AbstractAutologous Stem Cell Transplantation Research Articles

Trends in hematopoietic stem cell utilization and cost of cryopreservation

Abstract Autologous stem cell transplantation (ASCT) is the standard of care treatment for multiple myeloma. Standard ASCT procedures collect hematopoietic stem cells (HPSC) in excess for multiple transplants due to reports of high mobilization failure and unsuccessful ASCT collections following myeloablative treatments. Cost analysis studies estimate that one year of cryopreservation and one day of HPSC collection would each cost $5000 per patient. Limited data is available on the usage of the second transplant and the storage costs of non-transplanted products. This study evaluates the utilization of cryopreserved HPSC products and calculates the cost of cryopreservation. A retrospective chart review study of a cohort of 240 deceased MM patients, who received ASCT between January 2010 to December 2015. Demographic and clinical data were obtained from the laboratory and electronic medical record. The cohort was categorized into two groups, with 130 patients in Group 1 (≤60 years) and 110 patients in Group 2 (>60 years). Cumulative incidence of a second transplant was computed from the life table using the Kaplan Meier method. The cost of cryopreservation was calculated based on the time HPSC products remained in the freezers before disposal. PBSC was mobilized using Granulocyte Colony Stimulating Factor (GCSF), or GCSF and Mozobil. The average age of patients at first collection is 61 (IQR: 54-66) years and the average age of death is 64 (IQR: 58 -70) years. The average life span of patients after receiving the first transplant is 3 (IQR: 2-5) years. The average number of collection days is 2 (IQR: 1-3). 65 patients had 1-day collections, 105 had 2-day collections and 70 had ≥3-day collections. 175 patients (73%) had >1 day collection. Only 22 patients (9%) received a second transplant and 18 of them (82%) were in Group 1 (≤60). The cumulative incidence of a second transplant by 5 years is 23% for Group 1 and 4% for Group 2. Two-transplant collections required 492 days of apheresis with an overall cost of $2,500,000; however, one-transplant collections would cost $1,400,000 for 279 apheresis days. The median cost of cryopreservation for each patient who did not receive the second transplant is $15,000 (IQR: $8000 - $25,000). Therefore, the estimated cost for all patients in the study is $3,600,000 until the disposal of HPSC products. The incidence of a second transplant is low across all patients and significantly lower in patients greater than 60 years of age. Cryopreserved stem cell products remain under-utilized, leading to substantial financial burden. The duration of HPSC collection and cryopreservation must be re-evaluated for future treatment plans. Institutional policies should be revised based on the utilization trend to lower the operational cost of storage.

Purification of CD34+ cells in myasthenia gravis patient’s peripheral blood stem cells using the CliniMACS cell separation system

Autologous hematopoietic stem cell transplantation therapy has been widely used in recent decades for the treatment of hematological diseases, cancer, and autoimmune diseases. In autoimmune diseases, self-activated T lymphocytes and B lymphocytes secreting antibodies against host antigens are considered to be central in the pathogenesis of the disease. Autologous stem cell products that eliminates these pathological cells could be a lifesaver for patients with autoimmune diseases who are resistant to conventional therapy, in order to restore a healthy immune system, achieve long-term remission and limited recurrence. The aims of this study was to complete and evaluate the results of the CD34 positive stem cells purification procedure from a myasthenia gravis patient’s mobilized peripheral blood stem cells, for the purpose of autologous hematopoietic stem cell transplantation for Myasthenia gravis as well as other autoimmune diseases in Vietnam. We have completed the purification procedure of CD34-positive stem cells from mobilized peripheral blood stem cells of patient with myasthenia gravis using CliniMACS system with results of removing 99.99% of T lymphocytes; 99.81% of B lymphocytes; 99.99% of NK cells, while CD34+ recovery performance was 64.05% with CD34+ cell survival rate of over 99%, no bacterial contamination, ensuring quality assurance of stem cell product for transplantation.

