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1.  Rituximab Maintenance Therapy After Autologous Stem-Cell Transplantation in Patients With Relapsed CD20+ Diffuse Large B-Cell Lymphoma: Final Analysis of the Collaborative Trial in Relapsed Aggressive Lymphoma 
Journal of Clinical Oncology  2012;30(36):4462-4469.
Purpose
The standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL) is salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT). The impact of maintenance rituximab after ASCT is not known.
Patients and Methods
In total, 477 patients with CD20+ DLBCL who were in their first relapse or refractory to initial therapy were randomly assigned to one of two salvage regimens. After three cycles of salvage chemotherapy, the responding patients received high-dose chemotherapy followed by ASCT. Then, 242 patients were randomly assigned to either rituximab every 2 months for 1 year or observation.
Results
After ASCT, 122 patients received rituximab, and 120 patients were observed only. The median follow-up time was 44 months. The 4-year event-free survival (EFS) rates after ASCT were 52% and 53% for the rituximab and observation groups, respectively (P = .7). Treatment with rituximab was associated with a 15% attributable risk of serious adverse events after day 100, with more deaths (six deaths v three deaths in the observation arm). Several factors affected EFS after ASCT (P < .05), including relapsed disease within 12 months (EFS: 46% v 56% for relapsed disease after 12 months), secondary age-adjusted International Prognostic Index (saaIPI) more than 1 (EFS: 37% v 61% for saaIPI < 1), and prior treatment with rituximab (EFS: 47% v 59% for no prior rituximab). A significant difference in EFS between women (63%) and men (46%) was also observed in the rituximab group. In the Cox model for maintenance, the saaIPI was a significant prognostic factor (P < .001), as was male sex (P = .01).
Conclusion
In relapsed DLBCL, we observed no difference between the control group and the rituximab maintenance group and do not recommend rituximab after ASCT.
doi:10.1200/JCO.2012.41.9416
PMCID: PMC3646314  PMID: 23091101
2.  High dose methotrexate and extended hours high-flux hemodialysis for the treatment of primary central nervous system lymphoma in a patient with end stage renal disease 
This report discusses the case of a 52 year old female with post-transplant lymphoproliferative disorder, confined to the central nervous system, which was managed with high dose methotrexate (HDMTX) in the context of end stage renal disease. The patient received two doses of HDMTX followed by extended hours high-flux hemodialysis, plasma methotrexate concentration monitoring and leucovorin rescue. The hemodialysis technique used was effective in clearing plasma methotrexate and allowed delivery of HDMTX to achieve complete remission with limited and reversible direct methotrexate-related toxicity. Dialysis-dependent renal failure does not preclude the use of HDMTX when required for curative therapy of malignancy.
PMCID: PMC3301441  PMID: 22432089
High dose methotrexate; end stage renal disease; dialysis; primary central nervous system lymphoma; post-transplant lymphoproliferative disorder
3.  Salvage Regimens With Autologous Transplantation for Relapsed Large B-Cell Lymphoma in the Rituximab Era 
Journal of Clinical Oncology  2010;28(27):4184-4190.
Purpose
Salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT) is the standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL). Salvage regimens have never been compared; their efficacy in the rituximab era is unknown.
Patients and Methods
Patients with CD20+ DLBCL in first relapse or who were refractory after first-line therapy were randomly assigned to either rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) or rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP). Responding patients received high-dose chemotherapy and ASCT.
Results
The median age of the 396 patients enrolled (R-ICE, n = 202; R-DHAP, n = 194) was 55 years. Similar response rates were observed after three cycles of R-ICE (63.5%; 95% CI, 56% to 70%) and R-DHAP (62.8%; 95 CI, 55% to 69%). Factors affecting response rates (P < .001) were refractory disease/relapse less than versus more than 12 months after diagnosis (46% v 88%, respectively), International Prognostic Index (IPI) of more than 1 versus 0 to 1 (52% v 71%, respectively), and prior rituximab treatment versus no prior rituximab (51% v 83%, respectively). There was no significant difference between R-ICE and R-DHAP for 3-year event-free survival (EFS) or overall survival. Three-year EFS was affected by prior rituximab treatment versus no rituximab (21% v 47%, respectively), relapse less than versus more than 12 months after diagnosis (20% v 45%, respectively), and IPI of 2 to 3 versus 0 to 1 (18% v 40%, respectively). In the Cox model, these parameters were significant (P < .001).
