scholarly journals A Non-Invasive Determination of Ketosis-Induced Elimination of Chronic Daytime Somnolence in a Patient with Late-Stage Dementia (Assessed with Type 3 Diabetes): A Potential Role of Neurogenesis

2021 ◽  
pp. 1-20
Author(s):  
Leslie A. Lewis ◽  
Carl M. Urban ◽  
Sami A. Hashim
Keyword(s):  
Stem Cell ◽  
Late Stage ◽  
Low Dose ◽  
Functional Restoration ◽  
Mammalian Brain ◽  
High Dose ◽  
Daytime Somnolence ◽  
Type 3 Diabetes ◽  
Sigmoid Curve ◽  
Type 3

Background: The study involved a female patient diagnosed with late-stage dementia, with chronic daytime somnolence (CDS) as a prominent symptom. Objective: To explore whether her dementia resulted from Type 3 diabetes, and whether it could be reversed through ketosis therapy. Methods: A ketogenic diet (KD) generating low-dose 100 μM Blood Ketone Levels (BKL) enhanced by a brief Ketone Mono Ester (KME) regimen with high-dose 2–4 mM BKLs was used. Results: Three sets of data describe relief (assessed by % days awake) from CDS: 1) incremental, slow, time-dependent KD plus KME-induced sigmoid curve responses which resulted in partial wakefulness (0–40% in 255 days) and complete wakefulness (40–85% in 50 days); 2) both levels of wakefulness were shown to be permanent; 3) initial permanent relief from CDS with low-dose ketosis from 6.7% to 40% took 87 days. Subsequent low-dose recovery from illness-induced CDS (6.9% to 40%) took 10 days. We deduce that the first restoration involved permanent repair, and the second energized the repaired circuits. Conclusion: The results suggest a role for ketosis in the elimination of CDS with the permanent functional restoration of the awake neural circuits of the Sleep-Wake cycle. We discuss whether available evidence supports ketosis-induced bioenergetics alone or whether other mechanisms of functional renewal were the basis for the elimination of CDS. Given evidence for permanent repair, two direct links between ketosis and neurogenesis in the adult mammalian brain are discussed: Ketosis-induced 1) brain-derived neurotrophic factor, resulting in neural progenitor/stem cell proliferation, and 2) mitochondrial bioenergetics-induced stem cell biogenesis.

Nonmyeloablative allogeneic stem cell transplantation for the treatment of chronic myeloid leukemia in first chronic phase

Blood ◽  
2003 ◽  
Vol 101 (2) ◽  
pp. 441-445 ◽  
Author(s):  
Reuven Or ◽  
Michael Y. Shapira ◽  
Igor Resnick ◽  
Avraham Amar ◽  
Aliza Ackerstein ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Chronic Phase ◽  
Mixed Chimerism ◽  
High Dose ◽  
Disease Free

Reduced-intensity or nonmyeloablative stem cell transplantation (NST) is designed to induce host-versus-graft tolerance by engraftment of donor stem cells. The rationale behind NST is to induce optimal graft-versus-leukemia (GVL) effects for elimination of all malignant cells by donor alloreactive immunocompetent cells as an alternative to standard high-dose myeloablative chemoradiotherapy. NST based on the use of fludarabine, low-dose busulfan, and anti–T-lymphocyte globulin (ATG) was employed in 24 patients aged 3 to 63 years with chronic myeloid leukemia (CML) in first chronic phase (CP). Graft-versus-host disease (GVHD) prophylaxis consisted of low-dose cyclosporine (CSP), in some cases with low-dose methotrexate. Early discontinuation of CSP was attempted in cases of mixed chimerism in an attempt to amplify GVL effects. All 24 patients showed rapid 3-lineage engraftment, mostly without complete aplasia; 6 patients did not require transfusion of any blood products. NST was associated with minimal procedure-related toxicity. The incidence of acute GVHD (grade I or higher) was 54%; however, this incidence increased following CSP withdrawal. After a follow-up of up to 70 months (median, 42 months), 21 of 24 patients remained alive and disease free. The GVL effects induced by donor immunocompetent lymphocytes eradicated all host hematopoietic cells, as evidenced by molecular testing. The Kaplan-Meier probability of survival and disease-free survival at 5 years is 85% ± 8% (95% confidence interval, 70%-100%). NST may successfully replace myeloablative stem cell transplantation, providing a safer, well-tolerated therapeutic option for all patients with CML in first CP with a matched donor. However, this conclusion must be tested in a prospective randomized clinical trial.