Cardiovascular events among recipients of hematopoietic stem cell transplantation

Abstract Background Allogeneic and autologous hematopoietic stem cell transplantation (HSCT) are potential curative treatments for several hematological malignancies (1). Survival after HSCT has improved over the last decade, but survivors remain at risk for health issues after transplantation. Cardiovascular complications after HSCT are increasingly recognized (2). Cardiovascular diseases may be an important cause of mortality and morbidity in patients after HSCT owing to the toxicities of the cancer therapies; however, the incidence of cardiovascular events (CVEs) in this population has not been completely characterized. The objective of this systematic review is to summarize the evidence on the incidence of CVEs in HSCT recipients. Methods Medline and Embase were searched from inception to December 2020 without language restriction. Two authors independently screened the titles and abstracts. Inclusion criteria were: cohort studies and phase 3 randomized controlled trials that reported CVEs (i.e., heart failure, arrythmias, acute coronary syndrome, and stroke) or cardiovascular death among adults who underwent HSCT for a hematological malignancy. All-cause mortality, relapse-related mortality, and non-relapse-related mortality (NRM) were also collected. Studies in which the follow up period was not started immediately after HSCT were excluded due to the risk of immortal bias. Results Of 8151 nonduplicate articles, 30 studies including 14019 individuals post autologous HSCT, and 22 studies including 31049 individuals post allogeneic HSCT met the inclusion criteria. The cumulative incidence of CVEs in the first 100 days post autologous HSCT was 9% and arrhythmia (i.e., atrial fibrillation) was the most common CVE. In recipients of allogeneic HSCT, the 100-day cumulative incidence of CVEs was 3%, and heart failure (HF) was the most common reported CVE. In recipients of autologous and allogeneic HSCT, cardiovascular death was responsible for 43% and 10% of NRM within 100 days, respectively (Table 1). The incidence of CVEs was 4.96 per 1000-person years (95% CI; 4.21–5.80) in long-term survivors (beyond 100-days) of autologous HSCT, and HF was the most common CVE in this population. In long-term survivors of allogeneic HSCT, the incidence of CVEs was 1.90 per 1000-person years (95% CI: 1.59–2.24). Cardiovascular death was the most frequently reported CVE in long-term survivors of allogeneic HSCT (Table 2). Conclusion CVEs remain a major cause of non relapse morbidity and mortality in recipients of HSCT, especially recipients of autologous HSCT within the first 100 days. Future studies are needed to identify the risk factors for CVEs that are specific to HSCT recipients. Funding Acknowledgement Type of funding sources: None.

The influence of high-efficiency particulate air filtration on mortality among multiple myeloma patients receiving autologous stem cell transplantation

Autologous stem cell transplantation (ASCT) continues to be the standard treatment for transplant-eligible multiple myeloma (MM) patients. A portion of MM patients received ASCT in an isolation room with high-efficiency particulate air (HEPA) filtration. The effectiveness of the HEPA filtration on reducing treatment-related mortality (TRM) is controversial. We enrolled patients with newly diagnosed MM in Taiwan between 2000 and 2017. The primary endpoint of the study was TRM, which was defined as death within 100 days after ASCT. A total of 961 MM patients received ASCT. Of them, 480 patients (49.9%) received ASCT in an isolation room with HEPA filtration (HEPA group). The median overall survival from ASCT was 7.52 years for the HEPA group and 5.88 years for the remaining patients (non-HEPA group) (p = 0.370). The 100-day mortality rate was 1.5% and 1.0% for the HEPA and non-HEPA groups, respectively. In the multivariate analysis, the 100-day mortality had no difference between the HEPA and non-HEPA groups (adjusted hazard ratio 1.65, 95% CI 0.52–5.23). The median cost for ASCT inpatient care was $13,777.6 and $6527.6 for the HEPA and non-HEPA groups, respectively (p < 0.001). Although half of MM patients in Taiwan received ASCT in HEPA room, it didn’t affect 100-day mortality.

