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Adolescent and young adults (AYAs) currently undergoing treatment for cancer, in remission, or in survivorship, are missing a great deal of traditional academic activities during crucial formative years of their lives. To provide AYAs with exceptional opportunities for personal growth, the Adolescent and Young Adult College and Career Fair (AYACCF) was developed. The objective of the AYACCF is to meet the needs of this specific patient population in navigating the transitions from cancer treatment to academic, trade, or career life thereafter. By leveraging internal resources, the team was able to organize two in-person and one virtual event across 3 years. This article provides an overview of the process of designing, implementing, and refining an annual college and career readiness for AYA oncology patients. [ABSTRACT FROM AUTHOR]

The use of HSCT is the only potentially curative treatment for CAMT, but access is limited by the availability of suitable donors. We report five consecutive patients with CAMT who received MAC and partially HLA-mismatched, UCBT (unrelated, n = 4). Median times to neutrophil (>500/μL) and platelet (≥20 000 and ≥50 000/μL) engraftment were 19, 57, and 70 days, respectively. Acute GvHD, grade II, developed in one patient, who subsequently developed limited chronic Gv HD. At median follow-up of 14 yr, all patients are alive with sustained donor cell engraftment. To our knowledge, this is the largest single-center series of UCBT for patients with this disease and suggests that UCBT is a successful curative option for patients with CAMT. [ABSTRACT FROM AUTHOR]

Background: Adolescents and young adults (AYAs) are a very unique subset of our population journeying through a dynamic stage of their lives. This age group often remains understudied as a separate entity because they are commonly lumped into either pediatric or adult subgroups. Methods: Here we review acute and chronic issues surrounding hematopoietic stem cell transplantation (HSCT) with a focus on the AYA age group. Results: HSCT is a commonly used treatment modality for patients with certain types of cancers. AYA patients undergoing HSCT present a very unique perspective, circumstances, medical, psychological and social issues requiring a diligent workup, care and follow-up. Conclusion: The medical care of these patients should be approached in a multidisciplinary method involving the patient, caregivers, physicians, psychologists and social workers. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The curative potential of hematopoietic stem cell transplantation in patients with chronic granulomatous disease depends on availability of a suitable donor, successful donor engraftment, and maintenance of long-term donor chimerism. Twelve consecutive children (median age, 59.5 months; range, 8-140 months) with severe chronic granulomatous disease (serious bacterial/fungal infections pretransplantation; median, 3; range, 2-9) received myeloablative hematopoietic stem cell transplantation using sibling bone marrow ([SibBM]; n = 5), unrelated cord blood (UCB; n = 6), and sibling cord blood (n = 1) at our center between 1997 and 2010. SibBM and sibling cord blood were HLA matched at 6/6, whereas UCB were 5/6 (n = 5) or 6/6 (n = 1). Recipients of SibBM were conditioned with busulfan and cyclophosphamide ± anti-thymocyte globulin (ATG), whereas 6 of 7 cord blood recipients received fludarabine/busulfan/cyclophosphamide/ATG. Seven patients received granulocyte-colony stimulating factor-mobilized granulocyte transfusions from directed donors. The first 2 UCB recipients had primary graft failure but successfully underwent retransplantation with UCB. Highest acute graft-versus-host disease was grade III (n = 1). Extensive chronic graft-vs-host disease developed in 3 patients. All patients are alive with median follow-up of 70.5 months (range, 12-167 months) with high donor chimerism (>98%, n = 10; 94%, n = 1; and 92%, n = 1). Myeloablative hematopoietic stem cell transplantation led to correction of neutrophil dysfunction, durable donor chimerism, excellent survival, good quality of life, and low incidence of graft-vs-host disease regardless of graft source. [ABSTRACT FROM AUTHOR]

Background: Short telomere syndrome (STS) in children may result in phenotypically heterogenous clinical spectrum ranging from completely asymptomatic to typical dyskeratosis congenita (DC). Patients with this cancer predisposition syndrome may have multiple organ dysfunctions including pulmonary fibrosis, liver cirrhosis, and bone marrow failure. Not all mutations in telomerase or telomere genes have been identified, and STS may pose a diagnostic and management challenge. Methods: A retrospective chart review and literature search were done for this report. Results: Here, we report a case of atypical DC with a heterozygous germline missense mutation in the postmeiotic segregation increased 2 (PMS2) gene, exon 5, (c.466A>G (p. Thr156Ala)). The PMS2 (a mismatch repair protein) gene is known to be an important mediator of telomere‐induced aging. The patient was transfusion dependent and underwent successful umbilical cord blood transplant using a non‐myeloablative regimen with alemtuzumab, fludarabine, cyclophosphamide, and total body irradiation. Conclusion: In this case of atypical DC with a previously unreported germline missense mutation in PMS2, the patient was successfully treated with an umbilical cord blood transplant with a non‐myeloablative regimen. [ABSTRACT FROM AUTHOR]