scholarly journals Post Transplantation Cyclophosphamide Improves Outcome of Autologous Hematopoietic Stem Cell Transplantation in Animal Model of Multiple Sclerosis

2021 ◽  
Vol 69 (1) ◽  
Author(s):  
Kaja Kasarełło ◽  
Emilian Snarski ◽  
Dorota Sulejczak ◽  
Tomasz Ciesielski ◽  
Agnieszka Wiśniewska ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Low Dose ◽  
Clinical Symptoms ◽  
High Dose ◽  
Post Transplantation ◽  
Hematopoietic Stem

AbstractExperimental allergic encephalomyelitis (EAE) is the animal model of multiple sclerosis (MS). Autologous hematopoietic stem cell transplantation (AHSCT) has recently been recognized as the standard treatment for MS. The aim of our experiment was to investigate the effect of AHSCT with the addition of low-dose post-transplantation cyclophosphamide (Cy) on EAE in rats. Low dose post-transplantation Cy is used in haploidentical HSCT to reduce the risk of graft versus host disease. We hypothesized that it could bring additional benefit in autologous HSCT in autoimmune diseases. Rats with evoked EAE were treated with high dose (125 mg/kg) Cy, followed by AHSCT or high dose (125 mg/kg) Cy followed by AHSCT followed by low dose (20 mg/kg) Cy in two-time schedules—with the therapy applied during the pre-symptomatic or symptomatic phase of the disease. Both AHSCT and AHSCT with post-transplantation Cy in accordance with both time schedules reduce the intensity of the inflammatory response in the CNS, in comparison with non-treated EAE rats. The reduction of clinical symptoms was present in all AHSCT treatment protocols, however, it was significantly stronger when post-transplantation Cy was given during the symptomatic phase of the disease. AHSCT with the addition of post HSCT low dose Cy improved the results of AHSCT by not only reducing the intensity of inflammation in the CNS but also by significantly reducing the clinical symptoms in treated animals when compared to AHSCT alone. We provide an experimental rationale that the addition of post-transplantation Cy may improve the outcome of HSCT in MS. Graphic Abstract

scholarly journals One-Day Low-Dose Etoposide Is an Effective Chemomobilization Regimen with Minimal Toxicity for Autologous Stem Cell Transplantation in Patients with Multiple Myeloma: A Multicenter Study from Tertiary Hospitals in Korea

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3347-3347
Author(s):  
Yong Park ◽  
Dae Sik Kim ◽  
Ka-Won Kang ◽  
Byung-Hyun Lee ◽  
Eun Sang Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Febrile Neutropenia ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Low Dose ◽  
High Dose ◽  
Tertiary Hospitals ◽  
Stem Cell Collection