Autologous stem cell transplantation after anti-PD-1 therapy for multiply relapsed or refractory Hodgkin lymphoma

Autologous stem cell transplantation (ASCT) can be curative for patients with relapsed/refractory Hodgkin lymphoma (HL). Based on studies suggesting that anti-PD-1 monoclonal antibodies (mAbs) can sensitize patients to subsequent chemotherapy, we hypothesized that anti-PD-1 therapy before ASCT would result in acceptable outcomes among high-risk patients who progressed on or responded insufficiently to ≥1 salvage regimen, including chemorefractory patients who are traditionally considered poor ASCT candidates. We retrospectively identified 78 HL patients who underwent ASCT after receiving an anti-PD-1 mAb (alone or in combination) as third-line or later therapy across 22 centers. Chemorefractory disease was common, including 42 patients (54%) refractory to ≥2 consecutive systemic therapies immediately before anti-PD-1 treatment. Fifty-eight (74%) patients underwent ASCT after anti-PD-1 treatment, while 20 patients (26%) received additional therapy after PD-1 blockade and before ASCT. Patients received a median of 4 systemic therapies (range, 3-7) before ASCT, and 31 patients (41%) had a positive pre-ASCT positron emission tomography (PET) result. After a median post-ASCT follow-up of 19.6 months, the 18-month progression-free survival (PFS) and overall survival were 81% (95% CI, 69-89) and 96% (95% confidence interval [CI], 87-99), respectively. Favorable outcomes were observed for patients who were refractory to 2 consecutive therapies immediately before PD-1 blockade (18-month PFS, 78%), had a positive pre-ASCT PET (18-month PFS, 75%), or received ≥4 systemic therapies before ASCT (18-month PFS, 73%), while PD-1 nonresponders had inferior outcomes (18-month PFS, 51%). In this high-risk cohort, ASCT after anti-PD-1 therapy was associated with excellent outcomes, even among heavily pretreated, previously chemorefractory patients.

Autologous hematopoietic stem cell transplantation in the treatment of systemic sclerosis. Part 2. Safety and complications

Autologous hematopoietic stem cell transplantation (auto-HSCT) is presently the only disease-modifying strategy for the treatment of systemic sclerosis (SSs) that has Level A evidence, the effectiveness of which has been proven in three controlled clinical trials: ASSIST, ASTIS, and SCOT. Despite the positive results obtained with the use of this treatment option, the issues related to its tolerability and safety remain unresolved. The complications caused by obvious immunosuppression and higher frequency of infections are the main causes of death after autoHSCT for autoimmune diseases and occur mainly in the first month after treatment. Overall, the studies performed confirm the overall assessment of auto-HSCT as an effective and relatively safe treatment for severe SSs.

Results of a completely outpatient autologous stem cell transplant program for lymphoma patients receiving reduced-intensity conditioning

Autologous stem cell transplantation (ASCT) is commonly an in-patient procedure. However, outpatient ASCT grows as a cost-effective and feasible option for patients with lymphoma and reports assessing it after reduced-intensity conditioning (RIC) are sparse. We report the outcome of 102 patients with lymphoma who underwent ASCT on a full outpatient basis in a single-center transplant program between 2010 and 2020. Forty-two percent of the cohort required transfusion support, 36.3% experienced a neutropenic fever episode, 25.5% mucositis, and 9.8% developed severe infection. At a median time of 5 days (range 1–28), only 22.5% of the cohort required admission within the first 100 days after the autograft, median length of hospital stay was 0 days (range 0–14) and neutropenic fever was the most common reason for hospitalization. Non-relapse mortality at 1 year was 5%. ASCT in a completely outpatient setting is feasible, safe, and highly effective to treat lymphoma patients.

Melphalan 200 mg/m2 does not increase toxicity and improves survival in comparison to reduced doses of melphalan in multiple myeloma patients.

