Reduced-intensity conditioning stem cell transplantation: comparison of double umbilical cord blood and unrelated donor grafts

There are little data comparing umbilical cord blood (UBC) and conventional stem cell sources for reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT). We performed a retrospective analysis of RIC HCST using double UCB (dUCB) grafts and RIC HSCT using unrelated donor (URD) grafts. The study included 64 dUCB transplantations and 221 URD transplantations performed at Dana-Farber Cancer Institute and Massachusetts General Hospital between 2004 and 2008. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 14.1% for dUCB and 20.3% for URD (P = .32). The 2-year cumulative incidence of chronic GVHD was significantly lower in dUCB compared with URD (21.9% versus 53.9%; P < .0001). The 2-year cumulative incidence of nonrelapse mortality was significantly higher in dUCB (26.9% versus 10.4%; P = .0009). In our analysis, dUCB HSCT and URD HSCT had comparable 3-year overall survival (46% in dUCB and 50% in URD; P = .49) and progression-free survival (30% in dUCB and 40% in URD; P = .47). dUCBT was associated with greater nonrelapse mortality despite less chronic GVHD. Our findings suggest that the use of 2 partially matched UCB units appears to be a suitable alternative for patients undergoing RIC HSCT without an HLA-matched donor.     

The Next Wave: Confexting

Radiology conferences enable participants the opportunity to ask experts questions through question and answer (Q and A) sessions or individually. Given the time limitations and intimidating circumstances, we incorporated conference text messaging (confexting) as a method of increasing interactivity between the audience and speakers. During a 5-day radiology conference, text messaging was utilized for anonymous interactivity between the audience and speakers during Q and A sessions. There were 324 text messages; 76 of these were either follow-up statements or questions related to earlier text messages. Forty-two questions were submitted via paper notes. There was a general trend of an increasing number of text messages and a decreasing number of paper notes. The anonymous text messaging system was found to be an effective method for interactivity between the audience and the speakers. The questions and answers could be presented in a PowerPoint format at the formal Q and A sessions. Questions texted to the authors during their talks could be immediately answered or addressed in subsequent talks. Although difficult for some individuals to embrace technology, confexting allows for interactivity and prompts discussion. Confexting is an effective method for interactivity between the audience and speakers not previously utilized in a conference setting. The anonymity and asynchronous communication enable conference participants to submit more questions than in the traditional setting. The speakers may be able to explain more thoroughly difficult concepts more thoroughly with additional slides at Q and A sessions or may immediately answer texted questions during their talks.     

Developmental expression of polypeptide PEP-19 in cerebellar cell suspensions transplanted into the cerebellum of pcd mutant mice

Summary Cerebellar cell suspensions were prepared from normal mouse embryos and implanted into the cerebellum of Purkinje cell degeneration (pcd) mutant mice, which are characterized by a virtually complete degeneration of Purkinje cells between postnatal day (P) 17 and P45. The expression of immunoreactivity for PEP-19, a developmentally-regulated brain-specific polypeptide, was analyzed in normal mouse cerebellum, as well as in pcd mutants with or without grafts. In the normal cerebellum, PEP-19 immunoreactivity was present in Purkinje cells. In unoperated mutants, 45 days of age or older, Purkinje cells were absent. In grafted pcd mice, numerous PEP-19 immunoreactive, neuroblast-like cells were seen in the graft at 5 days after transplantation. By 9 days, large PEP-19 immunoreactive neurons were found in the host molecular layer; by 17 days after transplantation, such neurons displayed an extensive dendritic tree and resembled differentiated Purkinje cells. The vast majority of PEP-19 immunoreactive cells was located in the molecular layer of the host at 9 days after transplantation and beyond; nonetheless, the same cells extended axonal processes toward the graft, indicating an affinity for co-grafted (possibly deep nuclei) neurons. These results point to the ability of donor Purkinje cells for survival, migration into the host brain and morphological and chemical differentiation following transplantation to the degenerated cerebellar cortex of the recipient mutants.On sabbatical leave from the Institute of Neurosciences, National Yang-Ming Medical College, Taipei, Taiwan 112, ROC     

Mucositis after allogeneic hematopoietic stem cell transplantation: a cohort study of methotrexate- and non-methotrexate-containing graft-versus-host disease prophylaxis regimens.