Abstract Purpose Autologous stem cell transplantation (ASCT) is widely used as a part of induction treatment for transplantation-eligible patients with multiple myeloma. For successful ASCT, mobilizing hematopoietic stem cells from bone marrow to peripheral blood is essential because collecting a sufficient number of stem cells using apheresis is mandatory. As a method for mobilization, chemomobilization consisting of high-dose chemotherapy plus granulocyte-colony stimulating factor (G-CSF) or G-CSF alone (G-mobilization) has been used. However, the mobilization failure still remains a problematic issue. Given repeated mobilization attempts increase medical costs and the risk of morbidity related with apheresis, the mobilization process should be efficient. Chemomobilization is more effective than G-mobilization, however, chemomobilization has the risk of complication such as febrile neutropenia or chemotherapy-induced second malignancy. Thus, we compared the efficacy and safety of our new chemomobilization regimen, one-day low-dose etoposide with that of two-day low-dose etoposide, one-day high-dose cyclophosphamide, and G-mobilization. Methods We retrospectively analyzed 234 patients who underwent ASCT for MM between 2008 and 2018 in four tertiary hospitals in Korea. One-day low-dose etoposide regimen (E1) was the intravenous (IV) administration of etoposide (375 mg/m2) over 4 hours whereas two-day low-dose etoposide (E2) was the same dose of etoposide on 1st and 2nd day in outpatient clinic. G-CSF administration was started around on 10th day until the end of collection. In G-mobilization regimen (G), the injection of G-CSF was started four days (day -4) before initiation of apheresis (day 0), and G-CSF once a day was maintained untill the end of collection. One-day high-dose cyclophosphamide regimen (C) was the IV administration of cyclophosphamide (3.5 g/m2) on 1st day and the daily injection of G-CSF from 2nd day until the end of stem cell collection. Peripheral blood stem cell collection was started when CD34-positive cells or hematopoietic progenitor cells were more than 5000/μL in peripheral blood, or white blood cell count was more than 5000/μL. In this study, we defined the 'adequate mobilization' as CD34-positive cells more than 4ⅹ106/kg, and 'mobilization failure' as a collected CD34-positive cells less than 2ⅹ106/kg. Neutrophil and platelet engraftment was defined as more than 500/μL and 20,000/μL on consecutive two days, respectively. Results 31 patients received single dose etoposide (E1) between 2016 and 2018 whereas 28 patients received double dose etoposide (E2) between 2011 and 2018. The other two regimens were used in 105 (C, 2008-2015) and 70 patients (G, 2008-2017) according to physicians' decision. The comparison of four regimens showed the median CD34-positive cells of E1 regimen was 5.57ⅹ106/kg that was comparable to that of E2 and C (Table 1). The number of CD34-positive cells on 1st day of apheresis was 4.03ⅹ106/kg in E1 regimen, and it was higher than that of C and G (3.32 and 1.79ⅹ106/kg, respectively). As a result, E1 regimen achieved 'adequate mobilization' in 100% of patients (n=30) like E2 regimen (n=28, 100%). Mobilization failure did not occur in E1 and E2 regimens whereas 4-10% of patients experienced mobilization failure in C and G regimens (Table 1). All patients receiving E1 and E2 regimen but one patient in E1 could collect more than 4ⅹ106/kg of CD34-positive cells within three cycles of apheresis. The occurrence of febrile neutropenia was extremely lower in E1 regimen (7%) than E2 and C regimens (43% and 34%, respectively, p<0.001). Both neutrophil and platelet engraftment were the fastest in E1 (the median 9 days after ASCT, p<0.001). Conclusions One-day low-dose etoposide administration could be effective for chemomobilization in myeloma patients with reduced risk of complication compared to two-day low-dose etoposide, high-dose cyclophosphamide and G-mobilization. Table 1. Table 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation for Aplastic Anemia with Pre-Transplant Conditioning Using Fludarabine, Reduced-Dose Cyclophosphamide, and Low-Dose Thymoglobulin:Â Ksgct Prospective Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2101-2101
Author(s):  
Shinichi Kako ◽  
Yoshinobu Kanda ◽  
Makoto Onizuka ◽  
Nobuyuki Aotsuka ◽  
Kensuke Usuki ◽  
...  
Keyword(s):  
Stem Cell ◽  
Research Funding ◽  
Low Dose ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Reduced Dose ◽  
Company Limited ◽  
Otsuka Pharmaceutical

