Refining risk stratification in paediatric B-acute lymphoblastic leukaemia: Combining IKZF1plus and Day 15 MRD positivity.

This study investigates the potential utility of IKZF1 deletion as an additional high-risk marker for paediatric acute lymphoblastic leukaemia (ALL). The prognostic impact of IKZF1 status, in conjunction with minimal/measurable residual disease (MRD), was evaluated within the MRD-guided TPOG-ALL-2013 protocol using 412 newly diagnosed B-ALL patients aged 1-18. IKZF1 status was determined using multiplex ligation-dependent probe amplification. IKZF1 deletions, when co-occurring with CDKN2A, CDKN2B, PAX5 or PAR1 region deletions in the absence of ERG deletions, were termed IKZF1plus. Both IKZF1 deletion (14.6%) and IKZF1plus (7.8%) independently predicted poorer outcomes in B-ALL. IKZF1plus was observed in 4.1% of Philadelphia-negative ALL, with a significantly lower 5-year event-free survival (53.9%) compared to IKZF1 deletion alone (83.8%) and wild-type IKZF1 (91.3%) (p < 0.0001). Among patients with Day 15 MRD ≥0.01%, provisional high-risk patients with IKZF1plus exhibited the worst outcomes in event-free survival (42.0%), relapse-free survival (48.0%) and overall survival (72.7%) compared to other groups (p < 0.0001). Integration of IKZF1plus and positive Day 15 MRD identified a subgroup of Philadelphia-negative B-ALL with a 50% risk of relapse. This study highlights the importance of assessing IKZF1plus alongside Day 15 MRD positivity to identify patients at increased risk of adverse outcomes, potentially minimizing overtreatment.

Pediatric acute lymphoblastic leukemia with t(1;19)/TCF3-PBX1 in Taiwan.

BACKGROUND: In childhood acute lymphoblastic leukemia (ALL), t(1;19)(q23;p13.3) with TCF3-PBX1 fusion is one of the most frequent translocations. Historically, it has been associated with poor prognosis. Intensive treatment, however, has improved its outcome. We determined the outcome of children with this genotype treated with contemporary intensive chemotherapy in Taiwan. PROCEDURE: In Taiwan Pediatric Oncology Group 2002 ALL studies, genotypes were determined by cytogenetic analysis and/or reverse transcriptase polymerase chain reaction assay. Based on presenting features, immunophenotype and genotype, patients were assigned to one of the three risk groups: standard risk (SR), high risk (HR), or very high risk (VHR). The patients with t(1;19)/TCF3-PBX1 were treated in the HR arm receiving more intensive chemotherapy. The outcomes of patients with t(1;19)/TCF3-PBX1 were compared to that of patients with other subtypes of B-precursor ALL (B-ALL). RESULTS: Of the 1,129 patients with B-ALL, 64 (5.7%) had t(1;19)/TCF3-PBX1; 51 of whom were treated in the HR arm, but 11 were treated in the VHR and 2 in the SR arm because of physician's preference. As a group, 64 patients with t(1;19)/TCF3-PBX1 had similar 5-year event-free survival (83.3 ± 4.8%) as those with TEL-AML1 (85.2 ± 3.4%, P = 0.984) or those with hyperdiploidy >50 (84.0 ± 3.1%, P = 0.748). The cumulative risk of any (isolated plus combined) central nervous system relapse among patients with t(1;19)/TCF3-PBX1 (8.7 ± 3.8%) tended to be higher than that of patients with TEL-AML1 (5.8 ± 2.3%, P = 0.749) or those with hyperdiploidy (4.1 ± 1.8%, P = 0.135), albeit the differences did not reach statistical significance. CONCLUSIONS: With contemporary intensive chemotherapy, children with t(1;19)/TCF3-PBX1 fared as well as those with favorable genotypes (TEL-AML1 or hyperdiploidy).

Development of a gastric carcinoid tumor following allogeneic hematopoietic stem cell transplantation for early T-cell precursor acute lymphoblastic leukemia.