Conclusion
In patients who experience relapse more than 12 months after diagnosis, prior rituximab treatment does not affect EFS. Patients with early relapses after rituximab-containing first-line therapy have a poor prognosis, with no difference between the effects of R-ICE and R-DHAP.
doi:10.1200/JCO.2010.28.1618
PMCID: PMC3664033  PMID: 20660832
4.  Plasma protein C levels in immunocompromised septic patients are significantly lower than immunocompetent septic patients: a prospective cohort study 
Introduction
Activated Protein C [APC] improves outcome in immunocompetent patients with severe sepsis particularly in those who are perceived to have high mortality risk. Before embarking on a trial of APC administration in immunocompromised septic patients, a preliminary study on plasma levels of protein C in this cohort is essential.
Objective
To assess serum Protein C concentrations in immunocompromised patients as compared to immunocompetent patients during sepsis, severe sepsis, septic shock and recovery.
Methods
Prospective cohort study in a tertiary hospital. Patients satisfying inclusion criteria were enrolled after informed consent. Clinical variables were noted with sample collection when patients met criteria for sepsis, severe sepsis, septic shock and recovery. Protein C levels were measured using monoclonal antibody based fluorescence immunoassay.
Results
Thirty one patients participated in this study (22 immunocompromised, 9 immunocompetent). Protein C levels were found to be significantly lower in the immunocompromised group compared to the immunocompetent group, particularly observed in severe sepsis [2.27 (95% CI: 1.63-2.9) vs 4.19 (95% CI: 2.87-5.52) mcg/ml] (p = 0.01) and sepsis [2.59 (95% CI: 1.98-3.21) vs 3.64 (95% CI: 2.83-4.45) mcg/ml] (p = 0.03). SOFA scores were similar in both the groups across sepsis, severe sepsis and septic shock categories. Protein C levels improved significantly in recovery (p = 0.001) irrespective of immune status.
Conclusion
Protein C levels were significantly lower in immunocompromised patients when compared to immunocompetent patients in severe sepsis and sepsis categories. Our study suggests a plausible role for APC in severely septic immunocompromised patients which need further elucidation.
doi:10.1186/1756-8722-2-43
PMCID: PMC2772189  PMID: 19840396
5.  Significance of Abnormal Protein Bands in Patients with Multiple Myeloma following Autologous Stem Cell Transplantation 
The Clinical Biochemist Reviews  2009;30(3):113-118.
Aim
We studied the characteristics of small abnormal protein bands (APB) (including oligoclonal bands and new apparent monoclonal bands) that are frequently detected by serum protein electrophoresis (SPEP) and isoelectric focusing (IEF) in the post-autologous stem cell transplant setting.
Methods
In a retrospective analysis of patients with multiple myeloma undergoing transplantation, paraprotein identity and quantification were performed using standard immunofixation electrophoresis. The nature of any new bands was determined by IEF which distinguished between oligoclonal bands and apparent monoclonal bands.
Results
Of 49 myeloma cases, the median follow-up was 33.7 months (range, 5.6–97.5 months) and 24 patients had relapsed. Thirty six (73%) developed APB. 22 patients had more than one episode of APB and 6 patients had more than 2 episodes resulting in a total of 69 episodes of APB observed post-transplant. IEF demonstrated 54 of these APB were oligoclonal bands and 15 appeared to be monoclonal. Of the 15 episodes of apparent monoclonal bands, 10 had differing heavy or light chain restriction compared to the original myeloma paraprotein and 5 had the same heavy and light chain restriction but different band location in the SPEP lane. Ten of these apparent monoclonal bands resolved, 5 persisted, and only one represented true disease progression. The presence of APB impacted favourably on event-free survival (p=0.05).
Conclusion
Small APB are very frequent post-transplant for myeloma, and IEF can identify these APB as oligoclonal or monoclonal. Apparent monoclonal bands may represent relapsed disease, but in the vast majority of cases it does not, and most likely represents a transient phenomenon representing regeneration of a limited immune response.
PMCID: PMC2754999  PMID: 19841693

Results 1-5 (5)