Pegfilgrastim improves the outcomes of mobilization and engraftment in autologous hematopoietic stem cell transplantation for the treatment of multiple myeloma.

Autologous stem cell transplantation (ASCT) is the only curable therapy for multiple myeloma (MM), while its success primarily relies on mobilization to obtain sufficient hematopoietic stem/progenitor cells (HPC). Although the role of Pegfilgrastim (PEG), a novel PEGylated form of the recombinant G-CSF filgrastim (FIL), in mobilization has been demonstrated, it remains unclear whether this approach is cost-effective in MM treatment. Here, we performed a real-world analysis to evaluate the efficacy and cost of PEG for mobilization in a cohort of MM patients, of which 53% carried high-risk cytogenetic abnormalities. A total of 91 patients who received either a single dose of PEG (6 or 12 mg, n = 42) or multiple dosing of 10 µg/kg/day FIL (n = 49) after chemotherapy for HPC mobilization were included. The yield of MNCs and CD34+ cells per milliliter of blood collected via apheresis was significantly greater in the PEG group than that in the FIL group (P = 0.014 and P = 0.038). Mobilization with PEG yielded significantly higher median number of collected CD34+ cells than FIL (5.56 vs. 4.82 × 106/kg; P = 0.038). Moreover, the average time-to-recovery of leukocytes and platelets after transplantation was markedly shorter in the PEG group than that in the FIL group (leukocyte, 11.59 ± 1.98 vs 12.93 ± 2.83 days, P = 0.019; platelet, 12.86 ± 2.62 vs 14.80 ± 5.47, P = 0.085). However, the total cost of mobilization and apheresis using PEG or FIL was comparable (P = 0.486). Of note, mobilization with 12 mg PEG further shortened time-to-recovery of leukocytes (10.64 ± 0.51 vs. 12.04 ± 2.26 days, P = 0.05) and platelets (10.60 ± 2.89 vs. 13.33 ± 2.35 days, P = 0.031) compared with 6 mg PEG. Our results support a notion that PEG (especially 12 mg) combined with chemotherapy is a cost-effective and convenient regimen of mobilization, which might improve the outcome of ASCT in MM.

Temporal trends in treatment and survival of older adult diffuse large B-Cell lymphoma patients in the SEER-Medicare linked database.

To describe temporal trends in treatment among older adult (≥66 years) patients diagnosed with diffuse large B-cell lymphoma (DLBCL), we analyzed 18,058 DLBCL patients from the Surveillance, Epidemiology, and End Results linked Medicare (SEER-Medicare) database diagnosed between 2001 and 2013. Among 65% of patients receiving treatment after diagnosis, R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) was the most common frontline therapy, increasing with more recent treatment year: 51% (2001-2003) vs. 69% (2010-2014). Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) was uncommon in these Medicare patients. As the addition of rituximab increased over time, we also observed an improved survival rate over time. It is possible there is an association, but we cannot make this inference as effectiveness was not measured in this study. Overall survival estimates indicated that survival probabilities steadily improved in more recent years; however, 5-year survival was <40%, indicating the need for improved treatment options for older adult DLBCL patients.

Chimeric Antigen Receptor T-Cell Therapy.

Patients with relapsed or refractory (R/R) cancers have a poor prognosis and limited treatment options. The recent approval of 2 chimeric antigen receptor (CAR) autologous T-cell products for R/R B-cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma treatment is setting the stage for what is possible in other diseases. However, there are important factors that must be considered, including patient selection, toxicity management, and costs associated with CAR T-cell therapy. To begin to address these issues, NCCN organized a task force consisting of a multidisciplinary panel of experts in oncology, cancer center administration, and health policy, which met for the first time in March 2018. This report describes the current state of CAR T-cell therapy and future strategies that should be considered as the application of this novel immunotherapy expands and evolves.

Perfusion scintigraphy in the assessment of autologous cell therapy in diabetic patients with critical limb ischemia.

Perfusion scintigraphy with technetium-99-methoxy-isobutyl-isonitrile ((99m)Tc-MIBI) is often used for assessing myocardial function but the number of studies concerning lower limb perfusion is limited. The aim of our study was to assess whether (99m)Tc-MIBI was an eligible method for evaluation of the effect of cell therapy on critical limb ischemia (CLI) in diabetic patients. (99m)Tc-MIBI of calf muscles was performed before and 3 months after autologous cell therapy (ACT) in 24 diabetic patients with CLI. Scintigraphic parameters such as rest count and exercising count after a stress test were defined. These parameters and their ratios were compared between treated and untreated (control) limbs and with changes in transcutaneous oxygen pressure (TcPO(2)) that served as a reference method. The effect of ACT was confirmed by a significant increase in TcPO(2) values (p<0.001) at 3 months after ACT. We did not observe any significant changes of scintigraphic parameters both at rest and after stress 3 months after ACT, there were no differences between treated and control limbs and no association with TcPO(2) changes. Results of our study showed no significant contribution of (99m)Tc-MIBI of calf muscles to the assessment of ACT in diabetic patients with CLI over a 3-month follow-up period.

