Results of unrelated cord blood transplant in fanconi anemia patients: risk factor analysis for engraftment and survival.

We retrospectively analyzed results of unrelated cord blood transplantation (UCBT) in 93 Fanconi anemia (FA) patients. Median age at transplantation was 8.6 years (1-45). The units transplanted were HLA-A, -B, or -DRB1 identical in 12 cases, 1 HLA mismatch in 35 cases, and 2 or 3 HLA differences in 45 cases. The median number of nucleated cells (NC) and CD34+ cells infused of recipient weight was 4.9x10(7)/kg and 1.9x10(5)/kg, respectively. Participating centers selected the preparative regimen of their choice, in 57 patients (61%), it included Fludarabine. Graft-versus-host disease (GVHD) prophylaxis consisted mostly of cyclosporine with prednisone. Cumulative incidence (CI) of neutrophil recovery was 60+/-5% at day +60. In multivariate analysis, Fludarabine containing regimen and NC infused>or=4.9x10(7)/kg were associated with higher probability of recovery. CI of grade II-IV acute and of chronic GVHD (aGVHD, cGVHD) was 32%+/-5% and 16%+/-4%, respectively. Overall survival (OS) was 40%+/-5%. In multivariate analysis, factors associated with favorable outcome were use of Fludarabine in the conditioning regimen, number of NC infused>or=4.9x10(7)/kg, and negative cytomegalovirus (CMV) serology in the recipient. In conclusion, factors easily modifiable such as donor selection and a Fludarabine-containing regimen can considerably improve survival in FA patients given a UCBT. These data are the basis for designing prospective protocols.     

Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources

BACKGROUND: Umbilical-cord blood as an alternative to bone marrow for hematopoietic stem-cell transplantation may lower the risk of graft-versus-host disease (GVHD). METHODS: We studied the records of 113 recipients of cord blood from HLA-identical siblings from the period from 1990 through 1997 and compared them with the records of 2052 recipients of bone marrow from HLA-identical siblings during the same period. The study population consisted of children 15 years of age or younger. We compared the rates of GVHD, hematopoietic recovery, and survival using Cox proportional-hazards regression to adjust for potentially confounding factors. RESULTS: Recipients of cord blood were younger than recipients of bone marrow (median age, 5 years vs. 8 years; P<0.001), weighed less (median weight, 17 kg vs. 26 kg; P<0.001), and were less likely to have received methotrexate for prophylaxis against GVHD (28 percent vs. 65 percent, P<0.001). Multivariate analysis demonstrated a lower risk of acute GVHD (relative risk, 0.41; P=0.001) and chronic GVHD (relative risk, 0.35; P=0.02) among recipients of cord-blood transplants. As compared with recovery after bone marrow transplantation, the likelihood of recovery of the neutrophil count and the platelet count was significantly lower in the first month after cord-blood transplantation (relative risk, 0.40 [P<0.001], and relative risk, 0.20 [P<0.001]), respectively. Mortality was similar in the two groups (relative risk of death in the recipients of cord blood, 1.15; P=0.43). CONCLUSIONS: Recipients of cord-blood transplants from HLA-identical siblings have a lower incidence of acute and chronic GVHD than recipients of bone marrow transplants from HLA-identical siblings.     

Implementing a Transition Program from Paediatric to Adult Services in Phenylketonuria: Results after Two Years of Follow-Up with an Adult Team

We aimed to report the implementation of a phenylketonuria (PKU) transition program and study the effects of follow-up with an adult team on metabolic control, adherence, and loss of follow-up. Fifty-five PKU patients were analysed in the study periods (SP): 2 years before (SP1) and after the beginning of adult care (SP2). Retrospective data on metabolic control and number of clinic appointments were collected for each SP, and protein intakes were analysed. In SP2, three patients (6%) were lost to follow-up. There was a small but statistically significant increase in median number of annual blood spots from SP1 to SP2: 11 (7–15) vs. 14 (7–20); p = 0.002. Mean ± SD of median blood Phe remained stable (525 ± 248 µmol/L vs. 552 ± 225 µmol/L; p = 0.100); median % of blood Phe < 480 µmol/L decreased (51 (4–96)% vs. 37 (5–85)%; p = 0.041) and median number of clinic appointments increased from SP1 to SP2: (5 (4–6) vs. 11 (8–13); p < 0.001). No significant differences were found regarding any parameter of protein intake. Our results suggest that the implementation of an adult service was successful as impact on metabolic control was limited and attendance remained high. Continuous dietetic care likely contributed to these results by keeping patients in follow-up and committed to treatment.     

