Purpose: Approximately 30%-40% of pediatric acute myeloid leukemia (AML) patients relapse. In this study, we analyzed the outcome and prognostic factors of relapsed AML patients who had previously received first-line therapy at our institution. Materials and Methods: The study group consisted of 50 patients who had been diagnosed with AML from April 2009 to December 2018, and then showed first relapse. Thirty-two of the patients (64%) had previously received allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR). Results: Forty-five of the patients (90%) received intensive chemotherapy upon diagnosis of relapse, and 76% (34/45) of these patients achieved a second CR. Estimated 5-year overall survival for these 45 patients was 44.9%±7.6%. Time from diagnosis to relapse, extramedullary involvement (EMI) at diagnosis, core binding factor AML, and complex karyotype were significant prognostic factors; in multivariate study, both time from diagnosis to relapse and EMI at diagnosis proved significant. There was no difference in 5-year disease-free survival between patients previously treated with chemotherapy only and those who received HSCT in first CR (52.4%±14.9% vs. 52.6%±11.5%). Of the 19 patients who achieved second CR after previous allogeneic HSCT in first CR and subsequent relapse, 11 were treated with chemotherapy only, and seven survive disease-free. Conclusion Intensive therapy allowed for long-term survival in 40%-50% of patients, and 50% of patients who achieved second CR, regardless of prior treatment modalities in first CR. Intensive treatment may allow for salvage of a significant portion of patients with relapsed pediatric AML.

Hemophagocytic lymphohistiocytosis-like toxicity following chimeric antigen receptor (CAR)-T cell therapy (carHLH) is a rare and fulminant complication. Currently, there are neither well-established diagnostic criteria nor optimal treatment option for carHLH. Given the similarities of hyperinflammatory process and cytokine profiles between cytokine release syndrome (CRS) and carHLH, tocilizumab and corticosteroids are the suggested front-line treatment options for both conditions. However, when carHLH is refractory to front-line treatment, alternative or adjunctive agents should be introduced to ameliorate ongoing hyperinflammation. Anakinra, a recombinant interleukin (IL)-1 receptor antagonist, has shown promising results in the management of carHLH. Although prospective trials are limited, the use of anakinra for severe CRS and carHLH has been increasing. In this case report, we present two cases of carHLH to discuss its characteristic clinical features, diagnostic criteria, and treatment option. In addition, we also highlight the clinical efficacy of anakinra for managing carHLH which was refractory to tocilizumab and dexamethasone.

Purpose: Recent cooperative trials in pediatric acute lymphoblastic leukemia (ALL) report long-term event-free survival (EFS) of greater than 80%. In this study, we analyzed the outcome and prognostic factors for patients with precursor B cell ALL (n=405) diagnosed during a 10-year period (2005-2015) at our institution. Materials and Methods: All patients were treated with a uniform institutional regimen based on four risk groups, except for steroid type; patients diagnosed up till 2008 receiving dexamethasone, while subsequent patients received prednisolone. None of the patients received cranial irradiation in first complete remission. Results: The 10-year EFS and overall survival was 76.3%±2.3% and 85.1%±1.9%. Ten-year cumulative incidence of relapse, any central nervous system (CNS) relapse and isolated CNS relapse was 20.8%±2.2%, 3.7%±1.1% and 2.5%±0.9% respectively. A comparison of established, good prognosis genetic abnormalities showed that patients with high hyperdiploidy had significantly better EFS than those with ETV6-RUNX1 rearrangement (10-year EFS of 91.2%±3.0% vs. 79.5%±4.4%, p=0.033). For the overall cohort, male sex, infant ALL, initial CNS involvement, and Philadelphia chromosome (+) ALL were significant factors for lower EFS in multivariate study, while high hyperdiploidy conferred favorable outcome. For high and very high risk patients (n=231), high hyperdiploidy was the only significant factor for EFS in multivariate study. Conclusion Regarding good prognosis genetic abnormalities, patients with high hyperdiploidy had significantly better outcome than ETV6-RUNX1 (+) patients. High hyperdiploidy was a major, favorable prognostic factor in the overall patient group, as well as the subgroup of patients with higher risk.