Abstract [Background] Allogeneic hematopoietic stem cell transplantation (HSCT) is a potent treatment to cure in patients with aplastic anemia (AA). However, an optimal pre-transplant conditioning remains unclear. The combination of high-dose cyclophosphamide (CY) and anti-thymocyte globulin (ATG) has been used as an effective conditioning, but cardiotoxity due to high-dose CY has been a major concern especially in patients with iron overload by excessive transfusion. In addition, the appropriate dose and timing of ATG use is another unsolved topic in HSCT for AA. Therefore, we performed a prospective study to assess the safety and efficacy of a conditioning regimen using fludarabine (Flu), reduced-dose CY, and low-dose thymoglobulin in HSCT for AA. [Methods] Patients with severe AA, aged between 16 and 65 years, who have an HLA-matched or 1-locus mismatched, related or unrelated donor were prospectively included. A conditioning regimen consisted of Flu 30mg/m2 for 4 days, CY 25mg/kg for 4 days, and thymoglobulin 1.25mg/kg for 2 days (days -4, and -3). In patients who underwent transplantation from unrelated and/or HLA-mismatched donor, 2 Gy of total body irradiation was added. Cyclosporine for an HLA-matched related donor or tacrolimus for the other donors, together with short-term methotrexate were used as graft-versus-host disease (GVHD) prophylaxis. Granulocyte-colony stimulating factor was used from 1 day after transplantation. Primary outcome measure was an overall survival at 1 year after HSCT. This study was approved by the Institutional Review Board of all the participating institutions. [Results] Twenty-eight patients were enrolled between 2011 and 2017, and their median age was 36 years (range: 18 - 61y). Sixteen patients were male. A median time from diagnosis to transplantation was 1858 days in patients who had previously received immunosuppressive therapy (IST) using ATG (n = 16) and 121 days in those who had not received IST (n = 12). Sixteen patients received graft form related donors including 1 HLA-mismatched donor, and 12 patients did from unrelated donors including 3 mismatched donors. Stem cell source was bone marrow in 27 out of 28 patients. All patients but one, who died early due to infection, achieved neutrophil engraftment at a median of 19 days after HSCT. Mixed chimerism (MC) was observed in 6 patients at day 30, and 3 out of those 6 patients achieved complete donor chimerism by day 90. On the other hand, MC was newly observed in additional 2 patients at day 90. Only one patient experienced secondary engraftment failure, and which developed with complete donor-type chimerism at day 99. No patients developed grade 2-4 acute GVHD. However, the cumulative incidence of chronic GVHD was 39.9 % at 1 year, and one third of them had extensive type. With a median follow-up period of 1727 days for survivors, overall survival rates (OS) were 96.4 % at 1 year and 82.8 % at 5 years (Figure 1). Cytomegalovirus (CMV) antigenemia was detected in 17 patients, but no patients developed CMV disease. A high Epstein-Barr virus (EBV)-DNA load (more than 1×104 copies/mL) was detected in 2 patients at day 60 and 1 patient at day 90. Neither developed EBV-lymphoproliferative disorder (LPD) within a year. However, another patient, in whom high EBV-DNA load was not detected within 90days after HSCT, developed EBV-LPD and died at three and a half years after HSCT. [Conclusion] HSCT for AA using Flu, reduced-dose CY, and low-dose thymoglobulin as a conditioning regimen was safe and effective. Relatively high incidences of MC and chronic GVHD need further improvement. (This study is registered with www.umin.ac.jp as UMIN000006071.) Disclosures Kako: Takeda Pharmaceutical Company Limited.: Honoraria; Takeda Pharmaceutical Company Limited.: Honoraria; Celgene K.K.: Honoraria; Bristol-Myers Squibb: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Ono Pharmaceutical Co., Ltd.: Honoraria; Janssen Pharmaceutical K.K.: Honoraria. Kanda:Tanabe-Mitsubishi: Research Funding; Shionogi: Consultancy, Honoraria, Research Funding; Taisho-Toyama: Research Funding; Pfizer: Research Funding; Taiho: Research Funding; MSD: Research Funding; Sanofi: Research Funding; Novartis: Research Funding; Eisai: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Otsuka: Research Funding; Asahi-Kasei: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; CSL Behring: Research Funding; Ono: Consultancy, Honoraria, Research Funding; Nippon-Shinyaku: Research Funding; Astellas: Consultancy, Honoraria, Research Funding; Kyowa-Hakko Kirin: Consultancy, Honoraria, Research Funding; Dainippon-Sumitomo: Consultancy, Honoraria, Research Funding; Chugai: Consultancy, Honoraria, Research Funding; Takara-bio: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Mochida: Consultancy, Honoraria; Alexion: Consultancy, Honoraria. Usuki:Ono Pharmaceutical: Speakers Bureau; GlaxoSmithKline K.K.: Research Funding; Janssen Pharmaceutical K.K: Research Funding; Sanofi K.K.: Research Funding; Shire Japan: Research Funding; SymBio Pharmaceuticals Limited.: Research Funding; Celgene Corporation: Research Funding, Speakers Bureau; Daiichi Sankyo: Research Funding; Takeda Pharmaceutical: Speakers Bureau; Boehringer-Ingelheim Japan: Research Funding; Pfizer Japan: Research Funding, Speakers Bureau; Sumitomo Dainippon Pharma: Research Funding, Speakers Bureau; Novartis: Speakers Bureau; Chugai Pharmaceutical: Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Astellas Pharma Inc.: Research Funding; Nippon Shinyaku: Speakers Bureau; Mochida Pharmaceutical: Speakers Bureau; MSD K.K.: Speakers Bureau. Mori:Astella Pharma: Honoraria; Shire Japan: Honoraria; Janssen: Honoraria; SHIONOGI: Honoraria; Taisho Toyama Pharmaceutical Co: Honoraria; Novartis Pharma: Honoraria; Celgene: Honoraria; Japan Blood Products Organization: Honoraria; Pfizer: Honoraria; CHUGAI: Honoraria; MSD: Honoraria; Eisai: Honoraria; Novartis Pharma: Research Funding; Asahi Kasei: Research Funding; MSD: Research Funding; Kyowa Hakko Kirin: Honoraria; Ono: Honoraria.

