Stanton Goldman

A Comparison of Inpatient Length of Stay and Costs Among Patients with Hematologic Malignancies (Excluding Hodgkin Disease) Associated with and Without Acute Renal Failure

BACKGROUND Using data from the Healthcare Cost and Utilization Project 2004 Nationwide Inpatient Sample, we estimated inpatient resource utilization among patients with hematologic malignancies, with and without concomitant acute renal failure. PATIENTS AND METHODS We analyzed patients with hematologic malignancies (excluding Hodgkin disease), acute renal failure, and renal dialysis. Subgroup analyses were performed on specific types of hematologic malignancies, with and without acute renal failure and with and without renal dialysis. RESULTS Among those with hematologic malignancies, acute renal failure, with and without concomitant renal dialysis, increases inpatient length of stay and costs. Mean length of stay and costs for all patients with acute renal failure and renal dialysis (n = 5148), acute renal failure without renal dialysis (n = 27,654), and no acute renal failure or renal dialysis (n = 350,601) were 17.6, 12.2, and 7.4 days, and

Translocation (4;19)(q35;q13.1)–Associated Primitive round Cell Sarcoma: Report of a Case and Review of the Literature:

44,619,

Phase I/II dose escalation study of recombinant human interleukin-11 following ifosfamide, carboplatin and etoposide in children, adolescents and young adults with solid tumours or lymphoma: a clinical, haematological and biological study*

25,638, and

Potential use of granulocyte colon-stimulating factor and granulocyte-macrophage colony-stimulating factor in neonates.

13,947, respectively. CONCLUSION Treatment of hematologic malignancies and concomitant acute renal failure and renal dialysis places an economic burden on the health care system. Reducing the incidence of acute renal failure and concomitant renal dialysis with supportive care in patients with hematologic malignancies can reduce inpatient resource use.

Feasibility study of IL-11 and granulocyte colony-stimulating factor after myelosuppressive chemotherapy to mobilize peripheral blood stem cells from heavily pretreated patients.

We report the 4th case of a primitive round cell sarcoma with the translocation (4;19)(q35;q13.1) as the primary cytogenetic abnormality. This undifferentiated sarcoma shows some features of Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET), including a diffuse reactivity for FLI1, but it shows only focal and weak reactivity for CD99 and is negative for a rearrangement of EWS, the molecular signature of ES/PNET. Recognition of the histopathologic and cytogenetic features of this entity is necessary to avoid its misdiagnosis as ES/PNET, especially in small biopsy samples.

Abstract 2608: Ibrutinib significantly improves survival in a human Burkitt lymphoma (BL) xenograft NSG mouse model: Ibrutinib may be a potential adjuvant agent in the treatment of BL

Thrombocytopenia remains the major dose‐limiting toxicity of myelosuppressive chemotherapy in children with solid tumours. Recombinant human interleukin‐11 (rhIL‐11) has been approved by the Food and Drug Administration as treatment for adults with solid tumours and lymphomas with severe chemotherapy‐induced thrombocytopenia. We conducted a phase I/II trial of rhIL‐11 following ifosfamide, carboplatin and etoposide (ICE) chemotherapy in children with solid tumours or lymphomas. Patients received ifosfamide 1800 mg/m2/d for 5 d, carboplatin 400 mg/m2/d for 2 d and etoposide 100 mg/m2/d for 5 d with rhIL‐11 subcutaneous (s.c.) at 25–125 μg/kg/d on days 6–33. Forty‐seven patients with median age 10·5 years (range, 0·7–26 years) were studied. Median days to absolute neutrophil count ≥0·5 × 109/l, platelet count ≥50 × 109/l and platelet transfusions were 23, 18, 18, 16·5 and 18·5, 21, 20, 18 and 3, 3, 4, and 2 d at doses 25, 50, 75 and 100 μg/kg respectively. There was a dose‐dependent increase in Cmax (7·6–25·5 ng/ml), AUC0−ρ (57–209 ng·h/ml) and T1/2 (4–8·2 h) respectively. There was a 4% incidence of anti‐IL‐11 antibody formation. Clinically important adverse events to rhIL‐11 were papilloedema and periosteal bone formation. In summary, rhIL‐11 was well tolerated at doses of ≤50 μg/kg (maximal tolerated dose) and associated with improved haematological recovery and reduced platelet transfusion requirements compared with historical controls receiving similar ICE chemotherapy without rhIL‐11.

A randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumor lysis

The immaturity of neonatal phagocytic immunity contributes to increased mortality during neonatal sepsis. Neonates have both quantitative and qualitative neutrophil defects with decreased bone marrow neutrophil storage pool (NSP) reserves, an inability to increase neutrophil production, and defective neutrophil functional activity. Neonates respond to overwhelming sepsis with depletion of the NSP and the development of peripheral neutropenia. The myelopoietic cytokines granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been documented to induce neutrophilia in neonatal animals and human infants, increase the NSP, and upregulate neutrophils for improved functional activity. Preclinical studies in neonatal rats demonstrate increased survival with prophylactic G-CSF during experimental group B streptococcal sepsis. In pilot phase l/ll human trials, G-CSF and GM-CSF were demonstrated to be both safe and well tolerated and to induce significant increases in absolute neutrophil count and NSP. Prophylactic GM-CSF in the very low birth weight neonate may reduce the incidence of nosocomial infections. Phase III trials are needed to further delineate the clinical usefulness of these myelopoietic cytokines in neonates with a high predisposition to sepsis.

Excellent outcomes in children and adolescents with central nervous system-positive (CNS+) Burkitt lymphoma/leukemia (BL) or other mature B-NHL using intrathecal and systemic chemotherapy without CNS irradiation: results from FAB/LMB96 and ANHL01P1 studie

Purpose Pediatric patients with solid tumors treated with prolonged dose-intensive chemoradiotherapy are poor mobilizers of peripheral blood stem cells (PBSC). We have conducted a pilot study to mobilize PBSC in eight pediatric patients with relapsed solid tumors using ifosfamide, carboplatin, and etoposide (ICE) followed-up by IL-11 plus granulocyte colony-stimulating factor (G-CSF). Patients and Methods Patients received ifosfamide 1.8 g/m 2 per day for 5 days, carboplatin 400 mg/m 2 per day for 2 days, and etoposide 100 mg/m 2 per day for 5 days. After completion of ICE chemotherapy, patients received daily subcutaneous injections of G-CSF (5 &mgr;g/kg per day) and IL-11 (50–100 &mgr;g/kg per day) until peripheral stem cell apheresis. Results The median age was 11 years. Diagnosis included three relapsed Hodgkin disease, three relapsed central nervous system tumors, one relapsed Wilms tumor, and one relapsed rhabdomyosarcoma. The median number of apheresis procedures required to obtain 5 × 10 6 CD34 + cells/kg was one. The mean ± standard error of mean (SEM) total CD34 + cells collected was 14.0 ± 2.7 × 10 6 /kg. The mean ± SEM total CD34 + /CD41 + cells collected was 4.6 ± 1.9 × 10 6 /kg. Seven of the eight patients have subsequently undergone myeloablative chemotherapy with autologous PBSC transplantation and have reconstituted hematopoiesis with a median time to neutrophil recovery of 10 days and platelet recovery of 15.5 days. Conclusions We conclude that the regimen of ICE/IL-11 plus G-CSF is successful in mobilizing large numbers of CD34 + PBSC cells with a limited number (one) of apheresis collections in patients that have previously been heavily pretreated with chemotherapy/radiotherapy.

Ibrutinib Significantly Prolonged Survival in a Human Burkitt Lymphoma (BL) Xenograft NSG Mouse Model: Ibrutinib May be a Potential Adjuvant Agent in the Treatment of BL

BACKGROUND: Burkitt lymphoma (BL) represents approximately 40% of all childhood and adolescent non-Hodgkin lymphoma (Miles/Cairo, BJH, 2012). Children with relapsed or progressive BL develop chemotherapy-resistant disease and can rarely be cured with salvage therapy (Cairo et al, JCO, 2012). Bruton9s tyrosine kinase (BTK) is a regulator of normal B-cell development and is activated upon B-cell receptor (BCR) stimulation. Chronic active BCR signaling through BTK activation can be inhibited by the selective and covalent BTK inhibitor, ibrutinib (Young et al, Nat Rev, 2013). Ibrutinib has been highly effective in the treatment of refractory patients with CLL and MCL and has been approved by the FDA for patients with CLL or MCL who have received at least one prior therapy (USPI) (Byrd et al, NEJM, 2013 and Wang et al, NEJM, 2013). BL, however, is associated with tonic or possibly chronic active BCR signaling; while, both CLL and MCL have chronic active BCR signaling. We have previously demonstrated ibrutinib significantly decrease BL proliferation and viability in vitro (Lee/Cairo et al, ASH, 2014) OBJECTIVE: We hypothesize that ibrutinib may be a potential adjuvant agent in the treatment of BL. Therefore, we investigated the in vivo anti-tumor activity of ibrutinib in BL xenografted NOD/SCID (NSG) mice. METHODS: The luciferase expression plasmid (ffluc-Zeo), kindly provided by L. Cooper, MD) was transfected into Raji cells. Cells were subcutaneously injected into NSG mice (6-8wks old, NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ, Jackson lab). Tumor cells engraftment and progression were examined by Bioluminescent Imaging using the Xenogen IVIS-200 (Caliper Life Sciences). Mice were orally gavaged with vehicle control or Ibrutinib (1.25, 12.5 and 25mg/kg/day, generously provided by Janssen RD 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2608. doi:10.1158/1538-7445.AM2015-2608