Autologous stem cell transplantation (ASCT) conditioned with melphalan 200 mg/m2 (Mel200) is standard of care for young multiple myeloma (MM) patients. Lower doses of melphalan (MelRed) have been used to reduce toxicity, although data regarding their efficacy are not concordant. We retrospectively evaluated 313 MM patients receiving ASCT at Jena University Hospital between 2003 and 2017. Patients receiving MelRed were on average older (p < 0.001), had a worse renal function (p < 0.001) and more comorbidities (p < 0.001). No differences were seen in treatment response before ASCT between the two groups, whilst after ASCT the rate of at least very good partial responses (VGPR) was significantly higher for patients receiving Mel200 (93% vs. 76%, p < 0.001). PFS (39 vs. 20 months, p < 0.001) and OS (103 vs. 59 months, p = 0.001) were longer with Mel200. Toxicities were comparable in the two groups. After adjusting for age and clinical characteristics using the propensity score, for VGPR before and after ASCT and for double ASCT strategy in a Cox regression analysis, Mel200 was still associated with a lower risk of disease progression (HR = 0.40, 95% CI = 0.40-0.96) and of death (HR = 0.61, 95% CI = 0.35-1.07). Our results confirm that Mel200 is still the standard of care for ASCT eligible myeloma patients.

ITGA6+ Human Testicular Cell Populations Acquire a Mesenchymal Rather than Germ Cell Transcriptional Signature during Long-Term Culture.

Autologous spermatogonial stem cell transplantation is an experimental technique aimed at restoring fertility in infertile men. Although effective in animal models, in vitro propagation of human spermatogonia prior to transplantation has proven to be difficult. A major limiting factor is endogenous somatic testicular cell overgrowth during long-term culture. This makes the culture both inefficient and necessitates highly specific cell sorting strategies in order to enrich cultured germ cell fractions prior to transplantation. Here, we employed RNA-Seq to determine cell type composition in sorted integrin alpha-6 (ITGA6+) primary human testicular cells (n = 4 donors) cultured for up to two months, using differential gene expression and cell deconvolution analyses. Our data and analyses reveal that long-term cultured ITGA6+ testicular cells are composed mainly of cells expressing markers of peritubular myoid cells, (progenitor) Leydig cells, fibroblasts and mesenchymal stromal cells and only a limited percentage of spermatogonial cells as compared to their uncultured counterparts. These findings provide valuable insights into the cell type composition of cultured human ITGA6+ testicular cells during in vitro propagation and may serve as a basis for optimizing future cell sorting strategies as well as optimizing the current human testicular cell culture system for clinical use.

Characteristics of exceptional responders to autologous stem cell transplantation in multiple myeloma

Autologous stem cell transplantation (ASCT) is an important treatment modality in multiple myeloma (MM). However, relapse following ASCT is considered almost inevitable. This study aimed to characterize exceptional responders to ASCT, defined as progression-free survival (PFS) >8 years in the absence of maintenance therapy. We retrospectively analyzed patients treated at Mayo Clinic between August 1, 1998 and January 3, 2006, and included those with symptomatic MM, treated with an ASCT within 12 months of diagnosis. We found that 46 (9%) of the 509 patients who underwent ASCT during the study period were exceptional responders. The median duration of follow-up from diagnosis was 16.2 (interquartile range 14.3–17.7) years. The best response to therapy was a complete response (CR) or better in 34 (74%) of patients, and less than a CR in 12 (26%) of patients. The median PFS was 13.8 (95% confidence interval 10.5–18.5) years, and at the time of the last hematology assessment, 24 of 46 (52%) patients remained in remission. In conclusion, we showed that a small subset of patients with MM attains durable disease control without maintenance therapy post ASCT. Pre-emptive identification of these patients may help prevent undue toxicities and costs of subsequent therapy.

Stem cell transplantation and alemtuzumab - options for 'early reprogramming' in multiple sclerosis?

