Clofarabine with topotecan, vinorelbine, and thiotepa reinduction regimen for children and young adults with relapsed AML.

Effective reinduction regimens are needed for children with relapsed and refractory acute myeloid leukemia (AML), as outcomes remain poor. Therapeutic options are limited in this heavily pretreated patient population, many of whom have reached lifetime recommended doses of anthracycline chemotherapy. The development of effective non-anthracycline-based salvage regimens is crucial to these patients who are at significant risk of life-threatening cardiotoxicity.

Impact of Bridging Chemotherapy on Clinical Outcomes of CD19-Specific CAR T Cell Therapy in Children/Young Adults with Relapsed/Refractory B Cell Acute Lymphoblastic Leukemia.

Chimeric antigen receptor (CAR) T cells achieve response and durable remission in patients with relapsed/refractory (R/R) B cell malignancies. Following collection of patient T cells, chemotherapy ("bridging chemotherapy") is utilized during the manufacture of CAR T cells. However, the optimal bridging chemotherapy has yet to be defined.

11p15.5 epimutations in children with Wilms tumor and hepatoblastoma detected in peripheral blood.

Background: Constitutional or somatic mosaic epimutations are increasingly recognized as a mechanism of gene dysregulation resulting in cancer susceptibility. Beckwith-Wiedemann syndrome is the cancer predisposition syndrome most commonly associated with epimutation and is extremely variable in its phenotypic presentation, which can include isolated tumors. Because to the authors' knowledge large-scale germline DNA sequencing studies have not included methylation analysis, the percentage of pediatric cancer predisposition that is due to epimutations is unknown.

Toxicity and response after CD19-specific CAR T-cell therapy in pediatric/young adult relapsed/refractory B-ALL.

Chimeric antigen receptor (CAR) T cells have demonstrated clinical benefit in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We undertook a multicenter clinical trial to determine toxicity, feasibility, and response for this therapy. A total of 25 pediatric/young adult patients (age, 1-22.

Treatment of higher risk acute lymphoblastic leukemia in young people (CCG-1961), long-term follow-up: a report from the Children's Oncology Group.

Children's Cancer Group CCG-1882 improved outcome for 1-21-year old with high risk acute lymphoblastic leukemia and Induction Day 8 marrow blasts ≥25% (slow early responders, SER) with longer and stronger post induction intensification (PII). This CCG-1961 explored alternative PII strategies. We report 10-year follow-up for patients with rapid early response (RER) and for the first time details our experience for SER patients.

A case of fusion-associated acute megakaryoblastic leukemia.

Acute megakaryoblastic leukemia (AMKL) constitutes ∼5%-15% of cases of non-Down syndrome AML in children, and in the majority of cases, chimeric oncogenes resulting from recurrent gene rearrangements are identified. Based on these rearrangements, several molecular subsets have been characterized providing important prognostic information. One such subset includes a group of patients with translocations involving the gene, which has been associated with various fusion partners in patients with AMKL.

Maintenance chemotherapy to reduce the risk of a metachronous Wilms tumor in children with bilateral nephroblastomatosis.

From 2009 to 2018, 10 consecutive patients with Wilms tumors and bilateral nephroblastomatosis, who had completed standard therapy, were provided a maintenance chemotherapy regimen consisting of vincristine and dactinomycin every 3 months for 12 months in order to prevent an early metachronous Wilms tumor. One patient (10%) with Beckwith-Wiedemann syndrome developed a new tumor, without anaplasia. There were no significant toxicities reported during maintenance.

Outcome of children and adolescents with relapsed Hodgkin lymphoma treated with high-dose therapy and autologous stem cell transplantation: the Memorial Sloan Kettering Cancer Center experience.

To evaluate outcomes and prognostic markers among children with relapsed Hodgkin lymphoma (HL) treated with autologous stem cell transplant (ASCT), we conducted a retrospective analysis of 36 consecutive pediatric patients treated at Memorial Sloan Kettering Cancer Center from 1989 to 2013. With a median follow-up of 9.6 years, the 10-year overall survival (OS) and event-free survival (EFS) were 74.

Allogeneic Hematopoietic Stem Cell Transplantation with Myeloablative Conditioning Is Associated with Favorable Outcomes in Mixed Phenotype Acute Leukemia.

