Effect of Age on Outcome of Reduced-Intensity Hematopoietic Cell Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission or With Myelodysplastic Syndrome

Purpose Acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) primarily afflict older individuals. Hematopoietic cell transplantation (HCT) is generally not offered because of concerns of excess morbidity and mortality. Reduced-intensity conditioning (RIC) regimens allow increased use of allogeneic HCT for older patients. To define prognostic factors impacting long-term outcomes of RIC regimens in patients older than age 40 years with AML in first complete remission or MDS and to determine the impact of age, we analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR). Patients and Methods We reviewed data reported to the CIBMTR (1995 to 2005) on 1,080 patients undergoing RIC HCT. Outcomes analyzed included neutrophil recovery, incidence of acute or chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, disease-free survival (DFS), and overall survival (OS). Results Univariate analyses demonstrated no age group differences in NRM, grade 2 to 4 acute GVHD, chronic GVHD, or relapse. Patients age 40 to 54, 55 to 59, 60 to 64, and >= 65 years had 2-year survival rates as follows: 44% (95% Cl, 37% to 52%), 50% (95% Cl, 41% to 59%), 34% (95% Cl, 25% to 43%), and 36% (95% Cl, 24% to 49%), respectively, for patients with AML (P = .06); and 42% (95% Cl, 35% to 49%), 35% (95% Cl, 27% to 43%), 45% (95% Cl, 36% to 54%), and 38% (95% Cl, 25% to 51%), respectively, for patients with MDS (P = .37). Multivariate analysis revealed no significant impact of age on NRM, relapse, DFS, or OS (all P>.3). Greater HLA disparity adversely affected 2-year NRM, DFS, and OS. Unfavorable cytogenetics adversely impacted relapse, DFS, and OS. Better pre-HCT performance status predicted improved 2-year OS. Conclusion With these similar outcomes observed in older patients, we conclude that older age alone should not be considered a contraindication to HCT.

Light-Emitting Diode Therapy in Chemotherapy-Induced Mucositis

Background and Objective: Mucositis is the most common oral complication of cancer chemotherapy, which causes pain on mastication and swallowing, impairs patients` ability to eat and take oral drugs and may determine interruption of the treatment. The aim of this study was to evaluate the effect of light-emitting diode (LED) therapy on chemotherapy-induced mucositis in hamsters. Study Design/Materials and Methods: Animals of both experimental (Group 1; n = 32) and positive control (Group II; n = 32) groups received intraperitoneal injections of 5-fluorouracil on days 0 and 2. All animals had their right and left cheek pouch irritated by superficial scratching on days 3 and 4. In Group I, LED irradiation (630 nm +/- 10 nm, 160 mW, 12 J/cm(2)) was applied during 37.5 seconds at days 3, 4, 6, 8, 10, 12, and 14. In Group II, mucositis was induced, but LED therapy was not performed. The oral mucosa was photographed from day 4 to 14 at 2-day intervals. Photographs were randomly scored according to the severity of induced mucositis (0 to 5). In the negative control group (Group III; n = 6), no mucositis was induced. Biopsies of the cheek pouches of 8 animals (Group I and Group II) were surgically obtained on days 5, 9, 13 and 15 and processed for histological examination. Results: The statistical analysis showed significant differences between irradiated and non-irradiated groups (P < 0.05). However, muscular degeneration was observed in 18% of the samples of Group I. Conclusion: It may be concluded that the LED therapy protocol established for this in vivo study was effective in reducing the severity of oral mucositis, although the oral lesions were not completely prevented. Lasers Surg. Med. 40:625-633, 2008. (c) 2008Wiley-Liss, Inc.

Autofluorescence spectroscopy in liver transplantation: Preliminary results from a pilot clinical study

The evaluation of graft function at various stages after transplantation is relevant, particularly at the moment of organ harvest, when a decision must be made whether to use the organ. Autofluorescence spectroscopy is noninvasive technique to monitor the metabolic condition of a liver graft throughout its course, from an initial evaluation in the donor, through cold ischemia transportation, to reperfusion and reoxygenation in the recipient. Preliminary results are presented in six liver transplantations spanning the periods from liver harvest to implant. The laser-induced fluorescence spectrum at 532-mn excitation was investigated before cold perfusion (autofluorescence), during cold ischemia, at the back table procedure, as well as 5 and 60 minutes after reperfusion. The results showed that the fluorescence analysis was sensitive to changes during the transplantation procedure. Fluorescence spectroscopy potentially provides a real-time, noninvasive technique to monitor liver graft function. The information could potentially be valuable for surgical decisions and transplant success.

Cutpoint selection for discretizing a continuous covariate for generalized estimating equations

We consider consider the problem of dichotomizing a continuous covariate when performing a regression analysis based on a generalized estimation approach. The problem involves estimation of the cutpoint for the covariate and testing the hypothesis that the binary covariate constructed from the continuous covariate has a significant impact on the outcome. Due to the multiple testing used to find the optimal cutpoint, we need to make an adjustment to the usual significance test to preserve the type-I error rates. We illustrate the techniques on one data set of patients given unrelated hematopoietic stem cell transplantation. Here the question is whether the CD34 cell dose given to patient affects the outcome of the transplant and what is the smallest cell dose which is needed for good outcomes. (C) 2010 Elsevier BM. All rights reserved.

Bringing Japanese manufacturing systems to America: the feasibility of implementing just-in-time production in the United States

This paper addresses the feasibility of implementing Japanese manufacturing systems in the United States. The recent success of Japanese transplant companies suggests that Just-In-Time (JIT) production is possible within America's industrial environment. Once American workers receive proper training, they have little difficulty participating in rapid setup procedures and utilizing the kanban system. Japanese transplants are gradually developing Japanese-style relationships with their American supplier companies by initiating long-term, mutually beneficial agreements. They are also finding ways to cope with America's problem of distance, which is steadily decreasing as an obstacle to JIT delivery. American companies, however, encounter Significant problems in trying to convert traditionally organized, factories to the JIT system. This paper demonstrates that it is both feasible and beneficial for American manufacturers to implement JIT production techniques. Many of the difficulties manufacturers experience center around a general lack of information about JIT. Once a company realizes its potential for setup-time reduction, a prerequisite for the JIT system, workers and managers can work together to create a new process for handling equipment changeover. Significant results are possible with minimal investment. Also, supervisors often do not realize that the JIT method of ordering goods from suppliers is compatible with current systems. This "kanban system" not only enhances current systems but also reduces the amount of paperwork and scheduling involved. When arranging JlT delivery of supplier goods, American manufacturers tend to overlook important aspects of JIT supplier management. However, by making long-tenn commitments, initiating the open exchange of information, assisting suppliers in reaching new standards of performance, increasing the level of conununication, and relying more on suppliers' engineering capabilities, even American manufacturers can develop Japanese-style supplier relationships that enhance the effectiveness of the system.