocognitive performance to inform interventions to bolster neurocognitive development.

Plasmablastic lymphoma of bone in an adolescent boy: An unusual presentation of a rare pediatric malignancy

Background: Juvenile xanthogranuloma (JXG) is a rare non-Langerhans cell histiocytosis that typically presents as self-limiting cutaneous lesions in infants and young children. However, systemic involvement can lead to severe organ dysfunction and poses significant therapeutic challenges. Case presentation: We report a case of chemotherapy-refractory, multisystem JXG harboring BRAF V600E mutation in a 28-month-old male. The patient presented with recurrent fever, bilateral orbital involvement, and progressive multisystem infiltration without cutaneous lesions. First-line chemotherapy failed to control disease progression and was complicated by pulmonary infection. Oral dabrafenib monotherapy induced rapid clinical and radiologic remission, with clearance of BRAF V600E in peripheral blood cell-free DNA . The patient has maintained remission for four years, including two years off-therapy. Conclusion: This case demonstrates durable remission with dabrafenib in BRAF-mutant systemic JXG and highlights the potential of BRAF-targeted therapy as an effective and safer alternative to conventional chemotherapy in refractory cases.

Synchronous primary malignancies are rare in paediatric patients and usually develop based on inherited cancer predisposition. We report the case of a 4-year-old girl with lateralised overgrowth who was diagnosed with concomitant B-cell precursor acute lymphoblastic leukaemia and Wilms tumour. Methylation analysis at chromosome 11p15.5 revealed a mosaic gain of methylation at IC1 on the maternal allele in kidney tissue, which was absent in leukemic and remission blood cells, confirming the diagnosis of Beckwith-Wiedemann syndrome. We discuss the cause-and-effect relationship for both malignancies and point out diagnostic and therapeutic difficulties that were encountered in this patient.

A Unique Presentation of Early Onset Colon Cancer in the Setting of Helicobacter Pylori Positivity, IgA Deficiency and a Germline 18p DeletionKelsey Gay, DO1, Smita Dandekar, MBBS, MD11Division of Pediatric Hematology-Oncology, Penn State Health Children’s Hospital, Hershey, PA

Title: Concurrent Mixed Phenotypic Acute Leukemia and T-Lymphoblastic Lymphoma in an Adolescent MaleLaila Khatib, DO, MS1, Molly C. Mack, MD, MS1, M Clarise Valencia, MD, MBA1, Erika Moore, MD2, Erika Friehling, MD, MS31Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh 2Department of Pathology3Department of Pediatrics, University of Pittsburgh School of MedicineTo the Editor,We describe the first documented case of a patient presenting concurrently with two molecularly distinct malignancies, mixed phenotypic acute leukemia (MPAL) (B/Myeloid) and T-lymphoblastic lymphoma (T-LBL). MPAL is a rare, heterogeneous form of acute leukemia that exhibits both lymphoid and myeloid lineage features, whether within a single blast population (biphenotypic) or as distinct blast populations (bilineal). It accounts for less than 5% of all pediatric acute leukemias1. MPAL presents significant diagnostic and therapeutic challenges due to its phenotypic diversity and the lack of standardized treatment protocols. Furthermore, the simultaneous presentation of two distinct pediatric hematologic malignancies is exceedingly rare.A 15-year-old male presented with several weeks of progressively worsening facial swelling and dyspnea. Physical exam revealed absent right-sided breath sounds and supraclavicular lymphadenopathy without hepatosplenomegaly or testicular masses. Imaging showed a large anterior mediastinal mass compressing the superior vena cava and a large pleural effusion (Fig. 1A). Complete blood count revealed pancytopenia (WBC 4 × 10⁹/L, ANC 2.24 × 10⁹/L; hemoglobin 12.3 g/dL; platelets 17 × 10⁹/L) with rare circulating blasts, and an elevated LDH (684 IU/L). Supraclavicular lymph node biopsy (Fig. 1C) and pleural fluid cytology confirmed T-lymphoblastic lymphoma (IHC/flow as seen in Fig 1E: CD3⁺, CD19⁻, MPO⁻, CD33⁺, TdT⁺; cytogenetics: 46,XY with t(9;11)(q13;q2); fusion analysis: NUP214::ABL1). FISH was negative for BCR-ABL1 and KMT2A rearrangements. Staging bone marrow aspirate revealed 72.3% blasts with a mixed B/myeloid immunophenotype (CD19⁺, CD79a⁺, PAX5⁺, CD22⁻, CD10⁻, CD3⁻, MPO⁺, TdT⁻) (Fig. 1B, D). FISH demonstrated CDKN2A deletion and loss of CRLF2 signal. Molecular studies identified FLT3-ITD and WT1 variants. These features fulfilled WHO criteria for MPAL (B/myeloid subtype), distinct from the concurrent T-lymphoblastic process. There was no CNS involvement (CNS1). Germline testing with Blueprint Hereditary Leukemia Panel showed no cancer predisposition mutations.The patient was treated as per AALL1732, MPAL arm, with a four-drug induction (prednisone, vincristine, daunorubicin, asparaginase).2 Nelarabine was not included as it has not demonstrated improvement in outcomes for T-lymphoblastic lymphoma.3 The end of induction evaluation showed no measurable bone marrow minimal residual disease (MRD) for B-cell (sensitivity <0.01%), and T-cell and myeloid disease (sensitivity <0.02%). The mediastinal mass decreased in size by the end of induction and resolved by the end of consolidation with PET scan showing no avidity. Treatment-related adverse events included mercaptopurine–associated hepatotoxicity, requiring allopurinol and ursodiol, which subsequently resolved, and vincristine-induced neuropathy, which improved after dose reduction. The patient is currently in his third cycle of maintenance therapy and remains in complete remission.Simultaneous occurrence of T-lymphoblastic lymphoma and a distinct acute leukemia in the marrow has been reported in isolated adult cases, often with shared clonality, suggesting a common progenitor.4 However, in this pediatric patient, immunophenotypic and molecular findings support the presence of two independent neoplasms, each with separate lineage features and genetic alterations.Immunophenotyping remains the cornerstone of MPAL diagnosis and should include myeloid and lymphoid markers with attention to exclusion of AML subtypes such as t(8;21) or complex karyotypes that may mimic MPAL.5 Advanced genomic profiling has improved understanding of the heterogeneity of MPAL: mutations in FLT3-ITD, WT1, RUNX1, CDKN2A/B, and NOTCH1 are recurrent in pediatric series, while adult MPAL often shows complex cytogenetics, BCR-ABL1, or KMT2A rearrangements.6 Notably, FLT3-ITD and WT1, found in our patient, have been described as enriched in pediatric MPAL and may represent potential therapeutic targets.6Though there is no current standard of care for treatment, ALL-directed chemotherapy remains first-line for pediatric MPAL given the association with superior long-term survival and lower relapse rates compared to AML-style therapy.7 Published data largely consists of case series, but meta-analyses suggest chemotherapy with regimens designed for acute lymphoblastic leukemia (ALL) are associated with higher rates of complete remission after induction and equivalent overall survival.8 A comparative study found that ALL-directed therapy elicited superior response rates compared to myeloid regimens (p = 0.001).9 Furthermore, a cohort and consensus study from Children’s Oncology Group in 2020 suggests that ALL-directed therapy without hematopoietic stem cell transplant (HSCT) is the preferred initial treatment for MPAL in pediatric patients.10Overall, this case underscores several key lessons. First, it emphasizes the importance of comprehensive immunophenotyping and molecular evaluation as simultaneous hematologic malignancies may escape detection without these. Second, the genomic characterization plays an important role in potential targeted therapy options (e.g FLT3-ITD) in the case of future relapse or refractory cases. Third, this case supports the use of ALL-directed regimens in B/Myeloid MPAL and T-lymphoblastic lymphoma with good MRD response.This is the first known case of concurrent pediatric T-lymphoblastic lymphoma and MPAL of unrelated lineage. Awareness of such rare presentations is crucial for accurate diagnosis and therapeutic planning. Further case accumulation and studies are needed to guide management in these complex scenarios.