Purpose: Recent cooperative trials in pediatric acute lymphoblastic leukemia (ALL) report long-term event-free survival (EFS) of greater than 80%. In this study, we analyzed the outcome and prognostic factors for patients with precursor B cell ALL (n=405) diagnosed during a 10-year period (2005-2015) at our institution. Materials and Methods: All patients were treated with a uniform institutional regimen based on four risk groups, except for steroid type; patients diagnosed up till 2008 receiving dexamethasone, while subsequent patients received prednisolone. None of the patients received cranial irradiation in first complete remission. Results: The 10-year EFS and overall survival was 76.3%±2.3% and 85.1%±1.9%. Ten-year cumulative incidence of relapse, any central nervous system (CNS) relapse and isolated CNS relapse was 20.8%±2.2%, 3.7%±1.1% and 2.5%±0.9% respectively. A comparison of established, good prognosis genetic abnormalities showed that patients with high hyperdiploidy had significantly better EFS than those with ETV6-RUNX1 rearrangement (10-year EFS of 91.2%±3.0% vs. 79.5%±4.4%, p=0.033). For the overall cohort, male sex, infant ALL, initial CNS involvement, and Philadelphia chromosome (+) ALL were significant factors for lower EFS in multivariate study, while high hyperdiploidy conferred favorable outcome. For high and very high risk patients (n=231), high hyperdiploidy was the only significant factor for EFS in multivariate study. Conclusion Regarding good prognosis genetic abnormalities, patients with high hyperdiploidy had significantly better outcome than ETV6-RUNX1 (+) patients. High hyperdiploidy was a major, favorable prognostic factor in the overall patient group, as well as the subgroup of patients with higher risk.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for β-thalassemia major (TM) and sickle cell disease (SCD) in children. Graft-versus-host disease (GVHD) and treatment-related mortality (TRM) remain significant challenges to improving survival after HSCT. Here, we analyzed the outcome of TM and SCD patients, who received allogeneic HSCT with myeloablative conditioning at our institution. METHODS: Twenty-two patients (15 TM, 7 SCD), with a median age of 9 years (range, 1.6–16.9), underwent allogeneic HSCT using busulfan, cyclophosphamide and rabbit anti-thymocyte globulin-based conditioning. Cells were derived from either the bone marrow (8 patients), or peripheral blood stem cells (14 patients). The majority of patients received HSCT from a matched sibling donor (N=18). GVHD prophylaxis included cyclosporine and short course methotrexate. RESULTS: All patients achieved donor engraftment. Two SCD patients died from TRM-related grade IV gut GVHD (N=1) or severe bronchiolitis obliterans (BO) (N=1). Cumulative incidence of acute and chronic GVHD was 36.4% and 32.7%, respectively. Veno-occlusive disease (VOD) occurred in 8 patients (36.4%), but resolved in all instances. Epstein-Barr virus (EBV)-related post-transplantation lymphoproliferative disease (PTLD) occurred in 1 patient. The overall survival (OS) was 90.9% (TM 100%, SCD 71.4%), with all patients achieving transfusion independence, while 8 achieved complete donor chimerism. CONCLUSION: Busulfan, cyclophosphamide, and ATG-based conditioning for HSCT of TM and SCD patients did not result in graft failure, although modifications may be required to reduce VOD incidence. Further changes to donor type and cell source prioritization are necessary to minimize TRM and morbidity caused by GVHD.
Anemia, Sickle Cell ; Antilymphocyte Serum* ; beta-Thalassemia ; Bone Marrow ; Bronchiolitis Obliterans ; Busulfan ; Child ; Chimerism ; Cyclophosphamide ; Cyclosporine ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Hemoglobinopathies* ; Herpesvirus 4, Human ; Humans ; Incidence ; Methotrexate ; Mortality ; Siblings ; Stem Cells ; Tissue Donors ; Transplants

Non-Down syndrome pediatric acute megakaryoblastic leukemia (AMKL) may be classified according to the presence of recurrent genetic abnormalities with prognostic relevance. In this case study, we report on a girl with AMKL, 32 months old at the time of diagnosis, in whom we confirmed the presence of the cryptic, poor prognosis NUP98::KDM5A fusion. The patient achieved complete remission (CR) with the first course of chemotherapy, underwent haploidentical family donor hematopoietic stem cell transplantation (HSCT) without event, but relapsed 5 months after HSCT. Through this case report, we emphasize the good initial response to chemotherapy, and the early relapse despite undergoing HSCT in first CR. We review the limited literature on NUP98::KDM5A (+) pediatric AML, and underscore the need for further study to improve the outcome of patients with this rare AML subtype.

Non-Down syndrome pediatric acute megakaryoblastic leukemia (AMKL) may be classified according to the presence of recurrent genetic abnormalities with prognostic relevance. In this case study, we report on a girl with AMKL, 32 months old at the time of diagnosis, in whom we confirmed the presence of the cryptic, poor prognosis NUP98::KDM5A fusion. The patient achieved complete remission (CR) with the first course of chemotherapy, underwent haploidentical family donor hematopoietic stem cell transplantation (HSCT) without event, but relapsed 5 months after HSCT. Through this case report, we emphasize the good initial response to chemotherapy, and the early relapse despite undergoing HSCT in first CR. We review the limited literature on NUP98::KDM5A (+) pediatric AML, and underscore the need for further study to improve the outcome of patients with this rare AML subtype.

Non-Down syndrome pediatric acute megakaryoblastic leukemia (AMKL) may be classified according to the presence of recurrent genetic abnormalities with prognostic relevance. In this case study, we report on a girl with AMKL, 32 months old at the time of diagnosis, in whom we confirmed the presence of the cryptic, poor prognosis NUP98::KDM5A fusion. The patient achieved complete remission (CR) with the first course of chemotherapy, underwent haploidentical family donor hematopoietic stem cell transplantation (HSCT) without event, but relapsed 5 months after HSCT. Through this case report, we emphasize the good initial response to chemotherapy, and the early relapse despite undergoing HSCT in first CR. We review the limited literature on NUP98::KDM5A (+) pediatric AML, and underscore the need for further study to improve the outcome of patients with this rare AML subtype.