scholarly journals Continuous High-Dose (6 mg) vs. Low-Dose (3 mg) Intravitreal Ganciclovir for Cytomegalovirus Retinitis After Haploidentical Hematopoietic Stem Cell Transplantation: A Randomized Controlled Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Wei-Bin Chen ◽  
Ze Long ◽  
Jing Hou ◽  
Heng Miao ◽  
Ming-wei Zhao
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Dose Group ◽  
Low Dose ◽  
High Dose ◽  
Treatment Procedure ◽  
Hematopoietic Stem

Purpose: To evaluate the safety and efficacy of continuous high-dose (6 mg) intravitreal ganciclovir injections (IVG) for cytomegalovirus (CMV) retinitis (CMVR) after haploidentical hematopoietic stem cell transplantation (Haplo-HSCT), and to explore factors that may influence the treatment procedure.Design: Prospective, randomized, single-blinded, positive-controlled, interventional, comparative study.Methods: A total of 22 patients with CMVR (32 eyes) were randomized to either high-dose group (IVG 6 mg weekly) or low-dose group (IVG 3 mg given twice weekly for 2 weeks as induction phase and weekly thereafter as maintenance phase). Patients who were recorded any positive CMV DNAemia or other active CMV diseases and needed systemic anti-CMV treatment during the study period were excluded. The vision outcome, variables of the treatment procedure, and incidence of complication and CMVR recurrence were analyzed and compared. Logistic regression was applied to determine the factors that may have an impact on the treatment process at baseline.Results: Compared to the low-dose group, the high-dose group resulted in a median of two less intravitreal injections (4 vs. 6 times, respectively, P = 0.016), while the rate of vision stability or improvement (81.2 vs. 87.5%), the incidence of complication (6.2 vs. 18.8%), and CMVR recurrence (12.5% vs. 6.2%) were similar (all P &gt; 0.05). No drug-related toxicity was observed. Initial aqueous CMV-DNA load (OR: 6.872, 95% CI: 1.335–35.377, P = 0.021) and extension of lesion (OR: 0.942, 95% CI: 0.897 to .991, P = 0.020), but not dosing regimen (P = 0.162), were predictors of the treatment duration.Conclusions: Continuous high-dose regimen was well tolerated and resulted in less intravitreal injections, with similar vision outcomes and safety profiles. The clinical course of CMVR after Haplo-HSCT was determined by its own nature at baseline and could not be modified by treatment protocols under consistent immune background.