Autologous hematopoietic stem cell transplantation (aHSCT) has been repeatedly studied for treating multiple sclerosis (MS), yet evidence remains complicated as treatment was often administered to heterogenic patient collectives and in later stages of MS.

Optimization of methods for collecting peripheral hematopoietic stem cells in children with cancer: literature review

Autologous hematopoietic stem cell transplantation (auto-HSCT) is a standard for the treatment of oncological, hematologic, and also some immune diseases, ensuring the restoration of blood counts after high-dose chemotherapy. In children, the success of mobilization and collection of hematopoietic stem cells (HSCs) is especially important. Mobilization schemes for children are decided on an individual basis, which requires the development and implementation of recommendations for improving the efficiency of mobilization and collection of HSCs. Mobilization schemes include the use of granulocyte colony-stimulating factor in the form of monotherapy or in combination with CXCR4 antagonists. These schemes are ineffective in some children, which requires re-mobilization or rejection of transplantation, which negatively affects the prognosis. When preparing a patient for HSCs collection, it is necessary to take into account all previous therapy, the patient’s age, weight and height indicators, and general somatic state. Harvesting the required amount of HSCs will allow for high-dose therapy followed by auto-HSCT, and thereby increase the effectiveness of treatment. It is necessary to optimize the protocol for mobilization of HSCs with a large bias for pediatric patients, which will clearly define the criteria for mobilization, give indications for this procedure and determine the criteria for technical collection, which will allow to obtain the optimal number of CD34+ cells, which will ensure the success of the treatment.

Long-term survival without graft-versus-host-disease following infusion of allogeneic myeloma-specific V\u03b2 T cell families

BackgroundDespite chemo-induction therapy and autologous stem cell transplantation (ASCT), the vast majority of patients with Multiple Myeloma (MM) relapse within 7 years and the disease remains incurable. Adoptive Allogeneic T-cell therapy (ATCT) might be curative for MM, however current ATCT protocols often lead to graft versus host disease (GvHD). Transplanting only tumor reactive donor T cells that mediate a graft-versus-myeloma (GvM) but not GvHD may overcome this problem.MethodsWe used an MHC-matched/miHA-disparate B10.D2 → Balb/c bone marrow transplantation (BMT) murine model and MOPC315.BM MM cells to develop an ATCT protocol consisting of total body irradiation, autologous-BMT and infusion of selective, myeloma-reactive lymphocytes of T cell receptor (TCR) Vβ 2, 3 and 8.3 families (MM-auto BMT ATCT).ResultsPre-stimulation ex vivo of allogeneic T cells by exposure to MOPC315.BM MM cells in the presence of IL-2, anti-CD3 and anti-CD28 resulted in expansion of the myeloma-reactive T cell TCRVβ 2, 3 and 8.3 subfamilies. Their isolation and infusion into MM-bearing mice resulted in a vigorous GvM response without induction GvHD and long-term survival. Repeated infusion of naïve myeloma-reactive T cell TCRVβ 2, 3 and 8.3 subfamilies was also effective.ConclusionsThese data demonstrate that a transplantation protocol involving only selective tumor-reactive donor T cell families is an effective immunotherapy and results in long-term survival in a mouse model of human MM. The results highlight the need to develop similar ATCT strategies for MM patients that result in enhanced survival without symptoms of GvHD.

Successful hematopoietic stem-cell mobilization with plerixafor plus granulocyte-colony stimulating factor in multiple myeloma patients treated with pomalidomide.

Autologous stem-cell transplantation is an effective procedure for the treatment of multiple myeloma, and involves the collection of hematopoietic stem cells (HSCs). However, in some patients, HSCs in the bone marrow fail to mobilize. Pomalidomide upregulates CXCR4 in hematopoietic stem cells, in a manner similar to that of lenalidomide, and is, thus, likely to have a negative impact on hematopoietic stem-cell mobilization in multiple myeloma patients. Here, we report the two cases in which hematopoietic stem cells were mobilized using plerixafor plus granulocyte-colony stimulating factor after exposure to lenalidomide and pomalidomide. Use of plerixafor with a sufficient washout period may lead to successful mobilization following pomalidomide use, although further study of this potential use is needed.

