Autologous Peripheral Stem Cell Research Articles

Long-term follow-up of autologous peripheral blood hematopoietic stem cell transplantation for refractory lupus nephritis-a series study of 20 patients.

Autologous hematopoietic cell transplantation (ASCT) improves immunologic homeostasis in autoimmune diseases. ASCT-treated refractory lupus nephritis (LN) has been reported. Nevertheless, the long-term outcome of patients with refractory LN after ASCT remains unknown. This study reports the outcomes of 20 refractory lupus patients with 10-year of follow-up after receiving ASCT. Twenty-two patients with LN refractory to immunosuppressive therapy were enrolled. Twenty patients were examined closely and two cases died within 100 days after ASCT. Hematopoietic cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) was followed by collection of CD34+ positively selected cells. The conditioning regimen consisted of intravenous cyclophosphamide, rabbit antithymocyte globulin, methylprednisolone, and G-CSF. All immunosuppressive therapies were discontinued at the start of mobilization and corticosteroids were tapered rapidly after ASCT. Data was collected from 22 patients with refractory LN treated by ASCT. 59% were female, duration of lupus before ASCT was 46 (33-71) months, and median duration of follow-up after ASCT was 89.5 (56-108) months. 20 long-term followed up patients had an average follow-up time of 92 months (63.25-109.5). Eighteen patients achieved complete remission, one patient reached partial remission, one patient without remission started peritoneal dialysis at month 12, and one patient received short-term renal replacement therapy before ASCT started hemodialysis at 84 months after transplantation. Nine patients relapsed 10 times during the follow-up, and three patients received rituximab. Two patients relapsed during pregnancy after complete response and the Apgar scores of infants were 9 and 10, respectively. All nine patients received glucocorticoids and immunosuppressive medication after relapse and responded again. The 10-year overall survival, 10-year disease-free survival rate, and 10-year renal survival were 100%, 35%, and 90%, respectively. The rate of relapse was 45%. Complications included hypocytosis, infection, B-type insulin resistance syndrome, and monoclonal immunoglobulinemia. This study suggests ASCT is effective and safety in treating refractory LN and is beneficial to improve their long-term outcomes.

Comparison of etoposide combined with G-CSF and cyclophosphamide combined with G-CSF in mobilization of autologous peripheral hematopoietic stem cells in patients with newly diagnosed multiple myeloma

Comparison of etoposide combined with G-CSF and cyclophosphamide combined with G-CSF in mobilization of autologous peripheral hematopoietic stem cells in patients with newly diagnosed multiple myeloma

Factors influencing post-cryopreserved CD34+ cells viability in the harvested products of autologous haematopoietic stem cells.

The cryopreservation process of stem cells potentially cause the loss of CD34+ cells. The aim of this study is to evaluate association of patient, graft and technical characteristics with post cryopreserved CD34+ cells viability among lymphoproliferative disease namely multiple myeloma (MM) and lymphoma patients at Hospital Universiti Sains Malaysia (USM). This retrospective study was conducted in the Transplant Unit. A search of the hospital data (2008-2018) to identify 132 patients for both MM and lymphoma who underwent autologous peripheral blood haematopoietic stem cells (APBSC) mobilisation, and were successfully harvested and cryopreserved. Selected patients' profile as well as selected parameters of stem cell mobilization and cryopreservation were obtained from laboratory information system (LIS), record unit and the Transplant Unit. Multiple logistic regression (MLR) was used to find significant associated factors and P<0.05 was considered significant. The mean age of the patients was 39 years old with almost equal gender distribution and majority were lymphoma patients, 96 (72.7%) while 36 (27.3%) were multiple myeloma (MM) patients. The significant influencing factors of post-cryopreserved CD34+ cells viability were pre-cryopreserved CD34+ cell viability, total nucleated cells (TNC), and anti-platelet and antibiotics usage. Patients who are not on anti-platelet and have higher pre-cryopreserved CD34+ cells viability have higher chance for good post-cryopreserved CD34+ cells viability. While, those patients with higher TNC and on antibiotics have lower chance for good post cryopreserved CD34+ cells viability. This study showed patients who are not on anti-platelet and antibiotics will have higher probability of achieving good post cryopreserved CD34+ cells viability. The APBSC products with higher pre-cryopreserved CD34+ cells viability and lower TNC will achieve better post-cryopreserved CD34+ cells viability. The addition of extra plasma to the APBSC products is recommended to reduce the TNC.

Allogeneic peripheral blood haematopoietic stem cell transplantation for the treatment of dogs with high-grade B-cell lymphoma.