A Three-Year Longitudinal Study Comparing Bone Mass,Density, and Geometry Measured by DXA,pQCT, and Bone Turnover Markers in Children with PKU Taking L-Amino Acid or Glycomacropeptide Protein Substitutes

In patients with phenylketonuria (PKU), treated by diet therapy only, evidence suggests that areal bone mineral density (BMDa) is within the normal clinical reference range but is below the population norm. Aims: To study longitudinal bone density, mass, and geometry over 36 months in children with PKU taking either amino acid (L-AA) or casein glycomacropeptide substitutes (CGMP-AA) as their main protein source. Methodology: A total of 48 subjects completed the study, 19 subjects in the L-AA group (median age 11.1, range 5–16 years) and 29 subjects in the CGMP-AA group (median age 8.3, range 5–16 years). The CGMP-AA was further divided into two groups, CGMP100 (median age 9.2, range 5–16 years) (n = 13), children taking CGMP-AA only and CGMP50 (median age 7.3, range 5–15 years) (n = 16), children taking a combination of CGMP-AA and L-AA. Dual X-ray absorptiometry (DXA) was measured at enrolment and 36 months, peripheral quantitative computer tomography (pQCT) at 36 months only, and serum blood and urine bone turnover markers (BTM) and blood bone biochemistry at enrolment, 6, 12, and 36 months. Results: No statistically significant differences were found between the three groups for DXA outcome parameters, i.e., BMDa (L2–L4 BMDa g/cm²), bone mineral apparent density (L2–L4 BMAD g/cm³) and total body less head BMDa (TBLH g/cm²). All blood biochemistry markers were within the reference ranges, and BTM showed active bone turnover with a trend for BTM to decrease with increasing age. Conclusions: Bone density was clinically normal, although the median z scores were below the population mean. BTM showed active bone turnover and blood biochemistry was within the reference ranges. There appeared to be no advantage to bone density, mass, or geometry from taking a macropeptide-based protein substitute as compared with L-AAs.     

Effect of photobiomodulation therapy on the proliferation phase and wound healing in rats fed with an experimental hypoproteic diet

Lasers in Medical Science - Photobiomodulation therapy (PBMT) has been indicated for enforcement on healing skin wounds. This study evaluated the effects of PBMT on the healing of skin wounds...     

Donor Choriocarcinoma Transmission From Solid Organ Transplantation: A Case Report

Transplantation of any organ has some inherent risk of disease transmission, such as infection and malignancy. The present study aims to describe 2 cases of choriocarcinoma transmission after kidney and liver transplantation originating from the same patient. The donor was a 17-year-old woman who died of cerebral hemorrhage. Both organ recipients died of metastatic choriocarcinoma few months after the transplantation, within days after starting chemotherapy. Retrospective hCG (human chorionic gonadotropin hormone) analysis in donor's blood stored at the time of donation had a result of 9324 mIU/mL. Despite its rarity, clinicians should be aware of the risk of transplant-related choriocarcinoma from female donors in childbearing age. In some cases, hCG dosage should be performed before donation.     

New insights into tumor-host interactions in lymphoma metastasis

The metastatic process is characterized by a complex series of sequential steps involving constant interactions (mutual cross-talks) of metastasized tumor cells with their microenvironment (lymphocyte, macrophages, endothelial cells, etc.) in target organs. These interactions determine the outcome of metastasis (either the eradication of metastatic cells or their increased proliferation and invasion). Recently developed methods of tumor and host cell analysis at the molecular level allow better elucidation of molecular mechanisms of metastasis and of immune mechanisms involved in antitumor responses. Direct modulation of these processes will probably increase the success of clinical cancer treatment. Here we review data (a) on the expression of some costimulatory (MHC class II, CD80, sialoadhesin) and adhesion (LFA1, ICAM-1, VLA-4) molecules on both metastasized tumor cells and host cells and (b) on the production of a cytotoxic molecule, nitric oxide, by in situ activated Kupffer and endothelial cells in the process of liver metastasis. This study was performed with well-characterized murine ESbL T lymphoma cells transduced with the bacterial lacZ gene, which allows detection and quantification of metastases at the single cell level throughout lymphoma growth and metastasis. Experimental results are discussed in the context of recent literature.Abbreviations APC Antigen-presenting cells - hCRP Human C-reactive protein - ICAM Intercellular adhesion molecule - IFN Interferon - IL Interleukin - iNOS Inducible NO synthase - LFA Leukocyte function associated antigen - SER Sheep erythrocyte receptor - TA Tumor-associated rejection antigens - TNF Tumor necrosis factor - VCAM Vascular cell adhesion molecule - VLA Very late activated antigen     