Gastric carcinoid tumor is rarely diagnosed in children. We report a case of gastric carcinoid tumor that occurred after allogeneic HSCT. A 13-year-old girl with ETP acute lymphoblastic leukemia underwent allogeneic HSCT from a 7/8 HLA-matched unrelated donor. She presented with rashes, abdominal pain, and diarrhea, which were suggestive of GVHD, 7 months after HSCT. Immunosuppressive agents failed to resolve these symptoms well. After a series of evaluations, carcinoid syndrome caused by a gastric carcinoid tumor was diagnosed. The tumor was located in the antral region and resulted in partial gastric outlet obstruction. She received subtotal gastrectomy with regional lymph node dissection. However, she had a flare-up of GVHD 1 month after surgery, and immunosuppressive therapy was intensified accordingly. Although her GVHD was getting better, she developed respiratory syncytial viral pneumonia with rapid progression to respiratory failure. She died of multiple organ failure 2 months postoperatively. This is the first pediatric case of a gastric carcinoid tumor following allogeneic HSCT. Our case also highlights the necessity for pediatric transplant physicians to be aware of carcinoid syndrome caused by this rare tumor in the setting of GVHD with poor response to immunosuppressive agents.

Epstein-Barr Virus-related Posttransplant Lymphoproliferative Disorder in Children: A Single-institution Experience.

We report 4 pediatric cases of biopsy-proven posttransplant lymphoproliferative disorder (PTLD) in the context of allogeneic hematopoietic stem cell transplantation (HSCT). All cases showed diffuse staining with latent membrane protein-1 in immunohistochemistry. The median age at transplant of 4 patients with PTLD was 10.1 years (range, 2.2 to 13.2 y). The median interval between HSCT and the diagnosis of PTLD was 5.5 months (range, 4 to 8 mo). All patients were treated with rituximab at dosage of 375 mg/m at weekly intervals. Reduction of immunosuppression was warranted in all cases. All patients survived with median follow-up duration of 27 months. Although PTLD has been rare following allogeneic HSCT, reduction of immunosuppression combined with rituximab yielded significant response rates in patients with this infrequent but potentially lethal complication. The preliminary finding of this study demonstrated that severe aplastic anemia is closely associated with the development of PTLD in children.

Successful hematopoietic reconstitution by unrelated donor cord blood transplantation in children with Fanconi anemia: report of 3 cases.

To potentially reduce late effects of malignancy and chronic graft-versus-host disease in patients with Fanconi anemia, 3 patients received unmanipulated umbilical cord blood grafts with 0 or 1 HLA antigen mismatch. The conditioning regimen consisted of fludarabine (30 mg/m/d) for 6 days, cyclophosphamide (60 mg/kg/d) for 2 days, and rabbit antithymocyte globulin (ATG) (2.5 mg/kg/d) for 3 days. Radiation was not used in the preparative regimen. None of the patients had significant conditioning-related toxicity. All were engrafted within 10 to 19 days. All patients are well with stable or full donor chimerism after a median follow-up of 64 months (range, 13 to 69 mo).

Vitiligo and Alopecia Areata After Donor Lymphocyte Infusions in a Child With Relapsed Acute Myeloid Leukemia.

Rarely do patients with chronic graft-versus-host disease (cGVHD) experience vitiligo and alopecia areata. Nevertheless, the exact cause of vitiligo and alopecia areata is still not fully understood. The patient experienced a relapse of acute myeloid leukemia (AML) following a second complete remission after undergoing HLA-6/8 mismatched unrelated donor hematopoietic cell transplantation (HCT). Achieving full donor chimerism was successful during the initial stages of the transplant. Nevertheless, the molecular evidence of measurable residual disease remained, prompting the administration of donor lymphocyte infusions (DLI) following a dose-escalation protocol. After three cycles of DLI given at two-month intervals, the circulating blasts eventually vanished. After the third DLI dose, vitiligo developed despite achieving molecular remission. The dermatologist confirmed the presence of vitiligo and alopecia areata, along with cutaneous cGVHD. The outcome was the complete elimination of the molecular presence, and the patient experienced both clinical and molecular remission for a period of five years following DLI. Based on our observations, it was found that DLI could effectively eradicate molecular leukemia in cases of AML relapse after HCT. The development of vitiligo and alopecia areata was influenced by the destruction of melanocytes due to autoimmune reactions caused by cGVHD.