Adoptive Immunotherapy with Donor Lymphocyte Infusions after T-Cell Depleted Allogeneic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2014-2014 ◽  
Author(s):  
Renee M.Y. Barge ◽  
Eva Steel ◽  
Ingrid Starrenburg ◽  
Floor Beaumont ◽  
Willem M. Smit ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Low Dose ◽  
Mixed Chimerism ◽  
High Dose ◽  
Term Survival ◽  
Donor Lymphocyte Infusions

Abstract In this study we analyzed 40 patients with AML who received donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation (alloSCT). Patients with a median age of 42 (range, 11–66) were transplanted with an in vitro T-cell depleted (Campath in the bag) graft from an HLA matched sibling following a myeloablative (n=35) or a nonmyeloablative conditioning regimen (n=5). Patients received DLI for relapsed AML (n=28) or for mixed chimerism (n=12). All patients with relapsed AML were treated with a cytarabine-containing chemotherapy regimen or with gemtuzumab ozogamycin immediately prior to DLI treatment and received daily 3 x 106 U α-IFN sc. The DLI dose administered was depending on the protocol used. Fourteen relapsed patients received high dose DLI with a median of 50 x 106 CD3+ cells/kg and 14 low dose DLI with a median of 5 x 106 CD3+ cells/kg. Ten of 28 patients with relapsed AML obtained a complete remission after the combination of chemotherapy and DLI. One patient obtained a partial remission and fourteen patients showed no response. Three patients were not evaluable. No effect of cell dose was observed on the clinical response after DLI. The median percentage of donor chimerism in patients with relapsed AML before DLI was 74% (range, 5–96%) and increased after DLI to 97% (range, 5–100%). Six patients with relapsed AML became complete chimera after DLI. DLI caused in 12 of 28 relapsed patients grade 3–4 GVHD. cGVHD was observed in 3 patients of whom 2 developed extensive GVHD. With a median follow up of 11 months only 1 pt in the high dose and 4 pts in the low dose group are alive in CR and 23 have died due to progressive disease (16) or GVHD (7). Due to this low rate of long-term survival of relapsed AML patients treated with DLI, we recently developed a new DLI protocol for AML patients. Twelve patients with mixed chimerism at 6 months after T-cell depleted alloSCT were pre-emptively treated with 3 x 106 CD3+ cells/kg. Complete chimeric response was observed in 6 of these 12 patients. Two patients showed increasing mixed chimerism and three patients showed no response. Two of 12 patients treated for mixed chimerism developed aGVHD gr 1–2. No severe aGVHD was observed in this group. Two patients developed chronic GVHD, both after nonmyeloablative conditioning. Incidence of GVHD was significantly lower in this group compared to the relapsed patients. Currently, 7 patients are alive in CR. In conclusion: 1) Long term survival of patients with overt relapse AML after alloSCT treated with DLI remains poor 2) High dose DLI appeared to be less effective than low dose DLI due to increased toxicity 3) DLI for AML may be more successful when it is administered pre-emptively for mixed chimerism after T-cell depleted alloSCT.