Autologous peripheral blood haematopoietic stem cell transplantation (HCT) cures 33%-40% of dogs with high-grade B-cell lymphoma. We hypothesized, based on human allogeneic bone marrow transplantation literature, that transplanting dogs using canine donor leukocyte-matched CD34+ cells would lead to fewer relapses and increased cure rates. We retrospectively reviewed medical records of dogs diagnosed with high-grade B-cell lymphoma who received an identical allogeneic HCT. A total of 15 dogs transplanted at four facilities were identified. Five of fifteen dogs relapsed before transplant. The mean number of donor CD34+ cells/kg harvested and infused into recipient dogs was 8.0 × 106 /kg (range: 2.08 × 106 /kg-2.9 × 107 /kg). The median disease-free interval and overall survival of all dogs was 1095 days (range: 9-2920 days) and 1115 days (range: 9-2920 days), respectively. Two of five dogs, not in remission at transplant, died in the hospital. The median disease-free interval and overall survival of the remaining three dogs was 25 days (range: 15-250 days) and 1100 days (range: 66-1902 days), respectively. The median disease-free interval and overall survival of the 10 dogs who had not relapsed was 1235 days (range: 19-2920 days) and 1235 days (range: 19-2920 days), respectively. One dog died soon after discharge of presumed gastric-dilatation-volvulus. Eight of nine remaining dogs lived >4yrs post-alloHCT, leading to a cure rate of 89%. Acute graft versus host disease was seen in three dogs. These results suggest that allogeneic HCT can cure ~50% more dogs than those treated with autologous HCT.

Gastrointestinal Bleeding Secondary to High-Dose Melphalan Pretreatment in Patients with Multiple Myeloma Was Associated with the Mode of Melphalan Administration.

Objective To analyze the characteristics of gastrointestinal bleeding secondary to high-dose melphalan pretreatment in patients with multiple myeloma. Methods Between 1 January 2016 and 31 October 2021, 26 patients with multiple myeloma after autologous peripheral blood hematopoietic stem cell transplantation with high-dose melphalan pretreatment were recruited. They were assigned to either the oral administration group or the intravenous administration group according to the administration modes, or to either the gastrointestinal bleeding group or the nongastrointestinal bleeding group. Analyses were performed based on the differences in general gastrointestinal symptoms and hemorrhage between different administration modes and on the differences in the general gastrointestinal symptoms, platelet alterations, and the intestinal microecology before pretreatment between patients with and without gastrointestinal bleeding. Results Of the 26 included patients, heavy secondary gastrointestinal bleeding was found in 6 patients with intravenous pretreatment. In patients given intravenous melphalan, those with gastrointestinal bleeding showed more pronounced general symptoms such as nausea and vomiting versus those without. There was no significant difference in platelet alterations between the two groups. Gastrointestinal bleeding was associated with more significant microecological disturbances than no bleeding. Conclusion Gastrointestinal bleeding secondary to high-dose melphalan pretreatment in patients with multiple myeloma was associated with the mode of melphalan administration, adverse symptoms at pretreatment, and the intestinal microecology prior to pretreatment. Thus, improvement of the intestinal microecology prior to pretreatment and mitigation of adverse gastrointestinal symptoms during pretreatment may contribute to a lower incidence of secondary gastrointestinal bleeding and enhanced transplantation safety.

Impact of autograft-absolute lymphocyte count on survival in double/triple hit lymphomas post-autologous stem cell transplantation

The autograft absolute lymphocyte count (A-ALC) ≥0.5 × 109 cells/kg is a survival prognostic factor for lymphoma patients undergoing autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). However, the A-ALC has not be tested as prognostic factor against double hit/triple hit lymphomas (DHL/THL). Thus, we set up to investigate if A-ALC is a prognostic factor for overall survival (OS) and progression-free survival (PFS) for DHL/THL post-APBHSCT. From January 2012 until December 2020, we identified 77 DHL/THL patients treated with APBHSCT. All patients required to have the diagnosis of DHL/THL by FISH for rearrangements of MYC, BCL2, and BCL6. With a median follow-up of 20.4 months (range, 0.4-94.5 months), DHL/THL patients infused with A-ALC ≥0.5 x 109 cells/kg experienced superior OS (HR = 0.251, 95%CI 0.117–0.539, p < 0.0004) and PFS (HR = 0.347, 95%CI 0.160–0.753, p < 0.007). Multivariate analysis showed that A-ALC was an independent predictor for OS (HR =0.119, 95%CI 0.030–0.473, p < 0.003) and PFS (HR = 0.400, 95%CI 0.189–0.850, p < 0.02). Our study showed that A-ALC is a prognostic factor for survival in DHL/THL. Our current practice for lymphoma patients is to collect enough stem cell but also A-ALC to improve clinical outcomes post-APBHSCT.