Early Allogeneic Transplantation Favorably Influences the Outcome of Pediatric Acute Myeloid Leukemia-A Retrospective Study in a Single Center Over 2 Decades.

BACKGROUND: Transplantation advancements offer the potential for improving the prognosis of patients with acute myeloid leukemia (AML). Controversies surrounding indications and timing persist. We focused on identifying prognostic factors and exploring the advantages of early transplantation. PATIENTS AND METHODS: We studied 102 pediatric patients with AML (February 1999-August 2022), using Cox regression to analyze survival and hematopoietic cell transplantation (HCT) outcomes and Kaplan-Meier curves to assess HCT timing's impact on prognosis. RESULTS: "Treatment in First Complete Remission [CR1]: Chemotherapy" showed increased risk in multivariate and univariate Cox regression analyses, whereas "HCT during the study period" displayed divergent outcomes. Focusing on transplanted patients, "Treatment in CR1: Chemotherapy" still correlated with higher mortality risk. These findings emphasize the pivotal role of the treatment strategy adopted in CR1 on overall survival rather than HCT alone. Donor cytomegalovirus (CMV) positivity is also related to reduced mortality risk. Kaplan-Meier analysis supported superior 5-year survival rates with "HCT" compared with "chemotherapy" in CR1. In the 3-arm analysis, "HCT in CR1" demonstrated better 5-year overall survival (OS) and 5-year disease-free survival (DFS) compared with "Never HCT," whereas "HCT in CR2" had the least favorable prognosis (5-year OS: 79.2% vs 57.1% vs 50%, P = .056; 5-year DFS: 73.6% vs 55.2% vs 0%, P = .000). CONCLUSION: Our study highlights the benefits of transplantation during CR1 on prognosis. However, when contemplating CR1 transplantation recommendations, evaluation of various factors, such as the patient's clinical state, relapse risk, transplant-related mortality, CMV status, and other pertinent considerations, is vital. Comprehensive case discussions with patients and families are demanded in optimizing treatment.

Blinatumomab in Children with MRD-Positive B-Cell Precursor Acute Lymphoblastic Leukemia: A Report of 11 Cases.

Background/Objectives: Relapsed B-cell acute lymphoblastic leukemia (B-ALL) remains an unresolved matter of concern regarding adverse outcomes. This case study aimed to evaluate the effectiveness of blinatumomab, with or without door lymphocyte infusion (DLI), in treating measurable residual disease (MRD)-positive B-ALL. Methods: All patients who received blinatumomab salvage therapy were included in this study. Eleven patients were included in the study. All patients were evaluated for MRD-negativity. Results: Before starting blinatumomab therapy, seven patients tested positive for MRD, three tested negative, and one had refractory disease. Hematopoietic cell transplantation (HCT) was reserved for five patients with persistent MRD. Six patients became MRD-negative and subsequent HCT was not performed. Only two patients relapsed; one patient died of relapse, and the other one received carfilzomib-based therapy and was MRD-negative thereafter. Nine patients were MRD-negative at a median follow-up of 28 months (15-52 months). Two of three MRD-positive post-transplant patients remained in complete molecular remission after preemptive DLI at the last follow-up date. In the first salvage, blinatumomab may achieve complete remission and bridging to HCT in pediatric patients with end-of-induction MRD-positive B-cell precursor ALL. Conclusions: The decision on how to treat post-transplant relapse continues to affect survival outcomes. Blinatumomab combined with DLI may extend the armamentarium of release options for high-risk pediatric patients. This approach is encouraging for high-risk ALL patients who are MRD-positive post-transplantation.

Outcome of Tocilizumab Treatment in Febrile Neutropenic Children with Severe Sepsis/Septic Shock in a Single-Center Retrospective Case Series.

