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.

Cytogenetic aberration in mixed-phenotype acute leukemia in children: A single-center retrospective review.

BACKGROUND: Mixed-phenotype acute leukemia (MPAL) poses a diagnostic and therapeutic dilemma. No consensus exists on the strategy to assign patients with MPAL to either lymphoid- or myeloid-directed treatment. Thus, a better understanding of the characteristics of MPAL is a crucial unmet need. This study aims to provide information on a population-based cohort of children who received treatment based on standard, simple immunophenotypic criteria. METHODS: Single-center, retrospective clinical and laboratory reviews of patients with MPAL were provided by morphology, immunophenotyping, cytogenetics, and molecular methods. We identified 242 flow cytometry samples. Of all consecutive pediatric patients with acute leukemia, we identified 8 (3.3%) patients with MPAL fulfilling WHO 2016 criteria; these were classified as follows: B-lymphoid + myeloid (n = 4), T-lymphoid + myeloid (n = 2), and B + T-lymphoid (n = 2). RESULTS: Of 8 MPAL cases, 4 were boys and 4 girls [median age at diagnosis: 10.8 (range 1.1-17) years]. The b3a2 (p210) and e1a2 (p190) BCR/ABL fusion transcripts were detected in 1 patient with B/myeloid MPAL. Regarding the morphology, all patients were initially diagnosed as acute lymphoblastic leukemia, but no morphological characteristics or cytogenetic aberration was particularly predictive of an MPAL. Furthermore, 4 of 8 patients (50%) with MPAL were associated with chromosome 21 monosomy or partial trisomy. CONCLUSION: Despite no single recurrent chromosomal abnormality that could serve as a hallmark lesion in MPAL, cytogenetic alterations are frequent and predominantly associated with complex karyotype involving chromosome 21 abnormalities.

Clinical spectrum and treatment outcome of retinoblastoma with Group D and E diseases: A single institution retrospective review.

The purpose of our study was to evaluate the ocular survival and event-free survival after multimodal therapy for group D and E of retinoblastoma (RB). Enucleation of group D and E is controversial as the risks of chemotherapy must be weighed against the potential for vision.A 10-year retrospective study from one center of 86 patients with advanced intraocular disease defined as International Classification Retinoblastoma (ICRB) group "D" or "E." Cases with visible extraocular extension at diagnosis were excluded. Ocular survival and patient survival were assessed. Indirect ophthalmoscopy at examination under anesthesia to visualize the tumor was used to evaluate clinical response.The median onset age in 86 patients with group D or E eye was 16 months (1-167 months). There were 29 (34%) bilateral cases. Leukocoria was the most common presentation sign (61%). Chemoreduction was primarily used in the treatment of intraocular RB. Selective ophthalmic arterial injection (SOAI) was applied as a component of multimodal therapy in 34 of the 86 cases. The globe preservation rate in patients with group D or E eyes was 19%. Using chemoreduction for advanced eyes, more eyes are being preserved which enables 70% 5-year ocular survival in patients with group D eyes.In triaging appropriate patients, multidisciplinary strategy can reduce tumor size with chemoreduction and consolidate the regressed tumor with local ophthalmic therapy to ensure globe salvage.

Hyperammonemic encephalopathy after induction chemotherapy for acute lymphoblastic leukemia.

The syndrome of hyperammonemic encephalopathy occurs in patients who have received high-dose cytoreductive therapy for the treatment of hematologic malignancy. It is characterized by acute alteration in mental status and respiratory alkalosis associated with markedly elevated plasma ammonium levels in the absence of any identifiable cause and frequently results in cerebral edema, coma, and eventually death. Although the etiology of this syndrome is yet to be determined, it seems to be invariably multifactorial in nature. Optimal therapy remains elusive, and the critical step is increased awareness of the syndrome by measurement of plasma ammonia levels in patients with neurologic symptoms, leading to accurate diagnosis and the rapid implementation of therapy.

"Do-not-resuscitate" orders in patients with cancer at a children's hospital in Taiwan.

OBJECTIVES: To quantify the use of do-not-resuscitate (DNR) orders in a tertiary-care children's hospital and to characterise the circumstances in which such orders are written. DESIGN: Retrospective study conducted in a 500-bed children's hospital in Taiwan. PATIENTS: The course of 101 patients who died between January 2002 and December 2005 was reviewed. The following data were collected: age at death, gender, disease and its status, place of death and survival. There were 59 males and 42 females with a median age of 103 months (range 1-263 months). 50 children had leukaemias, and 51 had malignancies other than leukaemia. The t test and the chi(2) test were applied as appropriate. RESULTS: The study found that 44% of patient deaths occurred in the paediatric oncology ward; 29% of patient deaths occurred in the intensive care unit; and 28% of patients died in their home or at another hospital. Other findings included the following: 46 of 101 (46%) patients died after attempted cardiopulmonary resuscitation and 55 (54%) died with a DNR order in effect. The mean age at death was 9.8 years in both groups with or without DNR orders. CONCLUSIONS: From the study of patient deaths in this tertiary-care children's hospital, it was concluded that an explicit DNR order is now the rule rather than the exception, with more DNR orders being written for patients who have been ill longer, who have solid tumours, who are not in remission and who are in the ward.

Allogeneic related bone marrow transplantation in children--a single center experience.

We report our single-center experience with related allogeneic bone marrow transplantation (BMT) in pediatric recipients between April 1998 and December 2004. Allogeneic bone marrow grafts from 19 donors (18 human leukocyte antigen (HLA)-matched sibling donors and 1 one antigen-mismatched related donor) were transplanted into patients aged 3-17 years (16 with leukemia and 3 with non-malignant disease). The patients received a cell dose, with median total nucleated cell dose of 3.9 x 10(8)/kg (range, 0.7 - 8.7 x 10(8)) and median CD 34+ cell dose of 3.0 x 10(6)/g (range, 0.3 - 9.8 x 10(6)). Seventeen patients (89.4%) engrafted after a median of 19 days (range 14-20 days). Acute graft versus host disease (GVHD) grade II to IV developed in 8 patients (42. 1%), and limited chronic GVHD developed in 2 evaluable patients (10.5%). Twelve of the 19 patients were alive at a median follow-up of 1460 days (range, 270-2260 days). Full chimeric hematopoiesis was maintained in 11 of these 12 patients. Six patients (31.6%) had relapse of their underlying malignant disease, and one of them is still alive. Seven patients died (5 because of relapse and/or disease progression and 2 because of infectious complication). The underlying diseases were acute lymphoblastic leukemia (ALL; 4 cases: 3 CR2, 1 Ph+), acute myeloid leukemia (AML; 2 cases: 1 CR2, 1 refractory), and juvenile chronic myelogenous leukemia (JCML; 1 case). Relapsed leukemia at an extramedullary site occurred in 2 patients with ALL after BMT. Although our data should be interpreted cautiously considering the limited number of patients, isolated extramedullary relapse seems to be common after allogeneic BMT.