Skin Disinfection with 2% Chlorine Gluconate-Adine in Autologous Peripheral Hematopoietic Stem Cell Transplantation Patients

Skin Disinfection with 2% Chlorine Gluconate-Adine in Autologous Peripheral Hematopoietic Stem Cell Transplantation Patients

A Retrospective Analysis: Autologous Peripheral Blood Hematopoietic Stem Cell Transplant Combined With Adoptive T-Cell Therapy for the Treatment of High-Grade B-Cell Lymphoma in Ten Dogs.

In humans, a type of cellular immunotherapy, called adoptive T cell transfer (ACT), can elicit curative responses against hematological malignancies and melanoma. ACT using ex vivo expanded peripheral blood T-cells after multiagent chemotherapy enhances tumor-free survival of dogs with B-cell lymphoma (LSA). Since 2008, our group has been performing autologous peripheral blood hematopoietic stem cell transplants (autoPBHSCT) for the treatment of canine high-grade B-cell LSA, although relapse of residual disease is a common cause of reduced survival in ~70% of treated dogs. We reasoned that a more aggressive treatment protocol combining CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, autoPBHSCT, and ACT to treat 10 dogs with B-cell LSA could lead to better outcomes when compared to dogs treated with CHOP chemotherapy and autoPBHSCT alone. Using this protocol, once dogs achieved complete hematologic reconstitution post-autoPBHSCT, CD3+ CD8+ and CD3+CD4+ T-cells were expanded from the peripheral blood at a commercial laboratory. Two to four ACT infusions were given to each dog, with a total of 23 infusions given. Infusions were administered with no complications or adverse events. The median cell dose for all infusions was 5.62 x 106 cells/kg (range: 2.59 x 106-8.55 x 106 cells/kg). 4/10 (40%) of dogs were cured of their disease (defined as disease-free for ≥2 years post-autoPBHSCT). Our results confirm that the autoPBHSCT protocol did not hinder the in vitro expansion of autologous peripheral blood T-cells and that the final product could be administered safely, with no adverse events recorded. Finally, since only ten dogs were treated, our results can only suggest that the administration of ACT to dogs after multiagent chemotherapy and autoPHSCT did not lead to a statistically significant increase in median disease-free interval and overall survival when compared to dogs who received CHOP chemotherapy and autoPHSCT alone.

Mobilization of backup autologous peripheral stem cells in pediatric thalassemia patients: A single center experience

Mobilization of backup autologous peripheral stem cells in pediatric thalassemia patients: A single center experience

Immunologic Autograft Engineering: 13 Years Follow-up

Our group published a double blind, randomized phase III study (Porrata et al, BBMT 2016; 22: 1017-1023) showing that the infusion of autograft absolute lymphocyte count (A-ALC) ≥ 0.5 x 10 9 cells/kg is a survival prognostic factor for lymphoma patients undergoing autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). However, a limitation of the study was the short-term follow-up duration of two years post-APBHSCT. To assess if the A-ALC still provide survival benefit we looked at the 121 lymphoma patients enrolled in the phase III from December 10, 2007 until October 12, 2010 survival outcomes with a longer follow-up duration of up to 13 years post-APBHSCT. Since the accrual for the study, 52 patients had died of recurrence lymphoma, 4 patients of therapy-related acute myelogenous leukemia, 3 patients of unknown causes, 1 patient of acute respiratory distress syndrome, 1 patient of anaplastic astrocytoma, and 1 patient of septic shock. The current median follow-up is 86 months (range: 2.1-158.1 months) for the entire cohort and 127.8 months (range: 5.9-158.1 months) for patients still alive. Patients infused with an A-ALC ≥ 0.5 x 10 9 cells/kg continue to experience superior overall survival (OS) (HR = 0.392, 95%CI 0.224-0.687, P < 0.001) and progression-free survival (PFS) (HR = 0.413, 95%CI 0.253-0.677, P < 0.0004). The 10-year OS rates for the A-ALC ≥ 0.5 x10 9 cells/kg patients was 70% (95% confidence interval [CI], 55%-81%) and for the A-ALC < 0.5 x10 9 cells/kg patients was 36% (95% CI, 25%-49%) (Figure 1A). The 10-year PFS rates for the A-ALC ≥ 0.5 x10 9 cells/kg group was 57% (95% CI, 43%-70%) and for the A-ALC < 0.5 x10 9 cells/kg group was 28% (95% CI, 19%-40%) (Figure 1B). Autograft lymphocyte subset analysis including autograft-CD3 (A-CD3), autograft CD4 (A-CD4), autograft CD8 (A-CD8), and autograft natural killer cells (A-NK), showed that the infusion of A-NK was a predictor for OS (HR = 0.518, 95%CI 0.292-0.919, P < 0.02) and PFS (HR = 0.393, 95%CI 0.230-0.670, P < 0.0006). The 10-year OS rates for the A-NK ≥ 0.09 x10 9 cells/kg patients was 67% (95% confidence interval [CI], 50%-80%) and for the A-NK < 0.09 x10 9 cells/kg patients was 42% (95% CI, 31%-54%) (Figure 1C). The 10-year PFS rates for the A-NK ≥ 0.09 x10 9 cells/kg group was 59% (95% CI, 43%-73%) and for the A-NK < 0.09 x10 9 cells/kg group was 32% (95% CI, 23%-44%) (Figure 1D). Both the A-ALC and A-NK were independent predictor for OS [ A-ALC: HR = 0.367, 95%CI 0.195-0.690, P < 0.001) and A-NK: HR = 0.411, 95%CI 0.275-0.892, P < 0.01] and for PFS [ A-ALC: HR = 0.477, 95%CI 0.271-0.840, P < 0.01) and A-NK: HR = 0.490, 95%CI 0.266-0.903, P < 0.02]. With a longer follow-up of 13 years, this study shows that the infusion of A-ALC continues to provide better clinical outcomes to lymphoma patients undergoing APBHSCT. These study findings support our standard practice changed of not only collecting CD34 stem cell for hematologic engraftment, but also A-ALC for lymphoma patients undergoing APBHSCT to improve clinical outcomes. Further, autograft immune effector studies are warranted such as A-NK to develop a more immunocompetent targeted autologous graft verus tumor effect. [Display omitted] DisclosuresAnsell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Paludo: Karyopharm: Research Funding.