PURPOSE: To assess the efficacy of an IL-6 blockade with tocilizumab on treatment outcome of severe sepsis/septic shock in children with febrile neutropenia. METHODS: We performed a retrospective study of febrile neutropenic patients younger than 18 years old who developed severe sepsis/septic shock at a single medical center between November 2022 and October 2023. RESULTS: Seven patients with febrile neutropenia complicated with severe sepsis/septic shock were identified. Four of seven patients received tocilizumab in addition to standard of care. The median IL-6 level before administration of tocilizumab was 14,147 pg/mL (range: 672-30,509 pg/mL). All four patients successfully recovered from severe sepsis/septic shock. Three of seven patients received standard of care without tocilizumab. IL-6 levels were checked intwo2 patients, with a median of 1514.5 (range: 838-2191). Only one of three (33%) patients without tocilizumab therapy made a full recovery from severe sepsis/septic shock. The mortality rate was higher in patients without tocilizumab therapy compared to patients with tocilizumab therapy (67% vs. 0%). CONCLUSIONS: Administration of tocilizumab reduced mortality of severe sepsis/septic shock in children with febrile neutropenia. However, it warrants confirmation with a larger number of patients and a longer follow-up.

Harnessing and honing mesenchymal stem/stromal cells for the amelioration of graft-versus-host disease.

Allogeneic hematopoietic stem cell transplantation is a deterministic curative procedure for various hematologic disorders and congenital immunodeficiency. Despite its increased use, the mortality rate for patients undergoing this procedure remains high, mainly due to the perceived risk of exacerbating graft-versus-host disease (GVHD). However, even with immunosuppressive agents, some patients still develop GVHD. Advanced mesenchymal stem/stromal cell (MSC) strategies have been proposed to achieve better therapeutic outcomes, given their immunosuppressive potential. However, the efficacy and trial designs have varied among the studies, and some research findings appear contradictory due to the challenges in characterizing the in vivo effects of MSCs. This review aims to provide real insights into this clinical entity, emphasizing diagnostic, and therapeutic considerations and generating pathophysiology hypotheses to identify research avenues. The indications and timing for the clinical application of MSCs are still subject to debate.

Craniofacial involvement in Langerhans cell histiocytosis: A review of 44 cases at a single medical center.

BACKGROUND: Craniofacial bones are the most commonly involved site of Langerhans cell histiocytosis (LCH). The main purpose of this study was to clarify the relation between subsites of craniofacial bone and clinical presentation, treatment modalities, outcomes, and permanent consequences (PCs) in patients with LCH. METHODS: Forty-four patients diagnosed with LCH involving the craniofacial region presenting at a single medical center during 2001-2019 were collected and divided into four groups: single system with unifocal bone lesion (SS-LCH, UFB); single system with multifocal bone lesions (SS-LCH, MFB); multisystem without risk organ involvement (MS-LCH, RO-); and multisystem with risk organ involvement (MS-LCH, RO+). Data including demographics, clinical presentation, treatments, outcomes, and the development of PC were retrospectively reviewed. RESULTS: Temporal bone (66.7% versus 7.7%, p = 0.001), occipital bone (44.4% versus 7.7%, p = 0.022), and sphenoid bone (33.3% versus 3.8%, p = 0.041) involvement were more common in SS-LCH, MFB than they were in SS-LCH, UFB. No difference of reactivation rate was noted among the four groups. The most common PC is diabetes insipidus (DI), reported in 9 of the 16 (56.25%) patients with PC. The single system group was reported with the lowest incidence of DI (7.7%, p = 0.035). The reactivation rate was also higher in patients with PC (33.3% versus 4.0%, p = 0.021) or DI (62.5% versus 3.1%, p < 0.001). CONCLUSION: An increased risk of multifocal or multisystem lesions was associated with temporal bone, occipital bone, sphenoid bone, maxillary bone, eye, ear, and oral involvement, which may indicate poor outcomes. Longer follow-up may be indicated if there is the presence of PC or DI due to the high risk of reactivation. Therefore, multidisciplinary evaluation and treatment according to risk stratification are vital for patients diagnosed with LCH involving the craniofacial region.