Mixed phenotype acute leukemia (MPAL) represents a poorly characterized group of acute leukemias that lack an accepted therapeutic approach and are typically associated with poor outcomes. We present our experience of genomic profiling, pretransplantation therapy, and transplantation outcomes for 36 well-characterized pediatric and adult patients with MPAL, defined according to the 2016 World Health Organization leukemia update. A predominance of acute lymphoid leukemia (ALL)-associated mutations and cytogenetic abnormalities was noted.

Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia.

Somatic mutations affecting ETV6 often occur in acute lymphoblastic leukemia (ALL), the most common childhood malignancy. The genetic factors that predispose to ALL remain poorly understood. Here we identify a novel germline ETV6 p.

PET-adapted sequential salvage therapy with brentuximab vedotin followed by augmented ifosamide, carboplatin, and etoposide for patients with relapsed and refractory Hodgkin's lymphoma: a non-randomised, open-label, single-centre, phase 2 study.

Background: Pre-transplantation (18)F-fluorodeoxyglucose (FDG) PET-negativity is one of the strongest predictors of outcome after high-dose therapy and autologous stem-cell transplant (HDT/ASCT) for patients with relapsed or refractory Hodgkin's lymphoma. In this study, we assessed the feasibility and activity of PET-adapted salvage therapy with brentuximab vedotin, followed by augmented ifosfamide, carboplatin, and etoposide (ICE).

Methods: In this non-randomised, open-label, single-centre, phase 2 trial, we enrolled patients with relapsed or refractory Hodgkin's lymphoma who had failed one previous doxorubicin-containing chemotherapy regimen.

ALK-positive (2p23 rearranged) anaplastic large cell lymphoma with localization to the skin in a pediatric patient.

Anaplastic large cell lymphoma (ALCL) either as primary cutaneous or nodal disease is rare in children and difficult to distinguish, which is important both prognostically and for treatment purposes. We present a case of anaplastic lymphoma kinase (ALK)+ skin-limited ALCL that highlights this challenge and draws attention to pitfalls in assessing ALK status. The patient was an 11-year old girl with a twice recurrent nodule on her right shoulder.

High-dose cyclophosphamide for the treatment of refractory T-cell acute lymphoblastic leukemia in children.

Despite an almost 80% overall survival rate in pediatric T-cell acute lymphoblastic leukemia (T-ALL), there is a subset of patients who are refractory to standard chemotherapy regimens and could benefit from novel treatment approaches. Over a 2-year period, we treated 5 pediatric patients with refractory T-ALL, aged 3 to 15 years, with high-dose cyclophosphamide (CY) at a dose of 2100 mg/m for 2 consecutive days either alone (n=1) or in combination with other chemotherapy agents (n=4). Four of these 5 patients had a 1.

Phase II trial of clofarabine with topotecan, vinorelbine, and thiotepa in pediatric patients with relapsed or refractory acute leukemia.

Background: Outcomes for children with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) are dismal. In an effort to improve outcomes, we performed a phase I/II study of a novel clofarabine based combination regimen called TVTC. Herein, we report the response rates of patients in the phase II portion of the study.

Ten-year follow-up of pediatric patients with non-Hodgkin lymphoma treated with allogeneic or autologous stem cell transplantation.

Background: Autologous or allogeneic hematopoietic stem cell transplant (SCT) is often considered in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) but there are limited data on the use of SCT for the treatment of NHL in the pediatric setting.

Procedure: To evaluate the role of SCT for children with NHL, we reviewed 36 consecutive pediatric patients with NHL who underwent an allogeneic (n = 21) or autologous (n = 15) SCT at our institution between 1982 and 2004. Pathologic classification included: lymphoblastic lymphoma (n = 12), Burkitt lymphoma (BL) (n = 5), diffuse large B-cell lymphoma (n = 4), anaplastic large cell lymphoma (ALCL) (n = 13), peripheral T cell lymphoma (n = 1), and undifferentiated NHL (n = 1).

CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia.