Effective immune rejection of advanced metastasized cancer

A cellular cancer therapy is described with unique efficiency even in late-stage disease. in situ activated tumor-immune T cells, induced in allogeneic, tumor-resistant, MHC identical but superantigen different donor mice (B10.D2) could transfer strong graft-versus-leukemia (GvL) effects accompanied by only mild graft-versus-host (GvH) reactivity. Systemic immune cell transfer into 5 Gy irradiated DBA/2 mice bearing up to 4 week established syngeneic tumors and macrometastases led to massive infiltration of tumor tissues by CD4 and CD8 donor T lymphocytes. Upon interaction of immune CD4 donor T cells with host antigen presenting cells in synergy with immune CD8 donor T cells attacking the tumor cells directly, primary tumors (1.5 cm diameter) were encapsulated and rejected from the skin and liver metastases eradicated. For the first time, such adoptive cellular immunotherapy (ADI) was followed in individual live animals by P-31-NMR spectroscopy of primary tumors. An approximately 25,000 fold excess of metastatic tumor cells could be rejected as revealed quantitatively by FACScan analysis of lacZ gene transfected tumor cells.     

In-situ activated macrophages are involved in host-resistance to lymphoma metastasis by production of nitric-oxide

We studied nitric oxide (NO) production, adenosine deaminase (ADA) and 5'-nucleotidase (5-N) activity as a function of macrophage activation in the model of spontaneous metastasis of ESbL T lymphoma cells transduced with the lacZ gene. Liver and spleen macrophages were isolated and examined directly ex vivo without further experimental manipulation. Transient arrest of liver metastasis was accompanied by an increase of NO production and ADA activity and by a decrease of 5-N activity. An aggressive expansion of metastasis was correlated with a drop of NO production and ADA activity and with an increase of 5-N activity. To test the involvement of in situ activated Kupffer cells in an antimetastatic response, two immunotherapy protocols were used: i) active immunization with lymphoma cells and ii) adoptive transfer of antitumor immune spleen cells. Both treatments caused an upregulation of ADA activity and NO production in Kupffer cells, which correlated with host resistance against metastases.     

Years of life lost by mortality: a component of the burden of disease

INTRODUCTION: The register of death by cause, sex and age groups of residents in 1994 in Rio Grande do Sul (RS) and Santa Catarina (SC), two Brazilian southern states, were studied to calculate the years of life lost (YLL), one of the two components that summarize disability adjusted life years (DALY), in RS, SC and Brazil. METHODS: The methodology employed is the same used in the Global Burden of Disease study to quantify the mortality component (YLL) of DALY in the world. RESULTS: The results show that the greatest proportion and rates caused by Group II (Noncommunicable diseases), linked with more advanced stages of the epidemiological transition, in RS, SC and Brazil. But in both states and especially in Brazil, Group I (Communicable, maternal, perinatal and nutritional conditions) causes an important proportion of YLL. The Group III (Injuries) was the second more important group in RS and SC and the third in Brazil. Road traffic accidents are particularly important in SC, where the intentional injury rate is half than the one in RS. The leading causes of YLL were road traffic accidents, ischemic heart disease and cerebrovascular disease in SC, and ischemic heart disease, cerebrovascular disease and road traffic accidents in RS. CONCLUSIONS: Death certification in the southern region of Brazil has a complete coverage and miscoded death proportion is small, providing a reliable mortality information. DALY allow comparing fatal and nonfatal health outcomes to determine the importance of different diseases and to establish health priorities. DALY are also an useful tool to identify disadvantaged groups, target health interventions and provide information for social control of resource allocation.