Ibrutinib in Combination with Rituximab and High-Dose Methotrexate in Newly Diagnosed Primary Central Nervous System Lymphoma Patients

Ibrutinib in combination with rituximab and high-dose methotrexate in newly diagnosed primary central nervous system lymphoma patientsYixian Guo, Xiaoxi Lan, Xiaoli Chang, Guoxiang Wang, Dongmei Zou, Li Su, Wanling SunDepartment of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. ChinaCorresponding author: Wanling Sun, M.D. & Ph.D.Email: wanlingsun@xwhosp.orgBackground: Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphoma. Most PCNSL are pathologically classified as diffuse large B-cell lymphoma (DLBCL). In addition to the importance of high-dose systemic methotrexate (HD-MTX), there is no consensus on the optimal composition of induction and consolidation therapy for newly diagnosed PCNSL. BTK inhibitors are the second-line recommended choice in relapsed of refractory cases. In this study, we described our institutional experience with the oral BTK inhibitor, ibrutinib, combined with rituximab and HD-MTX (I-RM regimen) in newly diagnosed PCNSL. This study is registered with Chictr.org.cn, number ChiCTR1900027811.Methods: The study was a phase 1, investigator-initiated, clinical trial being conducted at Xuanwu Hospital, Capital Medical University . Patients definitely diagnosed as PCNSL-DLBCL by biopsy of brain lesion, systemic imageology, bone marrow and CSF examination, et al, and be suitable for the immunochemotherapy,were enrolled the clinical trial. The next-generatioin sequencing of the lesion tissue were used to detect hot spot mutations evolved in B cell lymphoma. The ibrutinib-based I-RM regimen consists of rituximab 375mg / m 2 on day 0, MTX 3.5g/m 2 on day1, and ibrutinib 560mg once daily starting from plasma MTX concentration <0.1umol/L to day 28, every 28 days is a cycle of treatment. After 4 cycles of I-RM induction therapy, patients who achieved CR/CRu/PR received autologous peripheral blood hematopoietic stem cell transplantation (HSCT) or the extra 2 cylces of I-RM regimen as consolidation therapy. Ibrutinib or lenalidomide monotherapy was prescribed as maintenance therapy, according to the willingness of patients until the disease progresses. The primary end point was the safety and efficacy of this regimen in newly diagnosed PCNSL.Results:There were totally16 patients enrolled in this clinical trial, between April 2018 and December 2020 (Table 1). All the patients were pathologically DLBCL, including 14 non-GCB subtypes and 2 GCB subtypes. The commonest hot spot mutations were PIM1 (68.75%), MYD88 (43.75%), and CD79B (37.50%). The median follow-up time was 24.5 (6-37) months up to June 30, 2021. After 4-cycles of I-RM induction therapy, CR were achieved in 8 patients (50%), PR in 7 patients (44%), and progressive disease in one patients(6%) who quit the clinical trial and transferred to other regimen，and the ORR of induction therapy was 94%. Among 15 responsers, 5 (33%) received HSCT and 10 (67%) received extra 2 cylces of I-RM regimen as consolidation therapy. After the consolidation therapy, 93% patients (14/15) received maintenance therapy, including 6 received lenalidomide and 8 received ibrutinib. Relapse happened in 2 patients during the maintenance therapy, including 1 death due to the progressed disease (Table 2). The median PFS and OS were not achieved, and the estimated 3-year OS and PFS were 88.9% and 86.5%, respectively (Figure 1). No grade 4 adverse event was observed. The grade 3 hematologic toxicities included lymphopenia in 3 cases and neutropenia in 1 case .The grade 3 non-hematologic toxicities including hypertension in 1 case and increased serum creatinine in 1 case.Conclusions: Our data preliminarily indicates that I-MR is active and safe as a first-line regimen in newly diagnosed PCNSL and might effectively improve the survival of these patients. More patients and longer follow-up are needed to confirm our conclusion. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Autograft-Absolute Lymphocyte Count Infusion Predicts Survival in Double/Triple Hit Lymphomas Post-Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation

The autograft absolute lymphocyte count (A-ALC) ≥ 0.5 x 10 9 cells/kg is a survival prognostic factor for lymphoma patients undergoing autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). However, the A-ALC ≥ 0.5 x 10 9 cells/kg has not been tested as prognostic factor against double hit/triple hit lymphomas (DHL/THL). Thus, we set up to investigate if A-ALC ≥ 0.5 x 10 9 cells/kg is a prognostic factor for overall survival (OS) and progression-free survival (PFS) for DHL/THL post-APBHSCT. From January 2012 until December 2020, we identified 77 DHL/THL patients treated with APBHSCT. All patients required to have the diagnosis of DHL/THL by FISH for rearrangements of MYC, BCL2, and BCL6. Of the 77 patients, 62 patients were classified as DHL and 15 patients as THL. Of the DHL, 82 % (52/68) had the MYC/BCL2 and 16% (10/62) the MYC/BCL6 rearrangements. Dividing the cohort into two groups (A-ALC ≥ 0.5 x 10 9 cells/kg and A-ALC < 0.5 x 10 9 cells/kg), both groups were balanced in regard to de novo versus transformed histology (p = 0.3), cell of origin (p = 0.6), DHL and THL (p = 0.6), MYC/BCL2; MYC/BCL6; and MYC/BCL2/BCL6 rearrangements (p = 0.6), first line chemotherapy (p = 0.2), salvage chemotherapy (p = 0.5), disease status prior to APBHSCT (CR1, CR, and PR) (p = 0.07), stem cell mobilization (Plerixafor versus not) (p = 0.6), and infusion of CD34 count (p = 0.2). With a median follow-up of 20.4 months (range, 0.4-94.5 months) for the entire cohort and with a median follow-up of 33.5 months (range, 3.5-94.5 months) for the patients that remained alive, DHL/THL patients infused with A-ALC ≥ 0.5 x 10 9 cells/kg experienced superior OS (HR = 0.251, 95%CI 0.117-0.539, P < 0.0004) and PFS (HR = 0.347, 95%CI 0.160-0.753, P < 0.007). The 5-year OS rates for the A-ALC ≥ 0.5 x10 9 cells/kg group was 73% (95% confidence interval [CI], 52%-87%) and for the A-ALC < 0.5 x10 9 cells/kg group was 18% (95% CI, 7%-39%) (Figure 1A). The 5-year PFS rates for the A-ALC ≥ 0.5 x10 9 cells/kg group was 73% (95% CI, 59%-85%) and for the A-ALC < 0.5 x10 9 cells/kg group was 13% (95% CI, 5%-33%) (Figure 1B). Multivariate analysis showed that A-ALC was an independent predictor for OS (HR =0.178, 95%CI 0.052-0.614, p <0.005) and PFS (HR = 0.400, 95%CI 0.189-0.850, p <0.02). Our study showed that A-ALC is a prognostic factor for survival in DHL/THL patients undergoing APBHSCT. Our current practice for all lymphoma patients is not only to collect enough stem cell for hematologic engraftment, but also A-ALC ≥ 0.5 x 10 9 cells/kg to improve clinical outcomes post-APBHSCT. [Display omitted] DisclosuresAnsell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Paludo: Karyopharm: Research Funding.