Simple Summary: Childhood acute lymphoblastic leukemia (ALL) has seen significant advances in treatment, yet children classified as high-risk still face challenging outcomes. Traditionally, the severity of ALL was assessed using basic clinical information at diagnosis, but now a deeper understanding of specific biological markers—such as molecular profiles, genetic variations, and immune system characteristics—has become crucial. These markers are not just keys to understanding the disease's mechanisms, but also indicators of how it may progress and respond to treatment. For instance, the development of drugs like tyrosine kinase inhibitors can be used to target high-risk leukemia with certain genetic mutations. By focusing on the intricacies of high-risk childhood ALL, research is paving the way for more personalized and precise treatments, offering hope for better management of this complex disease. Childhood acute lymphoblastic leukemia (ALL) has witnessed substantial improvements in prognosis; however, a subset of patients classified as high-risk continues to face higher rates of relapse and increased mortality. While the National Cancer Institute (NCI) criteria have traditionally guided risk stratification based on initial clinical information, recent advances highlight the pivotal role of biological markers in shaping the prognosis of childhood ALL. This review delves into the emerging understanding of high-risk childhood ALL, focusing on molecular, cytogenetic, and immunophenotypic markers. These markers not only contribute to unraveling the underlying mechanisms of the disease, but also shed light on specific clinical patterns that dictate prognosis. The paradigm shift in treatment strategies, exemplified by the success of tyrosine kinase inhibitors in Philadelphia chromosome-positive leukemia, underscores the importance of recognizing and targeting precise risk factors. Through a comprehensive exploration of high-risk childhood ALL characteristics, this review aims to enhance our comprehension of the disease, offering insights into its molecular landscape and clinical intricacies in the hope of contributing to future targeted and tailored therapies. [ABSTRACT FROM AUTHOR]

Background: There is paucity of data regarding outcomes of children, adolescents and young adults (CAYA) patients with non-Hodgkin lymphoma (NHL) undergoing autologous stem cell transplantation (ASCT). Methods: Patients aged 0–39 years undergoing first ASCT for NHL at MD Anderson Cancer Center between 2000 and 2020 were analyzed. Results: Two hundred twenty-one patients were included in the analysis, 129 (58%) were male and the median age was 32 (range 6–39) years. The most common histological subtypes were diffuse large B cell lymphoma (DLBCL) (44%), T-NHL (19%) and primary mediastinal B-Cell lymphoma (PMBCL) (19%). Younger patients (age ≤ 25) had lower incidence of DLBCL and higher incidence of PMBCL and T-NHL compared to older patients (age > 25) (P = 0.02). None of the younger patients had double hit (DH)/double expressor (DE) DLBCL, compared to 14 patients in the older age group (18%, P = 0.07). Considering the three main aggressive NHL subtypes (DLBCL, PMBCL and T-NHL), younger patients had numerically better 15-year post-transplant progression free survival (PFS) (67% vs. 54%) and overall survival (OS) (71% vs. 62%) compared to older patients, yet these differences did not reach statistical significance (P = 0.19 and P = 0.24, respectively). In multivariate analysis, not achieving a CR prior to ASCT was independently predictive of worse PFS [partial remission (PR) (HR, 3.9); stable disease (SD) (HR, 18.0), P = 0.03] and of worse OS [PR (HR, 4.2), SD (HR, 6.5) and progressive disease (HR, 4.7), P < 0.0001]. DH/DE status was an independent adverse predictor of PFS in multivariate analysis (HR 5.8, p = 0.03). Ten patients (4.5%) (all aged > 25 years) developed second primary malignancies (SPM), at a median of 34.4 (range, 1.0–196.6) months after ASCT, and SPM was the cause of death in five (50%) of them. Conclusions: CAYA NHL patients aged ≤ 25 years who received ASCT presented a distinct NHL histology as compared to older CAYA patients, and none in this younger age group had DH/DE DLBCL. We observed a trend towards improved PFS and OS in younger patients. Disease status at ASCT was predictive of both PFS and OS. DH/DE status was an adverse predictor of PFS. [ABSTRACT FROM AUTHOR]