Superior outcome of patients with favorable-risk acute myeloid leukemia using consolidation with autologous stem cell transplantation

Autologous stem cell transplantation (ASCT), intensifying anti-leukemic effects without significant treatment-related mortality (TRM), is particularly appealing in AML with favorable genetic/molecular profile. This study retrospectively evaluated the outcomes of post-remission treatment in consecutive favorable-risk AML patients. Sixty-six patients were included: 32 had mutated NPM1/wild-type FLT-ITD, 16 had t(8:21) and 18 – inv(16). Forty patients received chemotherapy alone, 26 underwent ASCT upfront. In time-dependent analysis, the ASCT group demonstrated higher relapse-free (RFS) (p = .001) and overall survivals (OS) (p = .0007). The 1-year RFS and OS were 44.2% vs 88% and 71% vs 96% for chemotherapy and ASCT, respectively. The corresponding TRM was 4/40 (10.0%) and 0/26 (0%), with relapse rates of 70.0% and 19.2% (p = .0002). In multivariate analysis, ASCT was associated with superior OS and RFS. In conclusion, ASCT offers significantly superior RFS and OS in favorable-risk AML in first complete remission. These data support the recent resurgence of interest in ASCT for AML.

Safety profile of autologous hematopoietic stem cell mobilization and transplantation in patients with systemic sclerosis

Autologous hematopoietic stem cell transplantation (AHSCT) is thought to be effective therapeutic approach in patients with poor prognosis systemic sclerosis; however, the toxicity remains a challenge. Between years 2003 and 2016, we enrolled 18 patients with systemic sclerosis at median age at transplant of 52 years (range 24–68). The median duration of disease before AHSCT was 14 months (range 2–85). Peripheral blood stem cells were mobilized with cyclophosphamide (CY) and granulocyte colony-stimulating factor. Conditioning regimen included CY (200 mg/kg) and alemtuzumab (median dose, 60 mg) [n = 11], melphalan (MEL; 140 mg/m2) and alemtuzumab [n = 2], CY and rabbit anti-thymocyte globulin (rATG; 7.5 mg/kg) [n = 4], and CY alone (n = 1). Four deaths occurred early after transplant. There were three males and one female at median age at death of 51 years (range 24–68). The AHSCT-related deaths have been observed on days + 1, + 4, + 9, and + 15 after procedure. The causes of death included bilateral pneumonia followed by multi-organ failure in three patients and myocardial infarction in one. Three patients expired late during post-transplant follow-up, after 5, 21, and 42 months. The causes of death were disease progression in two patients and sudden heart attack in one. Eleven patients are alive after median follow-up after AHSCT of 42.0 months (range 0–95). Before proceeding to AHSCT in systemic sclerosis, there is a strong need to optimize patient selection to reduce toxicity. The administration of alemtuzumab should be avoided due to high risk of life-threatening infectious complications.

The relationship of CD34+ dosage and platelet recovery following high dose chemotherapy and autologous CD34+ reinfusion in multiple myeloma

Autologous hematopoietic stem cell transplantation (ASCT) is an established treatment for multiple myeloma (MM), yet the impact of transplanted CD34+ cell dose remains unresolved, especially in patients over the age of 65 years. Data was collected from 207 consecutive ASCT patients to determine the relationship between CD34+ infusion count and short-term and long-term platelet recovery. For MM patients under the age of 65 years (n=155), CD34+ dosage correlates with time to platelet engraftment (p<0.001) and platelet count at 30 days (p=0.003), but not with long-term platelet counts at 180 or 360 days from the CD34+ reinfusion. For MM patients aged 65 years or older (n=46), CD34+ dosage did not correlate with time to platelet engraftment, but did correlate with both short-term and long-term platelet counts at 30 (p<0.001), 180 (p=0.021), and 360 days (p=0.005). Exploratory regression analysis was done to explore platelet stability following the current minimum CD34+ dosage reinfusion. For MM patients under the age of 65 years, the minimum standard CD34+ dosage of 2×106cells/kg was sufficient for a timing to platelet engraftment of <21 days and short-term platelets count ≥150×109/L at 30 days. Alternatively, for MM patients aged 65 years or older, the CD34+ dosage of 2×106cells/kg was insufficient for platelet counts ≥150×109/L at 30 and only marginally attainable at 360 days suggesting that in elderly MM patients a higher CD34+ dosage may be required for platelet recovery and possibly long-term platelet stability.