Oral mucositis occurs in up to 75% of recipients of high-dose chemoradiotherapy conditioning regimens used for allogeneic hematopoietic stem cell transplantation (HSCT). As a result of mucositis, narcotic analgesia and total parenteral nutrition (TPN) are commonly required after HSCT. Methotrexate, an antiproliferative graft-versus-host disease (GVHD) prophylaxis agent, impairs mucosal regeneration and worsens and prolongs mucositis. We assessed the effect of substituting sirolimus for methotrexate as GVHD prophylaxis on outcomes associated with mucositis. Two patient cohorts undergoing allogeneic HLA-matched related donor peripheral blood stem cell transplantation with cyclophosphamide/total body irradiation conditioning were prospectively analyzed for mucositis severity and retrospectively reviewed for correlative outcomes. GVHD prophylaxis consisted of sirolimus/tacrolimus (ST) in the study group and tacrolimus/methotrexate (TM) in the control group. Thirty patients received ST and 24 patients received TM as GVHD prophylaxis between October 2000 and May 2003. Mild, moderate, and severe mucositis was noted in 37%, 57%, and 7% of the ST group and 8%, 42%, and 50% of the TM group (P = .0002). Less TPN was used in the ST group than the TM group (17% versus 43% of posttransplantation hospital days; P = .02). The total number of narcotic days was lower in the ST group in comparison with the TM group (median, 13.5 versus 17 days; P = .08). The time to first hospital discharge was shorter in the ST group compared with the TM group (median, 18 versus 22 days; P = .07). The substitution of sirolimus for methotrexate as GVHD prophylaxis is associated with a reduction in mucositis severity. As a result, TPN and narcotic use are reduced, and hospitalization duration is shortened. Less toxic GVHD prophylaxis regimens without methotrexate may have a significant effect on patient quality of life, patient outcomes, and economic outcomes associated with allogeneic stem cell transplantation.     

Algorithm for the treatment of type 2 diabetes: a position statement of Brazilian Diabetes Society

The Brazilian Diabetes Society is starting an innovative project of quantitative assessment of medical arguments of and implementing a new way of elaborating SBD Position Statements. The final aim of this particular project is to propose a new Brazilian algorithm for the treatment of type 2 diabetes, based on the opinions of endocrinologists surveyed from a poll conducted on the Brazilian Diabetes Society website regarding the latest algorithm proposed by American Diabetes Association /European Association for the Study of Diabetes, published in January 2009.An additional source used, as a basis for the new algorithm, was to assess the acceptability of controversial arguments published in international literature, through a panel of renowned Brazilian specialists. Thirty controversial arguments in diabetes have been selected with their respective references, where each argument was assessed and scored according to its acceptability level and personal conviction of each member of the evaluation panel.This methodology was adapted using a similar approach to the one adopted in the recent position statement by the American College of Cardiology on coronary revascularization, of which not only cardiologists took part, but also specialists of other related areas.     

Effect of age on the pharmacokinetics of busulfan in patients undergoing hematopoietic cell transplantation; an alliance study (CALGB 10503, 19808, and 100103)

Purpose

Older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome have often been excluded from myeloablative-conditioning regimens containing busulfan because of non-disease-related morbidity and mortality. We hypothesized that busulfan clearance (BuCL) in older patients (>60 years) would be reduced compared to that in younger patients, potentially explaining observed differences in busulfan tolerability.

Methods

AML patients in three CALGB hematopoietic cell transplantation studies were treated with a conditioning regimen using IV busulfan, dosed at 0.8 mg/kg. Plasma busulfan concentrations were determined by LC–MS and analyzed by non-compartmental methods. BuCL was normalized to actual (ABW), ideal (IBW), or corrected (CBW) body weight (kg). Differences in BuCL between age groups were examined using the Wilcoxon rank sum test.

Results

One hundred and eighty-five patients were accrued; 174 provided useable pharmacokinetic data. Twenty-nine patients ≥60 years old (median 66; range 60–74) had a significantly higher BuCL versus those <60 years old (median 50; range 18–60): BuCL 236 versus 168 mL/min, p = 0.0002; BuCL/ABW 3.0 versus 2.1 mL/min/kg, p = 0.0001; BuCL/IBW 3.8 versus 2.6 mL/min/kg, p = 0.0035; BuCL/CBW 3.4 versus 2.6 mL/min/kg, p = 0.0005. Inter-patient variability in clearance (CV %) was up to 48 % in both age groups. Phenytoin administration, a potential confounder, did not affect BuCL, regardless of weight normalization (p > 0.34).

Conclusions

Contrary to our hypothesis, BuCL was significantly higher in older patients compared to younger patients in these studies and does not explain the previously reported increase in busulfan toxicity observed in older patients.