Impact of surgical innovation on tissue repair in the surgical patient.

BACKGROUND: Throughout history, surgeons have been prolific innovators, which is hardly surprising as most surgeons innovate daily, tailoring their intervention to the intrinsic uniqueness of each operation, each patient and each disease. Innovation can be defined as the application of better solutions that meet new requirements, unarticulated needs or existing market needs. In the past two decades, surgical innovation has significantly improved patient outcomes, complication rates and length of hospital stay. There is one key area that has great potential to change the face of surgical practice and which is still in its infancy: the realm of regenerative medicine and tissue engineering. METHODS: A literature review was performed using PubMed; peer-reviewed publications were screened for relevance in order to identify key surgical innovations influencing regenerative medicine, with a focus on osseous, cutaneous and soft tissue reconstruction. RESULTS: This review describes recent advances in regenerative medicine, documenting key innovations in osseous, cutaneous and soft tissue regeneration that have brought regenerative medicine to the forefront of the surgical imagination. CONCLUSION: Surgical innovation in the emerging field of regenerative medicine has the ability to make a major impact on surgery on a daily basis.

[STATE OF DEVELOPMENT OF HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THE EUROPE AND WORLD].

In this review, we summarize information about the current trends in hematopoietic stem cells transplantation (HSCT) in Europe and world. HSCT has represented one of the most innovative and highly expensive method of treatment for a set of malignant and non-malignant disorders. Differences in the number of HSCT and transplant rates (number of HSCT per 10 million inhabitants), indications and types of transplantations between countries have been reported. They were attributed mainly to differences in the economic situation of the countries and differences in prevalence of certain types of diseases. The gross national income per capita, health care expenditures per capita, number of transplant teams per 1 million inhabitants and team experience are the main impact factors influencing on transplant activity. These data provide a basis for health care planning, preparation of normative acts and future research in Ukraine for rapid expansion HSCT

Cost-effective use of autologous bone marrow transplantation: few answers, many questions, and suggestions for future assessments.

High dose chemotherapy with the support of autologous bone marrow transplantation (ABMT) or peripheral blood progenitor cells (PBPC) has been increasingly used in a variety of haematological and epithelial cancers over the last decade. The rationale of this approach is to overcome the chemotherapy resistance of tumour cells by increasing the dose of cytotoxic drugs. However, the clinical benefit of dose-intensification has been difficult to prove. Almost all studies of ABMT have been done without randomised comparisons with the standard form of therapy for a specific condition. From an economic perspective, the cost of ABMT has been steadily decreasing with improvements in supportive care primarily. Still, current ABMT cost estimates range from $US70 000 to $US150 000 for each uncomplicated procedure. Despite the lack of compelling evidence in support of dose-intensification, ABMT has become a default standard of care after relapse for many patients with lymphoma or leukaemia. We used a decision analysis model to estimate the cost effectiveness of the timing of ABMT in relapsed Hodgkin's disease. The model illustrates the difficulty of using available clinical trial data when follow-up of promising early reports is not available. The model showed that in most situations the optimal strategy is ABMT in second relapse despite growing consensus that immediate ABMT is the treatment of choice. ABMT for women with high-risk or early metastatic breast cancer is one of the most controversial areas in clinical oncology. In the US, several ongoing major randomised trials are addressing the role of ABMT in breast cancer. Using a Markov process we found that ABMT is the preferred strategy under almost all assumptions. The size of the benefit and cost effectiveness of ABMT varied markedly depending on the assumptions made. The model does not supplant the need for randomised trials that concurrently measure efficacy, quality of life, and resource utilisation. However, such analyses point out the critical areas where costs could be cut substantially without effecting efficacy. Drawing conclusions about the cost effectiveness of ABMT for all conditions is hampered by the lack of randomised comparisons of efficacy. Concurrent economic appraisals of selected phase III comparative trials should be considered since the supportive care costs associated with ABMT appear to be stabilising. However, the most important point is that randomised trials are the only mechanism for estimating the therapeutic effect of high dose chemotherapy.