Primary mediastinal large B-cell lymphoma in paediatric and adolescent patients: emerging questions in the era of immunotherapy Keywords: paediatric; refractory; mediastinal; B-Cell lymphoma EN paediatric refractory mediastinal B-Cell lymphoma e114 e117 4 07/20/20 20200715 NES 200715 Relapsed/refractory primary mediastinal large B-cell lymphoma (PMLBCL) is rare among paediatric patients and is associated with a dismal prognosis. None of these patients had prior CAR T-cell therapy or checkpoint inhibitors.13 Remission consolidation post-CAR T-cell therapy with allogeneic HCT in patients with PMLBCL remains an active debate. [Extracted from the article]

Summary: Multiple myeloma (MM) primarily affects older patients. There are scarce data on the outcomes of young adults undergoing autologous transplantation (auto‐HCT). In this single‐centre analysis, we included 117 younger patients, with a median age of 37 years (range 22–40) at transplant. Seventeen (15%) patients had high‐risk cytogenetics. Before transplant, 10% of patients achieved ≥CR and 44% achieved ≥VGPR. At best post‐transplant response, 56% and 77% of patients achieved ≥CR and ≥VGPR respectively. With a median follow‐up for survivors of 72.6 months (range 0.9–238.0), median PFS and OS were 43.1 months (95% CI 31.2–65.0) and 146.6 months (95% CI 100.0–208.1) respectively. Patients who underwent auto‐HCT after 2010 had better median PFS (84.9 months vs. 28.2 months, p < 0.001) and OS (NR vs. 91.8 months, p < 0.001) compared with those transplanted earlier. In multi‐variate analysis, achieving ≥CR as best post‐transplant response was associated with improved PFS (HR [95% CI] 0.55 [0.32–0.95], p = 0.032), while achieving ≥VGPR was predictive of superior OS (0.32 [0.16–0.62], p < 0.001). Three patients (3%) developed a second primary malignancy. Younger MM patients had durable survival after auto‐HCT, which further improved after the availability of novel anti‐myeloma drugs in recent years. Depth of response following transplant remains a key predictor of survival. [ABSTRACT FROM AUTHOR]

Hodgkin lymphoma, a hematological malignancy of lymphoid origin that typically arises from germinal-center B cells, has an excellent overall prognosis. However, the treatment of patients who relapse or develop resistant disease still poses a substantial clinical and research challenge, even though current risk-adapted and response-based treatment techniques produce overall survival rates of over 95%. The appearance of late malignancies after the successful cure of primary or relapsed disease continues to be a major concern, mostly because of high survival rates. Particularly in pediatric HL patients, the chance of developing secondary leukemia is manifold compared to that in the general pediatric population, and the prognosis for patients with secondary leukemia is much worse than that for patients with other hematological malignancies. Therefore, it is crucial to develop clinically useful biomarkers to stratify patients according to their risk of late malignancies and determine which require intense treatment regimens to maintain the ideal balance between maximizing survival rates and avoiding late consequences. In this article, we review HL's epidemiology, risk factors, staging, molecular and genetic biomarkers, and treatments for children and adults, as well as treatment-related adverse events and the late development of secondary malignancies in patients with the disease. [ABSTRACT FROM AUTHOR]

Despite advances in treatment options, the clinical outcomes of pediatric patients with advanced solid tumors have hardly improved in decades, and alternative treatment options are urgently needed. Innovative therapies, such as chimeric antigen receptor (CAR) T cells and oncolytic viruses (OVs), are currently being evaluated in both adults and children with refractory solid tumors. Because pediatric solid tumors are remarkably diverse and biologically different from their adult counterparts, more research is required to develop effective treatment regimens for these patients. Here, we first summarize recent efforts and advances in treatments for pediatric solid tumors. Next, we briefly introduce the principles for CAR T cell therapy and oncolytic virotherapy and clinical trials thereof in pediatric patients. Finally, we discuss the basis for the potential benefits of combining the two approaches in pediatric patients with advanced solid tumors. [ABSTRACT FROM AUTHOR]