Immersive Virtual Reality to Distract From Pain in Children Treated With L-asparaginase by Intramuscular Injection.

Background Treatment-related pain and discomfort are two of the most common manifestations in children with acute lymphoblastic leukemia (ALL). Patients with ALL are usually treated with L-asparaginase (L-ASP) by intramuscular injection. Children receiving L-ASP chemotherapy must bear adverse reactions such as pain caused by intramuscular injections. The use of virtual reality (VR) distraction technology could be a non-pharmacological intervention to bolster patients' comfort and decrease anxiety and procedure-related pain within hospital settings. Methodology The study explored the potential benefits of VR as a psychological intervention to induce positive emotions and reduce pain levels in participants receiving L-ASP injections. Participants in the study had the opportunity to select a nature theme of their choosing during their treatment session. The study provided a noninvasive solution that promoted relaxation to reduce anxiety by shifting an individual's mood positively during treatment. The objective was met by measuring participants' mood and pain levels before and after the VR experience and participant satisfaction with the use of the technology. This mixed-methods study of children aged six to 18 received L-ASP between April 2021 and March 2022, using a Numerical Rating Scale (NRS) with sheer numbers ranging from 0 (no pain) to 10 (extreme or most pain possible). Semi-structured interviews were conducted to collect new data and explore participants' thoughts and beliefs about a particular topic. A total of 14 patients participated. Descriptive statistics and content analysis are used to describe the data analyzed. VR is an enjoyable distraction intervention for managing treatment-related pain in ALL with intramuscular chemotherapy. Results Eight of 14 patients found a reduction in perceived pain after wearing VR. During the intervention implementation, the primary caregivers felt that the patient's pain perception was more positive when using the virtual reality device, and there was less resistance and less crying. Conclusions This study describes changes and experiences associated with pain and physical discomfort in children with ALL receiving intramuscular chemotherapy. This teaching model is applied to developing medical personnel, providing information about the disease and daily care, and educating the participants' family members. This study may expand the usage of VR applications so that more patients can benefit from them.

Association of CD34+ Cell Dose with Progression-free Survival after Allogeneic Peripheral Blood Hematopoietic Cell Transplantation in Children with Hematologic Malignancies.

BACKGROUND: A higher CD34+ cell dose is associated with improved engraftment but may also be associated with an increased risk of complications after allogeneic hematopoietic stem cell transplantation, including graft-versus-host disease (GVHD). METHODS: We retrospectively analyze the impact of CD34+ cell dose on OS, PFS, neutrophil engraftment, platelet engraftment, treatment-related mortality, and GVHD grading. RESULTS: For analyses, CD34+ cell dose was stratified into low (< 8.5 × 106/kg) and high (> 8.5 × 106/kg). A subgroup analysis of higher CD34+ cell dose leads to prolonged OS and PFS, but statistical significance was achieved only for PFS (OR 0.36; 95%CI 0.14-0.95; P = 0.04). CONCLUSIONS: This study reinforced that CD34+ cell dose at the time of allo-HSCT retained a positive impact on PFS.

Aloe vera gel for prevention of chemotherapy-induced hyperpigmentation: Four case reports.

RATIONALE: This study aimed to evaluate the efficacy of topical application of Aloe vera gel in preventing chemotherapy-induced hyperpigmentation (CIH). CIH is a common side effect of chemotherapy that causes skin irritation, redness, and itching. Aloe vera has been studied for its potential use in treating radiation-induced dermatitis, which may help alleviate some of the symptoms associated with this condition. PATIENT CONCERNS: In this study, 4 children requiring curative chemotherapy were prospectively enrolled and treated with Aloe vera gel. DIAGNOSIS: Acute skin reactions were monitored and classified according to the Common Terminology Criteria for Adverse Events Grading Scale. INTERVENTIONS: Patients were asked to use the gel on one-half of the body field twice daily from the beginning of treatment until 4 weeks after the completion of chemotherapy, with no medication to be used on the other half. OUTCOMES: The results indicate that applying Aloe vera gel may reduce the visibility of hyperpigmentation at subsequent time points. The most important observation was that the continued application of Aloe vera gel 4 weeks after the completion of chemotherapy was effective in reducing the grading of CIH. LESSONS: These effects highlight the potential of Aloe vera gel as a topical onconutraceutical treatment for CIH.