Autologous Stem Cell Transplant Followed by Low Dose Rituxan Maintenance in CR1 Is Effective for the Treatment of Mantle Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5427-5427 ◽  
Author(s):  
Seah H. Lim ◽  
William V. Esler ◽  
David Beggs ◽  
Colleen Burris ◽  
Yana Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Low Dose ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Mantle Cell

Abstract Conventional chemotherapy is non-curative for mantle cell lymphoma (MCL). Although the addition of Rituxan has improved the outcome of these patients, many patients still relapsed and died of their disease. High dose chemotherapy followed by autologous stem cell transplant (ASCT) has been investigated but produced conflicting results, ranging from no demonstrable benefit to a 2-year event-free survival (EFS) of 77%. A recent randomized study compared ASCT with interferon-a maintenance and showed benefits in both the EFS and overall survival for patients in the ASCT study arm. The conflicting results are probably related to the use of different chemotherapeutic agents as conditioning regimens for the transplant and also to different post-transplant therapy. In this study, we have chosen to induce patients with advanced MCL with R-CHOP and consolidate these patients with high dose single agent melphalan, a cytotoxic that has not been previously tested as a single agent in MCL. Since most patients relapsed within the first two years after transplant, low dose maintenance Rituxan therapy is given three-monthly during the first 2 years after ASCT. Following consent from the patients, 8 consecutive patients with advanced Stage III or IV MCL were treated. There were 5 male and 3 female, with a median age of 642 years (range 46–72 years). One patient had Stage III and the other 7 Stage IV diseases. All eight patients received remission + 2 courses of R-CHOP as induction chemotherapy. Autologous stem cells were harvested upon recovery from the last course of R-CHOP and ASCT carried out within 6 weeks from the last course of R-CHOP. High dose intravenous melphalan (200 mg/m2) was administered followed, 24 hours afterward, by the infusion of a minimum of 2 × 106/kg of CD34+ autologous stem cells. Rituxan maintenance therapy was initiated at a dose of 375 mg/m2 given as a single infusion once every three months starting Day +100. As of August 2006, with a median follow-up of 45.5 months from diagnosis (range 10–57 months) and 39 months from ASCT (range 4–52 months), seven patients are alive lymphoma-free, as defined by clinical and PET-CT examination. One patient died in CR of a myocardial infarction. Adverse effects were as expected from the high dose melphalan, except that delayed immunoglobulin reconstitution, as reported previously, was observed in all eight patients. Four of these hypogammaglobulinemic patients had recurrent infections (three with recurrent respiratory tract infection and one with a chronic diarrhea that was Vancomycin sensitive) and two required monthly intravenous immunoglobulin replacement. The result presented here is, therefore, extremely encouraging for a group of patients who normally have a very poor clinical outcome and warrants confirmation in larger multicenter study.

Combined Use of Multi-Day Doses of Palonosetron and Aprepitant with Low Dose Dexamethasone In Prevention of Nausea and Emesis Among Patients with Multiple Myeloma and Lymphoma Undergoing Autologous Hematopoietic Stem Cell Transplant (ASCT): A Pilot Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1335-1335
Author(s):  
Delva Deauna-Limayo ◽  
Omar Aljitawi ◽  
Siddhartha Ganguly ◽  
Sunil Abhyankar ◽  
Jo Wick ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Research Funding ◽  
Low Dose ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Combined Use ◽  
Delayed Cinv