Non-relapse mortality due to GVHD and infections represents a major source of morbidity and mortality in pediatric HSCT recipients. Post-transplant cyclophosphamide (PTCy) has emerged as an effective and safe GVHD prophylaxis strategy, with improved GVHD and relapse-free survival in matched (related and unrelated) and mismatched haploidentical HSCT adult recipients. However, there are no published data in pediatric patients with acute myeloid leukemia who received matched-donor HSCT with PTCy. We demonstrate, in this case series, that the use of PTCy in this population is potentially safe, effective in preventing acute GVHD, does not impair engraftment, is associated with reduced non-relapse mortality, and does not hinder immune reconstitution post HSCT. [ABSTRACT FROM AUTHOR]

The T‐cell engager monoclonal antibody, blinatumomab, is a potential therapeutic strategy for refractory B acute lymphoblastic leukemia after failure of CD 19 chimeric antigen receptor T‐cell therapy. [ABSTRACT FROM AUTHOR]

Previous studies in adults have shown that peripheral blood absolute lymphocyte and monocyte count ratio (ALC/AMC) after autologous stem cell transplantation (ASCT) can predict outcome in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL). We retrospectively reviewed all of our children, adolescent, and young adult (CAYA) patients (age ≤26) who underwent transplantation for R/R HL between 2004 and 2015. Seventy-six patients (median age, 21; range, 10 to 26 years) who reached day 100 disease free were analyzed; 33% of them had positron emission tomography (PET)–positive tumors before ASCT. Patients received high-dose carmustine, etoposide, cytarabine, and melphalan (n = 40) or gemcitabine/busulfan/melphalan (n = 36). Median follow-up after day 100 was 3.9 years (95% confidence interval [CI], 2.8 to 4.9). A day 100 ALC/AMC ratio >2.1 correlated with lower risk of relapse (hazard ratio,  .097; 95% CI, .03 to .29; P  <   .0001). Patients with day 100 ALC/AMC ratios >2.1 and ≤2.1 had 4-year relapse-free survival rates of 93% and 33%, respectively ( P  = .0001) and 4-year overall survival rates of 96% and 76%, respectively ( P  = .0001). In addition, an ALC/AMC ratio increase >1.8 from day 15 to day 100 correlated with lower risk of relapse (hazard ratio, .24; 95% CI, .08 to 0.73; P  = .01). Likewise, an ALC/AMC ratio change >.26 from day 30 to day 100 also correlated with a lower likelihood of relapse (hazard ratio, .20; 95% CI,  .081 to .51; P  = .0007). Multivariate analysis showed that a positive PET scan at ASCT, day 100 ALC/AMC ratio ≤ 2.1, and an ALC/AMC ratio change either ≤1.8 from day 15 to day 100 or ≤.26 from day 30 to day 100 were independent adverse predictors. In conclusion, our analysis confirms in CAYA patients prior observations in adults indicating a major prognostic effect of peripheral lymphocyte and monocyte counts at day 100 and earlier post-ASCT time points in R/R HL. [ABSTRACT FROM AUTHOR]

We conducted a retrospective analysis of outcomes for children and young adults with sAML/ sMDS who underwent HSCT at our institution. Thirty-two patients (median age 20 years) with sAML (n=24) and sMDS (n=8) received HSCT between 1990 and 2013. The median time from sAML/ sMDS diagnosis to HSCT was 4.1 months (range: 1.2-27.2 months). The transplant regimens were primarily busulfan based (n=19). BM was the primary donor source (n=15). Eleven recipients were transplanted with residual disease. At a median follow-up of 62.3 months (range: 0.4-250.9 months), 14 patients had disease recurrence. Acute GVHD, grade III/ IV, occurred in three patients. Causes of death were as follows: disease relapse (n=12), infection (n=2), pneumonia (n=1), pulmonary hemorrhage (n=1), acute GVHD (n=1), and graft failure (n=1). A PS of ≥90% at the time of HSCT had a significant impact on PFS ( P=.02). Patients achieving pretransplant primary CR (n=8) and those with sMDS and RA (n=6) had prolonged PFS ( P=.04). On multivariate analysis, shorter time to transplantation (≤6 months from diagnosis of sAML/ sMDS) was associated with superior OS ( P=.0018) and PFS ( P=.0005). [ABSTRACT FROM AUTHOR]