Adults with relapsed B cell acute lymphoblastic leukemia (B-ALL) have a dismal prognosis. Only those patients able to achieve a second remission with no minimal residual disease (MRD) have a hope for long-term survival in the context of a subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We have treated five relapsed B-ALL subjects with autologous T cells expressing a CD19-specific CD28/CD3ζ second-generation dual-signaling chimeric antigen receptor (CAR) termed 19-28z.

Effect of alternate-week versus continuous dexamethasone scheduling on the risk of osteonecrosis in paediatric patients with acute lymphoblastic leukaemia: results from the CCG-1961 randomised cohort trial.

Background: Acute lymphoblastic leukaemia (ALL) is curable in more than 80% of children and adolescents who exhibit high-risk features. However, treatments are associated with symptomatic osteonecrosis that disproportionately affects adolescents. Based on the findings from the CCG-1882 trial, the CCG-1961 trial was designed to assess whether dexamethasone dose modification would reduce the risk of osteonecrosis.

Factors associated with relapse and survival in Wilms tumor: a multivariate analysis.

Purpose: Lymph node metastasis and anaplasia predict relapse-free survival in Wilms tumor. We performed a multivariate analysis of our institutional database to identify factors independently associated with relapse-free and overall survival.

Methods: We retrospectively reviewed cases of confirmed Wilms tumor diagnosed between 1990 and 2010 and treated at our institution.

Successful treatment of refractory metastatic histiocytic sarcoma with alemtuzumab.

Background: Histiocytic sarcoma (HS) is an exceedingly rare tumor and carries a dismal prognosis when patients present with advanced-stage disease. Because of the poor response rates to conventional chemotherapy and the rarity of the disease, no standard of care exists for patients with HS. The authors report the single-agent use of the anti-CD52 antibody alemtuzumab in 2 patients who had advanced-stage HS.

Allogeneic hematopoietic stem cell transplantation for pediatric patients with treatment-related myelodysplastic syndrome or acute myelogenous leukemia.

The development of treatment-related myelodysplastic syndrome (tMDS) or treatment-related acute myelogenous leukemia (tAML) is a complication that can occur after chemotherapy or radiation therapy. Eighteen patients with a previous malignancy treated at our institution and three patients with a nonmalignant primary tumor received an allogeneic hematopoietic stem cell transplant (HSCT) on the pediatric bone marrow (BM) transplantation service for the treatment of tMDS/tAML over a 15-year period. Five patients proceeded to HSCT without induction chemotherapy.

Phase 2 trial of clofarabine in combination with etoposide and cyclophosphamide in pediatric patients with refractory or relapsed acute lymphoblastic leukemia.

The outcomes in children with refractory/relapsed (R/R) acute lymphoblastic leukemia (ALL) are dismal. The efficacy and safety of intravenous clofarabine 40 mg/m(2) per day, cyclophosphamide 440 mg/m(2) per day, and etoposide 100 mg/m(2) per day for 5 consecutive days in pediatric patients with R/R ALL was evaluated in this phase 2 study. The primary endpoint was overall response rate (complete remission [CR] plus CR without platelet recovery [CRp]).

Population pharmacokinetics of clofarabine and its metabolite 6-ketoclofarabine in adult and pediatric patients with cancer.

Clofarabine for injection is a second-generation nucleoside analog approved in the United States (Clolar(®)) and Europe (Evoltra(®)) for the treatment of pediatric relapsed or refractory acute lymphoblastic leukemia. This report describes the population pharmacokinetics of clofarabine and its metabolite 6-ketoclofarabine in adult and pediatric patients with hematologic malignancies or solid tumors. Clofarabine pharmacokinetics were best described by a 2-compartment model with linear elimination and first-order absorption after oral administration.

Effect of hemodialysis on the plasma levels of clofarabine.

Clofarabine, a nucleoside analogue for treatment of relapsed leukemia, is 50-60% excreted in urine. Clofarabine has not been studied in patients on hemodialysis. We measured levels in one patient in acute renal failure.

Intraventricular meningioma after cranial irradiation for childhood leukemia.

Meningiomas are among the most common brain tumors in adults. They are most commonly located over the cerebral convexities and are infrequently found in an intraventricular location. Ionizing cranial radiation is a risk factor for late occurrence of meningiomas within the radiation field.