Abstract Abstract 1335 High dose chemotherapy and autologous hematopoietic stem cell transplantation (ASCT) is a standard of care therapy patients with multiple myeloma and relapsed/refractory lymphomas. Unfortunately, high dose chemotherapy used in the preparative regimen is considered highly emetogenic. In one study, only 20% of patients undergoing ASCT managed to remain emesis-free. The 5-HT3 receptor antagonist is considered the backbone of anti-emetic regimens in this setting. Despite the combined use of these agents with dexamethasone, only 47% of recipients would achieve emetic control. Palonosetron, a second generation 5-HT3 antagonist, is approved as a single 0.25 mg IV dose in prevention of acute emesis in highly emetogenic chemotherapy regimens. Aprepitant represents a new class of oral anti-emetic which targets the NK-1 receptor. It is effective for both acute and delayed onset emesis. Objectives and Methods: Patients undergoing ASCT for multiple myeloma (MM) and relapsed lymphoma at the University of Kansas Medical Center were offered this study. The primary objective was to assess emetic responses to prophylactic multi-day doses of palonosetron, aprepitant and low dose dexamethasone. Emetic responses were assessed by daily patient diaries and the Multinational Association for Supportive Care in Cancer Antiemetic Tool (MAT). Nausea was measured using a Nausea Visual Score (NVS) of 0 to 10 with score of 0 having no nausea. A “modified” Osoba module was used to assess quality of life (QOL); and non-hematologic toxicities were evaluated. Preparative regimens were MEL140-200 for MM and BEAM or BEAC +/− rituximab for lymphomas. Standard doses aprepitant 125/80/80 mg were administered on days - 3, - 2, - 1 for MM group, and days - 7, - 6, - 5 for lymphoma group. Low dose dexamethasone 4 mg IV and multi-day doses of palonosetron 0.25 mg IV were administered on days - 3, - 2, -1, and on days - 7 thru - 3 for the MM and lymphoma groups, respectively. In both groups, palonosetron was repeated on day + 3. Acute chemotherapy-induced nausea/vomiting (CINV) was defined as nausea and/or vomiting within 24 hours of chemotherapy. Delayed CINV was defined as nausea and/or vomiting after 24 and up to 72 hours after chemotherapy; and extended CINV as nausea and/or vomiting after 72 hours of chemotherapy. Emetic responses were defined as follows: Complete Control (CC) – no emetic episode in 24 hours, no rescue medications and NVS of ≤ 2.5; Complete Emetic Response (CR) – 0 emetic episode, no rescue; Major Emetic Response (MR) – 1–2 episodes; Minor Emetic Response (MR) – 3–5 episodes; Failure - >5 episodes. Results: Between October 2007 and January 2010, 20 patients were enrolled, of which 18 were considered evaluable, 9 MM and 9 lymphoma – both Hodgkin's and non-Hodgkin's lymphoma. There were 11 males and 9 females. Median age was 55 (range: 35–66). All patients achieved at least a major emetic response in the acute, delayed and extended phases. Acute CINV responses were achieved in all patients: CC 2/9 (22%) and MR 7/9 (78%) in MM patients and CC 2/9 (22%), CR 2 (22%) and MR 5/9 (56%) in lymphoma patients. Delayed CINV responses were achieved in all patients: CC 2/9 (22%), CR 1 (11%) and MR 6/9 (67%) in MM patients and CC 4/9 (44%), CR 1 (11%) and MR 4/9 (44%) in lymphoma patients. Finally, all patients achieved extended CINV responses: CC 1/9 (11%) and MR 8/9 (89%) in MM patients and CC 2/9 (22%) and MR 7/9 (78%) in lymphoma patients. Eight patients developed grade 2–3 non-hematologic toxicities (arrhythmia, infection, febrile neutropenia, gastric mucositis, abdominal pain, and hyponatremia) attributed to the preparative transplant regimen. Only the arrhythmia was felt to be possibly related to the study drugs. Data on QOL will be presented during the conference. Conclusion: The combination of multi-day palonosetron combined with aprepitant and low dose dexamethasone appear to be well tolerated and effective in achieving at least a major emetic response in 100% of patients with MM and lymphoma undergoing high-dose therapy and ASCT. These encouraging results should warrant further evaluation in a larger population of ASCT patients. Disclosures: Deauna-Limayo: Eiasi: Research Funding. Aljitawi:Eisai: Research Funding.

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