Delayed engraftment is a major limitation of cord blood transplantation (CBT), due in part to a defect in the cord blood (CB) cells' ability to home to the bone marrow. Because this defect appears related to low levels of fucosylation of cell surface molecules that are responsible for binding to P- and E-selectins constitutively expressed by the marrow microvasculature, and thus for marrow homing, we conducted a first-in-humans clinical trial to correct this deficiency. Patients with high-risk hematologic malignancies received myeloablative therapy followed by transplantation with 2 CB units, one of which was treated ex vivo for 30 minutes with the enzyme fucosyltransferase-VI and guanosine diphosphate fucose to enhance the interaction of CD34+ stem and early progenitor cells with microvessels. The results of enforced fucosylation for 22 patients enrolled in the trial were then compared with those for 31 historical controls who had undergone double unmanipulated CBT. The median time to neutrophil engraftment was 17 days (range, 12-34 days) compared with 26 days (range, 11-48 days) for controls (P = .0023). Platelet engraftment was also improved: median was 35 days (range, 18-100 days) compared with 45 days (range, 27-120 days) for controls (P = .0520). These findings support ex vivo fucosylation of multipotent CD34+ CB cells as a clinically feasible means to improve engraftment efficiency in the double CBT setting. The trial is registered to www.clinicaltrials.gov as #NCT01471067. [ABSTRACT FROM AUTHOR]

Simple Summary: We present a case of a pediatric patient with symptomatic leukemia involving the heart without bone marrow involvement. The case is followed by a literature review of advances in leukemia treatment including immunotherapy, CAR T-cell therapy, improvement in the treatment of graft-versus-host disease, and the applicability of these treatments to leukemia involving areas outside of the bone marrow. We also explore the feasibility of treatments such as CAR T-cell therapy and blinatumomab and the associated risks for treating patients with leukemia infiltrating the heart. Isolated extramedullary relapse of acute lymphoblastic leukemia (ALL) occurs in soft tissues and various organs outside the testis and central nervous system. Treatments such as hematopoietic stem cell transplantation and more novel modalities such as immunotherapy have eradicated ALL at extramedullary sites. In some instances, survival times for relapsed ALL at these sites are longer than those for relapsed disease involving only the bone marrow. Isolated relapse of ALL in the myocardium is rare, especially in children, making diagnosis and treatment of it difficult. More recent treatment options such as chimeric antigen receptor T-cell therapy carry a high risk of cytokine release syndrome and associated risk of worsening cardiac function. Herein we present the case of an 11-year-old boy who presented with relapsed symptomatic B-cell ALL in the myocardium following allogeneic hematopoietic stem cell transplantation. This is an unusual presentation of relapsed ALL and this case demonstrates the associated challenges in its diagnosis and treatment. The case report is followed by a literature review of the advances in treatment of pediatric leukemia and their application to extramedullary relapse of this disease in particular. [ABSTRACT FROM AUTHOR]

Background Opportunistic infections are a significant cause of morbidity and mortality in children treated with chemotherapy. Historically, the neutropenic diet has been utilized to limit the incidence of infections by reducing exposure to potential pathogens. The neutropenic diet is utilized at our center for all allogeneic(allo) hematopoietic stem cell transplant (HSCT) patients at admission and restricts uncooked vegetables, fruits without thick peels, undercooked meats/seafood, and any restaurant food. Autologous (auto) HSCT patients follow a regular diet with food safety education according to Center for Disease Control (CDC) and Food and Drug Administration (FDA). The neutropenic diet is not endorsed by the CDC and FDA due to lack of evidence to support it. We hypothesize the neutropenic diet offers limited advantage over the FDA and CDC food safety guidelines in respect to rates of neutropenic fever or infection. Methods We performed a retrospective descriptive review of consecutive pediatric patients >1 year of age that underwent HSCT between June 2016 and February 2017 to assess fever and infectious complications occurring before engraftment. All patients were placed on prophylactic antibiotic therapy (cipro and pen VK) on admission until fever or engraftment. Results A total of 72 HSCT procedures were conducted on our inpatient unit (Auto, 24 and Allo 48). Median age at HSCT was 6 years (Range 1-24 years). Of 72 total transplants, 56 (78%) had at least one fever episode from the start of conditioning until engraftment. The median day of fever was day -2. 6 of 57 episodes of fever were due to blood steam infection (3 allogeneic; 3 autologous), Organisms included Bacillus species, Enterobacter cloacae, acid fast bacilli, Streptococcus oralis and Staph epidermidis. Twenty-eight patients had diarrhea, five had identified stool pathogens to include C.difficile (n=2), Adenovirus (n=3), Norovirus (n=1), E.coli (N=1), of note 2 patients had 2 concurrent infections present. Sixty seven(89%) patients received TPN for a median of 41 days (ranging from 9-233 days) for allogeneic and median of 20 days (ranging from 6-170 days) for autologous recipients. Thirty seven (49%) patients had clinically documented mucositis (see Table 1). Discussion Fevers were commonly chemotherapy related and infectious causes were rare for both auto HSCT on a regular diet and allo HSCT on a neutropenic diet. Antibiotic practices may contribute to outcomes. Further investigation evaluating the safety of the FDA diet during the neutropenic period of HSCT is warranted to improve overall nutrition and quality of life. [ABSTRACT FROM AUTHOR]

