Anaplastic large cell lymphoma treated with a leukemia‐like therapy

Abstract

Citropin 1.1, maculatin 1.1, and caerin 1.1 are short antibacterial cationic peptides from the skin glands of the Australian tree frog Litoria species. Several analogues have been synthesized to give a better insight into the relationship between the structure of the peptides and their antibacterial and haemolytic activity. Binding studies using a surface plasmon resonance (SPR) biosensor together with a vesicle‐capture sensor chip have been used to investigate selectivity of the peptides and their analogues for 1,2‐dimyristoyl‐sn‐glycero‐3‐phosphoglycerol (DMPG) and 1,2‐dimyristoyl‐sn‐glycero‐3‐phosphocholine (DMPC) vesicles, as well as for vesicles made from lipid extracts from Escherichia coli and bovine brain. Data obtained for membrane selectivity using natural lipid extracts show better correlation with minimum inhibitory concentration (MIC) values against Gram‐positive bacteria and haemolytic activity than that obtained using synthetic DMPG and DMPC. Electron microscopy and membrane leakage studies using Gram‐positive bacteria gave further insight into the membrane disruption properties of the peptides. For maculatin 1.1, it was found that the central proline residue, which is responsible for a bend in the α‐helical structure, is essential not only for the antibacterial activity but also for binding, and perturbation of membranes. The caerin analogues showed only small variations in their MIC values and membrane binding. In contrast, for citropin 1.1, the analogue replacing the aspartate with a lysine showed the lowest MIC against Gram‐positive bacteria and best membrane binding to E. coli lipid extracts, coinciding with an increased hydrophobic moment of the peptide. These data give further insight into these antimicrobial natural products, toward the development and evaluation of these and other analogues as potential antibiotics. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96:147–157, 2011.

Efficacy of peripheral blood stem cell transplantation versus conventional chemotherapy on anaplastic large-cell lymphoma:a retrospective study of 64 patients from a single center

“…However, these studies were all single arm, which makes it difficult to draw a definitive conclusion about the superiority of transplantation. In addition, in many studies concerning conventional chemotherapy, the long-term OS rates ranged from 62% to 85% with a median follow-up time longer than 5 years, which was similar to the results of transplantation[3]–[5]. Therefore, it is necessary to compare conventional chemotherapy and transplantation in one setting to further evaluate the efficacy of transplantation on systemic ALCL.…”

“…However, factors indicating poor prognosis were mostly identified in other aggressive lymphomas such as diffuse large B-cell lymphoma (DLBCL)[23]. In ALCL, some studies failed to show that these aggressive factors had the same prognostic value as they did in other lymphoma subtypes[4],[5]. Moreover, based on the findings of a study conducted in DLBCL, only patients with specific factors such as elevated LDH level or high IPI score benefit from PBSCT[24].…”

Lymphomas

“…The failure to detect a signifi cant difference among children with ALCL may be a result of the relatively small numbers of patients included in the registry. Benefi t to allogeneic HCT for relapsed ALCL is suggested in several small series and for those that relapse following autologous HCT (Woessmann et al 2006(Woessmann et al , 2011Cesaro et al 2005 ). Less convincing evidence exists for a graft-versus-DLBCL effect although responses to withdrawal of immunosuppression and infusion of donor lymphocytes are occasionally seen among those with persistent disease following allogeneic HCT (Lazarus et al 2010 ;Bishop et al 2008 ).…”

“…Protracted, leukemia-type therapy (modifi ed LSA 2 -L 2 ) administered over 24 months has been used by several groups with approximately two-thirds of patients surviving long term (Mora et al 2000 ;Rosolen et al 2005 ;Vecchi et al 1993 ). The Pediatric Oncology Group (POG) used a modifi ed APO regimen (doxorubicin, prednisone, vincristine, mercaptopurine) with and without methotrexate (1 g/m 2 ) and high-dose cytarabine after the induction phase (Laver et al 2005 ).…”

Potential Therapies for Anaplastic Lymphoma Kinase-Driven Tumors in Children: Progress to Date

“…Another study used a modified acute leukemia regimen with similar results. (15) In addition, progression while receiving chemotherapy portends a very poor prognosis in children with ALCL. In one study, only 25 % of patients who relapsed on therapy survived, even with aggressive salvage therapy.…”