Allogeneic stem cell transplantation without preconditioning in a child with therapy-related myelodysplastic syndrome: A case report.

RATIONALE: Infants with mixed-lineage leukemia (MLL)-rearranged leukemia are usually refractory to standard induction therapy and are not immediate candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Chromosome 11q23 translocations, resulting in MLL rearrangement, have been well characterized in infant acute lymphoblastic leukemia (ALL). While t(4;11) ALL continues to have carry a bleak prognosis, patients with therapy-related myelodysplastic syndrome (t-MDS) have a shorter median overall survival than those compared with de novo MDS. PATIENT CONCERNS: We describe a child with t-MDS who evolved from MLL-rearranged ALL and was successfully treated with HSCT without toxic preconditioning. DIAGNOSES: MDS diagnosis was based on morphological characteristics of bone marrow dysplasia in patients with clinical manifestations evidence of hematopoiesis impairments by different combinations of anemia, leukopenia, neutropenia, and thrombocytopenia. INTERVENTIONS: Although the best donor for allo-HSCT is generally considered an human leukocyte antigen-matched sibling, only ~ 30% of patients have a suitable sibling. HSCT from an unrelated donor is a suitable option for patients with t-MDS who do not have matched sibling donors. OUTCOMES: Allo-HSCT without recipient preconditioning could be a promising treatment option for t-MDS, especially for patients with recurrent or persistent infections. LESSONS: Cytogenetics, prognosis, and treatment of t-MDS are briefly discussed. Preconditioning before allo-HSCT seriously damages immune function. This work reviews our experience with a patient with t-MDS following ALL complicated by recurrent infections, and highlights our choice to omit preconditioning from allo-HSCT.

A case series and literature review on 98 pediatric patients of germ cell tumor developing growing teratoma syndrome.

INTRODUCTION: Malignant germ cell tumors (MGCTs) can develop either extracranially or intracranially. Growing teratoma syndrome (GTS) may develop in these patients following chemotherapy. Reports on the clinical characteristics and outcomes of GTS in children with MGCTs are limited. METHODS: We retrospectively collected the data, including the clinical characteristics and outcomes of five patients in our series and 93 pediatric patients selected through a literature review of MGCTs. This study aimed to analyze survival outcomes and risk factors for subsequent events in pediatric patients with MGCTs developing GTS. RESULTS: The sex ratio was 1.09 (male/female). In total, 52 patients (53.1%) had intracranial MGCTs. Compared with patients with extracranial GCTs, those with intracranial GCTs were younger, predominantly boys, had shorter intervals between MGCT and GTS, and had GTS mostly occurring over the initial site (all p < 0.001). Ninety-five patients (96.9%) were alive. However, GTS recurrence (n = 14), GTS progression (n = 9), and MGCT recurrence (n = 19) caused a substantial decrease in event-free survival (EFS). Multivariate analyses showed that the only significant risk factors for these events were incomplete GTS resection and different locations of GCT and GTS. Patients without any risk had a 5-year EFS of 78.8% ± 7.8%, whereas those with either risk had 41.7% ± 10.2% (p < 0.001). CONCLUSION: For patients with high-risk features, every effort should be made to closely monitor, completely remove, and pathologically prove any newly developed mass to guide relevant treatment. Further studies incorporating the risk factors into treatment strategies may be required to optimize adjuvant therapy.

Malignant testicular tumors in children: A single institution's 12-year experience.