Safety and efficacy of autologous non-hematopoietic enriched stem cell nebulization in COVID-19 patients: a randomized clinical trial, Abu Dhabi 2020

BackgroundThe novel SARS-CoV-2 has caused the coronavirus disease 2019 (COVID-19) pandemic. Currently, with insufficient worldwide vaccination rates, identifying treatment solutions to reduce the impact of the virus is urgently needed.MethodAn adaptive, multicentric, open-label, and randomized controlled phase I/II clinical trial entitled the “SENTAD-COVID Study” was conducted by the Abu Dhabi Stem Cells Center under exceptional conditional approval by the Emirates Institutional Review Board (IRB) for COVID-19 Research Committee from April 4th to July 31st, 2020, using an autologous peripheral blood non-hematopoietic enriched stem cell cocktail (PB-NHESC-C) administered by compressor (jet) nebulization as a complement to standard care therapy. The primary endpoints include safety and efficacy assessments, adverse events, the mortality rate within 28 days, and the time to clinical improvement as measured by a 2-point reduction on a seven-category ordinal scale or discharge from the hospital whichever occurred first.ResultsThe study included a total of 139 randomized COVID-19 patients, with 69 in the experimental group and 70 in the control group (standard care). Overall survival was 94.20% for the cocktail-treated group vs. 90.27% for the control group. Adverse events were reported in 50 (72.46%) patients receiving PB-NHESC-C and 51 (72.85%) in the control group (p = 0.9590), with signs and symptoms commonly found in COVID-19. After the first 9 days of the intervention, 67.3% of cocktail-treated patients recovered and were released from hospitals compared to 53.1% (RR = 0.84; 95% CI, 0.56–1.28) in the control group. Improvement, i.e., at least a 2-point reduction in the severity scale, was more frequently observed in cocktail-treated patients (42.0%) than in controls (17.0%) (RR = 0.69; 95% CI, 0.56–0.88).ConclusionsCocktail treatment improved clinical outcomes without increasing adverse events. Thus, the nebulization of PB-NHESC-C was safe and effective for treatment in most of these patients.Trial registrationClinicalTrials.gov. NCT04473170. It was retrospectively registered on July 16th, 2020.

Autologous stem cell transplantation in lymphomas: current indications

Hematopoietic stem cell transplantation is an established curative treatment for a number of conditions including malignant hematologic diseases and non-malignant congenital and acquired disorders involving the hematopoietic system and some types of solid tumors, e.g. germ cell tumors and soft tissue sarcomas. Hodgkin’s disease and non-Hodgkin lymphomas can be treated and, in a large number of cases cured, by first-line chemotherapy or radiotherapy. Unlike many other malignancies, relapse is not uniformly fatal but the treatment is usually markedly myelotoxic with the high doses of chemotherapy (HDC) used in relapse. Hematopoietic reconstitution with either autologous marrow or peripheral stem cells post-chemotherapy has made HDC relatively safe, with mortality rates as low as 2% in some centers. The choice of conditiong regimen has traditionally been based on institutional experience, and several regimens are considered standard and routinely used for patients with all histologies of lymphoma. Each HDC regimen is associated with its own unique toxicities, based on the individual agents or modalities used. Novel targeted and immunotherapy approaches, including chimeric antigen receptor T-cell therapy, are currently being studied in clinical trials with promising early results, so the role of autologous stem cell transplantation in the treatment of lymphomas could be changed. The current clinical indications for HDC followed by autologous hematopoietic stem cell transplantation in lymphomas management for patients with a bad prognosis (as a consolidation therapy) or relapsed/refractory disease are reviewed in this paper.

Factors affecting the mobilization and collection of autologous peripheral blood hematopoietic stem cells

Factors affecting the mobilization and collection of autologous peripheral blood hematopoietic stem cells

Age Is Not Important for Autologous Peripheral Hematopoietic Stem Cell Transplantation in Multiple Myeloma