Patients undergoing chemotherapy and especially hematopoietic stem cell transplantation (HSCT) require frequent transfusions, and thus, transfusion reaction (TR) vigilance is critical in this population. The reported incidence of TRs across all patients is 2%, and pediatric patients may experience 2-2.6 times more reactions than adults. However, the TR profile may differ in the immunocompromised population. There is a paucity of data in this area, as pediatric oncology and HSCT patients are often excluded from TR studies. Our goals were to assess the prevalence and describe TRs among immunocompromised pediatric patients and to improve recognition of TRs across this population. Pediatric clinical providers completed a TR training module in May – June, 2019. A single-institution retrospective review was conducted. All TRs in patients aged less than 25 years were reviewed over a 3-month period from July 1, 2019 to October 1, 2019. Over a 3-month period, 1,786 transfusions were administered in our designated population. Of those, 50.4% were platelets, 44.0% were red blood cells (RBC), 3.4% were cryoprecipitate, 1.4% were thawed plasma, and 0.8% were granulocytes. Those undergoing HSCT consumed 27.7% of total transfusions. Of all transfusions, there were 48 (2.7%) reported as possible TRs by nursing. Of those, 30 (1.7% of all transfusions) were adjudicated as true TRs. Fourteen (46.7%) of these true TRs were in patients with leukemia, 9 (30.0%) with HSCT, 5 (16.7%) with solid tumors, and 2 (6.7%) with aplastic anemia. Of the 9 reactions in HSCT patients, 4 occurred in allogeneic transplant recipients (3 umbilical cord blood and one matched unrelated donor) and 5 were in those receiving autologous HSCT. In HSCT patients, 1.8% of transfusions resulted in TRs compared to 1.6% in non-HSCT patients. Of the products triggering reactions, platelets accounted for 22 TRs (73.3%) and RBCs accounted for 8 TRs (26.7%). Of all 30 TRs, 15 (50%) were classified as febrile non-hemolytic transfusion reactions (FNHTR), 14 (46.7%) were considered allergic reactions, and 1 (3.3%) was diagnosed as transfusion-associated circulatory overload. Pre-medication was given in 22 (76.7%) of transfusions causing reactions. Of the 18 reports that were not adjudicated as true TRs, most (n=15) were generated for fever, but deemed unrelated to transfusion. Our baseline analysis revealed a higher prevalence than our historical institutional prevalence (1.7% vs. 1.3%), consistent with higher rates of TRs in the pediatric population, but lower than the 2% quoted in the literature, suggesting either underreporting or a different TR phenotype in this population. This population had a higher prevalence of FNHTR than the general pediatric population (50.0% vs. 31.5%). High rates of pre-medication and comorbidities (resulting in fevers) may influence TR presentation in this population. [ABSTRACT FROM AUTHOR]