Testicular neoplasms are not commonly found in children and are a formidable threat if treated inappropriately. However, there is no consensus regarding its management. This study aimed to create a holistic picture of the interprofessional team in the management of malignant testicular tumors. Seventeen patients had mixed germ cell tumors, 15 had pure yolk sac tumors, 2 had immature teratomas, 2 had teratocarcinomas, and 1 had a sex cord stromal tumor. Five lesions were diagnosed as nongerm cell tumors: 2 embryonal rhabdomyosarcomas, 2 lymphomas, and 1 acute myeloid leukemia. At initial presentation, retroperitoneal (n = 2), bone marrow (n =1), and mediastinal (n = 1) metastases were identified in 4 (10%) patients. The operative interventions performed included radical inguinal orchiectomy (n = 5), scrotal orchiectomy (n = 31), and testicular biopsy or testis-sparing enucleation of the tumor (n = 6). Postoperatively, 18 patients received either adjuvant chemotherapy (n = 14) or chemoradiation (n = 5). Five patients with mixed germ cell tumors (n = 2), group IV paratesticular rhabdomyosarcoma (n = 2), and acute myeloid leukemia with myeloid sarcoma (n =1) died of disease progression. Thirty-six patients remained alive and disease-free at the last visit. Malignant testicular tumors in children deserve proper diagnostic support from a therapeutic perspective. Any concern or suspicion of a testicular tumor warrants an inguinal approach to avoid scrotal violation.

Comparable Outcomes Between Adolescent/Young Adults and Children With Acute Myeloid Leukemia Following Allogeneic Hematopoietic Cell Transplantation: A Single-Center Experience.

BACKGROUND: The cytogenetics of acute myeloid leukemia (AML) increases exponentially with age. Adolescent and young adult (AYA) patients have specific psychosocial and other challenges, influencing their ability to access appropriate treatment. Therefore, in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for AML, inferior outcomes would be observed in AYA patients compared to children. METHODS: We defined the age range of AYA patients as 15 to 29 years. Sixty-three patients who underwent allo-HSCT from 1998 to 2020 at Chang Gung Children Hospital were enrolled in this study. Overall survival was the time duration from HSCT to death from any cause. Disease-free survival was the time duration from HSCT to the last follow-up or first event (failure to achieve complete remission, relapse, secondary malignancy, or death from any cause). RESULTS: Thirty-seven (59%) patients were <15 years of age during allo-HSCT, and 26 (41%) were 15 to 29 years of age. The median age during allo-HSCT was 6.3 years for those <15 years of age compared with 15.7 years for AYA patients. The median follow-up period was 2.2 years after hematopoietic stem cell transplantation for patients <15 years old and 3.8 years after hematopoietic stem cell transplantation for AYA patients. Univariate analysis revealed no significant difference in the 5-year overall survival or disease-free survival among all patients. CONCLUSIONS: Several distinct AML subtypes could be amenable to treatment deintensification and targeted therapies. Furthermore, we found that children and AYA patients who underwent allo-HSCT for AML had similar survival.

Molecular genetics of ß-thalassemia: A narrative review.

ABSTRACT: ß-thalassemia is a hereditary hematological disease caused by over 350 mutations in the ß-globin gene (HBB). Identifying the genetic variants affecting fetal hemoglobin (HbF) production combined with the α-globin genotype provides some prediction of disease severity for ß-thalassemia. However, the generation of an additive composite genetic risk score predicts prognosis, and guide management requires a larger panel of genetic modifiers yet to be discovered.Presently, using data from prior clinical trials guides the design of further research and academic studies based on gene augmentation, while fundamental insights into globin switching and new technology developments have inspired the investigation of novel gene therapy approaches.Genetic studies have successfully characterized the causal variants and pathways involved in HbF regulation, providing novel therapeutic targets for HbF reactivation. In addition to these HBB mutation-independent strategies involving HbF synthesis de-repression, the expanding genome editing toolkit provides increased accuracy to HBB mutation-specific strategies encompassing adult hemoglobin restoration for personalized treatment of hemoglobinopathies. Allogeneic hematopoietic stem cell transplantation was, until very recently, the curative option available for patients with transfusion-dependent ß-thalassemia. Gene therapy currently represents a novel therapeutic promise after many years of extensive preclinical research to optimize gene transfer protocols.We summarize the current state of developments in the molecular genetics of ß-thalassemia over the last decade, including the mechanisms associated with ineffective erythropoiesis, which have also provided valid therapeutic targets, some of which have been shown as a proof-of-concept.