Autologous stem cell transplantation in systemic sclerosis

Autologous hematopoietic stem cell transplantation (HSCT) is a very effective treatment option for patients with severe systemic sclerosis (SSc). In addition to various case series two randomized controlled trials could prove its superiority over intense cyclophosphamide pulse therapy. Nevertheless, HSCT is associated with a treatment-related mortality of approximately 10 %; therefore, further studies should be carried out to reduce the toxicity of HSCT by adaptation of the therapy regimen and the option of HSCT should be made available earlier to patients with a high risk of mortality. The mechanism of action of HSCT is still poorly understood. While profibrotic cytokines or even autoantibodies hardly appear to be influenced by the treatment, alterations to regulatory T‑cells may play a role. Further improvement of transplantation regimens as well as a better understanding of the underlying pathogenetic principles and mechanisms of action should be the aim of further studies on HSCT.

Tandem autologous versus autologous/allogeneic transplantation for multiple myeloma: propensity score analysis

Autologous hematopoietic stem cell transplantation (auto-HCT) is considered a standard therapy for transplant-eligible patients with multiple myeloma, while allogeneic HCT (allo-HCT) is controversial. We retrospectively analyzed 765 patients with myeloma who underwent tandem transplantation between 1998 and 2012 using Japanese registry data. We evaluated the clinical outcomes of tandem auto-HCT (n = 676) and auto/allo-HCT (n = 89). To adjust for a selection bias, we compared overall survival (OS) between the two groups by a propensity score analysis. The probability of OS at six years was 58.5% for the tandem auto-HCT group and 54.4% for the tandem auto/allo-HCT group (p = 0.47). In a matched-pair analysis based on the propensity score, the difference in survival between the two groups was not statistically significant, although the survival curve appeared to reach a plateau beyond five years in the auto/allo group. Further strategies to reduce treatment-related mortality and enhance a graft-versus-myeloma effect are necessary to improve OS.

Cryopreservation in Closed Bag Systems as an Alternative to Clean Rooms for Preparations of Peripheral Blood Stem Cells.

Autologous and allogeneic stem cell transplantation (SCT) represents a therapeutic option widely used for hematopoietic malignancies. One important milestone in the development of this treatment strategy was the development of effective cryopreservation technologies resulting in a high quality with respect to cell viability as well as lack of contamination of the graft.Stem cell preparations have been initially performed within standard laboratories as it is routinely still the case in many countries. With the emergence of cleanrooms, manufacturing of stem cell preparations within these facilities has become a new standard mandatory in Europe. However, due to high costs and laborious procedures, novel developments recently emerged using closed bag systems as reliable alternatives to conventional cleanrooms. Several hurdles needed to be overcome including the addition of the cryoprotectant dimethylsulfoxide (DMSO) as a relevant manipulation. As a result of the development, closed bag systems proved to be comparable in terms of product quality and patient outcome to cleanroom products. They also comply with the strict regulations of good manufacturing practice.With closed systems being available, costs and efforts of a cleanroom facility may be substantially reduced in the future. The process can be easily extended for other cell preparations requiring minor modifications as donor lymphocyte preparations. Moreover, novel developments may provide solutions for the production of advanced-therapy medicinal products in closed systems.