Title: Congenital Myelodysplastic Syndrome in a Newborn with Germline JAK2 Variant Treated with Liposomal Cytarabine-Daunorubicin and Allogeneic Hematopoietic Stem Cell TransplantAuthors:Kristin E. Zorn1*, Kathleen M. Bone2, Maria E. Hintzke2, Amy Moskop1, Zachary Graff1Affiliations:1. Division of Hematology/Oncology/Blood and Marrow Transplantation, Department of Pediatrics, Medical College of Wisconsin and Children’s Wisconsin, Milwaukee, WI2. Department of Pathology, Medical College of Wisconsin, Milwaukee, WI* Current Affiliation –Division of Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MOCorresponding author: Kristin E. ZornWashington University School of MedicineDivision of Pediatric Hematology/Oncology660 S. Euclid AveSt. Louis, MO 63110Phone: (314)-454-6018Fax: (844)-621-4392Email: zorn@wustl.eduWord count: 840Figures: 2Running Title: Congenital Myelodysplastic SyndromeKeywords: Myelodysplastic Syndrome, AML, JAK2Abbreviations:

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Background Anaplastic sarcoma of the kidney (ASK) is a DICER1-related neoplasm first identified as a distinctive tumor type through the evaluation of unusual cases of putative anaplastic Wilms tumors. Subsequent case reports identified the presence of biallelic DICER1 variants as well as progression from cystic nephroma, a benign DICER1-related neoplasm. Despite increasing recognition of ASK as a distinct entity, the optimal treatment remains unclear. Methods Individuals with known or suspected DICER1-related tumors including ASK were enrolled in the International Pleuropulmonary Blastoma/ DICER1 Registry. Additionally, a comprehensive review of reported cases of ASK was undertaken and data was aggregated for analysis with the aim to identify prognostic factors and clinical characteristics to guide decisions regarding genetic testing, surveillance, and treatment. Results Ten cases of ASK were identified in the Registry along with 37 previously published cases. Staging data, per Children’s Oncology Group guidelines was available for 40 patients: 13 were stage I, 12 were stage II, 10 were stage III, and 5 were stage IV. Outcome data were available in 37 cases. Most (38 of 46) patients received upfront chemotherapy and 14 patients received upfront radiation. Two-year event-free survival (EFS) for stage I-II ASK was 81.8% (95% confidence interval [CI]: 67.2-99.6%), compared with 46.6% EFS (95% CI: 24.7-87.8%) for stage III-IV ( p=.07). Two-year overall survival (OS) for stage I-II ASK was 88.9% (95% CI: 75.5-100.0%) compared with 70.0% (95% CI: 46.7-100.0%) for stage III-IV ( p=.20). Chemotherapy was associated with improved EFS and OS with hazard ratios of 0.09 (95% CI: 0.02-0.31) and 0.08 (95% CI: 0.02-0.42), respectively. Conclusion ASK is a rare DICER1-related renal neoplasm. In the current report, we identify clinical and treatment-related factors associated with outcome including the importance of chemotherapy in treating ASK. Ongoing data collection and genomic analysis are indicated to optimize outcomes for children and adults with these rare tumors.