Introduction: High-dose melphalan followed by autologous hematopoietic cell transplantation (auto HSCT) has become the standard procedure for patients with symptomatic multiple myeloma (MM). Retrospective analyses suggest that the benefit of HDT extends to elderly myeloma patients, which is an important finding considering that the median age at diagnosis is 69 years (range: 65-74) for MM in United States, using 2010-2014 US SEER data. The aim of our study was to determine the effect of age on stem cell collection and engraftment in patients with MM.Materyal and Methods: From January 2010 through April 2016, data from 260 myeloma patients below the age of 65 were compared to 41 myeloma patients above 65 years of age who were eligible for auto HSCT according to geriatric assessment (GA), depending on the results of IMWG report in 2015. All these data were obtained from the Ankara University Faculty of Medicine Center for Therapeutic Apheresis and written informed consent was signed according to our institution regulations. Mostly bortezomib based regimens were given as induction therapy to our patients. Ninety two percent of the patients received only GCSF at a dose of 5 µg/kg BW twice-daily s.c. until stem cell procurement. Patients underwent further PBSC collections until we obtained the target dose >20 CD34+ cells/µL blood. A maximum of 3 collections were performed in the first mobilization; if the cell dose was not achieved, we submitted patients to a second mobilization.Results: Forty-one of 301 patients were above 65 years of age (median age 68, range 65-75) and 260 patients were below the age of 65 (median age 56, range 29-64). Baseline characteristics of the older and younger patient cohorts are summarized in Table-1. The median follow-up was 48.5 months (range 1-90) for age <65 years old patients and 46 months (range 1-90) for age ≥65 years old patients. Mobilization regimens for the younger patient population were G-CSF only (n:241), cyclophosphamide based (n:12) and +plerixafor (n:7). Mobilization in the older population was with cyclophosphamide based (n:4), G-CSF only (n:36) and +plerixafor (n=1) in whom poor mobilization had been predicted. The chemotherapy regimens were not statistically different between both age groups (chi square p value 0.37). There were no significant statistical differences in time from diagnosis to mobilization, number of prior therapies or disease status between both patient groups. The number of CD34-positive circulating cells before scheduled leukapheresis was mean 23.26 cells/μL in all patients (including patients who failed mobilization). Neutrophil engraftment was seen faster in elderly group (mean 10.4±3.1 vs. 11.5±1.8; p=0.008) but platelet engraftment was similar compared the younger patients with older ones (Table-2). In The probability of 5-year progression free survival (PFS) and overall survival (OS) in elderly patients with ISS-3 was 82.4%±12.1% and 48.5±16.5%. No statistical significance was observed for mean estimated 5-year OS in terms of patient age (<65 and ≥65 years; 82.5%±2.8% and 74.3%±8.7% p=0.29) (Figure-1). Less relapse was occurred in elderly cohort (17.5% vs. 35.4%) but the number of patients in this group does not provide enough statistical power to confirm whether the differences in PFS were statistically significant.Conclusion: To date, accepted approach for elderly patients with MM is not only improving survival, also their quality of life. Based on this single center study, auto-HSCT is safe and efficient in the treatment of elderly myeloma patients but no statistical difference was demonstrated in respect to age groups. [Display omitted] DisclosuresIlhan:Novartis: Consultancy.

Predictorsof Early Engraftment in Autologous Peripheral Stem Cell Transplantation; a Single Center Experience

Introduction: Autologous stem cells transplantation (ASCT) is a treatment option used in various hematological malignancies. ASCT can prolong disease free survival, improve survival, and may be curative. We investigated the variables affecting engraftment among patients treated with high dose-chemotherapy and ASCT.Methods: 364 adult patients underwent 419 ASCT from 2001 to 2016, at the American University of Beirut Medical Center. There were 207 males and 157 females, with a median age of 45 years (17-74). The cohort included 126 multiple myeloma (MM), 120 non-Hodgkin lymphoma, and 108 Hodgkin lymphoma, while 10 patients had other malignancies. All patients received high-dose chemotherapy regimens without total body irradiation. The median time from diagnosis to first transplant is 11.9 months (range 2-288). The median number of apheresis was 1 (range 1-5).Results: The median number of infused CD34+ cells was 5.8x106/kg (range 0.71-24.9) which contained DMSO at a median dose of 0.2 g/kg BW (range 0.0375-0.91). Patients exhibited an absolute neutrophil count (ANC) recovery of ≥0.5x109/L at a median of 10 days (range 1-97). Platelet recovery to ≥20x109/L occurred at a median of 15 days (range 7-46). Status of the disease at transplant was: 130 patients (31%) were in complete remission (CR), 242 (58%) in partial remission (PR), and 47 (11%) patients were in relapse or progressive disease.The findings of univariate and multivariate analyses are summarized in Table 1. Diagnosis other than MM, low DMSO dose (< 0.2 g/kg BW), and high infused CD34+ cell count (>6x106/kg) were associated with engraftment of neutrophils within 10 days from stem cell infusion. Low DMSO dose and high infused CD34+ cell count were associated with engraftment of platelets within 15 days.Conclusion: Our results imply that the infused CD34+ cell count and the DMSO dose are important predictors of hematopoietic engraftment, namely neutrophil and platelet engraftment. These findings need to be verified in larger scale studies. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

High-dose Chemotherapy in Germ Cell Cancer Patients With Brain Metastases: Experience of an Expert Center.

