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N. Ganguly, L.A. Clough, L.K. DuBois, J.P. Mcguirk, S. Abhyankar, O.S. Aljitawi, N. O'Neal, C.L. Divine, S. Ganguly. Low-dose cidofovir in the treatment of symptomatic BK virus infection in patients undergoing allogeneic hematopoietic stem cell transplantation: a retrospective analysis of an algorithmic approach Transpl Infect Dis 2010: 12: 406-411. All rights reserved BK virus (BKV) reactivation occurs in 50% of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Standardized antiviral management of BKV infection has not been established. In order to develop a uniform guideline, a treatment algorithm for the management of symptomatic BKV replication was implemented for our allo-HSCT population. This is a retrospective analysis of patients treated according to the protocol between January 2008 and January 2009. Eighteen patients developed symptomatic BKV replication a median of 43 days after allo-HSCT. All patients had BK viruria and 12 patients had BK viremia in addition to viruria. Patients with isolated viruria were treated with intravenous (IV) low-dose cidofovir (0.5-1 mg/kg IV weekly) until symptom resolution. In patients with BK viremia, therapy was continued until virological clearance was achieved in the blood. Four patients also received intravesical instillation of cidofovir per physician discretion. Thirteen of 18 (72%) patients with viruria and 8 of 12 (75%) patients with viremia responded to treatment. Three patients developed transient renal dysfunction. Low-dose cidofovir is safe and effective in allo-HSCT recipients. In absence of randomized prospective data, an institutional algorithmic protocol removes variance in practice pattern and derives data that may be used for research and improved patient care. [ABSTRACT FROM AUTHOR]

Background Immunological and clinical effects of post-transplant growth factor administration have not been well studied. This report describes the outcome and immune functions of a total of 50 HLA-matched related donor allogeneic blood stem-cell transplantation patients who received post-transplant G-CSF (10 μg/kg) or placebo. Methods Immune status, including number of lymphocyte subsets and their functions, and serum immunoglobulin levels and clinical status--including GvHD, rate of relapse, event-free survival, and overall survival--were determined in the patients enrolled in this study. Results Twenty-eight patients survived 1 year after transplant, and 15 patients had available results to compare immune function by randomization assignment. At 12 months post-transplant, immune parameters in G-CSF versus placebo groups showed no statistically significant differences in number of circulating lymphocyte subsets CD3, CD4, CD8, CD19 and CD56 in the two groups. There was no significant (NS) difference in immunoglobulin IgG, IgA and IgM levels, NK or LAK cell-mediated cytotoxicity levels, and mitogen-induced proliferation between post-transplant G-CSF and placebo group. In addition, the analyses of immune parameters at earlier time-points on Days 28, 100, 180, and 270 revealed that, except for LAK cytotoxicity at Day 100, there was no differences between the two groups. Fourteen of 26 patients are alive in the G-CSF arm and nine of 24 in the placebo arm. Median follow-up of surviving patients is 43 months. Four year overall and event-free survival in the G-CSF and the placebo group were 53% and 35% (NS), and 44% and 36% (NS) respectively. Bacterial or fungal infections were the cause of six of 12 deaths in the G-CSF arm (all bacterial) and of four of 15 deaths in the placebo arm (two deaths from Aspergillus) (P=0.26). Two patients relapsed in the G-CSF arm and three in the placebo arm. Four year cumulative incidences of relapse were 8% versus 13% in G-CSF versus placebo arms, respectively, (NS). Chronic GvHD developed in 14 of 19 100-day survivors after G-CSF (11 extensive stage), and in 17 of 20 (14 extensive stage) in the placebo arm. The 4-year cumulative incidence of chronic GvHD was 56% [95% confidence interval (CI) 24-88%] after G-CSF and 71% (95% CI 48-94%) after placebo; this difference was not statistically significant (log rank P=0.41). Conclusion In summary, there were no significant immunological or alterations in clinical benefit of post-transplant G-CSF administration in T-replete allotransplant recipients. [ABSTRACT FROM AUTHOR]

We report a patient who developed breast masses 17 months after a T cell-depleted partially mismatched related donor (PMRD) bone marrow transplant (BMT) for chronic myeloid leukemia. The patient had severe chronic graft-versus-host disease (GVHD) and the masses were due to Epstein–Barr virus (EBV) lymphoproliferative disease (LPD). The patient expired from fungal pneumonia after chemotherapy for the EBV-LPD. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 64-year-old female with a history of chronic lymphocytic leukemia (CLL), who was admitted to the hospital due to large gluteal hematomas. She was given prednisone as initiated treatment for 1 week and stopped due to avascular necrosis followed by rituximab. The patient was also treated for chronic and moderate graft versus host disease (GVHD) in lungs, musculoskeletal system and liver.

Allogeneic hematopoietic stem cell transplantation used to manage hematologic malignancies, is frequently complicated by graft versus host disease (GvHD) leading to poor outcomes with increased non-relapse morbidity and mortality. Traditional immunosuppressive therapy has many side effects, thus, necessitating alternative therapies to treat GvHD. Based on their immunomodulation and immunosuppression properties, mesenchymal stem cells (MSCs) are being explored to treat acute GvHD. Currently, there are no cellular products approved in the United States to treat steroid refractory aGvHD. MSCTC-0010, manufactured at the Midwest Stem Cell Therapy Center's GMP facility, is an investigational product consisting of tissue-derived allogeneic, Wharton's Jelly MSCs. We investigated MSCTC-0010 for the treatment of de novo high-risk acute or steroid refractory GvHD in a Phase I, safety clinical trial (IND#17672). The MSCTC-0010 is manufactured by explantation, ex-vivo culture and expansion, and cryopreservation and is tested for identity, potency, sterility, and stability. MSCTC-0010 was delivered intravenously twice at a dose of 2 × 106cells/kg in the first cohort and 10 × 106cells/kg in the second cohort on day 0 and 7. GvHD was graded by organ (skin, liver, and gastrointestinal) involvement. The primary endpoint was to evaluate the safety of MSCTC-0010 in patients who experienced a treatment related adverse event. The secondary endpoints include achievement of complete response of aGvHD by day 42 and improvement of GvHD in 1 or more organs involved. Samples were drawn at regular intervals to explore biomarkers that correlate with biological response. The study enrolled 10 patients (ages 18-75). Safety of the MSCTC-0010 was demonstrated as there was no infusion related toxicity and no increased incidence of infections. The study showed aGvHD response in 7 of the 10 patients at day 28 (refer to table). A biomarker panel consisting of Reg 3-α and ST-2 was analyzed. Analysis of these two biomarkers showed a reduction from day 0 to day 42. Subjects who received the higher dose of MSCTC-0010 had a statistically significant decline in the Reg-3 α levels on day 7, 14, 21, and 28. The drop in levels correlated with the clinical response. ST-2 levels showed a significant decrease on day 28 and 42. This Phase 1 trial with MSCTC-0010 successfully met its primary endpoint of safety. Treatment with MSCTC-0010 shows promise in patients with high risk aGvHD. [ABSTRACT FROM AUTHOR]