Immune effector cell associated neurotoxicity (ICANS) and cytokine release syndrome (CRS) are unique potentially life-threatening complications associated with immune effector cell (IEC) therapies. ICANS presents with varying symptoms ranging from confusion to seizure and cerebral edema. There is no consensus on the precise pathophysiology related to ICANS. The incidence of this toxicity may vary based on the specific product, underlying diagnosis and host factors. Here, we characterize ICANS in pediatric and adult young adolescent (AYA) patients receiving IEC therapy at our institution. We reviewed clinical characteristics, neurological severity and outcomes in pediatric and AYA patients who received IEC standard of care products from 2018-2019 at MDACC. Severity was retrospectively assessed based on ASTCT Consensus Criteria. Nine patients, median age 15.5 (range: 3-25) years received standard of care, chimeric antigen receptor (CART) IEC therapy. The primary diagnoses were pre-B cell acute lymphoblastic leukemia (ALL) (n=8) and primary mediastinal large B-cell lymphoma (n=1). Of these patients, 4 (44%) developed ICANS within a median of 8 (range: 3-27) days of CAR T cell infusion. ICANS was associated with CRS in all affected patients, occurring within a median of 6 (range: 2-7) days after CRS. Median CRS and ICANS severity grade was 2 (range 1-4) in all 9 patients. Symptoms included altered mental status (AMS) (5), seizure (1), aphasia (2), impaired ability to write a standard sentence (4). Neuroimaging did not correlate to ICANS symptoms or severity. EEG was obtained in 3 affected patients but only correlated to background slowing in one with aphasia. Lumbar puncture was performed in 2 patients with ICANS and was remarkable for lymphocytosis. All patients had received prophylactic anti-epileptic medication. All patients received tocilizumab for concomitant CRS and 3 received steroids. Almost half of pediatric patients receiving standard of care CART products may experience ICANS within one week CAR T cell infusion that is associated with CRS. Pleocytosis in the CSF may be due to CAR-T trafficking into the CSF and prospective studies may clarify its significance. Impaired ability to write a standard sentence and the Cornell Assessment of Pediatric Delirium (CAPD) may be early indicators of ICANS in pediatric/AYA patients. [ABSTRACT FROM AUTHOR]

Introduction Matched related donor (MRD) hematopoietic cell transplant (HCT) is an accepted treatment for sickle cell disease (SCD). Alemtuzumab is a lymphocytic medication that can reduce the risk of GVHD; however, it is associated with mixed donor chimerism (MDC) and graft loss when used with submyeloablative conditioning. We explored the use of myeloablative chemotherapy with alemtuzumab in MRD HCT for SCD to concurrently prevent GVHD and promote durable engraftment. Methods We retrospectively reviewed outcomes for patients that underwent MRD HCT for SCD at Texas Children's Hospital between 2003-2017. All patients received busulfan intravenously every 6 hours for 4 days (target AUC: 800-1200 μM per minute) and cyclophosphamide 50 mg/kg daily for 4 days. GVHD prophylaxis included intravenous alemtuzumab daily for 3-4 doses starting on day -5 (5-15 kg=3 mg, 15-30 kg=5 mg, >30 kg= 10 mg daily), methotrexate and a calcineurin inhibitor. Donor chimerism was evaluated periodically via short tandem repeats or fluorescent-in-situ hybridization of nucleated cells from the peripheral blood. Persistent MDC was defined by the presence of recipient cells on 2 consecutive evaluations without return to full donor chimerism at last follow-up. Results Thirty-eight consecutive patients underwent MRD transplant (3 non-sibling and 35 sibling) with a median age at transplant of 8.6 yrs (range: 2.9-18.4 yr). Stem cell source consisted of bone marrow grafts for all patients. Two patients concurrently received cord blood from the same donor. Neutrophil engraftment was achieved in all patients at a median time of 19 days (range: 13-24 days). Incidence of persistent MDC was 60.5% with a median last chimerism of 94% donor cells (range: 24-100%). Three of 23 patients (13.0%) with persistent MDC had <50% donor cells. The single patient with severe MDC <25% stabilized at 24% at 2 yrs post-HCT with concurrent Hgb S <50% on electrophoresis reflective of sickle cell trait in the donor. Graft rejection and recurrence of SCD related symptoms were not observed in any patient. No additional cell products were given to manage mixed chimerism. Overall incidence of significant acute GVHD (grade II-IV) was 5.3%. One patient developed limited chronic GVHD. Overall survival was 94.7% with a median time to last follow-up of 2.9 yrs (range: 90-4627 days). Two deaths occurred secondary to transplant-related complications including 1 death <100 days from HCT due to disseminated Mycobacterium tuberculosis and 1 secondary to hemophagocytic syndrome on day +318. Conclusions Myeloablative conditioning was well tolerated, and the addition of alemtuzumab minimized occurrence of significant GVHD. Chimerism stabilized at >50% donor cells in most patients and no graft rejection or recurrence of SCD occurred. This regimen may be a promising approach for patients with SCD that can tolerate myeloablative chemotherapy. [ABSTRACT FROM AUTHOR]