Germ cell tumor (GCT) patients with brain metastases (BM) have a poor prognosis and high risk of treatment failure. Optimal therapies for these patients remain controversial. The aim of this study was to report the outcomes of all GCT patients with BM treated with high-dose chemotherapy (HDCT) in our French expert center for GCT. We carried out a retrospective study of 35 GCT patients with BM who were treated from 2003 to 2019 with HDCT, followed by infusions of autologous peripheral blood hematopoietic stem cells. The overall survival at 2 years was 36.9% (95% confidence interval, 19.7-54). The median overall survival was 12 months and the median progression-free survival was 8 months. No variables were associated with better survival in the univariable analysis. Among the 35 patients included in our study, 31 completed HDCT and 4 stopped treatments after mobilization. Eleven patients (11) showed favorable responses (complete, partial, or stable disease) to HDCT and 20 patients died of disease progression (17) or toxicities (3). Among the 11 patients with favorable responses to HDCT, 8 (72.7%) had metachronous BM, mostly isolated. The majority of these patients did not receive local treatment at diagnosis or at relapse. Together, our study reveals that GCT patients can experience long-term survival even in the presence of BM. Metachronous BM can also be cured with HDCT even in the absence of local treatment. Biological and radiologic responses to mobilization could be a predictor of favorable responses to HDCT.

Salivary Osteopontin as a Potential Biomarker for Oral Mucositis.

Osteopontin (OPN), a multifunctional phosphoglycoprotein also presents in saliva, plays a crucial role in tumour progression, inflammation and mucosal protection. Mucosal barrier injury due to high-dose conditioning regimen administered during autologous and allogeneic peripheral stem cell transplantation (APSCT) has neither efficient therapy nor established biomarkers. Our aim was to assess the biomarker role of OPN during APSCT, with primary focus on oral mucositis (OM). Serum and salivary OPN levels were determined by ELISA in 10 patients during APSCT at four stages of transplantation (day −3/−7, 0, +7, +14), and in 23 respective healthy controls. Results: There was a negative correlation between both salivary and serum OPN levels and grade of OM severity during APSCT (r = −0.791, p = 0.019; r = −0.973, p = 0.001). Salivary OPN increased at days +7 (p = 0.011) and +14 (p = 0.034) compared to controls. Among patients, it was higher at day +14 compared to the time of admission (day −3/−7) (p = 0.039) and transplantation (day 0) (p = 0.011). Serum OPN remained elevated at all four stages of transplantation compared to controls (p = 0.013, p = 0.02, p = 0.011, p = 0.028). During APSCT elevated salivary OPN is a potential non-invasive biomarker of oral mucositis whereas the importance of high serum OPN warrants further studies.

Renal Involvement and Outcomes in Severe COVID-19 Patients After Stem Cell Jet-Nebulization

<i>Introduction: </i>The COVID-19 pandemic presented an unprecedented challenge to identify effective drugs and means for their prevention and management. It is more difficult in severe cases due to complications in various vital organs such as the kidneys. <i>Methods: </i>An analytical study was carried out within the framework of the clinical trial “SENTAD-COVID Study” (ClinicalTrial.org, NCT04473170), whose objective was to describe acute kidney injury (AKI) in severe patients with COVID-19 and its relationship with clinical outcomes. A novel stem cells treatment for COVID-19 patients using an autologous peripheral blood nonhematopoietic-enriched stem cells cocktail was developed by the research team of the Abu Dhabi Stem Cells Center and applied at four Abu Dhabi Health Service Company hospitals. The sample consisted of the severe COVID-19 recruited patients: 20 in the experimental arm (Group A) and 24 controls (Group B). Both groups received COVID-19 standard treatment. <i>Results: </i>29.5% of the patients studied suffered AKI. Mortality was lower in group A compared to the control group (20% vs. 30%, respectively), group A showed 25% AKI while group B 35%, sepsis was significantly lower in the treated group A compared to controls (25% vs. 35%; p=0.0095) Hazard Ratio=0.38, (95% CI: 0.16–0.86), given a Number Needed to Treat=2.5 patients. Group A had a significant reduction in inflammation markers at 25 days compared to the day of recruitment: C-Reactive Protein (median: 207.05 mg/L vs. 27.30 mg/L), IL-6 (median: 355.80 pg/L vs. 35.87 pg/L), and group A was the only one that presented a better proportion of patient with the recovery to normal values of the Neutrophil/Lymphocyte Ratio at 25 days, from 100% to 71.42% p=0.0108. <i>Conclusions: </i>One-third of the patients studied suffered AKI, group A patients showed a clear tendency to improve compared to controls, suggesting that the proposed therapy promotes healing and early recovery in severe COVID-19, which might be related to the anti-inflammatory effect of cellular therapy.